OBJECTIVE:This frequentist network meta-analysis was conducted to compare vornorexant (VOR) and lemborexant (LEM) in terms of efficacy, tolerability, and safety outcomes in adults with insomnia disorder. METHODS:Efficacy outcomes evaluated at weeks 1 and 2 included subjective time to sleep onset (sTSO), which served as the primary outcome at week 2, as well as subjective total sleep time (sTST), subjective wake after sleep onset (sWASO), and subjective sleep efficiency. Tolerability outcome was treatment discontinuation due to adverse events. Safety outcomes included the incidence of death, suicidal behavior or ideation, at least one adverse event, somnolence, fatigue, dizziness, falls, headache, nightmares, cataplexy, and sleep paralysis. RESULTS:This network meta-analysis included seven trials (n = 2805, average age = 55.14 years, 69.22% female). Treatment arms comprised VOR 5 mg/day (VOR5), VOR 10 mg/day (VOR10), LEM 5 mg/day (LEM5), LEM 10 mg/day (LEM10), and placebo. All active treatments were associated with significantly greater improvements in sTSO at week 2 than placebo. The mean differences in sTSO at week 2 were -11.997 min (95% CI, -15.236 to -8.757) for LEM5, -14.856 min (95% CI, -18.038 to -11.674) for LEM10, -11.364 min (95% CI, -14.733 to -7.996) for VOR5, and -9.758 min (95% CI, -13.186 to -6.330) for VOR10. LEM5, LEM10, and VOR5 demonstrated significant improvements across all efficacy outcomes at weeks 1 and 2 over placebo. However, although VOR10 did not demonstrate superiority over placebo for sWASO at weeks 1 and 2, it was superior to placebo for all other efficacy outcomes. LEM5 and LEM10 were associated with a higher incidence of at least one adverse event and somnolence compared with placebo, whereas no significant differences in tolerability or safety outcomes were observed for VOR5 or VOR10 versus placebo. CONCLUSIONS:Dosage variations could influence both the clinical efficacy and safety profile of these agents.
OBJECTIVE:To determine the effect that paliperidone palmitate 6-month long-acting injectable formulation (PP6M) had on metabolic parameters including body weight (BW), and blood lipid profiles, a post-hoc analysis was conducted to assess changes in BW from baseline to the end of study based on age, body mass index (BMI), and changes in blood lipid profiles during a 12-month, phase 3, double-blind (DB) clinical study. Long term effects of PP6M on BW and BMI were further explored during a 24-month extension study in which participants were treated exclusively with PP6M. METHOD:In the 12-month DB phase, participants were randomized to receive PP6M or paliperidone palmitate 3-month long-acting injectable formulation (PP3M). The mean change in BW and abnormal weight percent change from baseline were calculated at endpoint by age, gender, and BMI. Additionally, treatment-emergent shifts from baseline for the four key lipid parameters (fasting low density lipoprotein [LDL], fasting triglycerides [TG], fasting total cholesterol [TC], and fasting high density lipoprotein [HDL]) during DB were assessed. Following this study, participants were given the opportunity to transition to a 24-month extension study and be treated with PP6M. The mean change and percent change in BW, and the mean change in BMI from DB baseline to the end of the extension study (36 months total) were calculated. RESULTS:Participants who were treated with PP6M showed numerically less weight gain, BMI, waist circumference, and more weight decrease compared to PP3M group during 12-month DB phase, though the proportion of participants reporting an abnormal change (≥7% change) in BW did not significantly differ between PP3M and PP6M. The weight differences were more pronounced in the younger age group (18-25 years) and those who were overweight (BMI: 25 to <30 kg/m2. Numerical differences in favor of PP6M were found in fasting blood lipids (HDL, LDL, TG, and TC). The changes in BW and BMI over time remained consistent throughout the 24-month extension, favoring PP6M in each instance. CONCLUSIONS:This post-hoc analysis demonstrated that PP6M was comparable to PP3M in terms of metabolic parameters; however, it may have a beneficial effect on weight gain, especially in young patients. TRIAL REGISTRATION:Post-Hoc Analysis of Studies NCT03345342 and NCT04072575 (ClinicalTrials.gov). Significant outcomes The findings from this study have highlighted that participants who were treated with the 6-month long-acting injectable formulation of paliperidone exhibited less weight gain during treatment overall, and significantly less weight gain in adolescents and young adults. Importantly, this trend continued over the course of long-term treatment, regardless of age. Participants treated with the 6-month formulation also had fewer shifts in blood lipids outside of the normal range and had more favorable changes in body mass index and waist circumference. These results suggest that when considering metabolic dysregulation as a factor in choosing a long-acting injectable antipsychotic, the 6-month formulation is a viable alternative to the 3-month formulation, particularly in younger patients with schizophrenia. Limitations Because this is a post hoc analysis and the study was not powered to test weight and metabolic changes, most endpoints were summarized descriptively and the statistical test was limited to the main endpoint (abnormal percent weight gain and loss).
From early life to adulthood, stress shapes brain circuits by impacting vulnerable neuron populations, with parvalbumin-expressing interneurons (PVIs) emerging as particularly sensitive targets. These fast-spiking interneurons orchestrate inhibitory control, maintain excitatory/inhibitory balance, and regulate network oscillations, all of which are crucial for cognitive and emotional function. In addition, PVIs play a central role in regulating stress vulnerability and resilience. Several cellular and molecular mechanisms have been implicated in stress-induced PVI deficits, including disrupted developmental trajectories, redox and metabolic vulnerabilities, inflammatory and microglia-associated signaling, and epigenetic modulation. Stress also remodels perineuronal nets (PNNs), specialized extracellular matrix structures that enwrap PVIs and contribute to their stabilization, the regulation of synaptic function, and protection against oxidative stress. This review synthesizes evidence from rodent models of stress, detailing putative mechanisms through which stress alters PVIs, their associated PNNs, and their circuit-level consequences across development and brain regions, including sex-dependent effects. It further discusses pharmacological and adjuvant interventions that may mitigate stress-induced PVI dysfunction, including monoaminergic modulators, ketamine and its derivatives, as well as anti-inflammatory and antioxidant strategies. By integrating mechanistic insights with potential strategies to protect or restore PVI function, we aim to provide a framework for understanding and reducing stress-induced psychiatric outcomes.
BACKGROUND:Major depressive disorder (MDD) is characterized by depressed mood, anhedonia, and loss of energy, which can be accompanied by associated symptoms and co-morbidities. Psychiatric scales such as the Montgomery Åsberg Depression Rating Scale (MADRS) must account for the complex nature of depression. METHODS:The MADRS total score change between baseline and week 8 was the primary outcome measure in a randomized, double-blind clinical trial investigating the antidepressant efficacy of 8 weeks' treatment with silexan compared to sertraline and placebo in patients with mild or moderate MDD. We report on a pre-planned, exploratory analysis of the individual MADRS items. Treatment effects were assessed using analyses of covariance with baseline adjustment, based on an estimand strategy. RESULTS:498 subjects (silexan 170, sertraline 171, placebo 157) were treated and analyzed. After 8 weeks, silexan was superior to placebo for 5 out of the 9 MADRS items analyzed ("apparent sadness", "reported sadness", "reduced appetite", "concentration difficulties", "lassitude"; P < .05) and showed clinically important adjusted mean value differences >0.2 points for 7 out of the 9 items. Item-level results for silexan and sertraline were mainly comparable. CONCLUSIONS:Silexan had a strong over-all antidepressant effect, with the most pronounced improvements affecting the cardinal symptoms of depression. TRIAL REGISTRATION:EudraCT2020-000688-22 first entered on 12/08/2020. Significance statement Patients with depressive disorders can show many different symptoms. To better characterize the clinical action of an antidepressant, it is therefore important to analyze not only the overall value of a depression scale but also the individual items that describe these symptoms. Silexan is a preparation from lavender oil whose antidepressant effect has been proven in a randomized, double-blind, placebo-controlled 8-week study in patients with mild or moderate major depressive disorder. Based on the individual items of the Montgomery Åsberg Depression Rating Scale that was used as the main outcome for efficacy, we found in an exploratory, hypothesis-generating analysis that silexan had a rather broad antidepressant effect in the participants of our study, with potentially clinically meaningful advantages over placebo for 7 out of the 9 individual items investigated. This applied in particular to the main symptoms of depression, namely sadness and lassitude. Our single-item analysis thus helps to understand the antidepressant effects of silexan in more detail. Significant outcomes In patients with mild to moderate major depressive disorder, lavender oil preparation silexan has a clinical profile similar to that of the selective serotonin re-uptake inhibitor sertraline based on an item-level analysis of the Montgomery-Åsberg Depression Rating Scale (MADRS). Silexan has a significant antidepressant effect that includes an alleviation of depressed mood, anhedonia, and loss of energy, the cardinal symptoms of depression. The broad improvement of symptoms of depression could not be explained by the proven anxiolytic efficacy silexan alone but indicates an independent, direct antidepressant effect. The present item-level analysis provides valuable and detailed additional insights into the therapeutic profiles of silexan and sertraline and may help clinicians to tailor antidepressant treatment to the specific symptoms of a patient. Limitations For item-level analyses of the MADRS, no validated thresholds for the assessment of the clinical importance of changes over time have been defined, taking into account that different items may have different thresholds. Even though our analyses were pre-defined, they were exploratory and did not include studywise type I error level control. Their generalizability beyond the study population is therefore limited.
