The study focuses on the concept of multifunctional traditional Chinese medicine (TCM) formulas and aims to evaluate the efficacy of the classical formula Xiaoyao San (逍遥散). Study employs the integrated evidence chain (Eff-iEC) method to organize, integrate, and evaluate its therapeutic efficacy in treating different diseases with the same therapy, and to investigate the feasibility of using Eff-iEC to evaluate the multifunctionality of TCM formulas. The evaluation covered Xiaoyao San's therapeutic effects on depression, premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Concurrently, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was used for evaluation, and authoritative medical documents were incorporated to corroborate the recognition of Xiaoyao San within the medical community. Depression and menopausal syndrome received higher ratings than other conditions in the Eff-iEC, GRADE, and Medical Community Recognition assessments. The Eff-iEC evidence grade for Xiaoyao San was rated as "High" or above for chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Premenstrual syndrome received a "Moderate ⁺" rating. The GRADE evidence level was "Low-〇〇⨁⨁" for depression, premenstrual syndrome, and chronic hepatitis; "Moderate-〇⨁⨁⨁" for dyspepsia and menopausal syndrome; and "Very Low-〇〇〇⨁" for irritable bowel syndrome. Depression and menopausal syndrome had the highest inclusion frequency, appearing in all 4 categories. Premenstrual syndrome, chronic hepatitis, and dyspepsia are not recommended in Western medical guidelines, but they are included in TCM guidelines, the China National Basic Medical Insurance Drug List, and the China National Essential Drug List. Irritable bowel syndrome appears only in the China National Basic Medical Insurance Drug List and China National Essential Drug List. The evaluation results obtained using the Eff-iEC method align with Medical Community Recognition, providing an objective and comprehensive assessment of Xiaoyao San's efficacy. The findings suggest that Xiaoyao San has strong evidence for treating depression and menopausal syndrome. However, further experimental and clinical trials are needed to assess its efficacy in treating premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, and dyspepsia. These results support the clinical efficacy and rational use of Xiaoyao San, expand the application scope of the Eff-iEC method, and offer valuable insights and methodological references for the comparative evaluation of multifunctional TCM formulas.

Objective:To analyze the distribution characteristics of sports facilities in China using geographic information system (ArcGIS) and to investigate their association with mortality risk among residents.Methods:This prospective cohort study included 97 912 community residents from the Chinese Family Database (CFD) between 2013 and 2017. After excluding participants lost to follow-up and those with incomplete data, 53 937 individuals were retained for the analysis. The distribution characteristics of sports facilities in China was mapped using ArcGIS, and the death events were recorded via structured interviews and questionnaires. The Poisson regression was used to assess the association between the distribution characteristics of sports facilities near participants′ residences and their mortality risk.Results:In 2013, a total of 79 714 sports facilities were identified across 262 districts (counties) in China, with large-scale sports facilities accounting for the highest proportion (87.09%). The median number of sports facilities within the residential buffer zone was 17 (4, 30), and the median distance from the residence to the nearest sports facility was 453.2 (341.5, 1 863.5) m. Among the 53 937 community residents analyzed in this study, there were 27 761 males and 26 176 females, 1 326 deaths (2.5%) occurred during the follow-up. Poisson regression revealed that a higher number of sports facilities in the buffer zone (≥21 vs 0-2) was associated with lower mortality risk ( RR=0.74, 95% CI: 0.64-0.85; P0.05). Subgroup analyses showed that being≥60 years old ( RR=0.82, 95% CI: 0.70-0.95), males ( RR=0.78, 95% CI: 0.64-0.95), females ( RR=0.79, 95% CI: 0.64-0.97), having a junior high school education or less ( RR=0.84, 95% CI: 0.71-0.99), and having a urban residence ( RR=0.77, 95% CI: 0.66-0.90) were all negatively associated with residents′ mortality risk (all P0.05). After adjusting for age, greater distance to the nearest sports facility ( RR=1.41, 95% CI: 1.08-1.83) and failing to meet the"10-minute fitness circle"criterion ( RR=1.25, 95% CI: 1.02-1.53) were associated with higher mortality risk among males (both P0.05). After adjusting for age and gender, urban residents with a greater distance to the nearest sports facility ( RR=1.29, 95% CI: 1.04-1.60) or not meeting the 10-minute fitness circle ( RR=1.18, 95% CI: 1.00-1.38) showed a significantly higher mortality risk (both P0.05). Conclusions:The ArcGIS analysis revealed that the distribution of sports facilities in China is characterized by a high proportion of large-scale facilities. Lower facility density within residential buffer zone and greater distance to the nearest facility increase mortality risk among adults.

