Objective To investigate the role of nuclear factor-κB(NF-κB)/NOD-like receptors family pyrin domain containing 3(NLRP3)pathway in limb ischemia-reperfusion injury(IRI)pretreated with ulinastatin(UTI).Methods Twenty-one SD rats were randomly divided into Sham group,IRI group,UTI group.In UTI group,ulinastatin was injected after anesthesia.After 10 minutes,the animal model was established by claming the femoral artery and ligaturing collateral circulation.After 3h of ischemia,the clamp and tourniquet were removed and the rats underwent 2h of reperfusion.In the other groups,the homologous saline was also injected in the same time.Plasma concentrations of lactate dehydrogenase(LDH)and creatine kinase(CK),interleukin(IL)-6,IL-18,tumor necrosis factor-α(TNF-α)were measured.The gastrocnemius muscle was harvested and immediately stored at-80℃.NF-κB and NLRP3 were detected by Western blot and PCR.The other section muscle was stored in triformol for HE staining.The wet/dry was also immediately detecting.Results The level of wet/dry,LDH,CK,IL-6,IL-18,TNF-α,NF-κB,NLRP3 IRI were higher than those in Sham group(P＜0.05).The level of wet/dry,LDH,CK,IL-6,IL-18,TNF-α,NF-κB,NLRP3 IRI were significantly lower than those in IRI group(P＜0.05).Conclusion Ulinastatin can reduce the cellular inflammatory response through the NF-κB/NLRP3 pathway,thereby achieving a protective effect on limb IRI in rats.

Objective To investigate the association between chewing ability and frailty in elderly adults in communities of China. Methods A total of 12, 678 elderly people in community were selected from data of Chinese Longitudinal Healthy Longevity and Happy Family Study(CLHLS-HF) as the study subjects. Multivariate Logistic regression analysis was used to explore the relationship between chewing ability and frailty of elderly people in community, and restricted cubic spline (RCS) based on Logistic regression analysis was used to analyze the dose-response relationship between the number of teeth and frailty risk in elderly people in community of China. Results Of the 12, 678 community-dwelling older adults, the mean age was (83.62±11.16) years, with an age ranging from 65 to 117 years; there were 5, 848 (46.1%) men and 6, 830 (53.9%) women. The Results of the multifactorial Logistic regression analysis showed that after adjusting for the covariates including gender, age, marital status, place of residence, ethnicity, living arrangement, years of education, healthcare availability and occupation before age of 60, self-rated economic status, body mass index (BMI), smoking status, alcohol consumption status, exercise status, self-rating health status variables, and participation in the annual medical check-ups or not, the Results showed that the chewing ability of community-dwelling older adults was associated with the risk of frailty (P < 0.05). The RCS plot showed a linear correlation between the number of natural teeth and the risk of frailty, with the risk of frailty increasing when the number of natural teeth was less than 10, and the risk of frailty gradually increased as the number of teeth decreased. Conclusion Chewing ability is associated with the risk of frailty in Chinese older adults, and the number of natural teeth and the use of dentures are important for the development of frailty in older adults.

Objective:To express NY-ESO-1 epitopes using circular RNA (circRNA) and construct circRNA cancer vaccines using a novel lipid-like material C1, and to evaluate the transfection efficiency and T cell activation potential at cellular level.Methods:In vitro transcription was used to synthesize mRNA and circRNA expressing EGFP and NY-ESO-1 epitopes. Then, they were transfected into COS7 cells and the expression of target proteins were detected in vitro. Lipid-like material C1 and commercial transfection agent TransIT-mRNA were used as delivery systems for mRNA NY-ESO-1 and circRNA NY-ESO-1, and their delivery efficiency was compared. Results:The expression of EGFP was observed under fluorescence microscopy after transfection of mRNA EGFP and circRNA EGFP into COS7 cells for 24 h. The secretion of IFN-γ by T cell receptor-engineered T (TCR-T) cells targeting NY-ESO-1/HLA-A2 was stimulated by COS7-A*02: 01 cells transfected with mRNA NY-ESO-1 and circRNA NY-ESO-1. Compared with mRNA NY-ESO-1, circRNA NY-ESO-1 was able to express the target antigen and stimulate the target cells to release IFN-γ more persistently. The delivery efficiency of C1 material was better than that of commercial transfection reagents when COS7 cells were transfected in vitro. Conclusions:Compared with the linear mRNA, transfection of COS7-A*02: 01 cells with circRNA can lead to more efficient and durable activation of T cells, suggesting that it could be a more suitable candidate for clinical treatment of tumors in the future. The lipid-like material C1 can effectively deliver linear mRNA and circular RNA molecules. This study provides reference for further research on circRNA tumor vaccines.

