Objective We aim to analyse semaglutide related adverse events in real-world,overall and by gender and age subgroups and compare the differences of different gender and age patients in adverse events,in order to supply references for security usage in the clinic.Methods OpenVigil 2.1 was used to search FDA Adverse Event Reporting System for semaglutide related adverse events from the establishment of the databases to April 2023.According to age and gender,patients were divided into 18-64 years old group and≥65 years old group,male group and female group.We selected ten adverse events which we interested(nausea,diarrhoea,vomiting,pancreatitis,cholecystitis,cholelithiasis,hypoglycaemia,diabetic retinopathy,acute kidney injury and thyroid cancer/medullary thyroid cancer)and analyzed overall and each group of semaglutide adverse events.Results A total of 5 330 cases and 15 558 adverse events were collected.2 935 patients aged 18-64 old group years with 8 553 adverse events;2 395 patients aged≥65 years old group with 7 005 adverse events.2 231 male group patients with 6 195 adverse events;3 059 female group patients with 9 277 adverse events.The sex of 40 patients was unknown.Nausea(1 089 cases/7.00％),vomiting(775 cases/4.98％)and diarrhoea(545 cases/3.50％)remained the most common adverse events.The constituent ratio of pancreatitis was significantly higher in patients aged 18-64 years old group than in patients aged 65 years old group(P＜0.05);the constituent ratio of diarrhoeaand cholelithiasis was significantly lower in patients aged 18-64 years old group than patients aged≥65 years old group(P＜0.05).The constituent ratio of diarrhoea,vomiting,pancreatitis,cholecystitis,cholelithiasis,diabetic retinopathy,and acute kidney injurywas significantly higher in male group patients than in female group(P＜0.05).Conclusion Nausea,diarrhoea and vomiting remined the most common adverse events of semaglutide.Male should be more concerned about gastrointestinal,pancreatitis,gallbladder events,retinopathy and acute kidney injury.Elderly patients should be more alert diarrhoea and cholelithiasis.

The incidence of intrahepatic cholangiocarcinoma (ICC) continues to rise, and there are no effective drugs to treat it. The immune microenvironment plays an important role in the development of ICC and is currently a research hotspot. Icaritin (ICA) is an innovative traditional Chinese medicine for the treatment of advanced hepatocellular carcinoma. It is considered to have potential immunoregulatory and anti-tumor effects, which is potentially consistent with the understanding of "Fuzheng" in the treatment of tumor in traditional Chinese medicine. However, whether ICA can be used to treat ICC has not been reported. Therefore, in this study, sgp19/kRas, an in situ ICC mouse model with intact immune system, was selected to evaluate the efficacy of ICA in the treatment of ICC in vivo for the first time, and the effects of ICA on the tumor immune microenvironment of ICC mice were analyzed by flow cytometry. This experiment was approved by the Experimental Animal Ethics Committee of Capital Medical University (approval number: AEEI-2023-138). In this study, sgp19/kRas ICC mouse model was treated with oral gavage of 100 mg·kg^-1 ICA. We found that ICA significantly inhibited tumor growth and tumor cell proliferation in the sgp19/kRas ICC mouse model after 3 weeks of treatment. Flow cytometry analysis indicated that ICA treatment markedly reduced the proportion of M2 macrophages and increased the number of CD3⁺CD4⁺ T cells. In vitro experiments demonstrated that ICA promoted macrophage polarization towards the M1 phenotype while inhibiting polarization towards the M2 phenotype. Furthermore, transcriptomic analysis suggested that ICA enhanced Toll-like receptor 9 (TLR9) expression, influencing macrophage nitric oxide metabolism synthesis pathways and receptor-related activities, thereby regulating macrophage polarization. In summary, this study demonstrates that ICA treatment significantly delays tumor progression in sgp19/kRas ICC mouse models. Mechanistically, ICA may achieve its anti-ICC effects by upregulating TLR9 receptor expression levels, promoting macrophage polarization towards the M1 phenotype, and altering the tumor immune microenvironment.

