Immunotherapy has significantly altered the treatment paradigm of non-small cell lung cancer (NSCLC), but not all patients experience durable benefits. Predictive biomarkers are needed to identify patients who may benefit from immunotherapy. We retrospectively collected tumor tissues from 65 patients with advanced NSCLC before treatment, and performed transcriptomic and genomic analysis. By performing single-sample gene set enrichment analysis, we constructed a predictor named IKCscore based on the tumor microenvironment characteristics. IKCscore is a robust biomarker predicting response to immunotherapy, and its predictive capacity was confirmed from public datasets across different cancer types (N = 892), including OAK, POPLAR, IMvigor210, GSE135222, GSE126044, and Kim cohorts. High IKCscore was characterized by inflammatory tumor microenvironment phenotype and higher T cell receptor diversity. The IKCscore exhibits promise as a bioindicator that can predict the efficacy of both immunotherapy and immunotherapy-based combination therapies, while providing guidance for personalized therapeutic strategies for advanced NSCLC patients.

BACKGROUND:Stroke persists as a paramount global health priority, maintaining persistently elevated incidence and mortality metrics across epidemiological registries. Post-stroke dysphagia, serving as a critical determinant of functional prognosis, imposes multidimensional burdens spanning aspiration pneumonia risk, nutritional compromise, and psychosocial well-being. This neurogenic deglutition disorder has consequently catalyzed clinical innovation in rehabilitation modalities, with scalp acupuncture emerging as a promising neuromodulatory intervention. METHODS:We conducted a systematic search of 8 databases for randomized controlled trials (RCTs) assessing scalp acupuncture treatment for post-stroke dysphagia. The primary outcomes included clinical efficacy, while the secondary outcomes comprised the Kubota Water Swallowing Test (WST), standardized swallowing assessment (SSA), videofluoroscopic dysphagia scale (VDS), and adverse events. Rigorous evaluation of potential biases within the selected studies was performed by the Cochrane Handbook (version 5.1.0) for systematic reviews of interventions. Heterogeneity among studies was addressed through sensitivity analysis. RESULTS:Based on data derived from 20 RCTs involving 1278 participants, the meta-analysis revealed significant clinical effective rate in the application of scalp acupuncture for post-stroke dysphagia [odds ratio = 4.45, 95% confidence interval (CI) (3.04, 6.51), P < .01], improvement in the Kubota WST [mean differences (MD) = -0.82, 95% CI (-1.04, -0.59), P < .00001], SSA [MD = -4.01, 95% CI (-4.59, -3.42), P < .00001], VDS [MD = -5.75, 95% CI (-8.33, -3.17), P < .0001], in comparison with the conventional rehabilitation protocols. Only one study reported adverse events. CONCLUSION:Current evidence suggests that scalp acupuncture therapy may be an effective measure for post-stroke dysphagia.

Primary Sjögren's syndrome (pSS) is an autoimmune disease with incompletely elucidated pathological mechanisms and a current lack of effective therapeutic agents. CP-25, a structurally modified derivative of paeoniflorin, demonstrates significant therapeutic effects in experimental Sjögren's syndrome (ESS) mouse models; however, its underlying mechanism remains elusive. In this study, we constructed an ESS mouse model induced by autoantigen immunization to explore the biological effects of CP-25 on pSS and its potential mechanisms. The study first revealed the overactivation of endoplasmic reticulum stress (ERS) and the impaired function of M3R-IP3R-Ca2+-AQP5 signaling pathway in human labial gland tissue. Critically, inhibiting ERS (using 4-PBA) was found to directly ameliorate the impaired M3R-IP3R-Ca2+-AQP5 signaling pathway function, as evidenced by normalized M3R expression, restored IP3R and AQP5 levels, and enhanced intracellular Ca2+ intensity in IFNα-stimulated HSGECs, resulting in significantly increased salivary flow rate and reduced salivary gland inflammation in vivo. Furthermore, CP-25 exerted its therapeutic effect by upregulating the M3R-IP3R-Ca2+-AQP5 signaling pathway function, regulating M3R membrane expression, and critically inhibiting ERS. Crucially, the beneficial effects of CP-25 on both ERS suppression and pathway restoration were demonstrated to be mechanistically dependent on disrupting the pathological interaction between the key ERS chaperone GRP78 and the IP3R calcium channel. In summary, impaired M3R-IP3R-Ca2+-AQP5 signaling contributes to pSS pathogenesis. CP-25 treats pSS by restoring this pathway through regulating M3R membrane expression, inhibiting ERS, reducing apoptosis, and decreasing GRP78-IP3R co-expression in HSGECs. This study provides experimental support for CP-25's mechanism and potential clinical application in pSS.

