BackgroundPreclinical studies suggest acupuncture may offer symptomatic relief or modify disease progression in Alzheimer's disease (AD), yet clinical evidence remains limited.ObjectiveThis study evaluated whether adding acupuncture to cholinesterase inhibitors improves outcomes in patients with mild AD and whether any benefits persist after treatment ends.MethodsIn this randomized, single-blind trial, participants with mild AD received either active or sham acupuncture three times per week for 14 weeks in addition to ongoing donepezil therapy, followed by a 14-week washout phase during which acupuncture was discontinued while donepezil was maintained. The primary outcome was change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog12) from baseline.ResultsA total of 160 participants were enrolled, and 157 were included in the primary analysis (78 active, 79 sham). At week 14, the mean change in ADAS-cog12 was -1.20 for the active acupuncture group versus 0.36 for the sham acupuncture group, yielding a difference of -1.50 (p < 0.001). After washout, no significant difference remained (difference, -0.31; p = 0.54). Adverse events occurred in 37.2% of the active and 45.6% of the sham group. Donepezil-related adverse events were less frequent with active acupuncture (6.4% versus 16.5%; p < 0.05).ConclusionsAcupuncture, when added to donepezil, improved cognition during active treatment and was associated with fewer cholinergic side effects in patients with mild AD. The cognitive benefits did not persist after acupuncture was discontinued, suggesting that acupuncture serves as an adjunctive symptomatic therapy rather than a disease-modifying intervention.Trial registrationClinicalTrials.gov [NCT05078944].

Objective The exact regulatory effect of acupuncture on intraocular pressure (IOP) in patients with glaucoma remains controversial. This review aimed to evaluate the current evidence regarding the effect of acupuncture on glaucomatous IOP and to identify the factors influencing therapeutic responses. Methods A narrative review combined with exploratory stratified analysis was conducted. Relevant clinical studies were identified and evaluated to comprehensively analyze the clinical effects and mechanisms of acupuncture in the regulation of glaucomatous IOP. Furthermore, exploratory stratified analysis was applied to investigate key variables, including baseline IOP, glaucoma subtype, acupoint selection, and stimulation parameters. Results Acupuncture induced three modulatory effects on IOP: reduction, biphasic changes (stress-induced elevation followed by reduction), and no significant effects, with IOP reduction being the predominant pattern. The analysis revealed that this heterogeneity was primarily associated with the patients’ baseline IOP level and needle retention time; a higher baseline IOP correlated with a greater reduction, whereas when the IOP was within the normal physiological range, acupuncture produced almost no further IOP-lowering effect. Acupuncture may indirectly improve the aqueous humor circulation by improving ocular blood circulation and modulating the autonomic nervous system. However, direct cellular evidence of this is lacking. Conclusion Current evidence suggests that acupuncture can effectively reduce pathologically elevated IOP in patients with glaucoma, particularly in those with a higher baseline IOP. However, its definitive long-term efficacy, ability to regulate 24 h IOP fluctuations, and whether it acts directly or indirectly on aqueous humor dynamics require further rigorous, large-scale clinical trials and in-depth molecular mechanistic studies.

