Ubiquitin-specific protease (USP) is a major member of the deubiquitinating enzymes (DUB) family. Dysregulation of DUB could lead to dysfunction of the ubiquitin system, which in turn regulates the tumor progression. USP regulates the development and progression of hepatocellular carcinoma (HCC) by selectively degrading or stabilizing substrate proteins related to oncogenes, tumor suppressors, DNA damage repair, and cell cycle. This article summarizes the research progress of USP in HCC and the application of USP-specific small molecule inhibitors, providing a reference for targeting USP as a diagnostic and therapeutic tool for HCC.

Objective:To establish an animal model of acute systemic cold injury in mice.Methods:There were 98 C57BL/6 mice, half male and half female, with body weight of 22-27 g and age of 10 weeks. The mice were randomly divided into 7 groups ( n=14) according to the changes of anal temperature in cold environment, namely, group A (38.5 ± 1) ℃, group B (35 ± 1) ℃, group C (30 ± 1) ℃, group D (25 ± 1) ℃, group E (20 ± 1) ℃, group F (15 ± 1) ℃, and group G (10 ± 1) ℃, among which, group A was the blank control group, and the rest groups were the experimental group. The mice in the blank control group were placed in the normal environment (20 ± 5) ℃, and the mice in the experimental group were placed in the low temperature artificial climate box at - 20℃. The anal temperature of the mice was measured intermittently (as the core temperature), and the time required for the core temperature of the mice to drop to groups B, C, D, E, F and G was recorded. The righting reflex was used to evaluate the consciousness state, the action ability and the general state of each organ of mice were observed, and the blood routine and HE staining of each organ were detected. Results:The lower the core temperature of the experimental group, the longer the time required. The consciousness state, action ability, general state of organs, blood routine, and HE staining of organs in groups B, C, and D were basically the same as those in group A, and there was no acute systemic cold injury. Therefore, the blood routine, general observation of organs, and HE staining of organs in groups B, C, and D were no longer displayed compared with those in group A. Compared with group A, mice in group E began to suffer from disturbance of consciousness and action ability. With the decrease of core body temperature, the damage was aggravated, and mice in group G died. Compared with group A, the indices of blood routine test (WBC, RBC, HGB, PLT) of mice in group E began to decrease, and the univariate variance calculation showed that only WBC changes had statistical significance ( P<0.05). Compared with groups A and E, the indices of blood routine test (WBC, RBC, HGB, PLT) of mice in group F were further reduced, and the changes of each index in univariate variance calculation were statistically significant ( P<0.05). The general observation results showed that compared with group A, the lung, liver and spleen surfaces of mice in group E began to darken, and compared with groups A and E, the lung, liver, spleen, kidney and heart of mice in group F were further deepened and darkened, with irregular edges. HE staining results of various organs showed that compared with group A, the mice in group E began to have partial alveolar structure destruction and a small amount of inflammatory cell infiltration, the central vein of the liver was slightly congested, and the red and white pulp of the spleen were indistinct. Compared with groups A and E, the pathological structure damage of the lung, liver, spleen, kidney, heart and brain tissues of the mice in group F was further aggravated. Conclusions:Detection of consciousness state, action ability, general state of organs, blood routine and HE staining indices of organs in mice under low temperature can simulate the progress of clinical acute cold injury, and the animal model of acute systemic cold injury was successfully prepared.