This study aimed to explore how miR-497-5p affects sevoflurane-induced neurotoxicity and cognitive impairment in neonatal rats, examining its role in promoting neuronal survival by regulating the protein SMURF2 and its effect on NOTCH1 signaling. Neonatal rats were exposed to sevoflurane, and their learning and memory were assessed using the Morris water maze and fear conditioning tests. RNA sequencing identified a significant decrease in miR-497-5p levels. To further investigate miR-497-5p's protective role, we treated neuronal cells with miR-497-5p mimics and sevoflurane, conducting cell viability assays, LDH release assays, apoptosis analysis and Western blotting for apoptosis markers. Bioinformatics tools predicted target genes of miR-497-5p, confirming that SMURF2 was a direct target through co-immunoprecipitation and dual-luciferase reporter assays. Increasing miR-497-5p levels improved cell viability and reduced apoptosis in neuronal cultures exposed to sevoflurane. MiR-497-5p directly targeted SMURF2, reducing its levels and increasing NOTCH1 protein levels. Silencing SMURF2 preserved NOTCH1 signaling and improved cell viability, while knocking down NOTCH1 eliminated these protective effects, highlighting its importance for neuronal survival. In vivo, miR-497-5p mimic treatment significantly alleviated sevoflurane-induced cognitive deficits and neuronal damage in rats by reducing hippocampal apoptosis, promoting neuronal proliferation, and restoring SMURF2/NOTCH1 signaling.These findings demonstrate that miR-497-5p protects against sevoflurane-induced neurotoxicity by affecting SMURF2 and NOTCH1 pathways. By improving cognitive function and supporting neuronal health, miR-497-5p could be a potential therapeutic target for reducing anesthetic-related neurotoxicity, emphasizing its role in preserving cognitive and neuronal integrity during anesthetic exposure and suggesting future research directions for neuroprotective therapies.

RATIONALE:With the development of magnetic resonance imaging (MRI) technology, most of the research tends to find that there is a significant positive correlation between white matter hyperintensities (WMHs) and cognitive dysfunction in cerebral small vessel vascular disease. In this paper, we report 2 cases of cerebral small vessel disease with significant differences in cognitive function and analyze them by multidimensional assessment using imaging technology so as to provide a methodological reference for identifying and diagnosing the causes of differences in cognitive function in cerebral small vessel disease patients. PATIENT CONCERNS:Patient 1 was a 64-year-old middle-aged man who presented 10 years ago with slow reaction time, memory loss, and loss of self-care ability, and MRI suggested multiple ischemic infarct foci with cerebral white matter changes. Patient 2 was a 69-year-old middle-aged woman, who did not have any significant abnormalities in cognitive function, and imaging suggested multiple ischemic foci, infarct foci, and cerebral white matter degeneration. DIAGNOSIS:MRI showed a large fusion of high signal in the cerebral white matter in both patients, which belonged to the category of cerebral small vessel disease according to the Fazekas classification of grade 3. INTERVENTIONS:We used imaging techniques to compare the 2 MRI brain white matter high signals in a multidimensional manner and further compared the differences in cognitive functioning between the 2 in terms of brain age, brain functional networks, focal loading of white matter fiber tracts, and neuropsychological scales. OUTCOMES:Brain age difference was assessed by whole-brain level and brain function network, white matter fiber bundle lesion load, and Montreal Cognitive Assessment and Mini-Mental State Examination scale scores; the results suggested that patient 1 had relatively poor cognitive function. LESSONS:In this paper, we concluded that the volume of high white matter signal in WMH is not positively correlated with the severity of cognitive impairment. In addition to cerebral WMHs, we believe that alterations in cerebral network connectivity and white matter microstructure may be the neuroimaging basis of cognitive decline in patients with WMH, which may provide a new idea for the early diagnosis of cognitive function in patients with cerebral small vessel disease.