Objective:To investigate the effect of triply periodic minimal surfaces (TPMS) structure and ceramic volume fraction on the mechanical properties of polymer-infiltrated ceramic network (PICN) composite and reveal its strengthening and toughening mechanism.Methods:In this study, TPMS structures with gyroid (G), primitive (P), diamond (D), and ceramic volume fraction (40%, 55%, 70%, 85%) were designed. Porous zirconia scaffolds were prepared using stereolithography technology, and resin was infiltrated into the scaffolds through a vacuum. Then, the PICN composites were obtained after curing. The bending strength, elastic modulus and fracture toughness of PICN were tested using an electronic universal testing machine, with commercial PICN as the control group. The micromorphology of PICN was observed through stereomicroscope and scanning electron microscope. The cytocompatibility of PICN was verified by using cell counting kit, live/dead cell staining and phalloidin staining.Results:The bending strength values of PICN with different ceramic volume fractions ranged from 82.0 MPa to 376.0 MPa, and they gradually increased as the ceramic volume fraction rised. The elastic modulus values of PICN with different ceramic volume fractions ranged from 12.1 GPa to 56.1 GPa. The fracture toughness values of PICN with different ceramic volume fractions ranged from 1.7 MPa·m 1/2 to 6.5 MPa·m 1/2. The bending strength of 85G PICN reached 306.0 MPa, and it had the highest fracture toughness (6.5 MPa·m 1/2) and an appropriate elastic modulus between that of the control group and that of enamel. Under scanning electron microscopy, it could be observed that the cracks branch and deflect at the interface and eventually terminate within the resin phase. After co-culture with PICN, the survival rate of mouse fibroblasts exceeded 80%, indicating that PICN had no cytotoxicity. Conclusions:The PICN composite with TPMS structure can satisfy the mechanical properties and cytocompatibility of dental prosthesis.

Objective To observe the clinical efficacy of Lingnan fire needling in the treatment of plaque psoriasis.Methods A total of 60 cases of patients with plaque psoriasis admitted to Bao'an Hospital of Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine from August 2021 to January 2023 were selected,and the patients were randomly divided into the observation group and the control group according to the random number table method,with 30 cases in each group.The observation group was given Lingnan fire needling for treatment,and the control group was given topical application of Calcipotriol Ointment.The course of treatment covered eight weeks continuously.After eight weeks of treatment,the clinical efficacy of the two groups was evaluated,and the changes of Psoriasis Area and Severity Index(PASI)scores and Dermatology Life Quality Index(DLQI)scores,as well as the diameter of glomus under dermoscopy of the patients in the two groups were observed before the treatment and after 2,4,6,and 8 weeks of treatment.Changes in Generalized Anxiety Disorder Scale(GAD-7)scores before treatment and after 2,4,6,and 8 weeks of treatment were compared between the two groups.Results(1)After 2,4,6 and 8 weeks of treatment,the scores of PASI,DLQI and GAD-7 of patients in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(2)The cured and markedly rate of the observation group was 86.67%(26/30);and that of the control group was 66.67%(20/30).The efficacy of the observation group was superior to that of the control group,the difference being statistically significant(P<0.05).(3)After 2,4,6,and 8 weeks of treatment,the diameter of glomus under dermoscopy of the patients in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).Conclusion Lingnan fire needling therapy for plaque psoriasis can effectively improve the clinical symptoms of the patients,relieve the anxiety symptoms induced by skin lesions and itching,so as to improve their quality of life.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

OBJECTIVE: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently develop central nervous system damage, yet the mechanisms driving this pathology remain unclear. This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant (lineage B.1.351). METHODS: K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant. Viral replication, pathological phenotypes, and brain transcriptomes were analyzed. Gene Ontology (GO) analysis was performed to identify altered pathways. Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot. RESULTS: Pathological alterations were observed in the lungs of both mouse strains. However, only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection, accompanied by neuropathological injury and weight loss. GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses, including type I interferons, pro-inflammatory cytokines, Toll-like receptor signaling components, and interferon-stimulated genes. Neuroinflammation was evident, alongside activation of apoptotic and pyroptotic pathways. Furthermore, altered neural cell marker expression suggested viral-induced neuroglial activation, resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks. CONCLUSION These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
Animals ; COVID-19/genetics* ; Mice ; Brain/metabolism* ; Apoptosis ; Mice, Inbred C57BL ; SARS-CoV-2/physiology* ; Pyroptosis ; Gene Expression Profiling ; Transcriptome ; Male ; Female