BACKGROUND: Ferroptosis in intestinal epithelial cells (IECs) acts as a crucial mechanism driving intestinal mucosal injuries and inflammatory reactions in colitis. Nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy, a primary pathway for intracellular iron storage, takes part in regulating ferroptosis. Nevertheless, it is yet unknown whether ferritinophagy plays a role in ferroptosis of IECs in colitis. Hence, this experiment used dextran sulfate sodium salt (DSS) to establish an inflammation model with NCM460 cells and an animal model of colitis to discover the role of ferritinophagy in ferroptosis in IECs and colonic mucosal inflammatory damage. RESULTS: DSS induced ferroptosis in IECs, presenting as significantly increased contents of Fe2+, reactive oxygen species (ROS), and malondialdehyde (MDA), decreased protein expression of glutathione peroxidase 4 (GPX4), and increased expression of cyclooxygenase-2 (COX2) (all P<0.05). Moreover, administration of ferroptosis inhibitor liproxstatin-1 and autophagy inhibitor methyladenine (3-MA) ameliorated colonic tissue damage in the animal model of colitis, reducing the disease activity index (DAI), colon macroscopic damage index (CMDI), and pathological score, as well as the serum contents of mucosal permeability markers diamine oxidase (DAO) and D-lactic acid (D-LA) (all P<0.05). Further, knockdown of NCOA4 downregulated the expression of microtubule-associated protein light chain 3 (LC3) and autophagy-related protein 5 (ATG5) proteins, upregulated the expression of ferritin heavy chain 1 (FTH1), inhibited ferritinophagy, and decreased ferroptosis in IECs induced by DSS, thus ameliorating colonic inflammatory damage and mucosal permeability (all P<0.05). On the contrary, overexpression of NCOA4 encouraged ferritinophagy and aggravated ferroptosis in IECs and intestinal damage. CONCLUSIONS: This study provided evidence supporting that NCOA4-mediated ferritinophagy participates in modulating colitis-related ferroptosis in IECs, and suppressing ferritinophagy protects IECs and promotes colonic mucosal repair.

BACKGROUND:The incidence of sudden sensorineural hearing loss (SSNHL) has been on the rise in recent years. This condition can cause permanent, irreversible hearing loss if left untreated. Acupuncture treatment for SSNHL has the potential advantages of safety, low cost, and promising benefits. AIM:This study aimed to explore the safety and efficacy of verum acupuncture (VA) vs sham acupuncture (SA) as an adjunctive therapy of intratympanic dexamethasone (ITD) for patients with SSNHL. DESIGN AND METHODS:This randomised, parallel, sham-controlled, single-centre prospective clinical trial was conducted from May 5, 2024, to May 31, 2025. Participants aged 18-65 with SSNHL were recruited at Eye & ENT Hospital, Fudan University, Shanghai, China. Eligible participants were randomly allocated (1:1) to receive VA combined with ITD or SA combined with ITD 4 times/week for 1-2 weeks and a 6-week follow-up. The primary outcome was the improvement of pure tone average (PTA) from baseline to week 2. RESULTS AND CONCLUSION:Of the 84 participants enrolled, 77 (91.7%) were included in the modified intention-to-treat analysis (44 men [57.1%]; median [IQR] age, 45.0 [34.0, 58.5] years). Between-group comparisons revealed significant differences in hearing improvement as measured by PTA at week 2 (9.026 [95% CI 2.127 to 15.926] dB; P = 0.011) in the VA+ITD group. VA combined with ITD may improve hearing among patients with SSNHL, producing more notable effects compared to SA combined with ITD. TRIAL REGISTRATION:Chinese Clinical Trial Registry Identifier: ChiCTR2400082916.

Objective: The exact regulatory effect of acupuncture on intraocular pressure (IOP) in patients with glaucoma remains controversial. This review aimed to evaluate the current evidence regarding the effect of acupuncture on glaucomatous IOP and to identify the factors influencing therapeutic responses. Methods: A narrative review combined with exploratory stratified analysis was conducted. Relevant clinical studies were identified and evaluated to comprehensively analyze the clinical effects and mechanisms of acupuncture in the regulation of glaucomatous IOP. Furthermore, exploratory stratified analysis was applied to investigate key variables, including baseline IOP, glaucoma subtype, acupoint selection, and stimulation parameters. Results: Acupuncture induced three modulatory effects on IOP: reduction, biphasic changes (stress-induced elevation followed by reduction), and no significant effects, with IOP reduction being the predominant pattern. The analysis revealed that this heterogeneity was primarily associated with the patients’ baseline IOP level and needle retention time; a higher baseline IOP correlated with a greater reduction, whereas when the IOP was within the normal physiological range, acupuncture produced almost no further IOP-lowering effect. Acupuncture may indirectly improve the aqueous humor circulation by improving ocular blood circulation and modulating the autonomic nervous system. However, direct cellular evidence of this is lacking. Conclusion: Current evidence suggests that acupuncture can effectively reduce pathologically elevated IOP in patients with glaucoma, particularly in those with a higher baseline IOP. However, its definitive long-term efficacy, ability to regulate 24 h IOP fluctuations, and whether it acts directly or indirectly on aqueous humor dynamics require further rigorous, large-scale clinical trials and in-depth molecular mechanistic studies.

