This study aimed to investigate halofuginone's inhibitory effect and mechanism on the activity of hepatocellular carcinoma cells. HepG2 cells were used to detect the effects of halofuginone. After treatment, cell activity, cell migration, cell cycle, and cell apoptosis were detected by CCK-8, transwell, and flow cytometry, respectively. The expression levels of growth and metabolism-related factors such as citrate synthase (CS), ketoglutarate dehydrogenase (OGDH), and isocitrate deoxygenase (IDH) were detected by real-time quantitative PCR and Western blot. Compared with the control group, the activity of HepG2 cells was significantly inhibited by halofuginone (P < 0.01), the migration rate of HepG2 cells was decreased (P < 0.01), the apoptosis of HepG2 cells was induced (P < 0.01), and the cell cycle was arrested in S phase (P < 0.01). The expression levels of tricarboxylic acid key enzymes CS, IDH3, and OGDH were up-regulated, the expression level of isocitrate dehydrogenase isoenzymes IDH1 and IDH2 were down-regulation. In conclusion, halofuginone can inhibit the proliferation and migration of HepG2 cells and promote apoptosis in a dose-dependent manner, which may be due to the promotion of the aerobic metabolism of cells.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative 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:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

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 compare the efficacy and safety between the drug winning the bidding for centralized procurement and the original drug of ticagrelor in acute coronary syndrome （ACS） patients one year after percutaneous coronary intervention （PCI）. METHODS Overall 420 ACS patients treated with PCI in our hospital from July 2021 to June 2023 were divided into centralized procurement group （156 cases） and original drug group （264 cases） according to the different varieties of ticagrelor. All patients were given Aspirin enteric-coated tablets 100 mg regularly， once a day； on this basis， patients in the centralized procurement group were given Ticagrelor tablets winning the bidding， while patients in the original drug group were given the original drug of Ticagrelor tablets. The dosage of Ticagrelor tablets taken by both groups of patients was 90 mg， twice a day， and the course of treatment was 12 months. The blood routine indicators were compared before treatment and one week after treatment， while the incidence of net adverse clinical events （NACE）， major adverse cardiovascular and cerebrovascular events （MACCE） and bleeding events， and the survival rate without MACCE and bleeding events during a one-year follow-up after PCI were also compared between two groups. RESULTS There were no statistically significant differences in blood routine indicators before treatment and one week after treatment， as well as the incidence of NACE， MACCE and bleeding events， survival rate without MACCE and bleeding events during a one-year follow-up after PCI between the two groups （P＞0.05）. CONCLUSIONS During a one-year follow-up after PCI， the efficacy and safety of the drug winning the bidding for centralized procurement of ticagrelor are comparable to the original drug.

Traditional decoction pieces have low efficiency, poor batch-to-batch consistency, and irregular physical form, making it difficult to meet the demands of modern automated production and precise and rapid clinical blending. Therefore, this study aims to develop a new type of granular drinking tablet to meet the demand for high-quality development in the traditional Chinese medicine industry. In the current study, the differences and similarities between the new Lonicerae Japonicae Flos (LJF) granular drinking tablets and the traditional ones were evaluated based on the flowability, the paste rate of the standard soup, the characterization fingerprint, the degree of pasting, the content of active ingredients, the transfer rate, and its traditional antipyretic and anti-inflammatory efficacy, using the traditional LJF decoction piece as a reference. The flowability experiments showed that the flowability of medium-sized granules (10-24 mesh) was significantly better than that of traditional drinking tablets (P < 0.01); the results of the paste rate showed that there was no significant difference between the different particle sizes and the original decoction pieces (P > 0.05), but the small particle sizes (24-65 mesh) had poor decoction clarity and gelatinization; the transfer rate was calculated as chlorogenic acid and luteoloside, and there was no significant difference in the transfer rate between traditional slices and different particle sizes (P > 0.05); the pharmacological results showed that the contents of rat tumor necrosis factor-α (TNF-α), rat interleukin-1β (IL-1β) and rat prostaglandin E₂ (PGE₂), xylene ear swelling inhibition rate and granuloma inhibition rate showed that there was no significant difference between the traditional and new granule decoction pieces (P > 0.05). In this study, by examining the fluidity, paste rate, paste degree, and antipyretic and anti-inflammatory effects of the new granular decoction piece of LJF, it was initially revealed that the new granular drinking tablets of LJF were consistent with the basic properties and pharmacological effects of the commercially available traditional drinking tablets. Still, the new granular tablets were characterized by high utilization rate, homogeneous quality, and ease of clinical transfer, which had a good prospect for application. The animal experiment was approved by the Ethics Committee of the China Academy of Chinese Medical Sciences (approval number. 2022B214).