To investigate the impact of preoperative serum follicle-stimulating hormone (FSH) levels on the probability of testicular sperm retrieval, we conducted a study of nonobstructive azoospermic (NOA) men with different testicular volumes (TVs) who underwent microdissection testicular sperm extraction (micro-TESE). A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital, Shenzhen, China) were retrospectively reviewed. The subjects were divided into four groups based on average TV quartiles. Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups. Overall sperm retrieval rate was 57.6%. FSH levels (median [interquartile range]) were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was <5 ml (first quartile [Q1: TV <3 ml]: 43.32 [17.92] IU l -1 vs 32.95 [18.56] IU l -1 , P = 0.048; second quartile [Q2: 3 ml ≤ TV <5 ml]: 31.31 [15.37] IU l -1 vs 25.59 [18.40] IU l -1 , P = 0.042). Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were <5 ml (adjusted odds ratio [OR]: 1.06 per unit increase; 95% confidence interval [CI]: 1.01-1.11; P = 0.011). In men with TVs ≥5 ml, larger TVs were associated with lower odds of sperm retrieval (adjusted OR: 0.84 per 1 ml increase; 95% CI: 0.71-0.98; P = 0.029). In conclusion, elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs <5 ml. In men with TV ≥5 ml, increases in average TVs were associated with lower odds of sperm retrieval.
Humans ; Male ; Azoospermia/surgery* ; Sperm Retrieval/statistics & numerical data* ; Adult ; Follicle Stimulating Hormone/blood* ; Retrospective Studies ; Testis/pathology* ; Microdissection ; Organ Size

OBJECTIVE: To investigate the effects of acupuncture on the neurotransmitter levels and gut microbiota in a mouse model of Tourette syndrome (TS). METHODS: Thirty-six male C57/BL6 mice were randomly divided into 4 groups using a random number table method: 3,3'-iminodipropionitrile (IDPN) group, control group, acupuncture group, and tiapride group, with 9 mice in each group. In the IDPN group, acupuncture group, and tiapride group, mice received daily intraperitoneal injections of IDPN (300 mg/kg body weight) for 7 consecutive days to induce stereotyped behaviors. Subsequently, in the acupuncture intervention group, standardized acupuncture treatment was administered for 14 consecutive days to IDPN-induced TS model mice. The selected acupoints included Baihui (DU 20), Yintang (DU 29), Waiguan (SJ 5), and Zulinqi (GB 41). In the tiapride group, mice were administered tiapride (50 mg/kg body weight) via oral gavage daily for 14 consecutive days. The control group, IDPN group, and acupuncture group received the same volume of saline orally for 14 consecutive days. Stereotypic behaviors were quantified through behavioral assessments. Neurotransmitter levels, including dopamine (DA), glutamate (Glu), and aspartate (ASP) in striatal tissue were measured using enzyme-linked immunosorbent assay. Dopamine transporter (DAT) expression levels were additionally quantified through quantitative polymerase chain reaction (qPCR). Gut microbial composition was analyzed through 16S ribosomal RNA gene sequencing, while metabolic profiling was conducted using liquid chromatography-mass spectrometry (LC-MS). RESULTS: Acupuncture administration significantly attenuated stereotypic behaviors, concurrently reducing striatal levels of DA, Glu and ASP concentrations while upregulating DAT expression compared with untreated TS controls (P<0.05 or P<0.01). Comparative analysis identified significant differences in Muribaculaceae (P=0.001), Oscillospiraceae (P=0.049), Desulfovibrionaceae (P=0.001), and Marinifilaceae (P=0.014) following acupuncture intervention. Metabolomic profiling revealed alterations in 7 metabolites and 18 metabolic pathways when compared to the TS mice, which involved various amino acid metabolisms associated with DA, Glu, and ASP. CONCLUSIONS Acupuncture demonstrates significant modulatory effects on both central neurotransmitter systems and gut microbial ecology, thereby highlighting its dual therapeutic potential for TS management through gut-brain axis regulation.
Animals ; Tourette Syndrome/metabolism* ; Gastrointestinal Microbiome ; Neurotransmitter Agents/metabolism* ; Acupuncture Therapy ; Male ; Mice, Inbred C57BL ; Mice

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers