In today's society， depression is a kind of highly prevalent chronic mental illness. It leads to a high disability rate and a heavy economic burden. Depression is defined by fundamental symptoms of low mood and diminished pleasure. Its causes and mechanisms remain unclear， and it presents a broad spectrum of symptoms and a persistent nature that significantly impacts both physical and mental well-being. Treatment in Western medicine primarily focuses on alleviating symptoms， yet it entails numerous adverse effects and contraindications. Traditional Chinese medicine （TCM） treatment is based on resolving depression， which is often accompanied by soothing liver， and the key medicine is Bupleuri Radix. Bupleuri Radix associated prescriptions refer to a class of prescriptions using Bupleuri Radix as the sovereign medicinal or having a high dose of Bupleuri Radix， which are widely used in the field of anti-depression. Previous studies from animal experiments， clinical research， and modern pharmacological research have confirmed that Bupleuri Radix associated prescriptions have precise anti-depression efficacy in multiple ways and at multiple levels， but lack a comprehensive and systematic summarization. This paper summarized and analyzed the literature related to the clinical application and mechanism of action of Bupleuri Radix associated prescriptions in anti-depression treatment. The results showed that the anti-depression mechanism of the Bupleuri Radix associated prescriptions （such as Xiaochaihu Tang， Xiaoyao San， Sini San， Chaihu Shugan San， and Chaihu jia Longgu Muli San） was associated with the effects of regulating monoamine neurotransmitters， the brain-derived neurotrophic factor （BDNF）， intestinal flora， and the hypothalamic-pituitary-adrenal （HPA） axis， inhibiting inflammatory responses， and modulating related signaling pathways. Applying them in clinical practice can effectively alleviate patient symptoms， lower the TCM syndrome score and the severity of depression， and also reduce adverse reactions. This underscores advantages of TCM in depression treatment， which offers patients a secure， effective， and more individualized alternative treatment regimen. On this basis， the shortcomings of current studies and the future trend were analyzed. This study aimed to provide an evidence-based medicine basis for the research and development of novel antidepressant medications.

BACKGROUND:Osteoblasts are the main cell types responsible for bone formation and remodeling,and the normal performance of their function is precisely regulated by various signaling pathways.Among them,the bone morphogenetic protein and Wnt signaling pathways play a key role in osteogenesis. OBJECTIVE:To review the role of bone morphogenetic protein/Wnt signaling pathway in the regulation of osteoblast function and analyze its changes in different physiological and pathological conditions in order to further reveal the molecular mechanism of bone formation and remodeling. METHODS:The Chinese and English search terms"BMP signaling pathway,Wnt signaling pathway,and osteogenesis"were searched in CNKI,Wanfang,and PubMed databases for original researches published from the inception to June 2023.Totally 61 articles were finally selected for analysis and summary.Using the method of the literature review,the studies of the bone morphogenetic protein/Wnt signaling pathway in regulating osteogenesis were sorted out and analyzed. RESULTS AND CONCLUSION:(1)Bone morphogenetic protein and Wnt signaling pathways play important roles in the differentiation,proliferation,and maturation of osteoblasts.Bone morphogenetic protein signaling pathway mainly regulates the expression of osteogenesis-related genes through the activation of Smad protein.Smad protein enters the nucleus and regulates the expression of genes related to osteogenesis.Different Wnt signaling pathway from bone morphogenetic protein mainly depends on the activation of β-catenin to exert its biological effects.(2)The regulatory effect of bone morphogenetic protein/Wnt signaling pathway will be affected by many factors in different physiological and pathological states.Growth factors,hormones,and mechanical stress can affect the activity of bone morphogenetic protein/Wnt signaling pathway to some extent.(3)Bone morphogenetic protein/Wnt signaling pathway interacts with other signaling pathways in the regulation of osteogenesis,and they together constitute a complex regulatory network.(4)Chinese medicine and natural compounds can promote bone health by regulating signaling pathways,providing new possibilities for treating bone diseases.(5)Future studies can further explore the interaction of bone morphogenetic protein/Wnt signaling pathway and other signaling pathways and its changes in different physiological and pathological conditions,resolve the key nodes and regulation mechanism in the complex network,to provide more precise targets for the treatment of bone-related diseases,and also provide new ideas to reveal the molecular mechanism of bone formation and remodeling.

