OBJECTIVE To investigate the effects of multiple doses of Shugan jieyu capsules on the pharmacokinetics of voriconazole， rivaroxaban and apixaban in rats. METHODS Male SD rats were randomly divided into voriconazole group （30 mg/kg）， rivaroxaban group （2 mg/kg）， apixaban group （0.5 mg/kg）， Shugan jieyu capsules+voriconazole group （145 mg/kg+30 mg/kg）， Shugan jieyu capsules+rivaroxaban group （145 mg/kg+2 mg/kg）， Shugan jieyu capsules+apixaban group （145 mg/kg+0.5 mg/kg）， with 6 rats in each group. After the rats in each group were consecutively administered solvent （0.5% sodium carboxymethyl cellulose solution） or Shugan jieyu capsules by intragastric gavage for 8 days， they were respectively given voriconazole， rivaroxaban and apixaban solution by intragastric gavage on the 8th day. Blood samples were then collected at different time points （in voriconazole group， rivaroxaban group and corresponding drug combination groups， blood was collected before administration and at 0.17， 0.34， 0.5， 0.75， 1， 1.5， 2， 3， 4， 5， 6， 8， 10 and 12 hours post-administration； in apixaban group and corresponding drug combination group， blood was collected before administration and at 0.08， 0.17， 0.25， 0.34， 0.5， 0.75， 1， 3， 5， 7， 10 and 12 hours post-administration）. Ultra-high performance liquid chromatography-tandem mass spectrometry method was employed to determine the mass concentrations of voriconazole， rivaroxaban and apixaban in rat plasma. The main pharmacokinetic parameters of these drugs were calculated using a non-compartmental model， and the comparisons were made between groups. RESULTS Compared with single drug group， after multiple administrations of Shugan jieyu capsules， AUC0－t， AUC0－∞ and cmax of voriconazole were significantly decreased， while CLz/F was significantly increased， and tmax was also significantly prolonged （P＜0.05）. For rivaroxaban and apixaban， their tmax values were both significantly prolonged （P＜0.05）. However， there were no statistically significant differences in the other pharmacokinetic parameters between the two groups （P＞0.05）. CONCLUSIONS The combination of Shugan jieyu capsules can decrease the exposure， increase the clearance， and delay the peak concentration of oral voriconazole. However， it does not affect the exposure levels of rivaroxaban and apixaban， but it does delay the time to reach peak concentration for both drugs.

The occurrence of sarcopenia is closely related to diabetes mellitus(DM).The occurrence of sarcopenia in DM patients is often associated with insulin resistance,inflammation,myostatin and its complications.This article reviews the research progress of diabetic sarcopenia experiments.

Climate change has led to an increasing frequency and intensity of extreme climate events such as heat and drought extremes with considerable global public health burden. This systematic review collected 87 domestic and international studies from 2000 to 2023, considering the impacts of heat extremes, drought extremes, and compound hot-dry events on infectious diseases attributable to various transmission pathways such as waterborne, foodborne, insect-borne, airborne, and contact-transmitted diseases. Our results showed that high temperature was associated with increased transmission risks of waterborne and foodborne diseases including infectious diarrheal diseases (cholera, dysentery, typhoid, and paratyphoid) and infectious gastroenteritis; vector-borne diseases including dengue fever, Zika virus (ZIKV) disease, chikungunya fever, malaria, West Nile fever, and Rift Valley fever; airborne diseases including influenza-like diseases, influenza A, measles, and mumps; and contact-transmitted diseases including HIV/AIDS, schistosomiasis, and leptospirosis. Additionally, drought conditions also amplified the transmission risks of waterborne and foodborne diseases including cholera, Escherichia coli infection, rotavirus infection, and hepatitis E; vector-borne diseases such as scrub typhus, schistosomiasis, hemorrhagic fever with renal syndrome, and West Nile fever; airborne diseases including meningococcal meningitis, pertussis, measles, and upper respiratory infections; and contact-transmitted diseases such as HIV/AIDS. Along with global warming, the frequency of compound high temperature and drought events shows a considerably increasing trend, causing more adverse health effects than heat or drought alone. However, there is limited research quantifying their effects on infectious diseases. These associations may be mediated through temperature and precipitation on infectious disease pathogens, transmission vectors, population susceptibility, public health services, and behaviors. In the context of climate change, the increasing occurrence of compound events of high temperatures and droughts raises health concerns, and further studies are needed to enhance our understanding of the impacts of climate change on infectious diseases and improve human adaption to climate change.

Jinlingzi San is a formula frequently used in treating pain syndrome， first recorded in the Collection of Writings on the Mechanism of Disease， Suitability of Qi， and the Safeguarding of Life as Discussed in the 'Basic Questions' written by LIU Wansu in the Jin Dynasty. Jinlingzi San is composed of 2 Chinese medicinals Toosendan Fructus and Corydalis Rhizoma with a concise composition and exact clinical efficacy， having been included in the Catalogue of Ancient Classical Formulas （Second Batch： Han Chinese Medicine）. The formula name， historic evolution， medicine origins， composition， dosage， decocting methods， and ancient and modern clinical application were sorted out and analyzed with the bibliometric method. A total of 209 pieces of information were collected from ancient books and literature. After screening， 49 pieces of effective data involving 45 ancient books were included. Results showed that the name of Jinlingzi San was first recorded in Secret Formulas of the Yang Family written by Yang Tan in the Southern Song Dynasty and developed into 3 other versions of the decoction. The Jinlingzi San included in the Collection of Writings on the Mechanism of Disease， Suitability of Qi， and the Safeguarding of Life as Discussed in the 'Basic Questions' written by LIU Wansu invariably plays a dominant role. As for the 3 other versions， although they have the same name of Jinlingzi San， their composition and indications are different from those of the original formula， which were therefore viewed as prescriptions based on Jinlingzi San and also included in the research. The medicine origins and processing of Jinlingzi San are suggested： Toosendan Fructus is the dry mature fruit of Melia toosendan of Meliaceae， and the crude is used after cleansing without putamen. Corydalis Rhizoma is the dry tuber of Corydalis yanhusuo of Papaveraceae， which is used after impurity removal， cleaning， and drying. Depending on the conversion from the measurement system in the Jin Dynasty to modern measurement， it is suggested that Toosendan Fructus and Corydalis Rhizoma （41.3 g each） are ground into fine powder， and one dose includes 12.39 g of the powder， which should be taken with an appropriate amount of wine. If wine is not suitable for the patient， the decoction can also be taken with warm water. Jinlingzi San has the effects of soothing the liver， discharging heat， and activating blood to stop pain. As recorded in ancient books， Jinlingzi San is specialized in treating heart pain caused by reversal heat， chest and abdominal pain， hypochondriac pain， jaundice， hernia， and other diseases. Modern studies have shown that modified Jinlingzi San can be used in treating diseases involving the digestive system， the integumentary system， the gynecological system， the reproductive system， and other systems and has wide clinical application in treating epigastric pain， herpes zoster， dysmenorrhea， and other diseases. This study has made clear the key information of Jinlingzi San by textual research of ancient books and literature in the hope of providing a theoretical reference for the clinical application， set prescriptions， and new drug development.

Objective:To investigate the efficacy and safety of prednisone combined with standard quadruple antituberculosis therapy (HRZE) in the treatment of tuberculous pleurisy.Methods:A prospective study was conducted involving 120 patients with tuberculous pleurisy who were admitted to the Shaanxi Provincial Tuberculosis Prevention and Control Hospital from February 2021 to February 2023. The patients were randomly assigned to a study group and a control group, with 60 patients in each group, using a computer-generated randomization method. The control group received HRZE alone, while the study group received prednisone therapy and HRZE. The efficacy, clinical indicators, adverse reactions, and serum inflammatory factor levels were compared between the two groups.Results:The total response rate in the study group was significantly higher than that in the control group [93.33% (56/60) vs. 78.33% (47/60), χ2 = 5.55, P < 0.05). In the study group, the time for clinical symptom improvement was (10.34 ± 1.65) days, the time for pleural effusion absorption was (21.37 ± 4.16) days, the pleural thickness measured (2.15 ± 0.35) mm, and the duration of hospitalization was (23.19 ± 4.56) days. They were significantly shorter or smaller than those in the control group [(13.27 ± 2.30) days, (27.25 ± 4.95) days, (2.62 ± 0.40) mm, (28.42 ± 5.60) days, t = 8.02, 7.04, 6.85, 5.61, all P < 0.05]. There was no significant difference in the incidence of adverse reactions between the two groups (χ2 = 2.91, P > 0.05). After 8 weeks of treatment, all serum inflammatory factors improved in both groups compared with baseline levels. In the study group, levels of interleukin-6 [(90.37 ± 12.05) ng/L] and interleukin-18 [(270.94 ± 14.58) ng/L] were significantly lower than those in the control group [(110.59 ± 16.90) ng/L, (296.10 ± 25.29) ng/L, t = 7.55, 6.68, both P < 0.05]. Levels of interleukin-10 [(78.91 ± 8.25) ng/L] and soluble interleukin-2 receptor [(1875.82 ± 359.23) pg/L] in the study group were significantly higher than those in the control group [(70.40 ± 7.16) ng/L, (1566.87 ± 311.02) pg/L, t = -6.03, -5.04, both P < 0.05]. Conclusion:The combination of prednisone and HRZE demonstrates good efficacy and safety, and it is beneficial for improving inflammatory factors.