Objective:To conduct quality evaluation and content analysis of adult postoperative nausea and vomiting (PONV) guidelines, so as to provide reference for management of clinical PONV.Methods:Web of Science, Embase, PubMed, UpToDate, SinoMed, Wanfang Database, China National Knowledge Infrastructure, VIP, domestic and foreign clinical practice guidelines and related professional association websites were systematically searched, and the search period was from database establishment to May 6, 2022. Four researchers independently evaluated the guidelines that met the inclusion and exclusion criteria using a clinical guideline research and evaluation system, and summarized the recommendations of the guidelines.Results:Finally, a total of 15 guidelines were included in this study. The overall quality evaluation of the guide was 3 A-level recommendations and 12 B-level recommendations. The average standardization percentages for 6 areas were 81.57% for scope and purpose, 49.91% for participants, 65.38% for rigor, 89.54% for clarity, 34.86% for applicability and 55.42% for independence. A total of 18 recommendations were summarized from five aspects, such as team and organizational management, PONV risk assessment, baseline risk reduction, multimodal prevention of PONV and effectiveness evaluation and monitoring.Conclusions:The guidelines for PONV management mainly come from foreign countries. It is recommended that clinical personnel should learn from foreign guidelines and combine them with domestic clinical situations to localize the recommended opinions and guide the development of clinical practice.

Objective To investigate the application value of Multi-Latex polygranular technique joint detection of kidney injury-related urinary microproteins in noninvasive diagnosis after renal transplantation. Methods Clinical data of 72 recipients undergoing renal transplantation were retrospectively analyzed. According to the level of serum creatinine (Scr), the recipients were divided into normal renal function group (group A, n=14), mild kidney injury (group B, n=37), and severe kidney injury group (group C, n=21). 20 healthy volunteers were selected as the healthy control group (HC group). The contents of urinary retinol binding protein (RBP), microalbumin (mAlb), IgG, transferrin (TRF), α₁-microglobulin (MG), and β₂-MG of subjects in each group were detected using the Multi-Latex polygranular technique. The correlation between urinary microproteins and Scr, blood urea nitrogen (BUN) was analyzed. The differences of urinary microproteins in each group were compared. And the diagnostic value of single and joint detection of urinary microproteins was evaluated. Results Six kinds of urinary microproteins in HC group and group A were significantly lower than those in group B and group C, and six kinds of urinary microproteins in group B were significantly lower than those in group C (all P < 0.01). Six kinds of urinary microproteins in renal transplant recipients were positively correlated with BUN. RBP, mAlb, α₁-MG, and β₂-MG were positively correlated with Scr. The correlations were statistically significant (P < 0.001-0.05). The diagnostic value of joint detection of urinary microproteins is better than the detection of single index, among which TRF+mAlb+RBP+α₁-MG quadruple detection had the highest diagnostic value. Conclusions Six kinds of urinary microproteins can be used as specific indicators to reflect graft renal function. The polygranular technique can simultaneously detect its contents and achieve noninvasive diagnosis. The diagnosis based on TRF+mAlb+RBP+α₁-MG quadruple detection is expected to further improve the noninvasive diagnosis system after renal transplantation.

This article, based on the current quality management of medical institutions in China, put forward the concept of implementing the core medical quality system by way of path-based management. This effort aims at achieving the homogenization of the medical quality core systems among different medical institutions,thus ultimately homogenizing the management and service homogeneity in different regions, levels and categories of medical institutions. The present experiment proves satisfactory within a small scale.

Objective To evaluate the effect of γ-aminobutyric acid (GABA) and its receptors upon the proliferation of CD8+T cells.Methods The splenic CD8+T cells of Balb/c mice were obtained by CD8+f cell magnetic bead sorting kit.Under the effect of CD3/CD28-activated magnetic bead,CD8+T cells were stimulated by different concentrations of GABA.5-bromo-2-deoxyuridine (BrdU) labeling and flow cytometry were performed to detect the proliferation of CD8+T cells.The expression levels of GABA-A and GABA-B receptor before and after CD8+T cell activation were compared by fluorescent quantitative real-time polymerase chain reaction (PCR).Result Flow cytometry result revealed that GABA could inhibit the proliferation of activated CD8+T cells,manifested as significant decrease in the quantity of CD152+CD8+T cells.Fluorescent quantitative real-time PCR demonstrated that GABA-A receptor subtypes α2,α6 and GABA-B receptor subtype 1a were expressed only when the CD8+T cells were activated.After CD8+T cell activation,the quantity of GABA-A receptor subtypes α3,αs,β2,β3,γ1,γ2 and θ were significantly increased,whereas the quantity of GABA-B2R and GABA-B1b did not significantly differ before and after CD8+T cell activation.Conclusions GABA can suppress the proliferation of activated CD8+T cells.The activation of CD8+T cells is regulated by GABA receptors.However,the underlying mechanism remains to be elucidated.

