The ubiquitin-specific protease ( USP) inhibitors influence many crucial cellular activities and some immune processes, such as anti-inflammatory, anti-infection and anti-tumor by silencing the functions of USP.The main USP inhibitors, which potency and specificity are underlined and current methods for detecting and identifying USP inhibitors are discussed of in this review.

The statistics of purified protein derivative (PPD) test and chest radiograph of freshmen at a university from 2007 to 2010 were collected and examined.The result showed 25 tuberculosis cases (a prevalence rate of 0.18％) and 1 790 cases (13.40％) with strong positive PPD.After giving informed consents,the students with strong positive result and no abnormality on chest radiograph were divided into two groups.The treatment group (n =814) received precautionary anti-tuberculosis treatment while the nontreatment group (n =976) had no treatment.And 34 tuberculosis cases were found during four years in school (0.25％).Except for freshmen in 2008,the prevalence rate of the strong positive PPD groups much higher than that of the positive and negative groups and the difference had statistic significance between the groups (x2 =23.20,10.58,18.80,P ＜ 0.05).Therefore PPD test and chest radiograph are two main methods for an early diagnosis of tuberculosis among freshmen.Adopting precautionary anti-tuberculosis treatment for students with strong positive PPD and regular physical examinations are effective measures for tuberculosis control at universities.

Objective To investigate the association between multi-drug resistant 1 (MDR1) gene C3435T and T129C polymorphism with refractory epilepsy in children. Methods A total of 260 children including 60 refractory epilepsy, 100 drug-responsive epilepsy, and 100 healthy children were enrolled. The genotypes for MDR1 polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism analysis.The distribution of genotypes and allele frequencies of the three groups were compared. Results The distribution of TT/TC/CC genotypes and T/C allele frequencies of C3435T showed no signiifcant difference between drug-resistant patients and drug-responsive patients or normal control group (P>0.05). Drug-resistant patients were more likely to have the TC genotype and the C allele at T129C when compared with the drug-responsive patients and the normal control group (P<0.05). Conclusions T129C polymorphism of the MDR1 gene was associated with refractory epilepsy in children.

Severe acute pancreatitis (SAP) is a common gastrointestinal disease, often accompanied by systemic inflammatory reactions and organ dysfunction. SAP has an acute onset, severe condition, rapid progression, and poor prognosis. The development of SAP is closely related to the excessive release of inflammatory factors. In the comprehensive treatment of SAP, continuous blood purification (CBP) can clear inflammatory mediators, improve the stability of Internal environment, improve organ function, reduce blood lipids, regulate immunity, and significantly improve the condition of SAP patients. It is an important means of treating SAP. This article reviews the research progress of CBP in the treatment of SAP.

The Mongolian gerbil currently used as laboratory animals worldwide all originates from China.As early as the 1930s,wild Mongolian gerbils were domesticated and introduced into medical research.Today,they have become recognized multifunctional laboratory animals and are extensively used in various fields such as brain nerve studies,parasitology and microbiology,and oncology,etc.Mongolian gerbils possess unique anatomical characteristics in the basal cerebral arteries,such as a congenital absence of the Willis'circle,making it possible to construct cerebral ischemia or cerebral ischemia-reperfusion injury models with simple procedures of unilateral common carotid artery ligation,while also enabling intra-individual control.These anatomical features also increase their sensitivity to cerebral ischemia and make them more prone to cochlear ischemia,therefore playing a crucial role in the preparation of auditory impairment models.The disease progression and pathological manifestations in Mongolian gerbils show many similarities to those observed in human patients.Researchers have successfully used Mongolian gerbils to develop models of cerebral ischemia,cerebral ischemia-reperfusion,cochlear ischemia,cochlear implantation,and sensorineural hearing loss,achieving significant results.This article focuses on the current methods and assessment indicators for constructing Mongolian gerbils models of cerebral ischemia and auditory impairment.It discusses the advantages and disadvantages of various modelling techniques,and explores their application progress,aiming to provide a theoretical basis and reference for the application of Mongolian gerbils in these two important research areas.

It is found that acupuncture can significantly improve the clinical symptoms of rheumatoid arthritis (RA) such as pain and joint stiffness, and improve rheumatoid factor, high-sensitivity CRP, ESR and other clinical indicators. It can inhibit the proliferation of synovial cells, the apoptosis of chondrocytes, and regulate polarization balabce of mononuclear macrophages, T cells, as well as inhibit the inflammatory function of multiple immune cells, in order to improve inflammation state of RA joints. In clinical treatment of RA, bladder meridian, stomach meridian, spleen meridian , and Governor Vessel are mostly selected. Acupoints with the efficacy of warming meridian, dispelling coldness and dredging collaterals were commonly selected such as Zusanli (ST36), Yanglinquan (GB34), Dazhui (GV14), Quchi (LI11). Several researches have proved that combined therapy of acupuncture and medicine is worthy promotion in clinic.