The field of post-marketing benefit-risk assessment for traditional Chinese medicine（TCM） is still in its nascent stage， lacking a universally accepted and cohesive evaluation framework and standards. This study presented a strategy developed for the benefit-risk assessment of post-marketing of TCM， and explored the critical techniques and specific implementation steps involved in the assessment process. Initially， appropriate qualitative assessment frameworks and quantitative analysis models were selected for the integrated qualitative and quantitative benefit-risk assessment. Subsequently， key technologies were outlined， including the establishment of a benefit-risk indicator system， the assignment of indicator weights， and the definition of criteria attributes. Furthermore， the implementation steps were elaborated， which involved defining decision-making issues， data collection， evaluation methodologies， variability factors， and sensitivity analysis. Finally， a case study of the benefit-risk assessment of a TCM injection for hepatitis B treatment was conducted to validate the feasibility of the proposed strategy. The objective of this research was to provide theoretical support and practical references for the development of a comprehensive post-marketing benefit-risk assessment system for TCM.

Aim To investigate the changes in the proliferation and apoptosis of Siha cells after knocking down Rho GTPase-activating protein 30(ARHGAP30).Methods After designing specific shARHGAP30 primers and connecting them to the pLKO.1 vector,we transformed them into Escherichia coli competent cells,then co-transfecting them with lentiviral helper plasmids into HEK-293T cells.We collected and filtered cell supernatant to obtain the vi-rus to infect Siha cells.RT-qPCR and Western blot were used to detect knockdown efficiency,as well as changes in the expression of Bax and Bcl-2 after trans-fection.The CCK-8 method was employed to measure the proliferation level of cells after knockdown.Results After successful construction of a lentiviral plasmid with knockdown of the ARHGAP30 gene and establish-ment of stably transfected Siha cells,ARHGAP30 tran-scription and translation(P＜0.01)in Siha cells de-creased,Bax/Bcl-2 significantly decreased(P＜0.01),indicating decreased apoptosis and increased cell proliferation(P＜0.01).Conclusions This study suggests the involvement of ARHGAP30 in the proliferation and apoptosis of Siha cells,and regulating the ARHGAP30 gene may interfere with the occurrence and development of cervical cancer.

Objective:To investigate the effects of selinexor,a inhibitor of nuclear export protein 1(XPO1)on the proliferation inhibition and apoptosis of Kasumi-1 cells in acute myeloid leukemia(AML).Methods:MTS method was used to detect the inhibitory effect of different concentrations of selinexor on the proliferation of Kasumi-1 cells at different time points.The apoptosis rate and cell cycle changes after treatment with different concentration of selinexor were detected by flow cytometry.Results:Selinexor inhibited the growth of Kasumi-1 cells at different time points in a concentration-dependent manner(r24 h=0.7592,r48 h=0.9456,and r72 h=0.9425).Selinexor inhibited Kasumi-1 cells growth in a time-dependent manner(r=0.9057 in 2.5 μmol/L group,r=0.9897 in 5 μmol/L group and r=0.9994 in 10 μmol/L group).Selinexor could induce apoptosis of Kasumi-1 cells in a dose-dependent manner(r=0.9732),and the apoptosis of Kasumi-1 cells was more obvious with the increase of drug concentration.The proportion of G0/G1 phase was significantly increased and the proportion of S phase was significantly decreased after the treatment of Kasumi-1 cells by selinexor.With the increase of drug concentration,the proportion of Kasumi-1 cells cycle arrest in G0/G1 phase was increased and the cell synthesis was decreased.Conclusion:Selinexor can promote the death of tumor cells by inhibiting Kasumi-1 cells proliferation,inducing apoptosis and blocking cell cycle.