Objective To summarise and analyse the qualitative studies on the factors that influence patient involvement in decision-making for the initial administration of insulin for the patients with Type II diabetes,from the perspectives of patients and healthcare staff in order to provide a reference to promote patient involvement in decision-making.Methods Systematic searches were conducted across databases,such as CINAHL,Cochrane Library,EMBASE,PubMed,Web of Science,PsycINFO,China National Knowledge Infrastructure(CNKI),Wanfang Data,VIP,and SinoMed,for qualitative studies on the factors that affect patient involvement in initial insulin decision-making for the patients with Type II diabetes.The search was limited to articles from the inception of the databases to 30th September,2023.Quality of the included studies was assessed using the Joanna Briggs Institute(JBI)evidence-based healthcare centre for qualitative research quality assessment tool.The results were integrated using a synthesising integration method.Results A total of 19 articles were included,yielding 20 study results,which were categorised into 7 themes of patient decision-making related values,patient role preferences in decision-making,condition of patient,the role of healthcare staff in patient participation in decision-making,professional quality of healthcare staff,relationship between patient and healthcare staff,and the support from a medical institution.The data were ultimately integrated into 4 overarching themes of patient personal factors,healthcare staff factors,patient-staff interaction factors and medical institution factors.Conclusion The involvement of the patients with Type II diabetes in the decision-making for the initial administration of insulin is influenced by patients themselves,healthcare staff and medical institutions.It requires efforts of multiple parties:not only with the patients actively participate in decision-making,but also with the healthcare staff and institutions who provide effective decision supports.

Objective·To investigate the potential causal relationship between type l diabetes and colorectal cancer by using Mendelian randomization(MR).Methods·Two-sample bidirectional MR was used to investigate the causal relationship between type 1 diabetes and colorectal cancer.All research data were collected from the IEU Open GWAS Project database.The dataset of type l diabetes included 9 266 cases and 15 574 controls,with correlation analysis in 12 783 129 single nucleotide polymorphisms(SNPs);the dataset of colorectal cancer included 5 657 cases and 372 016 controls,with correlation analysis in 29 999 696 SNPs.The instrumental variables SNPs were screened.The results derived from the inverse-variance weighted(IVW)method were used as the main indicator of effect.The results derived from other four methods,namely MR-Egger regression,weighted median,simple mode,and weighted mode,were used as reference.Sensitivity was analyzed with the leave-one-out method.Heterogeneity was analyzed with Cochran's Q test by using both IVW and MR-Egger methods.Pleiotropy was analyzed with MR-pleiotropy function,and Steiger test was used for directional research.The colocation analysis was used to find out whether the causal relationship between type 1 diabetes and colorectal cancer was caused by the same SNP.The genetic correlation between 2 diseases was analyzed by using the linkage disequilibrium score regression(LDSC).All tests were analyzed by using R language software(version 4.3.1).Results·After being screened,a total of 33 instrumental variables(SNPs)were used.The heterogeneity test results showed that there was heterogeneity among the SNPs(IVW and MR-Egger:P＜0.05),so the effect evaluation was based on the results of the random effect model.MR analysis showed that type 1 diabetes had a significant causal effect on colorectal cancer(P＜0.05)by using IVW,MR-Egger,weighted median and weighted mode.Sensitivity analysis showed that the results were stable.Pleiotropy was not detected in pleiotropy test(P＞0.05).Steiger test showed that the effect of type l diabetes on colorectal cancer was not interfered with by the reverse effect.Reverse MR analysis showed no causal effect of colorectal cancer on type l diabetes(P＞0.05).The results of colocalization analysis showed that the probability of H4 hypothesis was 45.7％,and the causal relationship between the 2 diseases was not caused by the same SNP in the gene sequences.LDSC analysis demonstrated that there was no genetic correlation between the two diseases.Conclusion·Type 1 diabetes may promote colorectal cancer,but colorectal cancer has no effect on type 1 diabetes.

