Aim To investigate the regulatory mecha-nism of butin on the proliferation,migration,cycle blockage and pyroptosis related inflammatory factors in human fibroblast-like synoviocytes of rheumatoid arthri-tis(HFLS-RA).Methods Cell proliferation,migra-tion and invasion were studied using cell migration and invasion assays.Cell cycle was detected by flow cytom-etry,and the expression of the pyroptosis-associated in-flammatory factors IL-1β,IL-18,caspase-1 and caspase-3 was detected by ELISA,RT-qPCR and West-ern blot.Results Migration and invasion experiments showed that the cell proliferation rate of the butin group was lower than that of the blank control group(P＜0.05).Cell cycle analysis demonstrated that in the G0/G1 phase,the DNA expression was elevated in the medium and high-dose groups of butin(P＜0.05),while in the G2 and S phases,the DNA expression was reduced in the medium and high-dose groups of butin(P＜0.05).The results of ELISA,RT-qPCR and Western blot assay revealed that the expression of IL-1β,IL-1 8,caspase-1,and caspase-3 decreased in the butin group compared with the IL-1β+caspase-3 in-hibitor group(P＜0.05).Conclusions Butin inhib-its HFLS-RA proliferation by inhibiting the synthesis of inflammatory vesicles by caspase-1 in the pyroptosis pathway,thereby reducing the production and release of inflammatory factors such as IL-1β and IL-18 down-stream of the pathway,and also inhibits HFLS-RA pro-liferation by exerting a significant blocking effect in the G1 phase,which may be one of the potential mecha-nisms of butin in the treatment of RA.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

OBJECTIVE: To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study. METHODS: A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 community older adults. After the baseline survey, the last follow-up was March 31, 2021 with an average 8.13 years of follow-up. Cox proportional hazard model was used to estimate the hazard ratios (HR) with 95% CI for cardiovascular disease (CVD) death and all-cause death in associations with baseline lipid indicators. RESULTS: A total of 4499 participants were recruited, and the mean levels of uric acid, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol (LDL-C) showed an upward trend with the increasing remnant cholesterol (RC) quarters (P_trend < 0.05), while the downward trend was found in high-density lipoprotein cholesterol (HDL-C). During the total 36,596 person-years follow-up, the CVD mortality and all-cause mortality during an average 8.13 years of follow-up was 3.87% (95% CI: 3.30%-4.43%) and 14.83% (95% CI: 13.79%-15.86%) with 174 CVD death participants and 667 all-cause death participants. After adjusting for confounders, the higher level of TC (HR = 0.854, 95% CI: 0.730-0.997), LDL-C (HR = 0.817, 95% CI: 0.680-0.982) and HDL-C (HR = 0.443, 95% CI: 0.271-0.724) were associated with lower risk of CVD death, and the higher level of HDL-C (HR = 0.637, 95% CI: 0.501-0.810) were associated with lower risk of all-cause death. The higher level of RC (HR = 1.276, 95% CI: 1.010-1.613) increase the risk of CVD death. Compared with the normal lipid group, TC ≥ 6.20 mmol/L group and LDL-C ≥ 4.10 mmol/L group were no longer associated with lower risk of CVD death, while RC ≥ 0.80 mmol/L group was still associated with higher risk of CVD death. In normal lipid group, the higher levels of TC, LDL-C and HDL-C were related with lower CVD death. CONCLUSIONS In community older adults, higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range. Higher RC was associated with higher CVD mortality, which may be a better lipid indicator for estimating the CVD death risk in older adults.

Objective To investigate the Gram-positive coccus resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Methods All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 1 974 pathogenic Gram-positive coccus from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,the prevalence of methicillin resistant Stapylococcus aureus(MRSA)and methicillin resistant Stapylococcus epidermidis(MRSE)were 36.4％and 79.9％respectively.No vancomycin insensitivity Staphylococcus was detected.Staphylococcus aureus were 100％susceptibility to linezolid and teicoplanin.Antibiotic resistance rate of Enterococcus faecalis and Enterococcus faecium to ampicillin were 3.1％and 92.9％.The detectation rate of vancomycin resistant Enterococcus(VRE)was 1.6％.Nonsusceptibility rate of Enterococcus faecalis to linezolid was 32.2％,two consecutive monitoring rises and nonsusceptibility rate of Enterococcus faecium(12.5％)was also significantly increased.The prevalence of penicillin non-susceptible Streptococcus pneumoniae(PNSSP)was 0.8％based on non-meningitis and parenteral administration criterion,decrease of nearly 30 percentage points from the previous surveillance.While for cases of oral penicillin,the rate was 71.8％,showing similar to last time.The results indicated that the number of strains with higher MIC value of penicillin(MIC ≥4 mg·L-1)decreased significantly.There were no significant differences of resistance rates of Stapylococcus aureus,Stapylococcus epidermidis,Enterococcus faecalis,Enterococcus faecium and Streptococcus pneumoniae among various groups such as different department,age,or specimen source.Conclusion VRE detection ratio stablized at a relatively low level.The number of Streptococcus pneumoniae with higher MIC value of penicillin decreased significantly compared with the previous monitoring.The increase of linezolidin-insensitive Enterococcus was noteworthy.

Objective To investigate the Gram-negative bacteria resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Method All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 4 066 pathogenic isolates from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,Escherichia coli and Klebsiella pneumoniae showed extended spectrum β-lactamase(ESBLs)phenotype rates of 55.0％and 21.0％,respectively,ESBLs phenotype rate of Klebsiella pneumoniae keep going down.The ratios of carbapenems resistance Klebsiella pneumoniae increased by 5 percentage points compared with the previous monitoring.Carbapenems,moxalactam,sitafloxacin,β-lactam combination agents,fosfomycin trometamol,and amikacin displayed desirable antibacterial activity against Enterbacterales,susceptibal rates were above 75％.In addition,tigacycline,omacycline,colistin and fluoxefin maintained good antibacterial activity against their respective effective bacteria/species,and the bacterial sensitivity rates by more than 80％.Resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannnii to imipenem were 26.3％and 72.1％and multidrug-resistant(MDR)detection rates were 41.1％and 77.3％,extensively drug-resistant(XDR)were 12.0％and 71.8％,respectively.Comparison of drug resistance rates from different wards,ages and specimen sources indicated that the proportion of resistance in Klebsiella pneumoniae and Acinetobacter baumannii isolated from intensive care unit(ICU)were significantly higher than non-ICU.Carbapenem resistance rates of Klebsiella pneumoniae isolated from ICU were more than 35％.Resistance rates of Haemophilus influenzae isolated in children to β-lactam,macrolide,clindamycin and ESBLs detection rate in Klebsiella pneumoniae isolated from children were more than those from adults and the old people,so bacterial resistance in children is an important problem in China.Conclusion ESBLs detection rate of Escherichia coli increased slightly after years of continuous decline.The proportion of carbapenem resistant Pseudomonas aeruginosa was stable,but the resistance rate of Klebsiella pneumoniae and Acinetobacter baumannii to carbapenems was still increased,which should be paid more attention.

Objective: To investigate the effects of glucose-6-phosphatase catalytic subunit (G6PC) recombinant adenovirus on proliferation and cell cycle regulation of liver cancer cells. Methods: Recombinant adenovirus AdG6PC was constructed. Huh7 cells and SK-Hep1 cells were set as Mock, AdGFP and AdG6PC group. Cell proliferation and clone formation assay were used to observe the proliferation of liver cancer cells. Transwell and scratch assay were used to observe the invasion and migration of liver cancer cells. Cell cycle flow cytometry assay was used to analyze the effect of G6PC overexpression on the proliferation cycle of liver cancer cells. Western blot was used to detect the effect of G6PC overexpression on the cell-cycle protein expression in liver cancer cells. Results: The recombinant adenovirus AdG6PC was successfully constructed. Huh7 and SK-Hep1 cells proliferation assay showed that the number of proliferating cells in the AdG6PC group was significantly lower than the other two groups (P < 0.05). Clone formation assay showed that the number of clones was significantly lower in AdG6PC than the other two groups (P < 0.05), suggesting that G6PC overexpression could significantly inhibit the proliferation of liver cancer cells. Transwell assay showed that the number of cell migration was significantly lower in AdG6PC than the other two groups (P < 0.05). Scratch repair rate was significantly lower in AdG6PC than the other two groups (P < 0.05), suggesting that G6PC overexpression can significantly inhibit the invasion and migration of liver cancer cells. Cell cycle flow cytometry showed that G6PC overexpression had significantly inhibited the Huh7 cells G(1)/S phase transition. Western blot result showed that G6PC overexpression had down-regulated the proliferation in cell-cycle related proteins expression. Conclusion: G6PC inhibits the proliferation, cell-cycle related expression, and migration of liver cancer cells by inhibiting the G(1)/S phase transition.
Catalytic Domain ; Cell Cycle Checkpoints ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glucose-6-Phosphatase/metabolism* ; Humans ; Liver Neoplasms/genetics*

OBJECTIVE: To analyze the risk factors for refracture of adjacent vertebrae after percutaneous vertebroplasty (PVP) in super-old patients with osteoporotic vertebral compression fractures(OVCFs). METHODS: A retrospective analysis was performed on 40 patients(age≥90 years) with OVCFs who underwent PVP between June 2012 and June 2019. There were 7 males and 33 females, age from 90 to 101 years old with an average of (94.6±1.6) years. Patients were divided into two groups according to whether adjacent vertebral refracture occurred after PVP. Among them, 20 patients occurred refracture after PVP (refracture group) and 20 patients did not occur it(control group). The general information, radiological data and pelvic parameters of the two groups were collected. The items included age, gender, body mass index (BMI), fracture site and bone mineral density(BMD) T-value, fracture to operation time, compression degree of injured vertebra, recovery degree of anterior edge of injured vertebra, bone cement injection amount, bone cement leakage, pelvic index(PI), pelvic tilt angle (PT), sacral angle(SS), et al. Factors that may be related to refracture were included in the single-factor study, and multivariate Logistic regression analysis was performed on the risk factors with statistical significance in the single-factor analysis to further clarify the independent risk factors for refracture of adjacent vertebral bodies after PVP. RESULTS: There were no significant differences in age, gender, fracture site, fracture to operation time, compression degree of injured vertebra and recovery degree of anterior edge of injured vertebra between two groups (P>0.05). There were significant differences in BMI, BMD T-value, bone cement injection amount and bone cement leakage rate between two groups(P<0.05). The PI and PT values of the refracture group were higher than those of the control group(P<0.05). There was no significant difference in SS between two groups (P>0.05). Multivariate Logistic regression analysis showed that decreased BMD T-value, bone cement leakage, increased PT and PI values increased the risk of recurrence of adjacent vertebral fractures in OVCFs (P<0.05). CONCLUSION There are many risk factors for the recurrence of adjacent vertebral fractures in super-old patients with OVCFs. Patients with high PI and PT values may be one of the risk factors.
Aged, 80 and over ; Bone Cements ; Female ; Fractures, Compression/surgery* ; Humans ; Male ; Osteoporotic Fractures/surgery* ; Retrospective Studies ; Risk Factors ; Spinal Fractures/surgery* ; Spine ; Treatment Outcome ; Vertebroplasty/adverse effects*