OBJECTIVE To explore mecha-nisms of imperatorin on regulating P-glycoprotein(P-gp)in blood-brain barrier(BBB)based on net-work pharmacology combined with in vitro experi-ment.METHODS Drug targets were predicted using the Pharmapper and Swiss targets data-bases;disease targets were obtained through the Genecards database;intersections between drugs and disease targets were screened by Cytoscape software;the obtained core targets were used to construct protein-protein interaction(PPI)network,gene ontology(GO)functions,and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.The effects of imperatorin(20,50,100 μ mol·L-1)on P-gp activity were monitored in hCMEC/D3in vitro BBB model,and the effects of imperatorin on the expression of target proteins were verified using Western blot method.RESULTS 55 drug targets and 3102 disease targets were obtained from the network pharmacology screening,and 37 core targets were obtained after the combination.Enrichment analysis showed that core targets were closely related to chemical synaptic trans-mission regulation,neurotransmitter receptor activity,proteinkinaseregulationactivity,G protein-coupled receptor signaling pathway,neural active ligand receptor interaction pathway,PI3K-Akt sig-naling pathway,VEGF signaling pathway,etc..In vitro experimental validation suggested that all tested concentration groups of imperatorin signifi-cantly reduced the activity and expression of P-gp,which were achieved by significantly downregu-lating the phosphorylation levels of PI3K and Akt,and repressing the expression of VEGFR2 pro-tein.CONCLUSION Network pharmacology was used to predict the core targets and signaling pathways of imperatorin on regulating P-gp in BBB and relevant validation was conducted through in vitro experiments,providing a refer-ence basis for further exploration of the mecha-nisms of imperatorin on regulating P-gp in BBB.

BACKGROUND: The 2019 novel coronavirus disease (COVID-19) emerges in China, which spreads rapidly and becomes a public health emergency of international concern. Chinese government has promptly taken quarantine measures to block the transmission of the COVID-19, which may cause deleterious consequences on everyone's behaviors and psychological health. Few studies have examined the associations between behavioral and mental health in different endemic areas. This study aimed to describe screen time (ST), physical activity (PA), and depressive symptoms, as well as their associations among Chinese college students according to different epidemic areas. METHODS: The study design is cross-sectional using online survey, from 4 to 12 February 2020, 14,789 college students accomplished this online study, participants who did not complete the questionnaire were excluded, and finally this study included 11,787 college students from China. RESULTS: The average age of participants was 20.51 ± 1.88 years. 57.1% of the college students were male. In total, 25.9% of college students reported depression symptoms. ST > 4 h/day was positively correlated with depressive symptoms (β = 0.48, 95%CI 0.37-0.59). COVID-19ST > 1 h/day was positively correlated with depressive symptoms (β = 0.54, 95%CI 0.43-0.65), compared with COVID-19ST ≤ 0.5 h/day. Compared with PA ≥ 3 day/week, PA < 3 day/week was positively associated with depression symptoms (β = 0.01, 95%CI 0.008-0.012). Compared with low ST and high PA, there was an interaction association between high ST and low PA on depression (β = 0.31, 95%CI 0.26-0.36). Compared with low COVID-19ST and high PA, there was an interaction association between high COVID-19ST and low PA on depression (β = 0.37, 95%CI 0.32-0.43). There were also current residence areas differences. CONCLUSIONS Our findings identified that high ST or low PA was positively associated with depressive symptoms independently, and there was also an interactive effect between ST and PA on depressive symptoms.
Adult ; COVID-19/psychology* ; China/epidemiology* ; Cross-Sectional Studies ; Depression/etiology* ; Exercise ; Female ; Humans ; Male ; Mental Health/statistics & numerical data* ; Screen Time ; Students/psychology* ; Time Factors ; Universities ; Young Adult

