Objective:To explore the effects of the fat mass and obesity-associated gene(FTO)on apoptosis and the inflammatory response of chondrocytes in osteoarthritis(OA).Methods:Differences in FTO expression between normal human cartilage tissue samples and OA cartilage tissue samples were examined.Primary OA chondrocytes were isolated and cultured, and a rat OA model was constructed.The expression of FTO was detected in clinical, animal and cellular samples.Cells were treated with an FTO knockdown lentivirus vector(sh-FTO)and an m 6A methylation inhibitor(cycloleucine). The amount of m 6A and the expression levels of inflammatory cytokines, interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α), were detected.Flow cytometry was used to detect apoptosis in OA chondrocytes, and Western blot was used to detect the expression levels of B-cell lymphoma 2(Bcl-2)and Bcl-2-associated X protein(Bax). Results:Compared with the normal control group, FTO mRNA and protein expression in human OA cartilage tissue, rat OA cartilage tissue and OA chondrocytes was significantly increased(all P<0.05). After FTO knockdown, the level of m 6A increased, the levels of IL-6 and TNF-α decreased considerably, the apoptosis rate decreased, the expression of the proapoptotic protein Bax decreased considerably, and the expression of Bcl-2 increased considerably in primary OA chondrocytes.However, cycloleucine intervention clearly reduced the level of m6A, increased the levels of IL-6 and TNF-α, promoted cell apoptosis and the expression of apoptosis-related proteins, and reversed the effect induced by the FTO knockdown lentivirus in OA chondrocytes(all P<0.05). Conclusions:FTO may be involved in mechanisms related to the action of m 6A to promote OA chondrocyte apoptosis and the inflammatory response, thus accelerating the progression of OA.

Danggui Sinitang is first recorded in the Treatise on Cold Damage written by ZHANG Zhongjing in the Han dynasty. It is composed of Angelicae Sinensis Radix， Cinnamomi Ramulus， Paeoniae Radix Alba， Asari Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Tetrapanacis Medulla， and Jujubae Fructus and serves as a classic formula for treating the syndrome of blood deficiency and cold reversal. This study systematically reviews the records of Danggui Sinitang in ancient Chinese medicine books of various dynasties and the modern clinical applications to probe into the composition， plant species， processing， dosage， decocting method， and indications of Danggui Sinitang， aiming to provide a reference for the development and clinical application of this classic formula. The review of the records showed that there were a variety of records of Danggui Sinitang with different composition， and the composition of this formula listed in the Treatise on Cold Damage has a significant impact on later generations and has been used by medical practitioners throughout history. Although the dosage of some drugs decreased during the Ming and Qing dynasties， the medical practitioners continued to use the original formula. In terms of processing， although there were slight changes in the processing of Angelicae Sinensis Radix， Paeoniae Radix Alba， Glycyrrhizae Radix et Rhizoma， and Tetrapanacis Medulla， the original processing method was inherited. In terms of indications， Danggui Sinitang was designed to treat cold reversal due to blood deficiency and dysentery. Furthermore， it was used to treat headache， convulsive disease， infantile convulsion， and private part adduction in the Ming and Qing dynasties. Nowadays， this formula is mostly used to treat diabetes peripheral neuropathy， rheumatoid arthritis， dysmenorrhea， Raynaud's disease and other diseases. In terms of precautions， ancient physicians believed that Danggui Sinitang should not be taken by pregnant women and should only be used for limb chills caused by blood deficiency and cold coagulation. For limb chills caused by other reasons， this formula should not be used indiscriminately. Modern research has not reported any serious adverse reactions related to this formula. Danggui Sinitang has a definite therapeutic effect. In subsequent research and development， quality control standards of Danggui Sinitang should be established while its safety is ensured， and the related preparations should be developed and applied.

