Background and purpose: Itch protein is an established regulator of T cell immune response thresholds, belong to a class of E3 ubiquitin-transferring enzymes, widely involve in the ubiquitination of several key signaling molecules, such as ZAP70, P85, VAV, PLC-γ, PKC-θ, etc, plays a critical role in tumor induced immu-nosuppression. Itch ligase activity regulate T-cell anergy and development of regulatory T cells in the periphery by modulating key components of T-cell receptor and transforming growth factor-βsignaling. Therefore, manipulation of Itch activities may provide the opportunities to develop future therapies for immune disorders such as autoimmunity and cancer. speciifc small interfering RNA(siRNA) was utilized to silence the expression of Itch gene of T-lymphocytes and investigate the cytotoxicity activity of transfected T lymphocytes against MFC stomach neoplasms cells in vitro. Methods:T lymphocytes were isolated from the spleen of 615 mice and transfected by speciifc siRNA to silence the expression of Itch gene, The expression of Itch protein were examined by Western bolt in each group;72 hours after transfection, The secretion level of IL-2, INF-γwere measured by enzyme-linked immunosorbent assay (ELISA). At the end, the cytotoxicity activity changes against MFC stomach neoplasms cells was compared between transfected T lym-phocytes, negative control and blank control in vitro. Results:Compared with control group, the expression rate of Itch protein of transfected T-lymphocytes was decreased to 16%after transfection 48 hours;72 hours after transfection, the secretion level of IL-2 in transfection group, negative control and blank control respectively were (1 891.96±141.91)pg/mL, (1 241.69±91.67)pg/mL and (1 175.03±89.14)pg/mL (P<0.001), the secretion level of INF-γin transfection group, negative control and blank control respectively were (958.33±75.46)pg/mL, (683.33±66.67)pg/mL and (691.72±68.72) pg/mL (P<0.05). Transfected T lymphocyte also showed more efifcient killing ability against MFC stomach neoplasms cells than negative control and blank control in vitro, the highest killing rate has reached (54.18±2.96)%. Conclusion:Silencing Itch gene can signiifcantly promoted the secretion level of IL-2, INF-γof mice T lymphocyte, enhanced the cytotoxicity activity of T lymphocyte against MFC stomach neoplasms cells in vitro.

Objective To investigate the effects of angiotensin Ⅱ (Ang Ⅱ) on the expression of C-terminal Src kinase (Csk) in Ang Ⅱ-infused rat model and cultured podocytes,and to explore the role of Csk in Ang Ⅱ-induced cytoskeletal rearrangement of podocytes.Methods Twenty-four Wista rats were randomly subjected to normal saline infusion,or Ang Ⅱ infusion at 400 ng · kg1 · min-1 (via subcutaneous osmotic minipumps) for 2 or 4 weeks.Renal histomorphology was evaluated through electron microscopy.The expression of glomerular Csk was analyzed by immunofluorescence and Western blotting.In vitro,conditionally immortalized mouse podocytes were cultured and treated with Ang Ⅱ doses ranging from 10-9 mol/L to 10-5 mol/L and for different hours.The expression of podocytes Csk was assessed by Western blotting.After transfection to podocytes with Csk siRNA,FITC-conjugated phalloidin was used to stain F-actin,to investigate the role of Csk in Ang Ⅱ-induced or cytochalasin D-induced cytoskeletal rearrangement.Results (1) Examination of Ang Ⅱ infusion rats glomerular and podocyte ultrastructure by electron microscopy revealed foot process effacement and fusion; (2) In Ang Ⅱ infusion rats,the expression of glomerular Csk was increased (P ＜ 0.05); (3) In vitro,Ang Ⅱ-stimuli up-regulated the expression of Csk (P ＜ 0.05),and the effects of Ang Ⅱ were on dose-dependent and time-dependent manner; (4) Ang Ⅱ-induced disruption of F-actin was alleviated by Csk siRNA transfection in cultured podocytes; furthermore,cytochalasin D depolymerized the F-actin cytoskeleton,while Csk siRNA stabilized the actin filaments.Conclusion The enhanced expression of Csk may be involved in Ang II-induced podocytes cytoskeletal rearrangement and foot process fusion.