Exosomes are lipid bilayer membranous vesicles actively secreted by various cells in the organism， which are like nanoparticles and have messenger targeting. Combining with the theory of supramolecular "Qi chromatography" of traditional Chinese medicine （TCM）， research ideas and strategies of modernization of TCM can be constructed. Exosomes are secreted by cells， and the membrane contains nucleic acids， proteins， lipids and small molecular metabolites and others， which can accurately coordinate the functions of each cell， concentrate and transmit the functional information of the parent cell， and is the concise form of reflecting cell functions. At the same time， it is loaded with the "imprinted templates" of the supramolecular "Qi chromatography" theory of TCM. If the "imprinted templates" carrying rules among the gene-protein-lipid-small molecules wrapped in it is studied， the modern experimental research ideas and strategies of TCM theory can be established for revealing the functions of the body's meridians and viscera. Firstly， the present situation of exosomes， including discovery， secretion， characteristics， functions， attribution， uptake， research methods and application status， were reviewed in this paper. And the natural properties of its precise messenger targeted delivery vehicle were elaborated， reflecting the operation law of microscopic substances in meridians and viscera. Secondly， to explore it as an important carrier of the concentrated "imprinted templates" of the supramolecular "Qi chromatography" theory of TCM， and integrating the research methods of exosomes and supramolecular chemistry of TCM， this paper proposes experimental research ideas and strategies on the microscopic material basis of meridians and viscera， compatibility of TCM compound， and targeting of TCM targeted preparations.

In the era of artificial intelligence based on big data， data acquisition， storage and processing are more convenient， which provides a guarantee for accelerating the development of traditional Chinese medicine （TCM）， but it has not yet achieved organic integration with TCM theory. Based on preliminary research on the supramolecular "Qi chromatography" theory of TCM， combined with the current development trend of artificial intelligence， this paper analyzed the biological intelligence attribute of the function of TCM supramolecular "imprinting template"， in order to provide reference for the development of TCM drug innovation. Both the human body and Chinese materia medica are giant complex supramolecular bodies evolved from natural organisms. According to the "imprinting template"， the "social molecules" are controlled step by step to form the meridians and viscera. The interaction produces the original theory of TCM， in which the self-recognition， self-assembly， self-organization and self-replication of the "imprinting template" reflect the "intelligence" function attributes：the human body uses the "imprinting template" to self-identify and sense the ingredients of TCM， and store the memory information database in the meridian and collateral organs in the form of "imprinting template"， and then pass the "imprinting template". The comparison， analysis， and judgment of imprinting templates guide the self-assembly， self-organization and self-replication among "molecular society"， synthesize biological machines， produce biological functions， repair or strengthen biological supramolecular bodies， and present the most basic "intelligence" attribute. This suggests that the theory of theory-method-prescription-medicine of TCM is the weak embodiment of biological "intelligence"， while the human brain function is the strong embodiment of biological "intelligence". Since the intelligent function of supramolecular "imprinting template" runs through the natural world， artificial intelligence that can characterize the strong "intelligence" form of the human brain will also be integrated into all aspects of the natural world， suggesting the development direction of "intelligence" functionalization of drug innovation mode.

Objective:To solve the problem of leg shaking caused by the sudden change of angular acceleration at the joint of periodic motion during circular gait training of lower limb rehabilitation robot. Methods:A kind of quasi-circular gait was proposed, which divided the periodic motion into three phases: start phase, middle phase and end phase. The time was equal in the start phase and the end phase, and could be adjusted with the parameter ratio. The joint trajectories of the two phases were planned by quintic polynomial, and the middle phase was still the circular gait joint trajectory. The trajectory of the proposed quasi-circular gait was simulated. Results:The angular velocity was continuously differentiable and 0, the angular acceleration was continuous and 0, and the end-effector trajectory became flat with the increase of ratio. The results on the physical prototype of the lower limb rehabilitation robot were principally consistent with the simulation, and the machine worked smoothly. Conclusion:The proposed variable quasi-circular gait had smooth angular acceleration at the junction of periodic motions, which effectively solved the jitter problem when using circular gait for lower limb rehabilitation training and avoided secondary injury to the patients.