Objective:To discuss the association between occupational acid fog exposure and accelerated biological aging of the workers,and to clarify its related risk factors.Methods:A total of 341 male workers exposed to occupational acid fog and 201 male workers without occupational exposure were selected as the study subjects,and they were divided into exposure group and control group,respectively.The general informations of the subjects in two groups were collected through questionnaires and physical examinations.The levels of red blood cell count(RBC),platelet count(PLT),albumin(ALB),urea(Urea),creatinine(CR),triglycerides(TG),total cholesterol(TC),glycated hemoglobin(HBA1c),and high-sensitivity C-reactive protein(Hs-CRP)in serum of the subjects in two groups were detected.The Klemera-Doubal method(KDM)was used to construct the composite aging measure,KDM-biological age(BA)(KDM-BA).The model parameters were trained using samples from the 2009 China Health and Nutrition Survey(CHNS)Database to calculate the BA acceleration of the subjects in two groups;stratified analysis based on the population characteristics was conducted to analyze the BA of the subjects in two groups with different population characteristics;generalized linear model was used to analyze the factors influencing BA acceleration due to acid fog exposure.Results:The model parameters were trained using samples from the 2009 CHNS Database,including 8 133 cases aged 20-79 years,of which 3 788 were male.The levels of Urea,CR,HBA1c,ALB,and TC,as well as systolic blood pressure(SBP),total working years,sleep duration,and body mass index(BMI)of the subjects between two groups had significant differences(P<0.05).Compared with control group,the BA acceleration of the subjects in exposure group was significantly increased(P<0.05).In entire population and exposure group,the BA acceleration in the smokers was significantly higher than that in the non-smokers(P<0.05).In entire population,control group,and exposure group,the BA accelerations of the subjects in different BMI groups were significantly decreased with the increase of BMI(P<0.05).Compared with control group,the BA acceleration of the subjects in exposure group was significantly increased(P<0.05),including those under 40 years old,with total working years of 4-7 years,Han nationality,unmarried,smokers,and sleep duration 6-7 h,and with overweight.Acid fog exposure,smoking,and BMI were associated with the BA acceleration(β=0.72,95%CI:0.24-1.21;β=0.59,95%CI:0.11-1.06;β=-0.29,95%CI:-0.35—-0.22).Conclusion:Occupational acid fog exposure may accelerate the biological aging in the workers,and acid fog is a risk factor to accelerate the biological aging of the body.

Objective:To analyze the distribution and genomic characteristics of SARS-CoV-2 variants isolated from imported cases of COVID-19 in Sichuan Province from December 2022 to January 2023.Methods:This study selected 108 nasal and throat swab samples with fluorescence threshold (Ct)≤32 that were collected from imported COVID-19 cases in Sichuan Province from December 2022 to January 2023. Targeted amplification and Illumina NextSeq? 2000 system were used for whole-genome sequencing. Nextclade and Pangolin online platforms were used to determine the virus genotypes and analyze the mutation loci. A phylogenetic tree was constructed using maximum likelihood.Results:A total of 55 SARS-CoV-2 whole genome sequences with coverage of >95% were obtained, and all of the strains were Omicron variants. Compared with the sequence of reference strain Wuhan-Hu-1, the median number of nucleotide mutation sites of 21L, 22B, 22D, 22E, and 22F genotypes were 93, 75, 92, 78, and 92, and the median number of amino acid mutation sites were 68, 53, 68, 69, and 65, respectively. From December 2022 to January 2023, the predominant circulating SARS-CoV-2 variants from imported cases in Sichuan Province were BA.5.2 (10.91%, 6/55), XBB.1.1 (9.10%, 5/55), BF.7.14 (7.23%, 4/55), and BQ.1.1 (7.23%, 4/55).Conclusions:The distribution of SARS-CoV-2 variants can reflect the global epidemic trend to a certain extent. However, it is different from the distribution of local circulating variants in the Chinese mainland. The XXB variants with transmission advantages can be detected in large numbers of inbound travelers before becoming the predominant circulating strains in the Chinese mainland.

The pathogenesis of Alzheimer's disease(AD)is complex and unclear.Existing drugs can only alleviate its symp-toms,and there is an urgent need to develop effective therapeutic drugs.As the representative drugs of tonic and enlightening medicine,ginseng and acorus calamus have pharmacological effects to improve memory,improve learning ability and reduce cognitive impairment,which are commonly used in Chinese med-icine for the treatment of dementia.The combination of ginseng and acorus calamus can further promote the active ingredients in-to brain to exert their medicinal effects,and delay the process of AD through anti-inflammatory,anti-oxidative stress,modulation of neuronal-synaptic plasticity and other multiple pathways,with multi-level,multi-system and multi-target action characteristics.This paper attempts to summarize the existing research results and lay the foundation for further exploring the synergistic mech-anism of action of ginseng-acorus calamus combination and the dose-effect relationship of the combination,so as to provide a sci-entific basis for the development of innovative Chinese medicines for the prevention and treatment of AD.