Objective:To explore the application effect of "connections, concepts, concrete practice and conclusions (4C)" teaching method combined with two-way evaluation method in nursing teaching of gastrointestinal surgery, so as to provide reference for personnel training and quality control of practice.Methods:A historical controlled study was conducted to prospectively include the nursing interns received by the Department of Gastrointestinal Surgery of the hospital from May 2020 to May 2022 as the subjects of this study. The interns were divided into the control group (64 interns from May 2020 to May 2021) and the research group (93 interns from June 2021 to May 2022) according to the order of admission of nursing interns. The control group was taught by traditional nursing teaching method, while the research group was taught by "4C" teaching method combined with two-way evaluation method. The scores of theoretical knowledge and operation of nursing students in the two groups were compared after 6 weeks of practice. The self-directed learning ability of nursing students in the two groups was compared before and after 6 weeks of practice [Chinese version of self-rating scale of self-directed learning (SRSSDL)]. The evaluation of teaching quality between two groups of nursing students were compared. SPSS 25.0 was used for t-test and Chi-square test. Results:One person in the control group voluntarily quit the internship, and two in the observation group voluntarily quit the internship. Finally, 63 people in the control group and 91 people in the research group entered the study. There was no statistical significant difference between the two groups in baseline data ( P>0.05). At 6 weeks of practice, the scores of theoretical knowledge (87.96±4.62) and operation (92.60±4.25) in the study group were higher than those in the control group [(86.02±4.53) and (88.27±4.31)] ( P<0.05). At 6 weeks of practice, the total scores of learning awareness, learning behavior, learning strategies, learning evaluation, interpersonal skills and self-directed learning ability of the two groups were higher than those before practice, and the study group was higher than the control group ( P<0.05). After 2 weeks, 4 weeks and 6 weeks of practice, the scores of the two groups of nursing students in evaluating the teaching quality of the teachers increased gradually compared with that of the first week of practice ( P<0.05). Conclusion:The "4C" teaching method combined with the two-way evaluation method in the nursing teaching of gastrointestinal surgery can improve the nursing students' theoretical knowledge, practical operation ability and self-directed learning ability, and is conducive to the improvement of teaching quality.

This study was aimed to observe the curative effect and safety of Danzhi Jiangtang Capsule ( DJC ) combined with atorvastatin on carotid artery intima-media thickness (IMT) in diabetes patients without hyper-tension . A total of 196 diabetes patients without hypertension with incrassate carotid artery IMT were randomly divided into the control group ( 98 cases ) and the treatment group ( 98 cases ) . The conventional diabetes thera-py was given to both groups . The atorvastatin of 20 mg/night was given to the control group . And the atorvas-tatin 20 mg/night added with DJC 9 . 0 g/night were given to the treatment group . The treatment course was
12 months . Carotid artery IMT , carotid atherosclerotic plaque area , FPG , FIns , HOMA-IR , HbA1c , blood lipids , hepatorenal function and etc . were examined before and after the treatment respectively . The results showed that there was a significant positive correlation between carotid artery IMT and FIns , HOMA-IR , HbAlc , LDL-C . After 12-month treatment , the total effectiveness is 85 . 87% in the treatment group . And there was significant difference compared with the control group ( P < 0 . 05 ) . The levels of FPG , FIns , HOMA-IR , HbAlc of the treatment group had no difference compared with the control group . Compared with the control group, TC and LDL-C of the treatment group was obviously decreased (P < 0.05). And HDL-C was significantly increased ( P < 0 . 05 ) . The carotid artery IMT of the treatment group decreased from ( 0 . 11 ±0 . 01 ) cm to ( 0 . 08 ± 0 . 01 ) cm . And compared with the control group , there was statistical significance ( P <0 . 05 ) . The carotid atherosclerotic plaque area of 58 cases in the treatment group decreased from ( 0 . 37 ±0.56) cm2 to (0.21 ± 0.25) cm2. However, there was no statistical significance compared to the control group. There were 5 adverse events in the control group and 9 adverse events in the treatment group . And there was no difference between two groups. It was concluded that DJC combined with atorvastatin can regulate lipid metabolism and reduce carotid artery IMT .

