With the aging of the global population， osteoporosis （OP） is becoming a major public health concern worldwide. Currently， the commonly used anti-osteoporosis drugs in clinical practice have limited application due to many side effects. Therefore， developing more effective and safer strategies for the prevention and treatment of OP has become a research focus in this field. In recent years， the clinical efficacy and advantages of traditional Chinese medicine （TCM） in treating OP have been gradually recognized. With the deepening pharmacological research on TCM for OP prevention and treatment， it is found that the active ingredients of Scutellaria baicalensis can promote bone formation or inhibit bone resorption by regulating signaling pathways， including Wnt/β-catenin， osteoprotegerin （OB）/receptor activator of nuclear factor-κB ligand （RANKL）/RANK （OPG/RANKL/RANK）， and bone morphogenetic protein 2 （BMP-2）/Smad， mitogen-activated protein kinase （MAPK）， and mammalian target of rapamycin （mTOR）. However， existing research on active ingredients of S. baicalensis for OP treatment is scattered， making it difficult for scholars to gain a systematic understanding of its research and application. This review summarized the literature on the active ingredients of S. baicalensis in OP treatment worldwide， clarified their mechanisms of action， and explored some issues， providing references for the integration of TCM in OP prevention and treatment.

With the aging of the global population， osteoporosis （OP） is becoming a major public health concern worldwide. Currently， the commonly used anti-osteoporosis drugs in clinical practice have limited application due to many side effects. Therefore， developing more effective and safer strategies for the prevention and treatment of OP has become a research focus in this field. In recent years， the clinical efficacy and advantages of traditional Chinese medicine （TCM） in treating OP have been gradually recognized. With the deepening pharmacological research on TCM for OP prevention and treatment， it is found that the active ingredients of Scutellaria baicalensis can promote bone formation or inhibit bone resorption by regulating signaling pathways， including Wnt/β-catenin， osteoprotegerin （OB）/receptor activator of nuclear factor-κB ligand （RANKL）/RANK （OPG/RANKL/RANK）， and bone morphogenetic protein 2 （BMP-2）/Smad， mitogen-activated protein kinase （MAPK）， and mammalian target of rapamycin （mTOR）. However， existing research on active ingredients of S. baicalensis for OP treatment is scattered， making it difficult for scholars to gain a systematic understanding of its research and application. This review summarized the literature on the active ingredients of S. baicalensis in OP treatment worldwide， clarified their mechanisms of action， and explored some issues， providing references for the integration of TCM in OP prevention and treatment.

Background: Isoliquiritigenin, a key pharmacologically active compound derived from the traditional Chinese medicine Glycyrrhizae Radix et Rhizoma, can be further modified into various high-value 5-deoxyflavones, demonstrating significant potential for pharmaceutical development. Currently, the supply of isoliquiritigenin primarily depends on plant extraction. However, heterologous synthesis using microbial cell factories presents a promising alternative, offering a solution to resource limitations caused by the dwindling availability of Glycyrrhiza uralensis. Objective: This study aimed to employ heterologous synthesis in yeast strains for the stable and high-efficiency production of isoliquiritigenin. Methods: First, a stable chassis strain for isoliquiritigenin production was constructed by integrating optimized biosynthetic pathway enzyme genes. A type IV noncatalytic chalcone isomerase-like protein and a synthetic protein scaffold system were employed to enhance the metabolic channeling of key pathway enzymes. Subsequently, yeast metabolism was fine-tuned to balance precursor supply, and cofactor engineering strategies were implemented to increase nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) availability, thereby ensuring the catalytic efficiency of the key enzyme chalcone reductase. Results: The engineered strain Y21-2 achieved a 24.4-fold increase in isoliquiritigenin titer compared to the original strain. Additionally, the proportion of the by-product naringenin chalcone was reduced by 67.8%, marking the first instance in which the ratio of C-5 hydroxylated by-products was minimized to 10.4% during the microbial synthesis of 5-deoxyflavones. Conclusion: This work provides a valuable reference for the efficient and sustainable production of isoliquiritigenin, laying a solid foundation for further pathway optimization and the biotechnological synthesis of other high-value natural 5-deoxyflavones.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. 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 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Hypokalemia,a common clinical electrolyte disorder,can affect multiple systems and can be life-threatening in severe cases.Identifying the cause of hypokalemia is crucial for its prevention and treatment.However,the etiology of hypokalemia is complex and often requires detailed differential diagnosis.This article reports a rare clinical case of hypokalemia caused by long-term excessive consumption of strong tea and discusses its pathogenesis.The aim is to raise clinical awareness and understanding of the etiology of such cases of hypokalemia and reduce misdiagnosis and missed diagnosis.