Objective Using of cumulative live birth rate(CLBR)per oocytes retrieved cycle,to assess the clinical outcomes of in vitro fertilization or intracytoplasmic sperm injection(IVF/ICSI),and to explore impact factors on CLBR following utilization of all fresh and frozen embryos in one complete IVF/ICSI cycle using gonadotropin-releasing hormone(GnRH)agonist, GnRH-antagonist and clomiphene mild stimulation protocols. Methods Of the patients who underwent IVF/ICSI from January 1st, 2014 to December 31st, 2015 in the First Affiliated Hospital, Nanjing Medical University, a total of 6 142 oocytes retrieved cycles were included. The clinical and laboratory parameters of different ovarian stimulation protocols, and the effects of the age, number of oocytes retrieved and number of embryos available on the CLBR of each oocytes retrieved cycle were analyzed.Results The CLBR was 69.0%(2 004/2 906)in the GnRH-agonist protocol versus 67.4%(644/955)in the GnRH-antagonist protocol (P>0.05); the CLBR of clomiphene mild stimulation protocol was 53.2%(1 215/2 281),significantly lower than those of the other two protocols (all P<0.05). The CLBR significantly decreased with age increased. When divided into four groups according to the patients′ age, we found that CLBR were not statistically significant using three different protocols in the 20-25 years old group(all P>0.05).There was a strong association between the number of oocytes retrieved and embryos available on CLBR. CLBR rose significantly with an increasing number of oocytes up to 6, then the rising trend slowed down. Patients were categorized into four groups according to the number of oocytes retrieved,CLBR was significantly higher using GnRH-antagonist protocol (50.0%)than mild stimulation protocol(37.0%)in low ovarian responder(0-4 oocytes)group(P<0.05). The CLBR were no significant difference among three protocols in normal(10-15 oocytes)and high responders(≥15 oocytes)group(all P>0.05).The incidence rate of ovarian hyperstimulation syndrome in GnRH-agonist protocols(5.2%,152/2 906)were significantly higher than those of GnRH-antagonist(4.4%, 42/955)and clomiphene mild stimulation protocols(1.5%,34/2 281;all P<0.05).Conclusions CLBR is an important index to assess the clinical outcomes of IVF/ICSI. Age, number of oocytes retrieved and embryos available could affect CLBR obviously. According to the different age and ovarian response of patients, we should design ovarian stimulation protocols based on target oocytes number in order to get higher CLBR and reduce complications.

Background:Previous studies have proved that neutrophil gelatinase-associated lipocalin(NGAL)plays an important role in the progression of Crohn's disease(CD),and may serve as a potential biomarker for disease activity prediction,severity assessment,treatment response evaluation and prognosis monitoring.However,the diagnostic value of NGAL in perianal fistulizing Crohn's disease(pfCD)is still unclear.Aims:To investigate the serum level of NGAL and its diagnostic value in patients with active pfCD.Methods:A total of 66 patients diagnosed as pfCD from July 2021 to June 2023 at Longhua Hospital,Shanghai University of Traditional Chinese Medicine were enrolled,including 36 active pfCD patients and 30 inactive pfCD patients.The disease activity and perianal fistula activity were assessed by Crohn's disease activity index(CDAI)and perianal disease activity index(PDAI),respectively.Serum NGAL,fecal calprotectin(FC),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),as well as CDAI score and PDAI score were compared between the active and inactive pfCD patients,and the correlations of NGAL with the other parameters in active pfCD patients were analyzed.ROC curve was drawn to evaluate the values of serum NGAL,FC,CRP and ESR for diagnosis of active pfCD.Results:The serum NGAL,FC,CRP,ESR,CDAI score and PDAI score in active pfCD patients were significantly higher than those in inactive pfCD patients(all P＜0.001).NGAL was positively correlated with FC(r=0.64,P＜0.001),CRP(r=0.55,P＜0.001),ESR(r=0.53,P＜0.001),CDAI score(r=0.59,P＜0.001)and PDAI score(r=0.54,P＜0.001)in active pfCD patients.The optimal cut-off values of NGAL,FC,CRP and ESR were 220.5 μg/L,146.0 μg/g,7.9 mg/L and 23.5 mm/h,respectively,for the diagnosis of active pfCD,and the area under the curve were 0.922(95％CI:0.850-0.995),0.888(95％CI:0.806-0.970),0.853(95％CI:0.763-0.944)and 0.830(95％CI:0.731-0.930),respectively.Conclusions:Serum NGAL level is associated with the disease activity of pfCD,and can be used as a non-invasive biomarker for the clinical diagnosis of active pfCD.

Successful pregnancy in placental mammals substantially depends on the establishment of maternal immune tolerance to the semi-allogenic fetus.Disorders in this process are tightly asso-ciated with adverse pregnancy outcomes including recurrent miscarriage (RM).However,an in-depth understanding of the systematic and decidual immune environment in RM remains largely lacking.In this study,we utilized single-cell RNA-sequencing (scRNA-seq) to comparably analyze the cellular and molecular signatures of decidual and peripheral leukocytes in normal and unex-plained RM pregnancies at the early stage of gestation.Integrative analysis identifies 22 distinct cell clusters in total,and a dramatic difference in leukocyte subsets and molecular properties in RM cases is revealed.Specifically,the cytotoxic properties of CD8+ effector T cells,nature killer(NK),and mucosal-associated invariant T (MAIT) cells in peripheral blood indicates apparently enhanced pro-inflammatory status,and the population proportions and ligand-receptor interac-tions of the decidual leukocyte subsets demonstrate preferential immune activation in RM patients.The molecular features,spatial distribution,and the developmental trajectories of five decidual NK(dNK) subsets have been elaborately illustrated.In RM patients,a dNK subset that supports embryonic growth is diminished in proportion,while the ratio of another dNK subset with cyto-toxic and immune-active signature is significantly increased.Notably,a unique pro-inflammatory CD56 + CD16 + dNK subset substantially accumulates in RM decidua.These findings reveal a com-prehensive cellular and molecular atlas of decidual and peripheral leukocytes in human early pregnancy and provide an in-depth insight into the immune pathogenesis for early pregnancy loss.

Objective:To construct a machine-learning model for predicting the progression of pancreatic cystic lesions (PCLs) based on clinical and CT features, and to evaluate its predictive performance in internal/external testing cohorts.Methods:Baseline clinical and radiological data of 200 PCLs in 177 patients undergoing abdominal thin slice enhanced CT examination at Peking Union Medical College Hospital from July 2014 to December 2022 were retrospectively collected. PCLs were divided into progressive and non-progressive groups according to whether the signs indicated for surgery by the guidelines of the European study group on PCLs were present during three-year follow-up. 200 PCLs were randomly divided into training (150 PCLs) and internal testing cohorts (50 PCLs) at the ratio of 1∶3. 15 PCLs in 14 patients at Jinling Affiliated Hospital of Medical School of Nanjing University from October 2011 to May 2020 were enrolled as external testing cohort. The clinical and CT radiological features were recorded. Multiple feature selection methods and machine-learning models were implemented and combined to identify the optimal machine-learning model based on the 10-fold cross-validation method. Receiver operating characteristics (ROC) curve was drawn and area under curve (AUC) was calculated. The model with the highest AUC was determined as the optimal model. The optimal model's predictive performance was evaluated on testing cohort by calculating AUC, sensitivity, specificity and accuracy. Permutation importance was used to assess the importance of optimal model features. Calibration curves of the optimal model were established to evaluate the model's clinical applicability by Hosmer-Lemeshow test.Results:In training and internal testing cohorts, the progressive and non-progressive groups were significantly different on history of pancreatitis, lesions size, main pancreatic duct diameter and dilation, thick cyst wall, presence of septation and thick septation (all P value <0.05) In internal testing cohort, the two groups were significantly different on gender, lesion calcification and pancreatic atrophy (all P value <0.05). In external testing cohort, the two groups were significantly different on lesions size and pancreatic duct dilation (both P<0.05). The support vector machine (SVM) model based on five features selected by F test (lesion size, thick cyst wall, history of pancreatitis, main pancreatic duct diameter and dilation) achieved the highest AUC of 0.899 during cross-validation. SVM model for predicting the progression of PCLs demonstrated an AUC of 0.909, sensitivity of 82.4%, specificity of 72.7%, and accuracy of 76.0% in the internal testing cohort, and 0.944, 100%, 77.8%, and 86.7% in the external testing cohort. Calibration curved showed that the predicted probability by the model was comparable to the real progression of PCLs. Hosmer-Lemeshow goodness-of-fit test affirmed the model's consistency with actual PCLs progression in testing cohorts. Conclusions:The SVM model based on clinical and CT features can help doctors predict the PCLs progression within three-year follow-up, thus achieving efficient patient management and rational allocation of medical resource.