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

Objective:To study the real-world outcome of China FDA-approved Sofosbuvir (SOF)/Velpatasvir (VEL) in Northwest China.Methods:In this multicenter, prospective, real-world cohort study, we recruited patients from 10 sites from Northwest China, who were chronically infected with HCV GTs 1-6 from 06/2018 to 09/2019. Patients received SOF (400mg)/VEL (100mg) for 12 weeks, and with ribavirin 900-1200 mg for GT3 cirrhosis and for any genotype decompensated cirrhosis. The primary endpoint was sustained virological response at 12-weeks post-treatment (SVR12) and safety. The secondary endpoint was the change of liver function after the achievement of SVR12.Results:Totally, 143 patients were enrolled in the study, four patients were lost to follow-up and one died during the follow-up, 138 patients were included in per-protocol analysis. Of the 138 patients, the mean age 53 years, 53.6% male, 94.2% Han nationality, 53.6% liver cirrhosis, 10.1% HBsAg +, 6.5% renal dysfunction, 5.1% treatment-experienced, and 16.7% patients received ribavirin treatment. The genotype distribution was as follows: 35.5% GT1, 42.8% GT2, 15.9% GT3, and 5.8% un-typed. The SVR12 rate was 96.5% (138/143, 95% CI: 93.5%-99.6%) for intention-to-treat analysis, and in per-protocol analysis, all 138 patients obtained SVR12 (100%). Compared with baseline, the serum total bilirubin, ALT and AFP levels decreased (all P < 0.05), as well as increased ALB and platelet count (all P < 0.001) at post-treatment 12-weeks. Overall adverse events (AEs) rate is 29.0%, and the most common AEs were anemia (14.5%) and fatigue (8.0%). Severe side effects (edema and fatigue) occurred in 2 patients, one of whom needed a short-term interruption of treatment due to fatigue. Conclusion:In this real-world cohort study, 12-week SOF/VEL regimen with or without ribavirin achieved high SVR12 rates (96.5%-100% overall) with excellent safety profile among patients with HCV GT1/2/3 infection including patients with GT3 and cirrhosis, and led to improvement of liver function.

Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.

Objective:To investigate the clinical efficacy of neoadjuvant chemotherapy for the resectable locally advanced adenocarcinoma at the gastroesophageal junction.Methods:A retrospective cohort study was conducted to analyze 86 patients with resectable locally advanced Siewert type Ⅱ and Ⅲ adenocarcinoma at the gastroesophageal junction (T 3-4N +M 0) who were admitted to the Panzhihua Central Hospital of Sichuan Province from January 2013 to January 2016. All the patients were divided into the neoadjuvant chemotherapy group [preoperative XELOX regimen (oxaliplatin + capecitabine) adjuvant chemotherapy + surgery + postoperative XELOX regimen adjuvant chemotherapy, 46 cases] and non-neoadjuvant chemotherapy group (surgery + postoperative XELOX regimen adjuvant chemotherapy, 40 cases) according to whether neoadjuvant chemotherapy was performed before surgery. The total gastrectomy + Roux-en-Y esophagojejunostomy + D 2 lymphadenectomy or proximal subtotal gastrectomy + esophageal gastric remnant anastomosis + D 2 lymphadenectomy were applied to patients by the same team of doctors. The observation indicators included treatment situations, results of postoperative pathological examination and prognosis in the two groups. Results:In the neoadjuvant chemotherapy group, 25 patients (54.3%) had partial remission (PR), 21 patients (45.7%) had stable disease (SD), the clinical response rate was 54.3% (25/46), tumor control rate was 100.0% (46/46), and clinical stage reduction rate was 37.0% (17/46). Compared with the non-neoadjuvant chemotherapy group, the neoadjuvant chemotherapy group had a higher R 0 resection rate [100.0% (46/46) vs. 80.0% (32/40), χ2 = 4.024, P = 0.045], and in the neoadjuvant chemotherapy group, the pathological complete remission [tumor regression grade (TRG) 0] rate was 13.0% (6/46), and the overall pathological response (TRG 1 + TRG 0) rate was 56.5% (26/46). The postoperative pathological examination showed that the neoadjuvant chemotherapy group and the non-neoadjuvant chemotherapy group had statistically significant differences in the longest tumor diameter, vessel carcinoma embolus, perineural invasion, and pathological TNM staging (all P < 0.05). However, there was no statistical difference in the total humber of lymph nodes, the number of positive lymph nodes, pathological T stage, N stage, and human epidermal growth factor receptor 2 (HER2) expression in specimens (all P > 0.05). In the neoadjuvant chemotherapy group, 6 patients had grade 3 adverse reactions, and chemotherapy was suspended or the dose was adjusted. Adverse reactions in the blood system included the red blood cells reduction, white blood cells reduction and thrombocytopenia. Other adverse reactions included nausea, vomiting, and decreased appetite. There were no deaths related to radiotherapy. In the neoadjuvant chemotherapy group, the median tumor-free survival time was 20 months (5-36 months), and the 1-year and 3-year tumor-free survival rates were 89.5% and 52.4%, respectively; the median postoperative overall survival time was 20 months (9-36 months), and the 1-year and 3-year overall survival rates were 91.0% and 48.0%, respectively; 12 patients had tumor recurrence. In the non-neoadjuvant chemotherapy group, the median tumor-free survival time was 19 months (10-35 months), and the 1-year and 3-year tumor-free survival rates were 87.3% and 30.0%, respectively. The median postoperative overall survival time was 20 months (10-35 months), the 1-year and 3-year overall survival rates were 87.0% and 18.6%, respectively; 14 patients had tumor recurrence. There was a statistical difference in the tumor-free survival between the two groups ( χ2 = 4.522, P = 0.03), and there was no statistical difference in the overall survival between the two groups ( χ2 = 3.717, P > 0.05). Conclusions:XELOX regimen neoadjuvant chemotherapy is safe and effective for patients with resectable locally advanced Siewert type Ⅱ and Ⅲ adenocarcinoma at the gastroesophageal junction. It can decrease the tumor clinical stage and increase the R 0 resection rate and tumor-free survival rate.