AIM To study the effects and possible mechanism of Fuke Qianjin Formula and its modifications on sequelae of pelvic inflammatory disease(PID)in rats.METHODS The SD rats were randomly divided into the normal group,the sham operation group,the model group,Kangfuyan group(FYK,0.756 g/kg),Fuke Qianjin Formula group(FKQ,2.7 g/kg),Yijun Formula group(YJ,2.7 g/kg),Kangyan Formula group(KY,2.7 g/kg)and Buyi Formula group(BY,2.7 g/kg).After 28 days of corresponding administration by gavage,the rats were put to death to procure their uterus,spleen,thymus and liver for the calculation of the organs indices levels;the observation of the general morphology of uterus and oviduct and histopathological examination of uterus and oviduct;the measurement of.the serum levels of IL-1β,IL-18 and IL-6 by ELISA;the detection of the uterine expressions of TGF-β1,caspase-1,NLRP3,IL-18 and CTGF by Western blot;and the detection of the expressions of CD4+and CD8+in spleen lymphocytes by flow cytometry.RESULTS Compared with the model group,FKQ and YJ group,KY group and BY group displayed decreased indices levels of the uterus,spleen and thymus(P＜0.01);FKQ group and KY group displayed reduced uterine swelling,increased endometrial glands,and reduced inflammatory exudation(P＜0.01),and lower serum levels of IL-1β,IL-18 and IL-6(P＜0.01);FKQ group,KYgroup and BY group displayed decreased protein expressions of TGF-β1 and CTGF(P＜0.05,P＜0.01);FKQ group and KY group displayed decreased protein expressions of NLRP3,caspase-1 and IL-18(P＜0.05,P＜0.01);and FKQ group and BY group displayed increased CD4+/CD8+ratio(P＜0.01).CONCLUSION Being protective to sequelae of PID rat models,Fuke Qianjin Formula and its modifications may contribute their anti-inflammatory efficacy by inhibiting the activation of NLRP3 body to hinder the activation of caspase-1,reduce the secretion and release of pro-inflammatory factor IL-18,and thus inhibit pyroptosis.

Based upon the experiences of planning and implementation of "Dynamic changes of Torque Teno virus load in Chinese renal transplant recipients with immunosuppressive therapy: A multi-center prospective observational double-blind cohort study", this article explored the current status and major difficulties of investigator-initiated multi-center prospective clinical trials of kidney transplantation in China. Various issues of organization design and implementation process management were discussed for enhancing the quality of implementing the relevant trials.

Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A-I ( 1, 4- 11), and two known ones ( 2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Objective:To investigate the home care needs and home resource integration expectations of elderly patients after hip fracture surgery so as to provide health care guidance after discharge.Methods:A mixed study method of consistent parallel design was used to conduct semi-structured interviews in 15 elderly patients after hip fracture surgery. Meanwhile, convenient sampling method was used to select elderly patients after hip fracture surgery to conduct health survey with interRAI-HC(International Resident Assessment Instrument Home Care), and comprehensive data results were analyzed.Results:Through the analysis and induction of the interview data, two main themes were extracted: the diversification of home care needs and the lack of integration of home service resources. There were 25 health problems in the elderly after hip fracture surgery. Health problems mainly focus on ADL limitation, insufficient social activity, limited social interaction, clinical health problems (fall risk, malnutrition, pain, cardiovascular and respiratory problems, weakness, fatigue), etc.Conclusions:For elderly patients after hip fracture surgery, it is necessary to strengthen the rehabilitation guidance at discharge, integrate home care resources to provide diversified nursing services in the transitional stage, promote the formation and continuity of patients' rehabilitation behavior, and improve the clinical outcome of patients.