Salvia miltiorrhiza (S. miltiorrhiza) represents a crucial component of traditional Chinese medicine, demonstrating effects on blood circulation activation and stasis removal, and has been widely utilized in asthma treatment. This study isolated a novel phenolic acid (S1) from S. miltiorrhiza and investigated its anti-asthmatic activity and underlying mechanisms for the first time. An allergic asthma (AA) model was established using ovalbumin (OVA). The mechanism of S1's effects on AA was investigated using multi-factor joint analysis, flow cytometry, and co-culture systems to facilitate clinical asthma treatment. S1 (10 or 20 mg·kg-1) was administered daily to mice with OVA-induced AA (OVA-AA) during days 21-25. The study examined airway responsiveness, lung damage, inflammation, and levels of immunoglobulin E (IgE), PGD2, interleukins (IL-4, 5, 10, 13, 17A), tumor necrosis factor α (TNF-α), GM-CSF, CXCL1, CCL11, and mMCP-1. Additionally, mast cell (MC) activation and degranulation were explored, along with T helper type 17 (Th17)/Treg immune cells and TLR4 pathway biomarkers. The antagonistic activity of that specific antagonist of TLR4 (TAK-242) (1 µmol·L-1), a specific TLR4 blocker, against S1 (10 µmol·L-1) was examined in co-cultured 16HBE cells and bone marrow-derived cells (BMDCs) or splenic lymphocytes (SLs) induced with LPS (1 µg·mL-1) to elucidate the TLR4 pathway's mediating role. S1 demonstrated reduced airway responsiveness, lung damage, and inflammation, with downregulation of IgE, PGD2, interleukins, TNF-α, GM-CSF, CXCL1, CCL11, and mMCP-1. It also impeded MC activation and degranulation, upregulated IL-10, and influenced Th17/Treg immune cell transformation following OVA challenge. Furthermore, S1 inhibited the TLR4 pathway in OVA-AA mice, and TLR4 antagonism enhanced S1's positive effects. Analysis using an OVA-AA mouse model demonstrated that S1 alleviates AA clinical symptoms, restores lung function, and inhibits airway response. S1's therapeutic effects occur through regulation of Th17/Treg immune cells and inflammation, attributable at least partially to the TLR4 pathway. This study provides molecular justification for S1 in AA treatment.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune disorder that impairs cognitive function. In this study, we investigated the impact of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on cognitive recovery in anti-NMDAR encephalitis. Our findings demonstrate that heparin-binding epidermal growth factor-like growth factor (HBEGF), a key functional factor secreted by hUC-MSCs, plays a pivotal role in ameliorating cognitive dysfunction. We elucidated that the HBEGF/epidermal growth factor receptor (EGFR) signaling pathway contributes to the enhancement of cognitive function following hUC-MSC exposure. Importantly, we employed a novel exosome-based intracellular therapeutic protein delivery technology—the mMaple3-mediated protein loading and release from exosomes (MAPLEX) system—for targeted HBEGF delivery. This approach facilitated a controlled, light-induced release of HBEGF from the exosomal membrane. Collectively, these findings support the involvement of HBEGF in mediating cognitive improvement in anti-NMDAR encephalitis induced by hUC-MSCs. Additionally, the MAPLEX system emerges as an effective delivery platform for HBEGF, potentially opening new avenues for the treatment of anti-NMDAR encephalitis.

Parkinson's disease (PD) is the second most common prevalent neurodegenerative disease. Recent studies revealed that dysregulation of copper homeostasis was associated with the progression of PD. However, safe and efficient therapeutic drugs were deficient. Our study first demonstrated that Artesunate (AS) targeted on astrocyte to attenuate 6-OHDA-induced dopamine (DA) neurotoxicity. Furtherly, using HuProt™ 20 K human proteome microarray and SPR analysis, it was demonstrated and validated that metallothionein 2 A (MT2A) was a direct AS-binding protein, which high-expressed in astrocyte and up-regulated by AS. In addition, AS decreased intracellular Cu2+ level and regulated the expression of cuproptosis-associated proteins, such as FDX1, CTR1 and Lip-DLAT. Finally, rescue experiments indicated that AS-mediated DA neuroprotection, Cu2+ reduction and anti-cuproptosis effects were eliminated by MT2A knockdown and MT2A-Lys-31 was a key functional site. Taken together, AS provided neuroprotection against PD via up-regulation of astrocyte MT2A expression, which further decreased intracellular Cu2+ level and improved DA neuronal cuproptosis. These findings provide a valuable resource for AS-binding proteins and present a potential application of AS on PD treatment.

BACKGROUND:Longer outpatient studies have demonstrated that hybrid closed loop (HCL) use has led to a concomitant reduction in glycated hemoglobin(HbA1c) by 0.3%-0.7%. However, reports have also indicated that HbA1c levels are not declined in the long-term use of HCL. Therefore, we wonder that 3 months use of HCL could improve glycated hemoglobin levels in adolescents and children with T1D. METHODS:Relevant studies were searched electronically in the Cochrane Library, PubMed, and Embase utilizing the key words "Pediatrics or Child or Adolescent", "Insulin Infusion Systems" and "Diabetes Mellitus" from inception to 17th March 2024 to evaluate the performance of HCL on HbA1c in adolescents, and children with T1D. RESULTS:Nine studies involving 927 patients were identified. Three months use of HCL show a beneficial effect on HbA1c management (p <0.001) as compared to standard of care in adolescents and children with T1D, without evidence of heterogeneity between articles (I2 = 40%, p = 0.10). HCL did significantly increase the overall average percentage of hypoglycemic time between 70 and 180 mg/dL (TIR) (p <0.001; I2 = 51%). HCL did not show a beneficial effect on hypoglycemic time <70 mg/dL and <54 mg/dL (p >0.05). The overall percentage of hyperglycemic time was significantly decreased in HCL group compared to the control group when it was defined as >180 mg/dL (p <0.001; I2 = 83%), >250 mg/dL (p = 0.007, I2 = 86%) and >300 mg/dL (p = 0.005; I2 = 76%). The mean glucose level was significantly decreased by HCL (p <0.001; I2 = 58%), however, no significant difference was found in coefficient of variation of sensor glucose (p = 0.82; I2 = 71%) and daily insulin dose (p = 0.94; I2 <0.001) between the HCL group and the control group. CONCLUSIONS:HCL had a beneficial effect on HbA1c management and TIR without increased hypoglycemic time as compared to standard of care in adolescents and children with T1D when therapy duration of HCL was not less than three months. TRIAL NUMBER AND REGISTRY URL:CRD42022367493; https://www.crd.york.ac.uk/PROSPERO, Principal investigator: Zhen-feng Zhou, Date of registration: October 30, 2022.

INTRODUCTION:Bougies and stylets are widely acknowledged as effective tools for managing endotracheal intubation, uncertainties persist regarding the comparative efficacy and safety of bougie versus stylet approaches in endotracheal intubation. EVIDENCE ACQUISITION:A comprehensive electronic search was conducted on the Cochrane Library, PubMed, and Embase databases from inception to December 9, 2023, using the keywords "endotracheal intubation," "bougie," and "stylet." This meta-analysis aims to evaluate and compare the performance of bougies and stylets in patients undergoing endotracheal intubation. EVIDENCE SYNTHESIS:A total of 12 articles, encompassing 2534 participants, were included in this meta-analysis. The bougie approach did not exhibit superiority in first-attempt success rate (83.6% vs. 81.7%; OR, 1.06, 95% CI, 0.49 to 2.29; P=0.89) and total intubation success rate (99.3% vs. 97.6%; OR, 2.32, 95% CI, 0.44 to 12.34; P=0.32, I2>50%, P<0.001). However, in patients with difficult airways, the bougie approach demonstrated a superior first-attempt success rate compared to the stylet approach (93.8% vs. 76.4%; OR, 5.25, 95% CI, 2.74 to 10.05; P<0.001). There was no significant difference in complications between the bougie and stylet approaches (P>0.05). CONCLUSIONS:For patients with difficult airway characteristics, our recommendation is to perform endotracheal intubation (ETI) using the bougie approach over the stylet approach, as it has been associated with a better first-attempt success rate. Notably, the advantages of using a bougie may be less pronounced for patients without signs of a difficult airway.

Research has indicated that general anesthesia may cause neuroapoptosis and long-term cognitive dysfunction in developing animals, however, the precise mechanisms orchestrating these outcomes remain inadequately elucidated within scholarly discourse. The purpose of this study was to investigate the impact of sevoflurane on the hippocampus of developing rats by analyzing the changes in microRNA and mRNA and their interactions. Rats were exposed to sevoflurane for 4 h on their seventh day after birth, and the hippocampus was collected for analysis of neuroapoptosis by Western blot and immunohistochemistry. High-throughput sequencing was conducted to analyze the variances in miRNA and mRNA expression levels, and the Morris water maze was employed to assess long-term memory in rats exposed to sevoflurane after 8 weeks. The results showed that sevoflurane exposure led to dysregulation of 5 miRNAs and 306 mRNAs in the hippocampus. Bioinformatic analysis revealed that these dysregulated miRNA-mRNA target pairs were associated with pathological neurodevelopment and developmental disorders, such as regulation of axonogenesis, regulation of neuron projection development, regulation of neuron differentiation, transmission of nerve impulse, and neuronal cell body. Further analysis showed that these miRNAs formed potential network interactions with 44 mRNAs, and two important nodes were identified, miR-130b-5p and miR-449c-5p. Overall, this study suggests that the dysregulation of the miRNA-mRNA signaling network induced by sevoflurane may contribute to neurodevelopmental toxicity in the hippocampus of rats and be associated with long-term cognitive dysfunction.

BackgroundIlex pubescens Hook. et Arn (IP), traditionally known for its properties of promoting blood circulation, swelling and pain relief, heat clearing, and detoxification, has been used in the treatment of thromboangiitis obliterans (TAO). Despite its traditional applications, the specific mechanisms by which IP exerts its therapeutic effects on TAO remain unclear.Aim of the studyThis study aims to uncover the underlying mechanisms in the therapeutic effects of IP on TAO, employing network pharmacology and metabolomic approaches.MethodsIn this study, a rat TAO model was established by injecting sodium laurate through the femoral artery, followed by the oral administration of IP for 7 days. Plasma coagulation parameters were measured to assess the therapeutic effects of IP. The potential influence on the femoral artery and gastrocnemius muscle was histopathologically evaluated. Network pharmacology was employed to predict relevant targets and model pathways for TAO. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was used for the metabolic profile analysis of rat plasma. Immunohistochemistry (IHC) was used to verify the mechanisms by which IP promotes blood circulation in TAO.ResultsThe study revealed that IP improved blood biochemical function in TAO and played a significant role in vascular protection and maintaining normal blood vessels and gastrocnemius morphologies. Network pharmacology showed that IP compounds play a therapeutic role in modulating lipids and atherosclerosis. Metabolomic analysis revealed that the pathways involved in sphingolipid metabolism and steroid biosynthesis were significantly disrupted. The joint analysis showed a strong correlation between lysophosphatidylcholine and IP components, including triterpenoid and iridoid components, which support the curative action of IP through the modulation of sphingolipid metabolism. Furthermore, decreased expression levels of SPHK1/S1PR1, TNF-α, IL-1β, and IL-6 were observed in the IP-treated group, suggesting that IP exerts a protective effect on the vasculature primarily by regulating of the SPHK1/S1PR1 signaling pathway.ConclusionIn this study, we found that IP protects the vasculature against injury and treats TAO by regulating the steady-state disturbance of the sphingolipid pathway. These findings suggest that IP promotes vasculature by modulating sphingolipid metabolism and SPHK1/S1PR1 signaling pathway and reduce levels of inflammatory factors, offering new insights into its therapeutic potential.

ObjectiveBoth 5:2 IF diet (intermittent fasting) and daily caloric restriction eating had been suggested for management of MAFLD (Metabolic-Associated Fatty Liver Disease), this study aimed to evaluate the effects of 5:2 IF diet on body weight and metabolic parameters in adults with MAFLD, in comparison to daily caloric restriction eating.MethodsThis single-center, double-blind, prospective, randomized controlled trial included 60 patients with MAFLD, who were administered either a 5:2 IF diet limited calories consumed for 2 days each week with no restrictions on the remaining 5 (Group 5:2 IF diet) or a daily calorie restriction eating (Group daily calorie restriction). Fibrotouch-B instrument assessment, ultrasound assessment of hepatic steatosis, anthropometric indices and body composition analysis, blood sample measurements were conducted during two distinct visits: initially on the day of study commencement (T1), and subsequently at the conclusion of the 12-week intervention period (T2).ResultsIn comparison to daily calorie restriction eating, the 5:2 IF diet significantly decreased the proportion of hepatic steatosis ≥moderate (29.6% vs. 59.3%, p = 0.028) and the degree of hepatic fibrosis F ≥ 2 (3.7% vs. 25.9%, p = 0.05), and fewer percentage of patients were diagnosed with fatty liver via upper abdominal ultrasound in the 5:2 intermittent fasting diet group (33.3% vs. 63.0%, p = 0.029). Additionally, the CAP (controlled attenuation parameter) and LSM (liver stiffness measurements) value were significantly lower in the 5:2 IF diet group (p < 0.05). No statistically significant differences were observed between the two groups in terms of weight, BMI (body mass index), WC (waist circumference), HC (hip circumference), and WHR (waist to hip ratio). Similarly, there were no significant differences in lipid profile, glycemic indices and adverse events (p > 0.05).ConclusionIn summary, although both 5:2 IF diet and daily caloric restriction eating achieved similar effect on body weight, liver enzymes, lipid profile and glycemic indices after 12 weeks treatment, 5:2 IF diet demonstrates better improvement in fibrosis and steatosis scores independently from weight regulation. Consequently, it is anticipated to emerge as a viable dietary modality for lifestyle intervention among patients diagnosed with MAFLD.Clinical trial registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier ChiCTR2400080292.