Depressed mood and sleep problems are prevalent among elderly people and tend to form a vicious cycle that seriously affects their quality of life and physical health. However， most of the existing studies rely on cross-sectional design， limiting the ability to clarify their predictive relationship and causal direction. ObjectiveTo explore the longitudinal association between nighttime sleep duration and depressed mood among the elderly in China over a 10-year period， providing scientific evidence for developing sleep-related interventions and depression prevention strategies tailored to the elderly. MethodsBased on nationally representative data from the China Health and Retirement Longitudinal Study （CHARLS） between 2011 and 2020， a sample of 5 954 elderly peolpe who had completed the baseline survey and at least one follow-up survey in 2011 was selected. Depressed mood was assessed using the 10-item Centre for Epidemiological Studies Depression Scale （CESD-10）. Basic information including nighttime sleep duration， was collected through a self-designed questionnaire. Cross-lagged path analysis （CLPA） model was employed to analyze the bidirectional relationship between nighttime sleep duration and depressed mood among the ederly. ResultsThe nighttime sleep duration in elderly people showed a negative correlation with CESD-10 scores at both baseline and the last follow-up （r=-0.299， -0.247， P<0.01）. The results of the CLPA model showed that the baseline CESD-10 scores negatively predicted nighttime sleep duration at the last follow-up （β=-0.100， P<0.01）， while baseline nighttime sleep duration also predicted CESD-10 scores at the last follow-up （β=-0.041， P<0.01）. ConclusionDepressed mood in elderly people exhibits a longitudinal association with nighttime sleep duration， demonstrating a bidirectional negative predictive relationship between the two factors.

Gastric cancer with peritoneal metastasis (GCPM) is a common and lethal manifestation of advanced gastric cancer, with a median survival of only 5-11 months. This consensus was developed by 30 experts from Asia (China, Japan, Korea, and Singapore) using the Delphi method and the GRADE evidence grading system. A total of 29 statements were formulated, covering the diagnosis and assessment of GCPM, indications for laparoscopic exploration and NIPS (normothermic intraperitoneal and systemic treatment), treatment regimens, prevention and management of complications, criteria for conversion surgery, and postoperative intraperitoneal therapy. The consensus aims to standardize clinical practice and improve the prognosis of patients with GCPM.

Objective:To investigate the effect of KRAS,NRAS and BRAF gene mutations on the efficacy of pre-operative short-course radiotherapy combined with chemotherapy and postoperative liver metastasis in patients with stage Ⅱ～Ⅲ mid-low rectal cancer.Methods:The clinical data of 149 patients with stage Ⅱ～Ⅲ low rectal cancer admitted to Dongnan Hospital of Xiamen University from January 2017 to June 2020 were retrospectively analyzed.All patients received neoadjuvant therapy with preoperative short-course radiotherapy combined with chemotherapy and radical surgery,and were followed up until June 30,2023.The mutations of KRAS,NRAS and BRAF genes were de-tected by pathological tissue before surgery.The effect of neoadjuvant therapy was evaluated according to tumor re-gression grade(TRG).The risk factors of postoperative liver metastasis were analyzed by Logistic multivariate analysis.Results:There were 44 cases of KRAS,10 cases of NRAS and 12 cases of BRAF gene mutation in 149 patients with stage Ⅱ～Ⅲ low rectal cancer,and the mutation rates were 29.53%,6.71%and 8.05%.The incidence of positive vas-cular invasion in patients with KRAS gene mutation was higher than negative(P＜0.05).In NRAS mutation patients,the incidence of positive lymph node metastasis was higher than negative(P＜0.05),and the incidence of maximum tumor diameter≥5 cm was higher than that of maximum tumor diameter＜5 cm(P＜0.05).The clinical stage of BRAF muta-tion was higher in stage Ⅲ than in stage Ⅱ(P＜0.05),and the incidence of positive lymph node metastasis was higher than negative(P＜0.05).During the follow-up period,liver metastasis occurred in 42 patients,and the liver metastasis rate was 28.18%.The KRAS,NRAS and BRAF gene mutations in the effective group were 25.81%,2.15%and 3.23%,lower than those in the ineffective group(35.71%,14.29%and 17.07%,P＜0.05).Multiple factors found clinical stage Ⅲ(OR=10.620,95%CI:2.645～22.575),lymph node metastasis was positive(OR=8.774,95%CI:1.878～19.645),neoadju-vant therapy failed(OR=3.373,95%CI:1.014～11.218),KRAS gene mutation(OR=6.245,95%CI:1.876～20.789),BRAF gene mutation(OR=9.497,95%CI:1.754～19.335)were independent risk factors for postoperative liver metastasis of stage Ⅱ～Ⅲ mid-low rectal cancer.Conclusion:Mutations in the KRAS and BRAF genes of middle are associated with poorer efficacy of neoadjuvant therapy in patients with stage Ⅱ～Ⅲ mid-low rectal cancer and are also indepen-dent risk factors for postoperative liver metastasis.