The biological clock(also known as the circadian rhythm)is the fundamental reliance for all organisms on Earth to adapt and survive in the Earth's rotation environment.Circadian rhythm is the most basic regulatory mechanism of life activities,and plays a key role in maintaining normal physiological and biochemical homeostasis,disease occurrence and treatment.Recent studies have shown that the biologi-cal clock plays an important role in the development of oral tissues and in the occurrence and treatment of oral diseases.Since there is cur-rently no guiding literature on the research methods of biological clock in stomatology,researchers mainly conduct research based on pub-lished references,which has led to controversy about the research methods of biological clock in stomatology,and there are many confusions about how to rationally apply the research methods of circadia rhythms.In view of this,this expert consensus summarizes the characteristics of the biological clock and analyzes the shortcomings of the current biological clock research in stomatology,and organizes relevant experts to summarize and recommend 10 principles as a reference for the rational implementation of the biological clock in stomatology research.

Objective A scoping review was performed to identify the effectiveness,characteristics,and behavior change techniques of intervention strategies for reducing sedentary behavior among older adults.Methods This study was guided by the scope review methodology framework proposed by Arksey and O'Malley.A comprehensive search of databases was conducted in PubMed,Embase,PsycINFO,Cochrane Library,CINAHL,and Sedentary Behavior Research Database to collect the literature on intervention strategies for reducing sedentary behavior among older adults.The search period was from the establishment of the databases to September 20,2022.The study selection and data extraction were performed independently by 2 reviewers.The resulting data were analyzed and arranged using the descriptive analysis and the social network analysis.Results A total of 31 separate studies published between 2011 and 2022 were included in this study.Most intervention strategies were developed based on the Social Cognitive Theory.Almost all sedentary behavior intervention strategies targeted the psychological and behavioral levels of the individual.The main contents of the intervention strategies included goals and plans,feedback and monitoring,natural consequences,social support,repetition and substitution.In the social network analysis,the behavior change techniques that ranked high in degree centrality included goal-setting(behavior),self-monitoring of behavior,action planning,information about health consequences,and feedback on behavior.These intervention strategies could reduce sedentary time from 23 to 151 min/day.Conclusion Domestic nursing researchers should pay attention to sedentary behavior in older adults,and develop intervention strategies for reducing sedentary behavior in local contexts based on the effectiveness,characteristics,and behavior change techniques of the existing sedentary behavior intervention strategies.

Objective: To understand the performance of 2019-nCoV nucleic acid detection in screening of contacts of COVID-19 cases in same flights and provide evidence for the effective screening of persons at high risk for the infection in domestic flights. Methods: The information of passengers who took same domestic flights with COVID-19 cases in China from April 1, 2020 to April 30, 2022 were retrospectively collected,and χ² test was used to analyze positive nucleic acid detection rates in the passengers in different times before the onsets of the index cases, in different seat rows and in epidemic periods of different 2019-nCoV variants. Results: During the study period, a total of 433 index cases were identified among 23 548 passengers in 370 flights. Subsequently, 72 positive cases of 2019-nCoV nucleic acid were detected in the passengers, in whom 57 were accompanying persons of the index cases. Further analysis of the another 15 passengers who tested positive for the nucleic acid showed that 86.67% of them had onsets or positive detections within 3 days after the diagnosis of the index cases, and the boarding times were all within 4 days before the onsets of the index cases. The positive detection rate in the passengers who seated in first three rows before and after the index cases was 0.15% (95%CI: 0.08%-0.27%), significantly higher than in the passengers in other rows (0.04%, 95%CI: 0.02%-0.10%, P=0.007),and there was no significant difference in the positive detection rate among the passengers in each of the 3 rows before and after the index cases (P=0.577). No significant differences were found in the positive detection rate in the passengers, except the accompanying persons, among the epidemics caused by different 2019-nCoV variants (P=0.565). During the Omicron epidemic period, all the positive detections in the passengers, except the accompanying persons, were within 3 days before the onset of the index cases. Conclusions: The screening test of 2019-nCoV nucleic acid can be conducted in the passengers took the same flights within 4 days before the onsets of the index cases on board. Passengers who seated within 3 rows from the index cases can considered as the close contacts at high risk for 2019-nCoV, for whom screening should be conducted first and special managements are needed. The passengers in other rows can be classified as general risk persons for screening and management.
Humans ; COVID-19 ; Retrospective Studies ; SARS-CoV-2 ; China ; Nucleic Acids