Objective:To understand the etiology,clinical characteristics and prognosis of secondary hemophagocytic syndrome(HLH),so as to improve the understanding of HLH and reduce the rates of misdiagnosis and missed diagnosis of HLH.Methods:A retrospective study was conducted to analyze the cause,clinical characteristics,laboratory findings,therapy and outcomes of 75 adult patients with secondary HLH admitted to our hospital from January 2015 to December 2021.Follow-up continued until the last discharge time.Results:Among 75 patients,infection-related HLH was the most common(45.33％),followed by lymphoma-related HLH(17.33％).Fever was the most common clinical manifestation(97.67％).Laboratory indicators such as NK cell activity(98.31％low or absent),sCD25(93.22％increased),and serum ferritin(94.44％elevated)had higher sensitivity in diagnosis.By comparing the clinical manifestations and laboratory indicators of HLH patients with different causes,sex,lymph node enlargement and bone marrow morphology were more valuable for the diagnosis of primary disease(all P＜0.05).By comparing the treatment and clinical outcomes of HLH patients with different causes,the highest clinical remission rate(83.3％)was achieved in patients with autoimmune disease-related HLH treated with hormone+cyclosporine(P＜0.05).The overall 12-month survival rate of all patients was 26.7％,in which the infection-related HLH was the lowest(14.7％)while autoimmune disease-related HLH was the highest(63.6％).Conclusion:The causes and clinical characteristics of adult secondary HLH are varied,with poor prognosis and heterogeneity in disease severity.It is important to identify HLH cause early for diagnosis and needed to further understand HLH.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

Objective:To explore the value of contrast enhancement T1 fluid-attenuated inversion recovery sequence (CE-T1FLAIR) based on modulated flip angle technique in refocused imaging with extended echo train (MATRIX) in detecting metastases.Methods:One hundred and seventy-six patients with pathologically diagnosed malignant tumors and brain metastases accepted enhanced 3.0T MRI scan in Department of Medical Imaging, He'nan Provincial Cancer Hospital from October 2023 to February 2024 were enrolled. Lianying's intelligent brain metastasis AI-assisted detection system and sequences of MATRIX CE-T1FLAIR, 3D GRE_fsp CE-T1FLAIR and FSE CE-T1FLAIR were used to detect the brain metastasis lesions, respectively. Length of the lesions was measured according to Lianying's intelligent brain metastasis AI-assisted detection system, and all lesions were divided into 3 categories: <3 mm, 3-10 mm, and >10 mm. Differences in detection rate in brain metastases of different lengths and locations among the 3 sequences were compared.Results:Detection rates of MATRIX CE-T1FLAIR, 3D GRE_fsp CE-T1FLAIR, and FSE CE-T1FLAIR in brain metastases were 99.67%, 90.52%, and 71.02%, which were decreased successively, with significant differences ( P<0.05). Detection rates of MATRIX CE-T1FLAIR, 3D GRE_fsp CE-T1FLAIR and FSE CE-T1FLAIR in brain metastases with length<3 mm (99.24%, 79.95% and 46.45%) or length of 3-10 mm (100%, 98.19% and 87.53%) were decreased successively, with significant differences ( P<0.05). Detection rates of MATRIX CE-T1FLAIR (100%, 80.56% and 64.24%), 3D GRE_fsp CE-T1FLAIR (100%, 97.25% and 76.11%), and FSE CE-T1FLAIR (100%, 91.18% and 70.59%) in metastases at the superficial area of the brain convexity, gray-white matter junction area, and cerebellum were decreased successively, with significant differences ( P<0.05). Detection rates of FSE CE-T1FLAIR in brain metastases in the basal ganglia and brainstem (69.33% and 50%) were significantly lower than those of MATRIX CE-T1FLAIR and 3D GRE_fsp CE-T1FLAIR (97.33% and 92.86%; 88% and 78.57%, P<0.05). Conclusion:MATRIX CE-T1FLAIR sequence is better than 3D GRE_fsp CE-T1FLAIR and FSE CE-T1FLAIR sequences in detecting brain metastases, especially for metastases with length<10 mm and metastases located at the superficial area of the brain convexity, gray-white matter junction area and cerebellum.