In order to further improve the diagnosis and treatment level of spinal "tendon off position and joint subluxation",and promote the normalization and standardization of methods and techniques of traditional Chinese medicine,the project was initiated by China Association of Traditional Chinese Medicine,led by the Department of Orthopedics and Traumatology of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine and based on the definition of the latest guidelines of the Institute of Medicine of the National Academies（IOM） in 2011.In addition,the Clinical Diagnosis and Treatment Guidelines for Spinal "tendon off position and joint subluxation" are planned to be jointly compiled by referring to the WHO Guideline Formulation Manual of the World Health Organization and the TCM Guideline Formulation Plan of the China Association of Traditional Chinese Medicine.This protocol will focus on the purpose and significance of guideline formulation,application population,clinical problem construction（PICO priniciple）,guideline formulation process,retrieval strategy,quality evaluation of evidence and recommendation formation process,etc.,in order to accept methodological supervision,make the guideline formulation process standardized and transparent,and further improve the scientificity and rigor of this guideline.

In order to cultivate high-quality clinical leaders in traditional Chinese and Western medicine,the BOPPPS improved model is applied in the teaching practice activities of "Introduction to Normal Human Anatomy Ⅰ" with the integration of Ideological＆ Political elements.The results show that the application of this model can effectively improve students’ learning interest,classroom participation,and learning effectiveness,and students’ abilities have been improved in various aspects,which also inspires other courses.

Ethnopharmacological relevance: Tripterygium wilfordii polyglycosides (TWP), extracted from the traditional Chinese herb Tripterygium wilfordii, has been widely used in the treatment of rheumatoid arthritis (RA). However, the toxicity of TWP to a variety of organs such as liver, kidney and testis greatly limits its clinical application. Salvia miltiorrhiza Bunge is often used in the treatment of RA due to its blood circulation promoting, stasis resolving, and anti-inflammatory effects. Salvia miltiorrhiza Bunge has also been reported to possess multiple organ protective effects.Aim of the study: To investigate the influences of two main components of Salviorrhiza miltiorrhiza Bunge, hy-drophilic salvianolic acids (SA) and lipophilic tanshinones (Tan), on the efficacy and toxicity of TWP in treating RA and to explore the underlying mechanisms.Materials and methods: SA and Tan were extracted from Salvia miltiorrhiza Bunge and the extracts were quanti-tated by HPLC and identified by UPLC-Q/TOF-MS. Then, a collagen-induced arthritis (CIA) rat model was established using bovine type II collagen (CII) and incomplete Freund's adjuvant (IFA). CIA rats were treated with TWP and/or SA/Tan. After 21 days of continuous treatment, arthritis symptoms and organs toxicity were evaluated. Meanwhile, serum metabolomics were investigated by the UPLC-Q/TOF-MS to understand the un-derlying mechanism.Results: SA and Tan extracts could significantly alleviate arthritis symptoms in CIA rats and decrease the serum levels of inflammatory factors TNF-& alpha;, IL-1 & beta; and IL-6 when combined with TWP. Meanwhile, both extracts alleviated injury of liver, kidney and testis caused by TWP, and the hydrophilic extract SA was superior. Moreover, a total of 38 endogenous differential metabolites were identified between the CIA model group and the TWP group, among which 33 metabolites were significantly recovered after the combination of SA or Tan. Metabolic pathway analysis showed that SA and Tan can affect metabolic pathways including linoleic acid metabolism, glycerophospholipid metabolism, sphingolipid metabolism and steroid biosynthesis metabolism pathway. Conclusions: Our findings indicated for the first time that two Salviorrhiza miltiorrhiza Bunge extracts could improve the efficacy and reduce the toxicity of TWP in the treatment of RA by adjusting metabolic pathways, and the hydrophilic extract SA was superior.

