This study applied the grading of recommendations assessment, development and evaluation(GRADE) system and the integrated evidence chain-based effectiveness evaluation of traditional Chinese medicine(Eff-iEC) to evaluate the evidence for 12 commonly used Chinese patent medicines for the treatment of osteoporosis, which are frequently recommended in guidelines or expert consensuses. The results showed that Xianling Gubao Capsules/Tablets were rated as C(low-level evidence) according to the GRADE system, and as BA~+B~+(intermediate evidence) according to the Eff-iEC system. Jintiange Capsules were rated as C(low-level evidence) by the GRADE system, and as AA~+B(high-level evidence) by the Eff-iEC system. Gushukang Granules/Capsules were rated as C(low-level evidence) by GRADE system, and as BA~+B~+(intermediate evidence) by Eff-iEC system. Zuogui Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Qianggu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B~+(high-level evidence) by Eff-iEC system. Zhuanggu Zhitong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BA~+B(intermediate evidence) by Eff-iEC system. Jingui Shenqi Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B(high-level evidence) by Eff-iEC system. Quanduzhong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AD~+B~+(low-level evidence) by Eff-iEC system. Epimedium Total Flavones Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AAB~+(high-level evidence) by Eff-iEC system. Yougui Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~(++)B~(+ )(high-level evidence) by Eff-iEC system. Qigu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BB~+B(intermediate evidence) by Eff-iEC system. Liuwei Dihuang Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Overall, the Eff-iEC system provides a more comprehensive assessment of the effectiveness evidence for traditional Chinese medicine(TCM) than the GRADE system. However, it still has certain limitations that hinder its wider promotion and application. In terms of clinical evidence evaluation, both the Eff-iEC and GRADE systems reflect that the current clinical research quality on Chinese patent medicines for the treatment of osteoporosis is generally low. High-quality clinical trials are still needed in the future to further validate clinical efficacy.
Drugs, Chinese Herbal/therapeutic use* ; Osteoporosis/drug therapy* ; Humans ; Nonprescription Drugs/therapeutic use* ; Evidence-Based Medicine ; Medicine, Chinese Traditional

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It has a high prevalence and poor prognosis. The application of antiarrhythmic drugs and even surgery cannot completely treat the disease, and there are many sequelae. AF can be classified into the category of "palpitation" in Chinese medicine according to its symptoms. Acupuncture has a significant effect on AF. The authors find that an important mechanism of acupuncture in AF treatment is to regulate the cardiac vagus nerve. Therefore, this article intends to review the distribution and function of vagus nerve in the heart, the application and the regulatroy effect for the treatment of AF.
Atrial Fibrillation/physiopathology* ; Humans ; Acupuncture Therapy ; Vagus Nerve/physiology* ; Animals

Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Castleman's disease is a rare polyclonal lymphoproliferative disorder.This article reports the diagnosis and treatment of a 45-year-old female patient with idiopathic multicentric Castleman's disease.The patient presented recurrent fever,enlarged lymph nodes,and elevated levels of inflammation markers.After multiple serological examinations and tissue biopsies,she was diagnosed with hyaline vascular-type Castleman's disease.Initially,the patient received siltuximab targeting interleukin-6,which significantly improved her condition.Considering the cost and convenience of long-term treatment,she subsequently switched the therapy to an oral treatment regimen of thalidomide,cyclophosphamide,and prednisone (TCP),which maintained disease control.This report aims to highlight the diagnostic complexity and diversity of treatment options for idiopathic multicentric Castleman's disease,demonstrating the potential of the TCP regimen as a cost-effective treatment choice.
Humans ; Castleman Disease/drug therapy* ; Female ; Middle Aged ; Thalidomide/therapeutic use* ; Prednisone/therapeutic use* ; Cyclophosphamide/therapeutic use* ; Antibodies, Monoclonal/administration & dosage*

Nodal marginal zone B-cell lymphoma(NMZL),the least common subtype of marginal zone lymphoma,represents a low-grade malignancy arising from the marginal zone of lymph node follicles,composed of small B-cells with an inert non-Hodgkin lymphoma nature.It accounts for 1.5% to 1.8% of all non-Hodgkin lymphomas and 10% of all marginal zone lymphomas.The low incidence and lack of typical clinical and pathological features pose a challenge to the diagnosis and clinical management of NMZL.In this article,we reported the diagnosis and treatment of a case of NMZL located in the parapharyngeal space of the left neck and reviewed the relevant literature from both domestic and international sources.We summarized the clinical manifestations,histopathological features,immunohistochemical characteristics,imaging features,diagnosis and treatment modalities,and prognosis of NMZL.
Humans ; Lymphoma, B-Cell, Marginal Zone/pathology* ; Lymph Nodes/pathology* ; Neck/pathology* ; Male

Chronic kidney disease(CKD)commonly used dietary assessments including 24-hour dietary recall(24 h DR)/3-day dietary recall(3DDR),food frequency questionnaire(FFQ),dietary records,and estimation of dietary protein intake based on nitrogen balance.Given the high prevalence of CKD patients in Asian population and the scarcity of research using FFQ method,it is crucial to develop an FFQ suitable for Chinese CKD patients.This review summarizes the advantages and disadvantages of dietary assessment methods for CKD,the current research status,and the content and steps involved in establishing an FFQ,with the aim of providing reference for the modification of FFQ for Chinese CKD patients.