OBJECTIVE:Efficacy of viloxazine ER (extended-release capsules; Qelbree®) for attention-deficit/hyperactivity disorder (ADHD) is attributed to its ability to increase extracellular norepinephrine and dopamine in the medial prefrontal cortex by inhibiting norepinephrine transporters (NET); however, studies also suggest potentially relevant activity at serotonin (5-HT) receptors. In this study, we evaluated the target engagement by viloxazine at 5-HT2 receptor subtypes, in species with close similarities with humans, and whether viloxazine engages 5-HT2 receptor subtypes within a clinically relevant plasma concentration range. METHODS:This study utilized positron emission tomography (PET) and was conducted to measure the relationship between viloxazine plasma concentration and the changes in binding of the agonist radioligand [11C]CIMBI-36 to 5-HT2C/5-HT2A receptors in the brain of Macaca fascicularis monkeys. RESULTS:Viloxazine administration reduced the binding of [11C]CIMBI-36 at 5-HT2C receptors at a concentration 10- to 20-fold lower than at 5-HT2A receptors (EC50: 4.1 vs 45.1 μM, respectively), consistent with receptor binding affinities previously measured in vitro (Ki: 0.66 vs 16.0 μM, respectively). Unbound viloxazine plasma concentrations during these PET scans were compared to human unbound concentrations at doses used to treat ADHD. Our data suggest that at clinically relevant plasma concentrations, viloxazine occupies 60%-72% of 5-HT2C receptors. CONCLUSION:Our results demonstrate that at unbound viloxazine plasma concentrations comparable with those clinically relevant for the treatment of ADHD, viloxazine occupies a high proportion of 5-HT2C receptors. Occupancy of and potential functional activity at 5-HT2C receptors could therefore contribute to the therapeutic activity of viloxazine in addition to inhibition of NET.
Objective:To evaluate the clinical efficacy of the governor vessel-unblocking and mind-refreshing acupuncture method combined with neuromuscular stimulation in treating patients with traumatic brain injury,as well as its effects on hemodynamics,limb function,and balance recovery. Methods:A total of 128 patients with traumatic brain injury were selected and randomly divided into three groups using a simple randomization method.The control group(n=42)received neuromuscular stimulation;the acupuncture group(n=43)received governor vessel-unblocking and mind-refreshing acupuncture;and the combined group(n=43)received governor vessel-unblocking and mind-refreshing acupuncture combined with neuromuscular stimulation.The clinical efficacy was assessed after 8 weeks of continuous treatment,and comparisons were made among the groups regarding the traditional Chinese medicine symptom score,limb function[Fugl-Meyer assessment(FMA)score],balance function[Berg balance scale(BBS)score],recovery status[activities of daily living(ADL)score],National Institutes of Health stroke scale(NIHSS)score,and Glasgow coma scale(GCS)score,as well as hemodynamic parameters[mean blood flow velocity(Vm)in bilateral internal carotid arteries,pulsatility index(PI),and peak systolic velocity(PSV)].Treatment safety was also assessed. Results:After treatment,the total effective rate in the combined group was 95.4%,which was higher than 76.2%and 81.4%in the control group and the acupuncture group,respectively(P<0.05);there was no statistically significant difference between the control group and the acupuncture group(P>0.05).Before treatment,there were no statistically significant differences in the scores for unconsciousness and inability to speak,pallor,wheezing in the throat,flaccid paralysis and weakness,cold extremities,or the total TCM symptom score among the three groups(P>0.05);after treatment,the scores for the aforementioned items in all three groups decreased(P<0.05);the combined group's scores were lower than those of the control and acupuncture groups(P<0.05);there was no statistically significant difference between the control group and the acupuncture group(P>0.05).Before treatment,there were no statistically significant differences in the FMA and BBS scores among the three groups(P>0.05);after treatment,the FMA and BBS scores in all three groups increased(P<0.05);the combined group had higher scores than the control and acupuncture groups,with statistical significance(P<0.05);there were no statistically significant differences between the control group and the acupuncture group(P>0.05).Before treatment,there were no statistically significant differences in the NIHSS,GCS,and ADL scores among the three groups(P>0.05).After treatment,NIHSS scores decreased,and GCS and ADL scores increased in all three groups.The combined group had a lower NIHSS score and higher GCS and ADL scores compared to the control and acupuncture groups,with statistical significance(P<0.05);however,there were no statistically significant differences between the control group and the acupuncture group(P>0.05).Before treatment,there were no statistically significant differences in the Vm,PI,or PSV among the three groups(P>0.05);after treatment,the Vm and PI increased,and the PSV decreased in all three groups,with statistically significant differences within each group(P<0.05);patients in the combined group had higher Vm and PI values and a lower PSV value than those in the control and acupuncture groups;the inter-group differences were all statistically significant(P<0.05);there was no statistically significant difference between the control group and the acupuncture group(P>0.05). Conclusion:The combination of governor vessel-unblocking and mind-refreshing acupuncture and neuromuscular stimulation for the treatment of patients with traumatic brain injury is more effective than either therapy used alone,and demonstrates greater advantages in improving patients'hemodynamics,enhancing limb function,and improving balance.