In this study, we investigated the effect of Cigu Xiaozhi formula on HSC-T6 activity in hypoxic microenvironment based on network pharmacology and computer-aided drug design, and predicted and verified its possible targets and related signaling pathways. The potential active components and targets of Cigu Xiaozhi formula were screened by searching Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Encyclopaedia of Traditional Chinese Medicine (ETCM) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) databases, and the liver fibrosis related targets retrieved from Gene Cards and Pharm GK database were integrated to obtain the potential targets of Cigu Xiaozhi formula in the treatment of liver fibrosis. GO enrichment analysis and KEGG signaling pathway enrichment analysis were performed on Omic Share platform, and Cytoscape software was used to construct the "potential active ingredient-key target-pathway" network. The active components and target proteins were subjected to molecular docking analysis by Auto Dock software. According to the results of molecular dynamics simulation and binding free energy calculation, the top 5 active components with degree were scored. The active components stigmasterol and β-sitosterol were subjected to molecular docking. CoCl₂ was used to induce HSC-T6 cells to construct hypoxia model in vitro. The cell viability was detected by CCK-8 assay, and the optimal time and concentration of hypoxia model of HSC-T6 cells was determined to be 100 µmol·L^-1 CoCl₂ for 24 h. Under hypoxia condition, HSC-T6 cells were activated, the wound healing rate was significantly increased, and the fluorescence signal of activation marker protein α-smooth muscle actin (α-SMA) was significantly enhanced. However, 6% drug-containing serum could inhibit the activation of HSC-T6 cells, and the wound healing rate was significantly decreased, and the fluorescence signal of α-SMA was significantly weakened. Further studies showed that the expressions of hypoxia-inducible factor-1α (HIF-1α), α-SMA and key proteins of Hedgehog (Hh) signaling pathway in HSC-T6 cells were up-regulated under hypoxia, while the expressions of HIF-1α, α-SMA, Patched-1 (Ptch-1) and glioma related oncogene homology-1 (Gli-1) were down-regulated in 6% drug-containing serum group, the YC-1 group and the cyclopamine group. These results indicated that HIF-1α and Hh signaling pathways were involved in the activation of HSC-T6 cells, and the traditional Chinese medicine Cigu Xiaozhi formula could inhibit the activation of HSC-T6 cells, and the mechanism may be related to the inhibition of HIF-1α expression and the blocking of Hh signaling pathway. In conclusion, Cigu Xiaozhi formula can inhibit the activation of HSC-T6 cells by directly acting on HIF-1α and Hh signaling pathway, and exert an anti-hepatic fibrosis effect. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Gansu University of Chinese Medicine, in compliance with the Institutional Animal Care Guidelines.

Objective:To systematically evaluate the efficacy of oral Chinese herbal prescriptions combined with transcatheter arterial chemoembolization （TACE） against primary hepatic carcinoma （PHC） and screen the basic Chinese herbs，in order to provide certain reference for clinical medication. Method:The randomized controlled trials concerning the treatment of PHC with oral Chinese herbal prescriptions plus TACE were retrieved from CBM，China National Knowledge Infrastructure （CNKI），Chongqing Weipu Database for Chinese Technical Periodicals （VIP），and Wanfang Data Knowledge Service Platform.The quality of the included trials was evaluated by Cochrane handbook，and the Meta-analysis was performed using RevMan 5.3.The enumeration data were expressed by odds ratio （OR），the measurement data by mean difference （MD） or standardized mean difference （SMD），and the effect size by 95% confidence interval （CI）.The data of oral Chinese herbal prescriptions involved in trials were sorted out and subjected to association rule analysis and frequency analysis based on the Traditional Chinese Medicine Inheritance Support System （TCMISS），for exploring the basic Chinese herbs and their dosages against PHC. Result:A total of 75 randomized controlled trials were included，involving 7 406 cases. As revealed by the Meta-analysis，oral Chinese herbal prescriptions combined with TACE was significantly better than TACE alone in improving the short-term curative effect ［OR=2.05，95%CI（1.83，2.29）］，decreasing alpha fetoprotein （AFP） ［MD=-59.02，95%CI（-79.03，-39.01）］，ameliorating liver function ［SMD=-1.23，95%CI（-1.58，-0.88）］，boosting immunity ［SMD=1.08，95%CI（0.84，1.32）］，adjusting Karnofsky Performance Status （KPS） scale score ［OR=2.7，95%CI（1.11，11.02）］，elevating survival rate ［OR=2.31，95%CI（1.96，2.71）］，and reducing adverse reactions ［OR=0.38，95%CI（0.34，0.43）］.Data mining results showed that the basic Chinese herbs against PHC were Bupleuri Radix，Paeoniae Alba Radix，Atractylodis Macrocephalae Rhizoma，Poria，and Glycyrrhizae Radix et Rhizoma，with their clinical dosages listed as follows：6-15 g for Bupleuri Radix，10-15 g for Paeoniae Alba Radix，9-15 g for Atractylodis Macrocephalae Rhizoma，10-15 g for Poria，and 3-10 g for Glycyrrhizae Radix et Rhizoma. Conclusion:The oral Chinese herbal prescriptions combined with TACE produce better effects in treatment of PHC as compared with TACE alone.These five basic Chinese herbs have anti-cancer effect，and their dosages are within the ranges stipulated in 2020 edition of Chinese Pharmacopoeia.This Meta-analysis has provided certain reference for clinical medication.