Objective To explore the improving effect and mechanism of saikosaponin A on insomnia rats based on cAMP/PKA/CREB pathway.Methods Seventy-five SD rats were randomly divided into blank group,model group,low-dose saikosaponin A group(0.625 mg·kg-1),high-dose saikosaponin A group(2.500 mg·kg-1)and Estazolam group(0.1 mg·kg-1),with 15 rats in each group.Insomnia rat model was established by intraperitoneal injection of Phenylalanine(PCPA,0.1 mg·kg-1).The general condition and circadian rhythm of rats were observed;the sleep latency and sleep duration of rats were measured by pentobarbital sodium righting experiment.The sleep phase of rats was observed,and the duration of slow wave sleep phase 1(SWS1),slow wave sleep phase 2(SWS2),rapid eye movement sleep phase(REMS)and total sleep time(TST)were recorded.The mRNA expression levels of hypothalamic circadian genes Clock,Bmal1 and clock-controlled genes Rev-erbα and Rorα were determined by qRT-PCR.The expression level of NeuN in hippocampus was determined by immunofluorescence.The level of cAMP in brain tissue was determined by ELISA.The expression levels of Clock,Bmal1,Rev-erbα,Rorα and cAMP/PKA/CREB pathway-related proteins in brain tissue were determined by Western Blot.Results Compared with the blank group,the rats in the model group had disordered circadian rhythms,extreme excitement,irritability,and reduced sleep;the sleep latency was significantly prolonged(P＜0.05),and the sleep duration and SWS1,SWS2,REMS and TST were significantly shortened(P＜0.05).The arrangement of neurons was disordered,and the IOD value of NeuN positive neurons was significantly decreased(P＜0.05).The mRNA and protein expression levels of Clock,Bmal1,Rev-erbα and Rorα in brain tissue were significantly decreased(P＜0.05).The expression levels of cAMP,p-PKA/PKA and p-CREB/CREB in brain tissue were significantly decreased(P＜0.05).Compared with the model group,the aggressiveness of the rats in the administration group was significantly weakened,the circadian rhythm was rhythmic,the activity was reduced,and the sleep was increased.The sleep latency was significantly shortened(P＜0.05),and the sleep duration and SWS1,SWS2,REMS and TST were significantly prolonged(P＜0.05).The disorder of neuronal arrangement was restored,and the IOD value of NeuN positive neurons was significantly increased(P＜0.05).The mRNA and protein expression levels of Clock,Bmal1,Rev-erbα and Rorα in brain tissue were significantly increased(P＜0.05).The protein expression levels of cAMP,p-PKA/PKA and p-CREB/CREB in brain tissue were significantly increased(P＜0.05).Conclusion Saikosaponin A may improve the circadian rhythm of insomnia rats by activating cAMP/PKA/CREB pathway.

ObjectiveTo construct the evidence body for revision of safety information on package inserts of Chinese patent medicines in post-marketing by taking Xiaoke'an capsules as an example， so as to provide reference for the revision of instructions of Chinese patent medicines in post-marketing. MethodThe construction of the evidence body was guided by the theory of traditional Chinese medicine（TCM） and the Technical Guiding Principles for Revision of Safety Information Items in Instructions for TCMs After Marketing， and 8 categories and 25 specific items were taken as the main body of the evidence body， and information inclusion， integration， screening and improvement were carried out， then expert demonstrations were conducted， and finally modifications were made based on the opinions of the Center for Drug Evaluation to complete the revision of the safety information in the instructions of Xiaoke'an capsules. Result［Adverse reactions］ of Xiaoke'an capsules was revised to "monitoring data show that the following adverse reactions can be seen with this product：individual hypoglycemic reaction reports". ［Contraindications］ was revised to "contraindicated for those allergic to this product and its ingredients". ［Precautions］ was revised to "（1）pregnant women should use with caution， （2）elderly people should consult a physician， （3）people with spleen deficiency and dampness， spleen and stomach deficiency and cold， or those who eat less and have diarrhea should use with caution， （4）this product contains ginseng， should not be taken at the same time with TCM prescriptions or patent medicines containing veratrum and Wulingzhi， （5）pay attention to monitoring blood sugar during medication， （6）if any other discomfort occurs during medication， you should seek medical attention in time". The warning was revised to "use with caution by pregnant women， and pay attention to regular monitoring of blood sugar". ConclusionIn accordance with the content and process of the evidence body for the revision of safety information in the instructions， the revision of the safety information in the instructions of Xiaoke'an capsules has been completed， providing a strong basis for the rational and safe use of medication in the clinic.