To observe the regulatory effect of herb-partitioned moxibustion (HPM) on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced Crohn disease (CD) rats with chronic inflammatory visceral pain (CIVP), aiming to investigate the spinal mechanism of HPM in relieving CIVP. Fifty-four clean-grade male Sprague-Dawley rats were randomly divided into a normal group, a model group, an HPM group, a sham HPM group, a c-Jun N-terminal kinase (JNK) inhibitor group, and a dimethyl sulfoxide (DMSO) solvent group, with 9 rats in each group. The CIVP rat model was induced by TNBS dissolved in 50

Acupuncture is used globally as an alternative treatment for patients with low back pain (LBP), effectively reducing pain and improving physical activity. However, the use and profile of acupuncture for LBP in middle-aged and older adults remains understudied. The aim of this study was to identify key factors associated with the use of acupuncture treatment in this population. Using the 2018 China Health and Retirement Longitudinal Study (CHARLS) dataset, a cross-sectional analysis of 7,929 respondents aged 45 years and older with LBP was conducted. A two-way stepwise regression model was used to identify significant correlates of demographics, health status, and healthcare choice factors with acupuncture use, and multiple theory-driven interaction terms were introduced into the stepwise model and assessed for their enhancement of model fitting and predictive performance by likelihood ratio tests with AUC comparisons. In addition, stratified analyses by gender, age (45–59, 60–74, and ≥ 75 years), and residence were conducted to verify the stability of the model findings. Among 7,929 respondents with LBP from the CHARLS 2018 dataset, 1,097 (13.8

·AIM:To analyze differential proteins associated with the pathogenesis of dry eye(DE)using bioinformatics methods,in order to reveal their potential molecular mechanisms. ·METHODS:Articles published in PubMed and EMBASE databases from the inception of the database to August 31,2023,that used proteomic methods to detect protein expression in clinical samples of dry eye were searched.Differential proteins were selected and further analyzed using the STRING database and Cytoscape software for hub gene screening and module analysis.Protein-protein interaction(PPI)analysis,gene ontology(GO)functional annotation,and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed. ·RESULTS:A total of 21 articles were included,identifying 74 differentially expressed proteins.The most frequently occurring differential proteins were calgranulin A(SA1008),lipocalin-1(LCN1),lysozyme C(LYZ),mammaglobin-B(SCGB2A1),proline-rich protein 4(PRR4),transferrin(TF),and calgranulinB(S100A9).The top 10 hub genes were serum albumin(ALB),tumor necrosis factor(TNF),interleukin 6(IL6),IL1B,IL8,matrix metalloproteinase 9(MMP9),alpha-1-antitrypsin(SERPINA1),IL10,complement component 3(C3),and lactotransferrin(LTF).Module analysis suggested MMP9 and PRR4 as seed genes.KEGG analysis showed that differential proteins were mainly enriched in the IL17 signaling pathway(61.9％). ·CONCLUSION:The results reveal potential molecular targets and pathways for DE and confirm the association between the pathogenesis of DE and inflammation.Further in-depth research is needed to confirm the significance of these biomarkers in clinical practice.