Objective: To study the chemical constituents in the dry roots of Dolomiaea souliei (Franch.) Shih.Methods: Various chromatographic methods were used to isolate and purify the chemical constituents of Dolomiaea souliei, and the structures were elucidated through the analysis of spectral data and literatures.Results: Six compounds including 3 sesquiterpene compounds and 3 fatty acids were obtained and identified as dihydrodehydrocostuslactone(Ⅰ), vladimenal(Ⅱ), arbusculin A(Ⅲ), n-hendecane(Ⅳ), butanedioic acid(Ⅴ) and methyl linoleate(Ⅵ).Conclusion: Compounds Ⅳ-Ⅵ are obtained from the genus of Dolomiaea for the first time.

To study the chemical constituents of K. oblongifolia, silica gel column chromatography, MCI and Sephadex LH-20 were used to separate the 70% acetone extract of the stems of K. oblongifolia. The structures of the isolated compounds have been established on the basis of physicochemical and NMR spectroscopic evidence as well as ESI-MS in some cases. Twenty compounds were obtained and identified as heteroclitalignan A (1), kadsulignan F (2), kadoblongifolin C (3), schizanrin F (4), heteroclitalignan C (5), kadsurarin (6), kadsulignan O (7), eburicol (8), meso-dihydroguaiaretic acid (9), kadsufolin A (10), tiegusanin M (11), heteroclitin B (12), (7'S)-parabenzlactone (13), angeloylbinankadsurin B (14), propinquain H (15), quercetin (16), kadsulignan P (17), schizanrin G (18), micrandilactone C (19) and (-)-shikimic acid (20). Compouds 1, 5, 8, 11-15, 18 and 20 were isolated from this plant for the first time. Toxicity of compounds 1-10 were evaluated with zebrafish model to observe the effect on its embryonic development and heart function. The results showed that compounds 7, 9 and 10 caused edema of zebrafish embryo and decreased the heart rate of zebrafish, which exhibited interference effect on heart development of zebrafish.

With the surge of high-throughput sequencing technology, it is becoming popular to perform the phylogenetic study based on genomic data. A bundle of new terms is emerging, such as phylogenomics, pharmacophylogenomics and phylotranscriptomics, which are somewhat overlapping with pharmaphylogeny. Phylogenomics is the crossing of evolutionary biology and genomics, in which genome data are utilized for evolutionary reconstructions. Pharmaphylogeny, advocated by Prof. Pei-gen Xiao since 1980s, focuses on the phylogenetic relationship of medicinal plants and is thus nurtured by molecular phylogeny, chemotaxonomy and bioactivity studies. Phylogenomics can be integrated into the flow chart of drug discovery and development, and extend the field of pharmaphylogeny at the omic level, thus the concept of pharmacophylogenomics could be redefined. This review gives a brief analysis of the association and the distinguished feature of the pharmaphylogeny related terms, in the context of plant-based drug discovery and sustainable utilization of pharmaceutical resource.