Objective:To develop an R script that can efficiently and accurately filter genome-wide association studies (GWASs) from the GWAS Catalog Website.Methods:The selection principles of GWASs were established based on previous studies. The process of manual filtering in the GWAS Catalog was abstracted as standard algorithms. The R script (gwasfilter.R) was written by two programmers and tested many times.Results:It takes six steps for gwasfilter.R to filter GWASs. There are five main self-defined functions among this R script. GWASs can be filtered based on "whether the GWAS has been replicated" "sample size" "ethnicity of the study population" and other conditions. It takes no more than 1 second for this script to filter GWASs of a single trait.Conclusions:This R script (gwasfilter.R) is user-friendly and provides an efficient and standard process to filter GWASs flexibly. The source code is available at github ( https://github.com/lab319/gwas_filter).

Circular RNA (circRNA) is a kind of RNA with a circular structure. The unique structure of circRNA endows it with various cell biological functions and characteristics. It has become a research hotspot recently. CircRNA can play a role via mechanisms, such as microRNA (miRNA) sponge, RNA binding protein, peptide translation and regulation of gene transcription. CircRNA was found to be associated with disc degeneration, spinal cord injury, scoliosis, and facet arthritis. Some techniques, including bioinformatics and molecular biology techniques, microarray and high-throughput sequencing, can be used to predict and to discover disease-related circRNA, aiming to evaluate whether circRNA can be used as a molecular biomarker for spinal and spinal cord diseases. Based on the current role of circRNA, the corresponding therapeutic strategies have been carried out in experimental animals, which can provide theoretical basis for gene therapy. At present, the researches in circRNA for spinal and spinal cord diseases are still insufficient compared with those in other fields. Currently, the main direction focuses on the miRNA sponge mechanism of circRNA. Due to the variety of diseases in spinal surgery, the research progress of circRNA is also varied. In addition, the development of microarray and high-throughput sequencing technology have greatly promoted the researches in circRNA. The availability of public database is of great significance in the study. The present review summarized the current researches status of circRNA in spinal and spinal cord diseases, aiming to deepen understanding of circRNA in spinal and spinal cord diseases.

Objective: To investigate the inhibitory effect of recombinant oncolytic adenovirusAd-Apoptin-hTERTp-E1A(ATV) on luciferase-labeled human lung cancer cells (A549-luc) and human lung cancerA549 cells, and to compare the differences in the inhibitory effect on two cell lines. Methods:ATV was used to infectA549-luc cells andA549 cells respectively. WST-1 and crystal violet staining were used to determine the difference in the inhibitory effect of ATV. Hoechst and Annexin V-FITC/PI staining were used to verify the inhibition mode ofATV. Results: WST-1 and crystal violet staining showed thatATV had significant inhibitory effect on bothA549-luc and A549 cells ( P <0.05). ATV showed significant inhibitory effect on both cells at 24, 48 and 72 h ( P <0.05 or P <0.01), and reached the peak at 72 h; ATV at concentrations of 1, 10 and 100 MOI all showed inhibitory effect on both cells, and reached the peak at 100 MOI. Hoechst staining showed that A549-luc cells and A549 cells infected with ATV showed typical nuclear fragmentation and marginal set. The results of Annexin V-FITC/PI Flow cytometry showed that ATV infection resulted in apoptosis of A549-luc and A549 cells, which was in a time-dependent manner and reached the peak at 72 h( P <0.05 or P <0.01). Conclusion: Insertion of luciferase didn’t significantly change the inhibitory effect and inhibitory mode ofATV onA549-luc cells.ATV exerted its in vitro inhibitory effect onA549-luc and A549 cells by inducing cell apoptosis.