Objective:To study and analyze the varieties across long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in spinal cord, construct the competing endogenous RNAs (ceRNAs) network, and discuss the possible central mechanism in the development of chronic inflammatory visceral pain (CIVP). Methods:The colitis-associated CIVP rat model was prepared using 2,4,6-trinitrobenzene sulfonic acid (TNBS) enema. The abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL) were used to evaluate the rat's pain behaviors. The whole transcriptome sequencing technique was adopted to analyze the differentially expressed lncRNAs, miRNAs, and mRNAs in the spinal cord. LncRNA-associated ceRNA network was constructed and identified using the ceRNA MuTATE method and the hypergeometric distribution algorithm. The sequencing result was then verified using the quantitative real-time PCR (RT-qPCR). Results:Compared to the normal group, CIVP rat models had significantly increased AWR and decreased MWT and TWL (all P<0.05), suggesting hyperalgesia. In the spinal cord of CIVP rats, 158 lncRNAs, 24 miRNAs, and 1216 mRNAs were found to be differentially expressed. 3 top-scored lncRNAs, 1 pain-related lncRNA, 3 downstream miRNAs, and 2 mRNAs were selected for RT-qPCR verification, and 2 lncRNAs, 3 miRNAs, and 2 mRNAs were verified (all P<0.05). Conclusion:LncRNA TCONS_00001477 and TCONS_00019815 may regulate Col2a1 and Hoxd10 mRNAs by competitively binding to miR-3120, miR-542-5p, and miR-450b-3p, thereby participating in colitis associated CIVP.

Background: China is seeing a growing demand for rehabilitation treatments for post-stroke upper limb spastic paresis (PSSP-UL). Although acupuncture is known to be effective for PSSP-UL, there is room to enhance its efficacy. Objective: This study explored a semi-personalized acupuncture approach for PSSP-UL that used three-dimensional kinematic analysis (3DKA) results to select additional acupoints, and investigated the feasibility, efficacy and safety of this approach. Design, setting, participants and interventions: This single-blind, single-center, randomized, controlled trial involved 74 participants who experienced a first-ever ischemic or hemorrhagic stroke with spastic upper limb paresis. The participants were then randomly assigned to the intervention group or the control group in a 1:1 ratio. Both groups received conventional treatments and acupuncture treatment 5 days a week for 4 weeks. The main acupoints in both groups were the same, while participants in the intervention group received additional acupoints selected on the basis of 3DKA results. Follow-up assessments were conducted for 8 weeks after the treatment. Main outcome measures: The primary outcome was the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) response rate (>= 6-point change) at week 4. Secondary outcomes included changes in motor function (FMA-UE), Brunnstrom recovery stage (BRS), manual muscle test (MMT), spasticity (Modified Ashworth Scale, MAS), and activities of daily life (Modified Barthel Index, MBI) at week 4 and week 12. Results: Sixty-four participants completed the trial and underwent analyses. Compared with control group, the intervention group exhibited a significantly higher FMA-UE response rate at week 4 (chi(2) = 5.479, P = 0.019) and greater improvements in FMA-UE at both week 4 and week 12 (both P < 0.001). The intervention group also showed bigger improvements from baseline in the MMT grades for shoulder adduction and elbow flexion at weeks 4 and 12 as well as thumb adduction at week 4 (P = 0.007, P = 0.049, P = 0.019, P = 0.008, P = 0.029, respectively). The intervention group showed a better change in the MBI at both week 4 and week 12 (P = 0.004 and P = 0.010, respectively). Although the intervention group had a higher BRS for the hand at week 12 (P = 0.041), no intergroup differences were observed at week 4 (all P > 0.05). The two groups showed no differences in MAS grades as well as in BRS for the arm at weeks 4 and 12 (all P > 0.05). Conclusion: Semi-personalized acupuncture prescription based on 3DKA results significantly improved motor function, muscle strength, and activities of daily living in patients with PSSP-UL. Trial registration: Chinese Clinical Trial Registry ChiCTR2200056216. Please cite this article as: Huang XY, Liao OP, Jiang SY, Tao JM, Li Y, Lu XY, Li YY, Wang C, Li J, Ma XP. Three-dimensional kinematic analysis can improve the efficacy of acupoint selection for post-stroke patients with upper limb spastic paresis: A randomized controlled trial. J Integr Med. 2025; 23(1): 15-24.

BACKGROUND:Myofascial pain syndrome (MPS) is a widespread musculoskeletal disorder characterized by myofascial trigger points. Needling trigger points is one of the most common therapeutic interventions to treat MPS. However, it is unclear whether needling trigger points is superior to other non-pharmacological interventions. METHODS:Randomized clinical trials (RCTs) which compared the effectiveness of needling trigger points and other non-pharmacological therapies for treating MPS, were searched in the databases of PubMed, Web of Science, Embase, Cochrane Library, CNKI, WanFang, VPCS, and Sinomed, from their inception to August 25th, 2024. Two independent reviewers extracted relevant data on study characteristics and assessed the risk of bias using the Cochrane Risk of Bias Tool. RESULTS:Of the 1968 articles initially screened, 13 RCTs were included. Needling trigger points treatment were more efficacious than non-pharmacological therapies in reducing Visual Analog Scale (VAS) scores (MD = -1.32; 95 % CI = -1.84 to -0.81; P < 0.0001) and the Roland-Morris Disability Questionnaire (RMDQ) scores (MD = -2.77; 95 % CI = -3.58 to -1.97; P < 0.0001). CONCLUSION:This systematic review has shown that needling trigger points could be a more effective option than other non-pharmacological therapies to improve the symptoms of MPS. Clinical trials of robust quality are required to promote further the evidence-based application of needling trigger points for MPS.

Background: Kinematic analysis has been recommended to quantify the upper limb motor function after stroke. However, previous studies have rarely reported the kinematic data of the post-stroke patients with moderate to severe upper limb paresis due to the poor accomplishment of the complex tasks. Methods: 27 post-stroke individuals and 20 non-disabled people participated in the study. The trunk and upper limb movements during the Hand-to-mouth task were captured by the motion capture system and upper extremity kinematic analysis software automatically. The subgroup analysis within stroke group were conducted layering by the Fugl-Meyer Assessment for Upper Extremity scores (severe: 16-31; moderate: 32-50). Findings: The paretic upper limbs in the stroke group tended to use more trunk and shoulder compensatory strategies to offset the impact of spasticity and weakness compared with non-disabled controls. The less-affected limbs in the stroke group also showed abnormal kinematic data. There were significant differences between the kinematic metrics of severe and moderate subgroups. Interpretation: The Hand-to-mouth task is a good and feasible option for kinematic analysis of these patients. It is essential to layer the severity of the paresis and put more emphasis on trunk movements in the future kinematic studies.

This study aimed to unveil the central mechanism of moxibustion treating chronic inflammatory visceral pain (CIVP) from the angle of circRNA-miRNA-mRNA networks in the spinal cord. The rat CIVP model was established using a mixture of 5% (w/v) 2,4,6-trinitrobenzene sulfonic acid and 50% ethanol at a volume ratio of 2:1 via enema. Rats in the moxibustion group received herb-partitioned moxibustion at Tianshu (ST25, bilateral) and Qihai (CV6) points. The abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL) were adopted for pain behavior observation and pain sensitivity assessment. The circRNA, miRNA, and mRNA expression profiles were detected using the high-throughput sequencing technique. Relevant databases and bioinformatics analysis methods were used to screen for differentially expressed (DE) RNAs and build a circRNA-miRNA-mRNA (competing endogenous RNA) ceRNA regulatory network. The real-time quantitative PCR was employed to verify the sequencing result. CIVP rat models had a significantly higher AWR and lower TWL and MWT than normal rats. Between normal and model rats, there were 103 DE-circRNAs, 16 DE-miRNAs, and 397 DE-mRNAs in the spinal cord. Compared with the model group, the moxibustion group had a lower AWR and higher TWL and MWT; between these two groups, there were 118 DE-circRNAs, 15 DE-miRNAs, and 804 DE-mRNAs in the spinal cord. Two ceRNA networks were chosen to be verified. As a result, moxibustion's analgesic effect on visceral pain in CIVP rats may be associated with regulating the circRNA_02767/rno-miR-483-3p/Gfap network in the spinal cord and improving central sensitization.

Purpose: Choroidal dysfunction is implicated in various ocular pathologies. The parasympathetic pterygopalatine ganglion (PPG) innervates orbital vessels supplying the choroid. While PPG stimulation has been shown to dilate cerebral blood flow, its effects on the choroid, particularly in human subjects, require further elucidation. This study aimed to investigate the short-term influence of PPG stimulation via electroacupuncture on choroidal structure. Methods: In this crossover study, 22 healthy adults received PPG electrical stimulation and sham stimulation for one session each on two separate days in a randomized order. Measurements including choroidal thickness (ChT), choroidal vascularity index (ChVI), central subfield thickness, axial length, anterior chamber depth, and lens thickness were recorded before and at intervals (0, 15, 30, 45, and 60 minutes) postintervention. Results: The ChT on the side receiving PPG stimulation demonstrated a sustained increase, peaking at 15 minutes poststimulation (17.2 mu m, P < 0.001) and persisting for up to 60 minutes. Conversely, the ChVI exhibited a more immediate response, with a peak increase immediately poststimulation (3.8%, P = 0.003), followed by a gradual return to baseline. ChT and ChVI in the contralateral eye showed a nonsignificant trend to decrease. Additionally, a notable reduction in ipsilateral axial length was observed at specific time points poststimulation. Conclusions: PPG activation via electroacupuncture elicited a short-term increase in ChT and ChVI in the ipsilateral eye compared to sham stimulation, with ChT increases trailing those of ChVI but displaying greater persistence. Translational Relevance: Electrical stimulation of the PPG can produce a short-term increase in ipsilateral ChT and ChVI.

Oxidative stress is crucial in ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC). Intestinal epithelial cells (IECs) are an important component of the intestinal barrier. In previous studies, we have demonstrated that suppressing microRNA-222-3p (miR-222-3p) can protect against oxidative stress in IECs, which ameliorates colonic injuries in UC mice and prevents the conversion of UC to CAC. In this case, we hope to explore whether moxibustion can alleviate UC and CAC by inhibiting miR-222-3p based on mouse models of UC and CAC. After herb-partitioned moxibustion (HPM) intervention, the disease activity index (DAI) and colon macroscopic damage index (CMDI) were significantly reduced in UC mice, and the number and volume of intestinal tumors were decreased considerably in CAC mice. Meanwhile, we found that HPM suppressed miR-222-3p expression and upregulated the mRNA and protein expression of Brahma-related gene 1 (BRG1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), while inhibiting Kelch-like ECH-associated protein 1 (Keap1) expression in IECs of UC and CAC mice. With changes in reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and inflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α), we verified that HPM protects against oxidative stress and inflammation in IECs of UC and CAC mice. The effect of HPM was inhibited in miR-222-3p overexpression mice, further demonstrating that the protective effect of HPM on UC and CAC mice was through inhibiting miR-222-3p. In summary, HPM regulates the BRG1/Nrf2/HO-1 pathway by inhibiting miR-222-3p to attenuate oxidative stress in IECs in UC and CAC.

Objective To investigate the central mechanism of moxibustion in treating chronic inflammatory visceral pain (CIVP) and its analgesic effect from the perspective of the p38 mitogen-activated protein kinase (MAPK)/Ets-like transcription factor 1 (ELK1) signaling pathway in the spinal cord. Methods Clean-grade male Sprague-Dawley rats were randomly divided into a normal group, a model group, a herb-partitioned moxibustion (HPM) group, a sham-HPM group, a p38 MAPK inhibitor group, and a dimethyl sulfoxide (DMSO) group. CIVP rat models were prepared using an enema mixture of 2,4,6-trinitrobenzene sulfonic acid solution and 50% ethanol. The HPM group was treated with HPM; the sham-HPM group was treated the same as the HPM group, but the moxa cones were not ignited; rats in the p38 MAPK inhibitor group received L5-L6 intrathecal injection of p38 MAPK inhibitor (SB203580); rats in the DMSO group received L 5 -L 6 intrathecal injection of 2% DMSO. Abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL) were used to observe pain-related behaviors in each group. Hematoxylin-eosin staining was used to observe the morphological changes in rat colon tissue. Western blotting and real-time quantitative reverse-transcription polymerase chain reaction were used to detect the phosphorylated protein and mRNA expression of apoptosis signal-regulating kinase 1 (ASK1), MAPK kinase (MKK) 3/6, p38 MAPK, ELK1, and mitogen and stress-activated protein kinase 1 (MSK1) in the spinal cord. Results Compared with the normal group, CIVP rats had severe colonic inflammatory injuries, and the pathological injury scores increased significantly, along with increased AWR scores under different colorectal distension (CRD) stimulation pressures and decreased MWT and TWL; the mRNA and phosphorylated protein expression of p38 MAPK, ELK1, MSK1, ASK1, MKK3, and MKK6 all increased in the spinal cord ( P <0.01). After HPM treatment, the colon injuries were repaired, and the pathological injury scores decreased; under different CRD stimulation pressures, the AWR scores decreased, and the MWT and TWL increased; the mRNA and phosphorylated protein expression of p38 MAPK, ELK1, ASK1, and MKK3 in the spinal cord also decreased, with statistically significant differences compared with the model group and the sham-HPM group ( P <0.01). There were no significant differences in the above indicators between the HPM group and the p38 MAPK inhibitor group ( P >0.05), and the same was true regarding the comparisons between the model group and the DMSO group. Conclusion HPM exerted analgesic effects via downregulating the mRNA and phosphorylated protein expression of ASK1, MKK3, p38 MAPK, and ELK1 in the spinal cord of CIVP rats. The inhibition of spinal p38 MAPK/ELK1 signaling pathway activation may be one of the mechanisms by which HPM relieves pain in CIVP.

Oxidative stress is an important pathogenic factor in ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC), further impairing the entire colon. Intestinal epithelial cells (IECs) are crucial components of innate immunity and play an important role in maintaining intestinal barrier function. Recent studies have indicated that microRNA-222-3p (miR-222-3p) is increased in colon of UC and colorectal cancer (CRC) patients, and miR-222-3p is a crucial regulator of oxidative stress. However, whether miR-222-3p influences IEC oxidative stress in UC and CAC remains unknown. This study investigated the effect of miR-222-3p on the regulation of IEC oxidative stress in UC and CAC. An in vitro inflammation model was established in NCM460 colonic cells, mouse UC and CAC models were established in vivo , and IECs were isolated. The biological role and mechanism of miR-222-3p-mediated oxidative stress in UC and CAC were determined. We demonstrated that miR-222-3p expression was notably increased in dextran sulfate sodium (DSS)-induced NCM460 cells and IECs from UC and CAC mice. In vitro , these results showed that the downregulation of miR-222-3p reduced oxidative stress, caspase-3 activity, IL-1β and TNF-α in DSS-induced NCM460 cells. We further identified BRG1 as the target gene of miR-222-3p, and downregulating miR-222-3p alleviated DSS-induced oxidative injury via promoting BRG1-mediated activation Nrf2/HO-1 signaling in NCM460 cells. The in vivo results demonstrated that inhibiting miR-222-3p in IECs significantly relieved oxidative stress and inflammation in the damaged colons of UC and CAC mice, as evidenced by decreases in ROS, MDA, IL-1β and TNF-α levels and increases in GSH-Px levels. Our study further demonstrated that inhibiting miR-222-3p in IECs attenuated oxidative damage by targeting BRG1 to activate the Nrf2/HO-1 signaling. In summary, inhibiting miR-222-3p in IECs attenuates oxidative stress by targeting BRG1 to activate the Nrf2/HO-1 signaling, thereby reducing colonic inflammation and tumorigenesis.