Objective:To observe the therapeutic effect and safety of cupping therapy in treating patients with acute-stage scapulohumeral periarthritis(SP)of a wind-cold-dampness pattern. Methods:A total of 60 patients with acute-stage SP of a wind-cold-dampness pattern were divided into a treatment group and a control group according to a random number table method,with 30 cases in each group.Both groups received active exercise.The treatment group was additionally treated with cupping therapy,while the control group was additionally treated with conventional medication.After 2 consecutive weeks of treatment,changes in the pain degree,shoulder joint function,and traditional Chinese medicine(TCM)symptom score were observed.The total effective rate and adverse reactions were compared between the two groups. Results:Before treatment,there were no statistically significant differences between the two groups in the visual analog scale(VAS)score,TCM symptom score,or Constant-Murley score(CMS)of shoulder joint function(P>0.05).After treatment,the VAS and TCM symptom scores in the treatment group were significantly lower than those in the control group(P<0.05),while the CMS and total effective rate were significantly higher than those in the control group(P<0.05).No obvious adverse reactions occurred in either group during treatment. Conclusion:On the basis of active exercise,cupping therapy can effectively relieve pain and improve shoulder joint function in patients with acute-stage SP of a wind-cold-dampness pattern,with fewer adverse reactions.
Objective:To observe the effects of acupuncture combined with electromyographic biofeedback(EMGBF)on feeding ability and swallowing function in patients with poststroke dysphagia. Methods:A total of 106 patients with poststroke dysphagia were selected and divided into an observation group and a control group according to the random number table method,with 53 cases in each group.Both groups received routine rehabilitation training.The control group additionally received EMGBF therapy,while the observation group additionally received acupuncture therapy on the basis of the treatment protocol used in the control group.After treatment,the clinical efficacy was compared between the two groups,and changes in the water swallowing test(WST)grade,surface electromyography(sEMG),standardized swallowing assessment(SSA)score,and serum amyloid A(SAA)level were observed. Results:After treatment,the clinical efficacy in the observation group was superior to that in the control group(P<0.05).After treatment,the WST grade in each group was significantly different from that before treatment(P<0.01),and the grading in the observation group was superior to that in the control group(P<0.01).Compared with before treatment in the same group,the swallowing time,SSA score,and serum SAA level significantly decreased after treatment in both groups(P<0.05),while the maximum amplitude of sEMG and videofluoroscopic swallowing study(VFSS)score significantly increased(P<0.05);the changes in the observation group were superior to those in the control group(P<0.05).There was no statistically significant difference in the adverse reactions between the two groups(P>0.05). Conclusion:On the basis of routine rehabilitation training,acupuncture combined with EMGBF is superior to EMGBF alone in the treatment of poststroke dysphagia.It can improve feeding ability and swallowing function and reduce the serum SAA level in the patients.
To observe the clinical efficacy of wrist-ankle acupuncture plus auricular point sticking for poststroke shoulder-hand syndrome (PS-SHS) in phase I and its effect on pain and range of motion (ROM). A total of 90 patients with PS-SHS in phase I were enrolled and divided into a conventional group, an auricular point group, and a combination group according to different treatment methods, with 30 cases in each group. The conventional group was treated with conventional rehabilitation training, and the auricular point group was treated with additional auricular point sticking. The combination group was treated with additional wrist-ankle acupuncture on the basis of the auricular point group treatment. The treatment was performed consecutively for 5 d per week, followed by 2 d of rest, with each group undergoing consecutive treatment for 6 weeks. The clinical efficacy, pain score, ROM indicator, serum levels of endothelin-1 (ET-1), nitric oxide (NO), and bradykinin (BK), quality of life (QOL), and adverse reaction incidence rate were compared among the three groups. After treatment, the total effective rate of the combination group was 96.7
To observe the effect of pressing manipulation on pain sensitization of spinal cord dorsal horn (SCDH) in rats with myofascial trigger points. Thirty-two male Sprague-Dawley rats were divided into a blank group (n=10) and a group for modeling (n=22) using the random number table method. Rats in the group for modeling were subjected to blunt blow plus centrifugal motion, and 20 rats successfully modeled were randomly divided into a model group and a pressing manipulation group, with 10 rats in each group. Rats in the blank group and the model group were reared routinely. Rats in the pressing manipulation group were subjected to pressing manipulation for 7.5 min continuously at 10 times/min, once every other day for a total of 7 times. After the values of pressure pain threshold (PPT) and soft tissue tension (STT) D0.2 were measured in each group, the histomorphological changes at trigger points were observed. The expression levels of vesicular glutamate transporter 1 (VGluT1), M1 microglia marker (CD86), and M2 microglia marker (CD206) in lumbar enlargement’s SCDH were detected by immunohistochemistry. Western blotting was used to observe the expression levels of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), N-methyl-D-aspartic acid receptor 2B (NR2B), phosphorylated nuclear factor-kappa B p65 subunit (p-p65), interleukin (IL)-6, and tumor necrosis factor (TNF)-α. Compared with the blank group, the values of PPT and STT D0.2 were significantly decreased (P<0.05), and the morphological structure of muscle cells was changed with different sizes; the nucleus moved inward, inflammatory cells infiltrated between cells, and fibroblasts were increased in the model group. Compared with the model group, the values of PPT and STT D0.2 were significantly higher (P<0.05), the morphological structure of muscle cells showed improvement, and the phenomena of nuclear migration, inflammatory cell infiltration, and fibroblast proliferation were all reduced in the pressing manipulation group. Compared with the blank group, the expression levels of VGluTl, CD86, p-ERK1/2, NR2B, IL-6, TNF-α, and p-p65 were significantly increased (P<0.05), and the expression level of CD206 was decreased (P<0.05) in the lumbar enlargement’s SCDH in the model group. Following pressing manipulation intervention, the expression levels of the aforementioned proteins were significantly reduced (P<0.05), while the expression level of CD206 was elevated (P<0.05) in the lumbar enlargement’s SCDH in the pressing manipulation group. The pressing manipulation in Tuina (Chinese therapeutic massage) may promote microglial polarization from M1 to M2 in lumbar enlargement’s SCDH in trigger point rats, reduce the release of inflammatory factors, and inhibit the activity of glutamate neurons and their synapses, thereby inhibiting pain sensitization and relieving pain.
To observe the effects of the governor vessel-unblocking and mind-regulating acupuncture method on miR-152-3p, miR-145-5p, key molecules of the calcium/calmodulin-dependent protein kinase II (CaMK II)/nuclear factor (NF)-κB signaling pathway, and downstream inflammatory factors in cornu ammonis area 1 (CA1) in chronic unpredictable mild stress (CUMS) model rats, thereby exploring the possible mechanism of the governor vessel-unblocking and mind-regulating acupuncture method in treating depression. Twelve of 48 Sprague-Dawley rats were randomly selected as a blank control group, and the other rats were subjected to CUMS for 28 consecutive days to prepare a depression rat model. The successful model rats were randomly divided into a model group, an acupuncture group, and a fluoxetine group, with 12 rats in each group. The blank control and model groups did not receive intervention. The acupuncture group received acupuncture at Baihui (GV20), Shuigou (GV26), Shenting (GV24), and Dazhui (GV14), 6 d a week for a total of 4 weeks; the fluoxetine group was administered fluoxetine by gavage for 28 consecutive days. The behavioral changes of rats in each group after intervention were observed; hematoxylin-eosin staining and Nissl staining were used to observe the pathological morphology and neuronal damage of the hippocampal CA1 region. The levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, IL-10, and 5-hydroxytryptamine (5-HT) in the hippocampus and serum were detected by enzyme-linked immunosorbent assay. Relative expression levels of miR-152-3p, miR-145-5p, and mRNAs of CaMK II and NF-κB p65 in the hippocampus were detected by reverse transcription real-time fluorescence quantitative polymerase chain reaction. The expression levels of CaMK II, NF-κB p65, IL-1β, IL-6, TNF-α, and IL-10 in the hippocampal CA1 region were detected by immunofluorescence. Relative expression levels of CaMK II and NF-κB p65 protein in the hippocampus were detected by Western blotting assay. Compared with the blank control group, CUMS rats showed decreased numbers of squares crossed and upright standings and consumption rate of sucrose (P<0.01), and increased swimming immobility time (P<0.01); obvious inflammatory injury in hippocampal CA1 region; increased levels of IL-1β, IL-6, and TNF-α in the hippocampus and serum (P<0.01), and decreased levels of IL-10 and 5-HT (P<0.01); decreased relative expression levels of miR-152-3p and miR-145-5p in the hippocampus (P<0.01) and increased relative mRNA and protein expression levels of CaMK II and NF-κB p65 in the hippocampus (P<0.01), increased mean fluorescence intensities of CaMK II, NF-κB p65, IL-1β, IL-6, and TNF-α (P<0.01), and decreased mean fluorescence intensity of IL-10 (P<0.01) in hippocampal CA1 area. Compared with the model group, rats in the acupuncture group and the fluoxetine group had increased numbers of squares crossed and upright standings and consumption rate of sucrose (P<0.01), and significantly reduced swimming immobility time (P<0.01); reduced neuroinflammatory reaction in hippocampal CA1 region; decreased levels of IL-1β, IL-6, and TNF-α (P<0.01), and increased levels of IL-10 and 5-HT (P<0.01) in the hippocampus and serum; increased relative expression levels of miR-152-3p and miR-145-5p in the hippocampus (P<0.01), and decreased relative mRNA and protein expression levels of CaMK II and NF-κB p65 in the hippocampus (P<0.01); decreased mean fluorescence intensities of CaMK II, NF-κB p65, IL-1β, IL-6, and TNF-α in hippocampal CA1 area (P<0.01), while increased mean fluorescence intensity of IL-10 (P<0.01). Relative expression levels of miR-152-3p and miR-145-5p in rat hippocampus were negatively correlated with CaMK II mRNA (-1
To observe the clinical efficacy of herb cake-insulated moxibustion at Shenque (CV8) in treating primary dysmenorrhea (PD) of cold-induced blood stasis pattern, and its influence on serum inflammatory factors. A total of 60 patients with PD of cold-induced blood stasis pattern were randomly divided into an herb cake-insulated moxibustion group and a medication group by the random number table method, with 30 cases in each group. The medication group was treated with oral ibuprofen sustained-release capsules, initiated 3 d before menstruation and continued until the end of the menstrual period. The herb cake-insulated moxibustion group received herb cake-insulated moxibustion at Shenque (CV8), once daily starting 3 d before menstruation until menstruation ended. One menstrual cycle was defined as one treatment course, and both groups received treatment for 3 courses in total. The scores of visual analog scale (VAS) and traditional Chinese medicine symptoms were observed and recorded before and after treatment. In both groups, changes in the serum levels of interleukin (IL)-6, prostaglandin (PG) F2α, PGE2, and β-endorphin (β-EP) were determined before and after treatment. The clinical efficacy was evaluated. The total effective rate was 93.3
Objective:To observe the effect of warming needle therapy combined with rehabilitation training on postoperative recovery in patients with lumbar disc herniation(LDH)after percutaneous endoscopic lumbar discectomy(PELD). Methods:A total of 125 patients with LDH who underwent PELD were enrolled and randomized into two groups using a random number table method(63 cases in the observation group and 62 in the control group).Both groups received identical comprehensive rehabilitation training,while the observation group additionally received warming needle therapy at Jiaji(EX-B2)points.The intervention lasted for one month in both groups.Short-term clinical efficacy was evaluated after treatment,and changes in traditional Chinese medicine(TCM)symptom and visual analog scale(VAS)scores were observed.All patients were followed up for 6 months,during which Japanese Orthopaedic Association(JOA)and Oswestry disability index(ODI)scores were measured to assess lumbar spine function. Results:The total effective rate in the observation group was 93.7%,which was higher than 77.4%in the control group(P<0.05).At 1 week and 1 month postoperatively,the TCM symptom and VAS scores in both groups decreased compared with the preoperative levels(P<0.05),and the scores at 1 month postoperatively were lower than those at 1 week postoperatively(P<0.05).Moreover,the scores in the observation group were lower than those in the control group(P<0.05).Compared with the preoperative values,the JOA score in both groups increased at 6 months postoperatively(P<0.05),and it was higher in the observation group than in the control group(P<0.05).The ODI score in both groups decreased(P<0.05),and it was lower in the observation group than in the control group(P<0.05). Conclusion:Compared with comprehensive rehabilitation training alone,warming needle therapy at Jiaji(EX-B2)points combined with comprehensive rehabilitation training demonstrates greater advantages in alleviating clinical symptoms,improving lumbar function,and reducing pain in LDH patients after PELD.
Adolescent idiopathic scoliosis (AIS) is a common spinal deformity characterized by a complex etiology, rapid progression, and great difficulty in treatment. Based on the muscle region theory of traditional Chinese medicine (TCM), Professor SHEN Guoquan has proposed a therapeutic concept for AIS, namely, “treating the sinews first and giving equal importance to both sinews and bones”. This concept aims to restore the mechanical balance of the spine by precisely regulating the soft tissues surrounding it, along with the osseous structures, in accordance with the holistic concept of TCM. By summarizing Prof. SHEN’s distinctive clinical experience treating AIS with Tuina (Chinese therapeutic massage), this paper discusses the theoretical basis and clinical characteristics, providing ideas and references for the non-surgical treatment of AIS.
To assess the efficacy and safety of Tuina (Chinese therapeutic massage) for non-specific low back pain (NLBP) by employing a Bayesian network meta-analysis, with the aim of providing robust evidence-based insights for clinical applications. A comprehensive search was conducted for randomized controlled trials (RCTs) evaluating Tuina for NLBP across multiple databases, including China National Knowledge Infrastructure, China Science Periodical Database, Chinese Science Citation Database, Chinese Biomedical Literature Database, PubMed, Embase, Cochrane Library, and Web of Science, from each database’s inception to February 13, 2025. The included studies were assessed for the risk of bias using the Cochrane risk-of-bias assessment tool tailored for RCTs. A network meta-analysis was conducted using Stata 19 and R version 4.2.0. The mean difference (MD) and confidence interval (CI) were used for statistical descriptions. No statistically significant differences were noted in the efficacy among various interventions. However, the surface under the cumulative ranking curve (SUCRA) indicated that the combination of Tuina and acupuncture yielded the most favorable outcomes. Regarding the visual analog scale, Tuina combined with routine exercise training exhibited notable benefits compared with Tuina [MD=−1.41; 95
BACKGROUND:This study was to explore how serum ghrelin levels modulate the relationship between interleukin-6 (IL-6) and outcomes of antidepressant treatment, specifically focusing on 12-week remission and 24-month relapse in patients with depressive disorders. METHODS:This investigation involved the analysis of baseline serum levels of ghrelin and IL-6 among 1086 patients enrolled in a naturalistic study of stepwise antidepressant therapy. Remission was determined by a Hamilton Depression Rating Scale (HAMD) score of 7 or less at 12 weeks. Those who responded (HAMD score ≤ 14) at this juncture were subsequently monitored for relapse (HAMD score > 14) quarterly over a 24-month period. The study employed logistic regression models, adjusted for various sociodemographic and clinical factors, to evaluate the interaction between these biomarkers and treatment outcomes. RESULTS:Findings revealed that while serum ghrelin levels did not independently affect treatment outcomes, they significantly influenced the association between elevated IL-6 levels and the risks of non-remission at 12 weeks and relapse at 24 months. Specifically, high IL-6 levels correlated with poorer outcomes predominantly in the presence of lower ghrelin levels, with these interactions reaching statistical significance in relapse outcomes post-adjustment. CONCLUSION:The study highlights the complex interplay between IL-6 and ghrelin in shaping the efficacy of antidepressant treatments, demonstrating divergent influences on remission and relapse. These results emphasize the importance of incorporating multiple biomarkers into predictive models to tailor antidepressant strategies more effectively. Continued research is needed to dissect the underlying dynamics of these biomarker interactions.