Background:In recent years, the incidence of ulcerative colitis (UC) has increased year by year in China, and the number of elderly patients with UC is growing significantly.However, the difference in clinical characteristics between elderly and non-elderly UC patients was not fully clarified.Aims:To investigate the difference in clinical characteristics between elderly and non-elderly UC patients.Methods:A total of 163 UC patients admitted from Jan.2012 to Jun.2015 at the Affiliated Jiangyin Hospital of Southeast University Medical College were retrospectively recruited and divided into elderly group (no less than 60-year-old, n=32) and non-elderly group (less than 60-year-old, n=131) according to the age of onset.The clinical data were collected, and the general conditions, clinical manifestations and extent of the disease were compared between the two groups.Results:There were no significant differences in gender, family history of inflammatory bowel disease, history of smoking and appendectomy between elderly and non-elderly groups (P>0.05).Hematochezia and mucous bloody stool were less prevalent in elderly group than in non-elderly group (P<0.05), and the prevalence of abdominal pain, diarrhea and weight loss was comparable between the two groups (P>0.05).More extraintestinal manifestations were seen in non-elderly group, but the difference was not statistically significant (P>0.05).Lesions in elderly group mainly located in left hemicolon, while pancolitis was predominant in non-elderly group (P<0.05).Conclusions:In elderly patients with UC, hematochezia and mucous bloody stool are not frequently seen, and the disease is not extensive and mainly located in left hemicolon.

Objective To study the value of MSCT angiography(MSCTA)in diagnosing lower extremities arterial disease (LEAD) of diabetic foot ulcers and analyze the possible influential factors on the onset of diabetic foot ulcers.Methods 80 diabetic patients for MSCTA examination were divided into two groups by whether combined with foot ulcers.The tibial artery calcification score (TACS) and peripheral arterial occlusion index (PAOI) were calculated and the possible risk factors of diabetic foot ulcer were analyzed.Results There were 30 cases suffered with foot ulcer and 18 cases occurred lower extremity arterial occlusion (LEAO), the average PAOI was 4.40(3.60, 5.75).Non-foot ulcer cases were 50, and there were 8 cases suffered with LEAO, the average PAOI was 2.05(1.43, 3.10).Compared to patients without foot ulcer, patients with foot ulcer were older, had a lower BMI, and were more likely to have a history of tobacco use.They usually had higher TACS and severer peripheral arterial occlusive disease (PAOD).Stepwise regression model showed that foot ulcers had significant correlation with TACS and PAOI.Partial correlation analysis showed TACS was independent from PAOI in impacting diabetic foot ulcer.Conclusion MSCTA has important clinical value in diagnosing and valuing diabetic foot ulcer LEAD.Age, smoking history,BMI,TACS and PAOI affect the incidence of diabetic foot ulcers, and TACS and PAOI are the independent risk factors for diabetic foot ulcers.