Objective:To summarize the genotype and clinical characteristics of chylomicron retention disease (CMRD) caused by secretion associated Ras related GTPase 1B (SAR1B) gene variations.Methods:Clinical data and genetic testing results of 2 children with CMRD treated at Children′s Hospital of Fudan University and Jiangxi Provincial Children′s Hospital from May 2022 to July 2023 were summarized. To provide an overview of the clinical and genetic characteristics of CMRD caused by SAR1B gene variations, all of the literature was searched and reviewed from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China VIP database, China Biology Medicine disc and PubMed database (up to January 2024) with "chylomicron retention disease" "Anderson disease" or "Anderson syndrome" as the search terms. All relevant literatures were reviewed to summarize the clinical and genetic features of CMRD caused by SAR1B gene variations.Results:One 11-year-old boy and one 4-month-old girl with CMRD. Both patients had lipid malabsorption, failure to thrive, decreased cholesterol, elevated transaminase and creatine kinase, and Vitamin E deficiency, with homozygous variations (c.224A>G) and compound heterozygous variations (c.224A>G and c.554G>T) in SAR1B gene, respectively. Case 1 was followed up for over a month, and he still occasionally experienced lower limb muscle pain. Case 2 was followed up for more than a year, and her had caught up to normal levels. Both patients had no other significant discomfort. Literature search retrieved 0 Chinese literature and 22 English literatures. In addition to the 2 cases reported in this study, a total of 51 patients were identified as CMRD caused by SAR1B gene variations. Twenty-one types of SAR1B variants 10 missense, 4 nonsense, 3 frameshift, 1 in-frame deletion, 1 splice, 1 gross deletion, and 1 gross insertion-deletion were found among the 51 CMRD cases. Among all the patients, 49 cases had lipid malabsorption (43 cases had diarrhea or fatty diarrhea, 17 cases had vomiting, and 12 cases had abdominal distension), 45 cases had lipid soluble Vitamin deficiency (43 cases had Vitamin E deficiency, 10 cases had Vitamin A deficiency, 9 case had Vitamin D deficiency, and 5 cases had Vitamin K deficiency), 35 cases had failure to thrive, 32 cases had liver involvement (32 cases had elevated transaminases, 5 cases had fatty liver, and 3 cases had hepatomegaly), 29 cases had white small intestinal mucosa under endoscopy, and 17 cases had elevated creatine kinase, 14 cases had neuropathy, 5 cases had ocular lesions, 2 cases had acanthocytosis, 1 case had decreased cardiac ejection fraction, and 1 case was symptom-free.Conclusions:Early infancy failure to thrive and lipid malabsorption are common issues for CMRD patients. The laboratory tests are characterized by hypocholesterolemia with or without fat-soluble Vitamin deficiency, elevated liver enzymes and (or) creatine kinase. Currently, missense variations are frequent among the primarily homozygous SAR1B genotypes that have been described.

Isolation rearing (IR) enhances aggressive behavior, and the central serotonin (5-hydroxytryptamine, 5-HT) system has been linked to IR-induced aggression. However, whether the alteration of central serotonin is the cause or consequence of enhanced aggression is still unknown. In the present study, using mice deficient in central serotonin Tph2 and Lmx1b, we examined the association between central serotonin and aggression with or without social isolation. We demonstrated that central serotonergic neurons are critical for the enhanced aggression after IR. 5-HT depletion in wild-type mice increased aggression. On the other hand, application of 5-HT in Lmx1b mice inhibited the enhancement of aggression under social isolation conditions. Dopamine was downregulated in Lmx1b mice. Similar to 5-HT, L-DOPA decreased aggression in Lmx1b mice. Our results link the serotoninergic system directly to aggression and this may have clinical implications for aggression-related human conditions.