To observe the effects of moxibustion at Shenshu (BL23) and Zusanli (ST36) point areas on the transient receptor potential vanilloid type 1 (TRPV1) channel and the inflammatory network mediated by the Toll-like receptor 4 (TLR4) signaling pathway in the articular synovial tissue of rheumatoid arthritis (RA) rat models, and to explore the target role of the TRPV1 channel in moxibustion intervention for synovial inflammatory pain in RA. A total of 56 healthy male Sprague-Dawley rats were divided into 7 groups using the random number table method, namely a normal group, a model group, a moxibustion group, a TRPV1 agonist group (capsaicin group), a moxibustion + TRPV1 agonist group (moxibustion + capsaicin group), a TRPV1 antagonist group (capsazepine group), and a moxibustion + TRPV1 antagonist group (moxibustion + capsazepine group), with 8 rats in each group. Except for the normal group, the other 6 groups were established as RA models using a composite modeling method combining wind-cold-damp environmental factors with Freund’s complete adjuvant. After successful modeling, the moxibustion group received mild moxibustion with moxa sticks of 0.9 cm in diameter at bilateral Shenshu (BL23) and Zusanli (ST36) point areas, 30 min per time, once daily for 14 consecutive days. The TRPV1 agonist group and TRPV1 antagonist group were subcutaneously injected with capsaicin and capsazepine, respectively, at bilateral Shenshu (BL23) and Zusanli (ST36) point areas, once daily for 14 consecutive days. The moxibustion + TRPV1 agonist group and moxibustion + TRPV1 antagonist group received moxibustion intervention 30 min after subcutaneous injection of capsaicin or capsazepine at the above point areas, with the same moxibustion protocol as in the moxibustion group, for 14 consecutive days. After the intervention, hematoxylin-eosin staining and transmission electron microscopy were used to observe the pathological changes of synovial tissue and cells. Immunohistochemistry was applied to detect the contents of interleukin (IL)-1β, IL-6, IL-17, and tumor necrosis factor (TNF)-α in the synovial tissue. Western blotting and reverse transcription-polymerase chain reaction were performed to measure the relative expression levels of TLR4, myeloid differentiation factor 88 (Myd88), TRPV1 proteins and mRNAs in the synovial tissue. Enzyme-linked immunosorbent assay was used to determine the contents of IL-1β, IL-2, IL-6, IL-17, and TNF-α in the serum. Compared with the normal group, the model group showed obvious pathological damage in rat synovial tissue, with significantly increased contents of IL-1β, IL-6, IL-17, and TNF-α (P<0.01 or P<0.05) in the synovial tissue, significantly upregulated protein expression of TLR4, Myd88, and TRPV1 (P<0.01), significantly increased relative mRNA expression levels of TLR4, Myd88, and TRPV1 (P<0.01), and significantly elevated serum contents of IL-1β, IL-2, IL-6, IL-17A, and TNF-α (P<0.01). Compared with the capsazepine group, the capsaicin group exhibited marked pathological damage in the synovial tissue, with significantly higher contents of IL-1β, IL-6, IL-17, and TNF-α in the synovial tissue (P<0.01), significantly increased protein expression of TLR4, Myd88, and TRPV1 (P<0.01), significantly elevated relative mRNA expression levels of TLR4, Myd88, and TRPV1 (P<0.01), and significantly higher serum contents of the above inflammatory cytokines (P<0.01). Compared with the model group, the moxibustion group had significantly alleviated pathological damage in the synovial tissue, with markedly decreased contents of IL-1β, IL-17, and TNF-α in the synovial tissue (P<0.01), no significant decrease in the IL-6 content (P>0.05), significantly downregulated protein expression of TLR4, Myd88, and TRPV1 (P<0.01), significantly reduced relative mRNA expression levels of TLR4, Myd88, and TRPV1 (P<0.01), and significantly lower serum contents of the above inflammatory cytokines (P<0.01); the capsaicin group showed aggravated pathological damage in the synovial tissue, with a significantly increased IL-6 content (P<0.01), but no significant elevation in the contents of IL-1β, IL-17, or TNF-α in the synovial tissue; meanwhile, the protein and mRNA expression levels of TLR4, Myd88, and TRPV1 in the synovial tissue and serum inflammatory cytokine contents were all significantly increased (P<0.01). Compared with the capsaicin group, the moxibustion + capsaicin group had significantly relieved pathological damage in the synovial tissue, with markedly decreased contents of IL-1β and IL-6 in the synovial tissue (P<0.01), but no significant reduction in the IL-17 or TNF-α content (P>0.05), significantly downregulated protein expression of TLR4, Myd88, and TRPV1 (P<0.01), significantly reduced relative mRNA expression levels of TLR4, Myd88, and TRPV1 (P<0.01), and significantly lower serum contents of the above inflammatory