Objective To investigate the relationship of pancreatic β-cell function and insulin resistance with microalbuminuria in a cross -sectional study of patients with type 2 diabetes.Methods A total of 524 partici-pants with type 2 diabetes were recruited in this cross -sectional study.All subjects'height,weight,waist circumfer-ence and blood pressure were measured.Venous blood samples were drawn to measure fasting plasma glucose (FPG), fasting lipids,glycated hemoglobin A1c (HbA1c),fasting C -peptide (FPC).24h -urine was collected to measure urinary albumin excretion rate (UAER).Homeostasis model assessment of pancreatic β-cell function (HOMA -B) and insulin resistance (HOMA -IR)were estimated using fasting plasma C -peptide.According to HOMA -B quar-tile,the subjects were divided into four groups,including q1 -q4.According to HOMA -IR,the subjects were also divided into four groups,including Q1 -Q4.We assessed the crude associations across quartiles of these data with demographic and clinical parameters using a nonparametric test for trend across ordered groups (trend using Stata software).Multivariable logistic regression analysis was performed to assess the relationships of pancreatic β-cell function and insulin resistance with microalbuminuria in patients with type 2 diabetes.Results Trend test showed that UAER gradually reduced with increase of HOMA -B.The UAER values in subjects with q1,q2,q3 and q4 were 8.92(5.53 -28.65),8.55(5.52 -20.95),7.57(4.79 -19.83)and 7.84(5.23 -14.38)μg/min,respectively, and the trend was statistically significant(z =-2.1,P <0.05 ).With HOMA -IR increasing,UAER gradually increased.The UAER values in subjects with Q1,Q2,Q3 and Q4 were 6.73(4.85 -16.52),8.61 (5.2 -20.37), 8.31(4.88 -27.04),8.75(6.03 -25.21)μg/min,respectively,and the trend was also statistically significant(z =2.41,P <0.05).Multivariable logistic regression analysis showed that subjects with the highest quartile of HOMA -B had lower possibility of microalbuminuria than patients with the lowest quartile of HOMA -B (adjusted OR q4 vs. q1 =0.39,95% CI:0.20 -0.76,Wald =7.59,P =0.006).Subjects with the highest quartile of HOMA -IR had higher risk of microalbuminuria than those with the lowest quartile of HOMA -IR (adjusted OR Q4 vs.Q1 =2.00, 95% CI:1.08 -3.72,Wald =4.84,P =0.028).Conclusion Insulin resistance is associated with an increased prevalence of microalbuminuria in type 2 diabetes,while improved pancreatic β-cell function is linked to decreased rates of microalbuminuria for those patients.

OBJECTIVETo investigate the incidence and the gene mutation frequencies and patterns of α-thalassemia in preschool children in Chongqing city.

METHODSCluster random sampling was used. A total of 1057 preschool children in three areas of Chongqing were screened by using routine blood test and hemoglobin electrophoresis analysis. Molecular analysis carried out for all the samples.

RESULTSOf the 1057 samples, 55 cases were diagnosed as being carriers of α-thalassemia, which included 80 allele genes. Therefore, the frequency of α-thalassemia carriers in Chongqing was 5.20%. Of the 55 α-thalassemia carriers, five different deletions of α-thalassemia were identified, the three most common deletion types and proportions were 54.55% for the -α(3.7) deletion, 18.18% for --(SEA) deletion, and 9.08% for the -α(4.2) deletion, respectively; eight types of nondeletion defects were determined, containing one case of Hb Quong Sze and seven novel mutations of a-globin gene. Furthermore, 24 cases of α-Triplication were detected with the α-Triplication carrier rate of 2.55%. In addition, in this study we also found two cases of abnormal hemoglobin disorders occurred on α-globin gene, Hb J-Wenchang-Wuming and Hb Arya. Hb Arya was characterized in the Chinese population for the first time confirmed by literature retrieval.

CONCLUSIONIn this study, we have clarified the carrier frequency and molecular spectrum of α-thalassemia in Chongqing, and we first reported the carrier incidence of α-Triplication in Chongqing. The materials obtained from this study would be of valuable reference for genetic counseling and the examination instruction of children in this area.

Asian Continental Ancestry Group ; Child, Preschool ; China ; epidemiology ; Humans ; Incidence ; Mutation ; Prevalence ; alpha-Globins ; metabolism ; alpha-Thalassemia ; epidemiology ; metabolism