Objective To understand the current situation and influencing factors of abnormal glucose metabolism in junior middle school students in Yanqing District, Beijing. Methods With the mothod of stratified cluster random sampling, the questionnaire, physical examination and fasting capillary blood glucose were conducted in 2 493 students from 4 junior high schools. Results The prevalence of diabetes, impaired fasting glucose, and abnormal glucose metabolism were 2.5%, 11.4%, and 13.9%, respectively. The prevalence of abnormal glucose metabolism varied significantly among different ages, grades, regions, obesity, central obesity and hypertension (all P<0.05); Unconditional multiple Logistic regression analysis showed that urban, centripetal obesity, and hypertension were positively associated with the risk of abnormal glucose metabolism in middle school students in Yanqing District; daily breakfast was negatively associated with the risk of abnormal glucose metabolism. Conclusion The prevalence of abnormal glucose metabolism is high among junior middle school students, urban, central obesity, high blood pressure and daily breakfast are influencing factors of abnormal glucose metabolism in Yanqing District of Beijing.

Objective:To investigate the effect of IL-34 on the phenotype of monocyte derived dendritic cells in RA,and to speculate the role of IL-34 in the differentiation of myeloid dendritic cells.Methods:The peripheral blood of RA patients was collected to harvest PBMC by Ficoll density gradient centrifugation and cultured for 4h.Adherent cells were stimulated with GM-CSF+IL-4,IL-4, IL-4+IL-34 for 3 days,and then the expression of CD83,CD86 and CD14 was tested by flow cytometry.In addition,the cells stimulated by GM-CSF and IL-4 were added by TNF-α with or without IL-34 for another four days.The expression of CD83,CD86 and/or CD14 was detected by flow cytometry.Results:(1)The expression of CD83 and CD86 on immature DC induced by IL-34+IL-4 was upregulated compared with IL-4 alone(P<0.01),but no difference of the CD14 levels between the two groups(P>0.05).The levels of CD86 and CD14 induced by IL-34+IL-4 were slightly decreased compared with GM-CSF+IL-4 stimulation(P<0.05),but no difference of CD83 expression between the two groups(P>0.05).(2)The expression of CD83 and CD86 stimulated by GM-CSF+IL-4+IL-34 was lower than the GM-CSF+IL-4+TNF-α group(P<0.05),but no difference compared with GM-CSF+IL-4 group(P>0.05). (3)The CD83 expression induced by GM-CSF+IL-4+TNF-α+IL-34 was lower than GM-CSF+IL-4+TNF-α group(P<0.05),but there was no difference of CD86 and CD14 expression between the two groups(P>0.05).Conclusion:IL-34 played roles in the process of immature DC differentiation,but the effect was slightly weaker than that of GM-CSF.IL-34 did not effect the phenotype change of mature DC,but involved in the maintainence of immature DC.

OBJECTIVETo explore the correlation of immune T cell subsets and expression levels of TNF-α, IFN-γ and sFas with the severity and prognosis of aplastic anemia(AA) patients.

METHODSNinety-five patients with aplastic anemia treated in our hospital were selected and enrolled in AA group, 43 cases of which were included in the acute group and 52 cases in the chronic group according to the disease status of patient's. Then, 50 cases of healthy volunteers in the same period were enrolled in the control group, and the changes of immune T cell subsets, and sFas serum TNF-α, IFN-γ and levels of the 3 groups were compared. The ROC curve was used to analyze the value of each index for evaluating the severity of the disease, 95 patients with aplastic anemia were followed up and the Kaplan-Miere survival curve was used to analyze the effect of different index levels on the progression-free survival of the patients.