cytokines (P<0.01). Compared with the capsazepine group, the moxibustion + capsazepine group showed alleviated pathological damage in the synovial tissue, with insignificantly decreased contents of IL-1β, IL-6, IL-17, or TNF-α in the synovial tissue (P>0.05); the TLR4 protein expression was significantly decreased (P<0.01), while the protein expression of Myd88 and TRPV1 was reduced without statistical significance (P>0.05); the relative mRNA expression levels of TLR4 and Myd88 were significantly decreased (P<0.05, P<0.01), while that of TRPV1 was reduced without statistical significance (P>0.05); the serum contents of the above inflammatory cytokines were all significantly decreased (P<0.01). Activation of the TRPV1 channel exacerbates the inflammatory response mediated by the TLR4 signaling pathway in RA model rats. Moxibustion can exert anti-inflammatory and analgesic effects and ameliorate RA synovial inflammatory injury by regulating the dual “point-synovium” TRPV1 channels and inhibiting the inflammatory response mediated by the TLR4 signaling pathway. The TRPV1 channel located on point receptors and the targeted synovium may be potential spatially specific therapeutic targets for moxibustion intervention for RA synovial inflammation.
OBJECTIVE:Secondary Restless Legs Syndrome (RLS) has repeatedly been associated with psychopharmacotherapy, especially antidepressants and antipsychotics. However, existing evidence is conflicting in terms of the magnitude of the association as well as the significance of substance classes or individual compounds. The objective of the present study was to evaluate secondary RLS linked to psychotropic medication in real-world, inpatient clinical routine treatment settings. METHODS:A large dataset from a multinational pharmacovigilance program in German-speaking countries (Arzneimittelsicherheit in der Psychiatrie, "Drug safety in Psychiatry") from January 2001 to December 2016 was retrospectively analyzed. RESULTS:In a total of 340 099 monitored inpatients, 67 cases of newly diagnosed and severe RLS related to psychotropic drug treatment were recorded equivalent to a relative frequency of 0.02%. Over 80% of the cases were attributable to two compounds: the antidepressant mirtazapine and the antipsychotic quetiapine. Mirtazapine was found in 39 patients, while quetiapine was found in 16 patients with secondary RLS. For both substances, drug dosages were generally low at onset of secondary RLS. Most cases exhibited an onset within 1 or 2 days after dosage start or change. CONCLUSION:Histamine neurotransmission may represent a crucial common denominator in terms of secondary RLS in association with psychopharmacotherapeutics, as both substances exhibit antihistamingeric effects at lower dosages.
OBJECTIVE:Cannabis-nicotine co-use is common and may affect cessation outcomes, yet whether recent cannabis exposure alters nicotine's acute effects in humans remains unclear. We examined whether recent, non-daily cannabis exposure modulates the acute subjective effects of intravenous (IV) nicotine. METHODS:We pooled data from 2 randomized, double-blind, placebo-controlled studies using IV nicotine to isolate nicotine's pharmacodynamics in adults who smoke tobacco cigarettes (N = 60). Participants completed 3 sessions (placebo, 0.1 mg, 0.2 mg nicotine/70 kg). Recent cannabis exposure was defined a priori (past-30-day use with positive urine 11-nor-9-carboxy-delta-9-tetrahydrocannabinol vs no past-30-day use with negative screen). Primary outcomes were peak Drug Effects Questionnaire (DEQ) composites-stimulatory, pleasurable, aversive-within 10 minutes post-infusion. Secondary outcomes included nicotine self-administration behavior (proportion of nicotine choices) and cardiovascular responses (heart rate, blood pressure). Linear mixed-effects models included dose, cannabis exposure, sex, and FTND. RESULTS:Nicotine increased all DEQ domains dose-dependently (P < .0001). Aversive effects showed a significant dose x cannabis exposure interaction (χ2 = 13.31, P = .001): participants with recent cannabis exposure reported greater aversive responses at 0.2 mg (Cohen's d' = 0.83), with minimal between-group differences at placebo/0.1 mg. Nicotine self-administration did not differ by cannabis exposure status, and no dose x cannabis exposure interactions were observed for cardiovascular responses. CONCLUSIONS:Recent, non-daily cannabis exposure is thus associated with selectively greater aversive responses to a clinically relevant IV nicotine dose, without differential cardiovascular reactivity or altered nicotine choice. These findings support a shift in the aversive limb of nicotine's dose-response and inform mechanistic and clinical studies on how cannabis exposure shapes nicotine reinforcement and cessation outcomes. CLINICAL TRIAL REGISTRATION:NCT01495819, https://clinicaltrials.gov/study/NCT01495819.