Objective To investigate the impact and mechanism of Liraglutide on autophagy and apoptosis of human podocyte induced by high glucose.Methods Human podocytes were cultured in vitro,and grouped into normal control group(NC group),high glucose group(HG group),25 nmol/L Liraglutide group(HG+Lir 25 group),50 nmol/L Liraglutide group(HG+Lir 50 group),Liraglutide+LY294002 group(HG+Lir+LY294002 group),and Liraglutide+3-MA group(HG+Lir+3-MA group).The podocyte activity was detected by CCK-8.The apoptosis rate and morphology of podocytes were detected by flow cytometry and Hoechst 33342 staining.The expression of autophagic body and autophagic marker LC3 protein in podocyteswas observed by transmission electron microscopy and immunofluorescence staining.Western blot was applied to detect the expression of apoptosis,autophagy and phosphoinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)pathway related proteins in podocytes.Results Compared with NC group,the activity of podocytes and the expression of Bcl-2,Bcl-2/Bax,LC3 Ⅱ/LC3 Ⅰ,p-PI3K/PI3K,p-Akt/Akt proteins in HG group were decreased(P＜0.05),while the apoptosis rate and the expression of Bax,p62,p-mTOR/mTOR proteins were increased in HG group(P＜0.05).There were many podocytes with pyknotic nuclei,the number of autophagic bodies and the number of green fluorescent spots of LC3 protein were decreased in HG group.Compared with HG group,the activity of podocyte increased,and the expression of Bcl-2,Bcl-2/Bax,LC3 Ⅱ/LC3 Ⅰ,p-PI3K/PI3K,p-Akt/Akt protein increased(P＜0.05),while the apoptosis rate and the expression of Bax,p62,p-mTOR/mTOR protein decreased(P＜0.05)in HG+Lir 25 group and HG+Lir 50 group.The number of podocytes with karyopyknosis was reduced,the number of autophagosomes and the number of green fluorescent spots of LC3 protein were increased in HG+Lir 25 group and HG+Lir 50 group,and the above changes indexes were more obvious in the HG+Lir 50 group group.Compared with HG+Lir 50 group,PI3K/Akt/mTOR pathway could be regulated,and reduce the improvement of Liraglutide on podocyte viability,apoptosis and autophagy induced by high glucose in HG+Lir+LY294002 group and HG+Lir+3-MA group.Conclusion Liraglutide may promote the autophagy of human podocyte induced by high glucose and inhibit its apoptosis through PI3K/Akt/mTOR pathway.

Objective Meta-analysis was conducted to assess the risk of secondary infection caused by tocilizumab(TCZ)in the treatment of Corona Virus Disease 2019(COVID-19),in order to provide an evidence-based basis for the safety of tocilizumab in patients with COVID-19.Methods Cochrane Library,PubMed,Web of Science,CNKI,SinoMed and Wanfang databases were searched in computer to collect randomized controlled trial and cohort study of treating COVID-19 with tocilizumab from December 19,2019 to December 30,2022.A meta-analysis of the results of each study was performed using RevMan 5.4.1 software.Results A total of 1691 references were screened and eighteen studies involving 3933 patients were included.The incidence of secondary infection in the tocilizumab with the standard treatment group and standard treatment group was 19.14%(331/1729)and 12.11%(267/2204),respectively.Meta-analysis showed that the tocilizumab + standard treatment group had a higher incidence of secondary infection than the standard treatment group[RR = 1.35,95%CI(1.05,1.74),P = 0.02].The results of the subgroup analysis showed that the risk of secondary infection with different doses of tocilizumab was different.The incidence of secondary infection was significantly higher in the subgroup with doses of 400～800 mg/d tocilizumab than in the standard care group[RR = 1.48,95%CI(1.19,1.84),P = 0.0004].The incidence of secondary infection in subgroups with doses of≤400 mg/d tocilizumab was also significantly higher than that in the standard treatment group[RR = 1.87,95%CI(1.28,2.72),P = 0.001].However,there was no statistical significance between the subgroup 6～8 mg/kg tocilizumab and the standard treatment group.Conclusions Tocilizumab may increase the risk of secondary infection in patients with COVID-19 compared with standard treatment,and the benefits and risks of tocilizumab should be carefully evaluated before clinical administration.Moreover,large and high-quality studies are needed for further evaluation.