ObjectiveTo observe the effect of acupuncture in the treatment of accommodative myopia in children.MethodsA total of 76 children with accommodative myopia who met the inclusion criteria were divided into a control group or a test group according to the random number table method, with 38 cases in each group. The control group was given education on eye hygiene, and the test group was treated with acupuncture twice a week for 2 months in addition to the intervention used in the control group. The patient's uncorrected visual acuity (UCVA), refraction, and axial length (AL) were measured before treatment and 1 month and 2 months after treatment.ResultsAfter 1 month of treatment, there was no significant difference in the UCVA between the two groups (P>0.05); after 2 months of treatment, the UCVA of the test group was better than that of the control group (P<0.05). After 1 and 2 months of treatment, the refraction of the two groups was significantly different from that before treatment (P<0.01), but there was no significant difference between the two groups (P>0.05). After 1 and 2 months of treatment, the AL in the control group was increased compared with that before treatment (P<0.05), while there was no significant change in the test group (P>0.05), and there was no significant difference between the two groups (P>0.05).ConclusionAcupuncture treatment can improve UCVA in children with accommodative myopia.

IntroductionDry eye (DE) is a multifactorial ocular surface disease causing considerable medical, social and financial implications. Currently, there is no recognised long-term, effective treatment to alleviate DE. Clinical evidence shows that electroacupuncture (EA) can improve DE symptoms, tear secretion and tear film stability, but it remains controversial whether it is just a placebo effect. We aim to provide solid clinical evidence for the EA treatment of DE.Methods and analysisThis is a multicentre, randomised, sham-controlled trial. A total of 168 patients with DE will be enrolled and randomly assigned to EA or sham EA groups to receive 4-week consecutive treatments and follow-up for 24 weeks. The primary outcome is the change in the non-invasive tear break-up time (NIBUT) from baseline to week 4. The secondary outcomes include tear meniscus height, the Schirmer I test, corneal and conjunctival sensation, the ocular surface disease index, corneal fluorescein staining, the numerical rating scale and the Chinese DE-related quality of life scale.Ethics and disseminationThe trial protocol and informed consent were approved by the Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine (identifier: 2021–119), Shanghai Eye Disease Prevention and Treatment Center (identifier: 2022SQ003) and Eye and ENT Hospital of Fudan University (identifier: 2022014).Trial registration numberNCT05552820.

Introduction:Acupuncture is used as an adjuvant therapy for Alzheimer's disease (AD), but available evidence for efficacy is limited so far. Growing studies suggest that resident gut microbiota contributes to the development and progression of AD. Meanwhile, acupuncture is reported to treat gastrointestinal and neurodegenerative disorders via the gut-brain axis. Therefore, our aim is to confirm the adjunctive therapeutic effects of acupuncture for AD, and explore the relationship between clinical efficacy and shifts of gut microbiota. Methods and analysis:This is a randomized, participant-masked, sham-controlled trial. One hundred and sixty participants with mild AD will be randomly assigned (1:1) to either active acupuncture or non-penetrating sham acupuncture (three times weekly for 14 weeks) added to donepezil treatment (5 mg per day for 28 weeks). The primary efficacy outcome is the change from baseline to week 28 in the Alzheimer's disease Assessment Scale (ADAS-cog12). Secondary efficacy outcomes include other assessments of the Mini-Mental State Examination (MMSE), the Alzheimer's disease Cooperative Study-Activities of Daily Living (ADCS-ADL), and Neuropsychiatric Inventory (NPI). Gut microbiota will be measured using 16S rRNA tag sequencing. Discussion:This rigorous trial will provide high-quality evidence on the efficacy of acupuncture as adjunctive treatment for mild AD, and identify the possible mechanisms of acupuncture from gut microbiota. Clinical Trial Registration:[https://clinicaltrials.gov/ct2/show/NCT05078944], ClinicalTrials.gov [NCT05078944]. Registered 15 October 2021.