Background The Wisconsin upper respiratory symptom survey (WURSS) is a validated English questionnaire to evaluate the quality of life and severity of upper respiratory tract infections (URTIs). We aimed to develop a Mandarin Chinese version of WURSS-24 (WURSS-24-C) and evaluate its reliability, validity and minimal important difference (MID). Methods The WURSS-24-C was developed using the forward-backward translation procedure. People with URTIs' symptoms within 48 h of onset were recruited and asked to fill in the WURSS-24-C daily for up to 14 d. Exploratory and confirmatory factor analyses were used to suggest domains. The 8-Item Short Form Health Survey (SF-8) assessing general mental and physical health was used to assess validity. Reliability estimated by Cronbach's alpha and mean day-to-day change for those indicating minimal improvement as MID were evaluated. Results The WURSS-24-C was found to be acceptable, relevant, and easy to complete in cognitive debriefing interviews. A total number of 300 participants (age 28.4 +/- 9.3, female 70%) were monitored for 2500 person-days. Four domains (activity and function, systemic symptoms, nasal symptoms and throat symptoms) of the WURSS-24-C were confirmed (comparative fit index [CFI] = 0.93). The reliability of this 4-domain-structure is good (Cronbach's alphas varied from 0.849 to 0.943). Convergent validity is moderate (Pearson correlation coefficients between daily WURSS-24-C and the SF-8 were -0.780 and -0.721, for the SF-8 physical and mental health, respectively). Estimates of MID for individual items varied from -0.41 to -1.14. Conclusions The WURSS-24-C is a reliable and valid questionnaire for assessing illness-specific quality-of-life health status in Chinese-speaking patients with URTIs. Key messages The Wisconsin upper respiratory symptom survey (WURSS) series are patient-oriented questionnaire instruments assessing the quality of life and severity of upper respiratory tract infections (URTIs). The WURSS-24 was translated into Mandarin Chinese using the forward-backward translation procedure, and evaluated its validity, reliability and minimal important difference (MID) in 300 Chinese participants with URTIs. The WURSS-24 Chinese version (WURSS-24-C) seems to be a reliable and valid questionnaire for assessing illness-specific quality-of-life health status in Chinese patients with URTIs.

目的:探讨基于超星教学平台的人体寄生虫学课程线上混合式教学实践情况及评价效果。方法:选取蚌埠医学院2018级临床医学专业学生进行教学，通过问卷调查对教学方案和效果进行评价。结果:问卷显示，81.13%同学对线上混合式教学模式感兴趣，64.10%以上同学认为线上教学目标清晰、教学时间安排合理、教学内容有扩展性、教学节奏紧凑。大部分同学认同在线上授课中学习了完整的课程知识，提升了解决问题能力、自主学习能力、创新科研能力。结论:基于超星平台构建的人体寄生虫学线上混合式教学方案保证了教学质量，强化了课程信息化建设与教学的融合，为进一步深化教学改革提供了有益借鉴。

深入了解大学生生命教育的现状,对当代大学生生命教育做出总结和反思,以便更有效地开展大学生生命教育.

ETHNOPHARMACOLOGICAL RELEVANCE:Paeoniflorin, a bioactive compound extracted from the traditional Chinese herb, Paeonia lactiflora Pall, has been demonstrated to possess efficient antidepressant activity in previous studies.AIM OF THE STUDY:Our systematic review and meta-analysis aimed to assess the effectiveness of paeoniflorin in relieving depressive-like behaviors in animal models.MATERIALS AND METHODS:We searched for in vivo studies on the antidepressant effects of paeoniflorin in rodents using electronic databases from their inception to April 2021. The measurements of animal behavioral tests, including the sucrose consumption, forced swimming, tail suspension, and open field tests, were regarded as the outcomes.RESULTS:Fourteen studies involving 416 animals met the inclusion criteria and were included in the meta-analysis. Statistical analysis revealed remarkable differences between the paeoniflorin and control groups. Furthermore, the paeoniflorin group showed great efficiency in improving depressive-like symptoms of animals in the sucrose consumption, forced swimming, tail suspension, and open field tests.CONCLUSIONS:Our meta-analysis demonstrates that paeoniflorin can significantly improve depressive-like symptoms in animals and suggests that it can be a potential therapy for patients with depression in the future.