RESULTSthe serum level of CD4 level and CD4 /CD8 ratio in AA group were significantly lower than those in the control group (P<0.05), and the CD8 level in AA group was significantly higher than that in the control group (P<0.05). The CD4 level and CD4 /CD8 ratio in the acute group was significantly lower than those in the chronic group (P<0.05), and the CD8 level in the acute group was significantly higher than that in the chronic group (P<0.05). The serum level of TNF-α and IFN-γ of the patients in AA group was significantly higher than those in the control group (P<0.05), and the level of sFas in AA group was significantly lower than those in the control group (P<0.05). The levels of serum TNF-α and IFN-γ in the acute group were significantly higher than that in the chronic group (P<0.05), and the level of sFas was significantly lower than that in the chronic group (P<0.05). The analysis of each index value for predicting the severity of AA by ROC showed that the area under curve of CD4 /CD8 , TNF-α, IFN-γ and sFas for predicting the patients' condition was 0.954, 0.763, 0.853 and 0.857, respectively. Kaplan-Miere survival curve analysis showed that CD4 /CD8 ratio had a significant effect on progression-free survival (P<0.05), the TNF-α, IFN-γ and sFas levels had no significant effect on progression-free survival (P>0.05).

CONCLUSIONThe patients with aplastic anemia have significantly abnormal T lymphocyte subsets, there is a certain correlation between the serum TNF-α, IFN-γ and sFas levels with aplastic anemia, each index can reflect the disease severity, and the changes of T lymphocyte subsets has important influence on the clinical prognosis of the patients.

The contents of five heavy metals (Cu, Pb, As, Cd, Hg) in 17 batches of Cordyceps sinensis were determined by microwave digestion-ICP-MS, and their distribution in C. sinensis were analyzed. The results showed that the contents of Cu, Pb, Cd and Hg in all batches were in accordance with the international standards of Chinese Medicine-Chinese Herbal Medicine Heavy Metal Limit, with their contents in the stroma higher than that in the caterpillar body, and the excess rate of As, which mainly concentrated in the caterpillar body part of C. sinensis, was 88.24%, as the content of As in the caterpillar body was 7 to 12 fold of that in the stroma. In this study, the distribution of five heavy metals in C. sinensis was clarified, and the existing problems of arsenic limit of heavy metal in C. sinensis were analyzed, and some suggestions were put forward. It is hoped that the reference standard can be provided for the limited standard of arsenic in C. sinensis.

Fluoroquinolone can cause pathologic lesions in tendon tissue (tendinopathy).In some cases,fluoroquinolone usage can lead to partly rupture or complete rupture of the tendon and substantial subsequent permanent disability.This article reviews fluoroquinolone tendinopathy symptoms,diagnosis,risk factors and toxic mechanisms.

Chitinases(EC3.2.1.14), which are present in various organisms, catalyze the hydrolytic cleavage of chitin and play a vital role in plant defense mechanisms against fungal pathogens.In addition, the chitinases are well known to regulate plant growth and development and are involved in programmed cell death(PCD).A chitinase expressed sequence tag(EST) was isolated from Panax notoginseng, and the full-length cDNA of this EST was cloned with the method of rapid amplification of cDNA ends and named as PnCHI1. PnCHI1 was 1 022 bp in length and contained an intact open reading frame(ORF) of 822 bp, a 26 bp 5'-untranslated region(UTR), and a 174 bp 3'-UTR.The predicted protein of PnCHI1 with 273 amino acid residues belongs to glycoside hydrolase family 19 and fell into the class IV of chitinases through phylogenetic analysis.QRT-PCR analysis showed that the expression of PnCHI1 was induced by methyl jasmonate, ethylene, H2O2, and salicylic acid.PnCHI1 was quickly induced after inoculation with Alternaria panax.Moreover, the expression level of PnCHI1 was increased after pretreatment with methyl jasmonate, and then the transcription level of PnCHI1was sharp increased after inoculation with Fusarium solani,and the highest transcription level was achieved at 4 h post inoculation.But the expression level of PnCHI1 in the sterile water pretreated P.notoginseng was increased gradually after inoculation with F.solani, and the highest expression level was achieved at 48 h post inoculation.All the results of present study indicated that PnCHI1 was involved in defense response of P.notoginseng against the F.solani and A.panax.