Ankylosing spondylitis is a chronic immunoinflammatory disease that mainly affects the spine and the sacroiliac joint， the mechanism of which is closely related to signaling pathways， such as osteoprotegerin （OPG）/receptor activator of nuclear factor-κB （RANK）/RANK ligand， mitogen-activated protein kinase （MAPK）， Wnt/β-catenin （β-catenin）， phosphoinositide 3- kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）. Traditional Chinese medicine has the characteristics of multiple components and targets， and is widely used for the treatment of autoimmune diseases due to its low toxicity， strong specificity， and high efficacy. This review found that monomers and compounds of traditional Chinese medicine can exert anti ankylosing spondylitis effects by intervening in the aforementioned signaling pathways， regulating immune inflammatory responses， and inhibiting biological processes such as bone destruction， ectopic osteogenic differentiation， cell apoptosis， and autophagy.

Benign anastomotic stenosis remains a common complication after bilojejunal anastomosis. Its pathogenesis includes the histology of bile duct, bile erosion, and inappropriate choice of surgical anastomosis or suture materials. Biliojejunal anastomotic stenosis can be determined preoperatively by MRCP, CT, and three-dimensional image reconstruction. Surgery remains treatment of choice for most cases, including surgical reconstruction and minimally invasive treatment, while the incidence of restenosis, residual stone, and reoperation is still high. Surgeons are still in search of optimal treatment modality to avoid anastomotic stenosis. In this article, we review the literature and summarize the latest clinical progress in the diagnosis and treatment of biliojejunal anastomotic stenosis combined with hepatic ductal stones.

Tumor heterogeneity is one of the characteristics of malignant tumors, which refers to the molecular biology or genetic changes in the daughter cells of tumors after multiple division and proliferation during the growth process, resulting in changes in tumor growth rate, invasion ability, drug sensitivity, and prognoses. Pituitary adenomas (PAs) are generally considered as benign tumors without obvious heterogeneity, but the identification of reliable heterogeneity markers still plays a key role in clinical diagnosis and treatment. In clinical practice, the heterogeneity of parenchymal PAs includes differences in imaging findings, histopathological findings, and molecular information. This article reviews the research results in PAs heterogeneity so as to provide better enlightenment for clinical research and practice.

Objective In this study,we used artificial intelligence(AI)technology to explore for automated medical record quality control methods,standardize the process for medical record documentation,and deal with the drawbacks of manually implemented quality control.Methods In this study,we constructed a medical record quality control system based on AI.We first designed and built,for the system,a quality control rule base based on authoritative standards and expert opinions.Then,medical records data were automatically collected through a data acquisition engine and were converted into structured data through a post-structured engine.Finally,the medical record quality control engine was combined with the rule base to analyze the data,identify quality problems,and realize automated intelligent quality control.This system was applied to the quality control of medical records and five quality control points were selected,including similarities in the history of the present illness,defects in the description of chief complaints,incomplete initial diagnosis,missing in formation in the history of menstruation,marriage,and childbirth,and mismatch between the chief complaints and the history of the present illness.We randomly selected 2 918 medical records of patients discharged in January 2022 to conduct AI quality control.Then we organized medical record quality control experts to conduct an accuracy review,made a comparison with previous manual quality control records,and analyzed the results.The number of quality problems that were verified in the accuracy review was taken as the gold standard and receiver operating characteristic(ROC)curves were drawn for the 5 quality control points.Results According to the accuracy review performed by medical record quality control experts,the accuracy of AI quality control reached 89.57％.For the sampled medical records,the results of AI quality control were compared with those of previous manually performed quality control and only one problem detected by manual quality control of the sampled medical records was not detected by the AI quality control system.The number of medical record quality problems correctly detected by AI quality control was about 2.97 times that of manual quality control.Analysis of the ROC curves showed that the AUC of the five quality control points of the AI quality control system were statistically significant(P＜0.05)and all the AUC values approximated or exceeded 0.9.In contrast,results obtained through manually performed quality control found significant AUC(0.797)for only one quality control point—similarities in the history of present illness(P＜0.05).Comparison of the AUC values of the two quality control methods showed that AI quality control system had an advantage over manually performed quality control for the five quality control points.Conclusion Through the application of medical record quality control system based on AI,efficient full quality control of medical record documentation can be achieved and the detection rate of quality problems can be effectively improved.In addition,the system helps save manpower and improve the quality of medical record documentation.

SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

Objective:To explore the correlation between post-transplant non-HLA antibodies and humoral rejection(HR)after kidney transplantation(KT).Methods:A retrospective study was conducted for KT recipients with non-HLA antibody level detected from September 2019 to January 2021.The recipients with biopsy confirmed HR and donor-specific HLA antibodies negative or feeble positive at the time of HR were designated as HR group while recipients with stable renal allograft function from 2 weeks post-KT to the time of detecting non-HLA antibody as stable group.The levels of HLA antibody, MHC classⅠchain-related gene A(MICA)antibody and 32 non-HLA antibodies were tested by Luminex single antigen bead and the levels of angiotensin Ⅱ type 1 receptor(AT1R)antibody quantified by enzyme-linked immunosorbent assay (ELISA). Inter-group differences in positive rate of non-HLA antibodies and number of positive non-HLA antibodies were analyzed.Results:Twenty-four recipients had positive non-HLA antibodies while the remainders had no positive non-HLA antibodies.Three HR recipients were positive for actin antibody, collagen Ⅲ antibody, glutathione S-transferase theta-1 antibody or IFN-γ antibody respectively.However, all four non-HLA antibodies of stable recipients were negative.There was significant inter-group difference( P=0.017). Four HR recipients were positive for collagenⅡantibody while only 1 stable recipient was positive for collagenⅡantibody.The positive rate of collagenⅡ antibody was significantly higher in HR recipients than that in stable recipients( P=0.023). HR recipients had an average of 2.36 positive non-HLA antibodies while stable recipients had an average of 0.90.There was significant inter-group difference ( P=0.008). Conclusions:A high level of non-HLA antibodies may elevate the risk of HR after KT.

Objective: To analyze anxiety and its influencing factors of medical college students during the epidemic of COVID-19, so as to provide theoretical basis for targeted mental health promotion. Methods: Participants were selected through convenient sampling in 2 medical colleges, and general situation questionnaires, anxiety self rating scale(SAS), were csuected through questionnaire stars among to 6 276 medical college students anonymously through online platforms such as WeChat and QQ during the COVID-19 epidemic. Results: SAS scores of medical students was(38.52±7.76), anxiety detection rate was 8.9%. Anxiety detection rate varied significantly by gender, the frequency of protection alerting by the counselor, college level, residence, self reported health status, confirmed cases in the community, personal attention, disinfection, perceived risk of infection,as well as panic in the outbreak of COVID-19 (all P <0.05). Multivariate Logistic analysis showed that undergraduate( OR = 1.25 ), high perceived risk of infection( OR =1.71); extreme panic ( OR =2.75) were associated with high detection rate of anxiety. Female students( OR =0.62), rural residents( OR =0.80), moderate health status( OR =0.06), in good health( OR =0.11), in excellent health( OR =0.30); know or don t know there were COVID-19 patients in their residential areas( OR =0.67), close attention to COVID-19 1-2 times/d( OR = 0.47 ), or frequently( OR =0.38); moderate inevitable disinfection( OR =0.53), few inevitable disinfection ( OR =0.32) were associated with low detection rate of anxiety. Conclusion During the epidemic of COVID-19, anxiety among the medical college students was high, which varies by gender and college level. Psychological adjustment, appropriate attention and positive attitude towards COVID-19 should be promoted among medical college students. School counsellors should pay more attention and care to students while providing COVID-19 information through various ways.

The recent discovery of activator compounds binding to an allosteric site on the NAD

RAS, a member of the small GTPase family, functions as a binary switch by shifting between inactive GDP-loaded and active GTP-loaded state. RAS gain-of-function mutations are one of the leading causes in human oncogenesis, accounting for ∼19% of the global cancer burden. As a well-recognized target in malignancy, RAS has been intensively studied in the past decades. Despite the sustained efforts, many failures occurred in the earlier exploration and resulted in an 'undruggable' feature of RAS proteins. Phosphorylation at several residues has been recently determined as regulators for wild-type and mutated RAS proteins. Therefore, the development of RAS inhibitors directly targeting the RAS mutants or towards upstream regulatory kinases supplies a novel direction for tackling the anti-RAS difficulties. A better understanding of RAS phosphorylation can contribute to future therapeutic strategies. In this review, we comprehensively summarized the current advances in RAS phosphorylation and provided mechanistic insights into the signaling transduction of associated pathways. Importantly, the preclinical and clinical success in developing anti-RAS drugs targeting the upstream kinases and potential directions of harnessing allostery to target RAS phosphorylation sites were also discussed.

Objective To explore the rapid diagnosis and clinic treatment of donor-derived carbapenem-resistant Klebsiella pneumoniae (CRKP) infection in renal transplant recipients .Methods Retrospective analysis was performed for clinical data and the diagnosis and treatment of 9 renal transplant recipients with donor-derived CRKP infection from March 2017 to May 2019 .Results Among 526 renal transplant recipients ,nine were diagnosed with donor-derived CRKP infection by bacterial culture or KPC enzyme gene test .The infection rate was 1 .71％ .One recipient receiving carbapenem and tigecycline died while the remainders survived after a treatment of ceftazidime-avibactam and carbapenem . One recipient underwent graft resection . Among 8 recipients on ceftazidime-avibactam ,5 cases received a standard dose of 3 .75 g/d while another 3 cases had a high dose of 7 .5 g/d .One patient in standard-dose group underwent graft resection due to an arteriorrhexis of artery anastomosis .After graft resection ,the patient received a high dose of ceftazidime-avibactam and survived to date .The grafts of three patients in high-dose treatment group survived .Conclusions KPC enzyme gene detection plus injecting lavage fluid into blood culture bottle for bacterial culture is rapid and accurate for diagnosing donor-derived CRKP infection . A combination of ceftazidime-avibactam plus carbapenem is effective for donor-derived CRKP infection .A high dose of ceftazidime-avibactam may improve the efficacy without obvious side effects .