OBJECTIVE: To summarize the gene therapy strategies for neurofibromatosis type 1 (NF1) and related research progress. METHODS: The recent literature on gene therapy for NF1 at home and abroad was reviewed. The structure and function of the NF1 gene and its mutations were analyzed, and the current status as well as future prospects of the transgenic therapy and gene editing strategies were summarized. RESULTS: NF1 is an autosomal dominantly inherited tumor predisposition syndrome caused by mutations in the NF1 tumor suppressor gene, which impair the function of the neurofibromin and lead to the disease. It has complex clinical manifestations and is not yet curable. Gene therapy strategies for NF1 are still in the research and development stage. Existing studies on the transgenic therapy for NF1 have mainly focused on the construction and expression of the GTPase-activating protein-related domain in cells that lack of functional neurofibromin, confirming the feasibility of the transgenic therapy for NF1. Future research may focus on split adeno-associated virus (AAV) gene delivery, oversized AAV gene delivery, and the development of new vectors for targeted delivery of full-length NF1 cDNA. In addition, the gene editing tools of the new generation have great potential to treat monogenic genetic diseases such as NF1, but need to be further validated in terms of efficiency and safety. CONCLUSION Gene therapy, including both the transgenic therapy and gene editing, is expected to become an important new therapeutic approach for NF1 patients.
Humans ; Neurofibromatosis 1/pathology* ; Neurofibromin 1/metabolism* ; GTPase-Activating Proteins ; Mutation ; Genetic Predisposition to Disease ; Genetic Therapy

Objective To explore the protein expression levels of serum neurite outgrowth inhibitor-A(Nogo-A),energy balance related protein(Adropin),zonula occludens-1(ZO-1)and angiopoietin-like protein 4(ANGPTL4)in patients with acute cerebral hemorrhage and their predictive efficacy for prognosis.Methods A total of 148 patients with acute cerebral hemorrhage treated in the hospital from April 2020 to May 2022 were selected as the study group,and another 150 healthy people who came to the hospital for gen-eral physical examination during the same period were selected as the control group,and a retrospective analy-sis was conducted.The protein expression levels of Nogo-A,Adropin,ZO-1 and ANGPTL4 in serum of the two groups were detected by enzyme-linked immunosorbent assay(ELISA)and compared.Spearman correla-tion coefficient was used to analyze the correlation between serum Nogo-A,Adropin,ZO-1,ANGPTL4 protein expression levels and the occurrence of acute cerebral hemorrhage.Receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic efficacy of the combined detection of the above four indicators for a-cute cerebral hemorrhage.In addition,patients in the study group were followed up for 6 months,and were di-vided into good group(91 cases)and poor group(57 cases)according to the prognosis.Serum protein expres-sion levels of Nogo-A,Adropin,ZO-1 and ANGPTL4 were compared between the two groups.ROC curve was used to verify the predictive efficacy of the combined detection for the prognosis of these patients.Results Compared with the control group,the protein expression levels of Nogo-A,ZO-1 and ANGPTL4 in the study group were significantly increased,while the protein expression level of Adropin was significantly decreased(all P<0.05).Spearman correlation coefficient analysis showed that serum Nogo-A,ZO-1,ANGPTL4 pro-tein expression levels were positively correlated with the incidence rate of acute cerebral hemorrhage,while Adropin protein expression level was negatively correlated with the incidence rate of acute cerebral hemor-rhage(all P<0.05).ROC curve verification showed that the combined detection of Nogo-A,Adropin,ZO-1 and ANGPTL4 protein expression levels had high diagnostic efficacy in the evaluation of acute cerebral hemor-rhage,with the sensitivity and the specificity of 92.57%and 90.67%,respectively.Compared with good group,the protein expression levels of Nogo-A,ZO-1 and ANGPTL4 in poor group were significantly higher,while the protein expression level of Adropin was significantly decreased(all P<0.05).ROC curve showed that compared to single detections,the area under the curve of the combined detection of protein expression levels of Nogo-A,Adropin,ZO-1 and ANGPTL4 was larger(P<0.05),with the sensitivity of 84.21%and the specificity of 89.01%.Conclusion The protein expression levels of Nogo-A,Adropin,ZO-1 and AN-GPTL4 are abnormal in patients with acute cerebral hemorrhage,and the protein expression levels of Nogo-A,Adropin,ZO-1 and ANGPTL4 are closely related to the development of acute cerebral hemorrhage.The com-bined detection of the four indicators could not only assist clinical accurate judgment of acute cerebral hemor-rhage,but also have important clinical value in predicting the prognosis of patients.

BACKGROUND:Grape seed extract has been shown to be effective in inhibiting the growth of androgen-dependent tumors(e.g.,breast cancer),and thus grape seed extract could theoretically inhibit epiphyseal closure induced by estrogen in late adolescence. OBJECTIVE:To screen the effects of grape seed extract on apoptosis of growth plate chondrocytes and epiphyseal closure in rats. METHODS:(1)In vitro experiment:Growth plate chondrocytes from rat large tibia and femur at logarithmic growth stage were obtained and cultured in groups:normal control group,model control group(adding 17β-estradiol to induce apoptosis),positive control group(adding letrozole and 17β-estradiol),grape seed extract group(adding 17β-estradiol and 10 μg/mL grape seed extract),Caspase-9 inhibitor group(adding 17β-estradiol and Caspase-9 inhibitor),Caspase-9 agonist group(adding 17β-estradiol and Caspase-9 agonist).Cell apoptosis was detected by flow cytometry after 48 hours of culture.(2)In vivo experiment:Thirty 3-month-old Sprague-Dawley rats were randomly divided into model control group,positive control group and low-,medium-and high-dose groups,with five rats in each group.All rats were injected subcutaneously with 17β-estradiol(3 times per week)to establish epiphyseal closure models,followed by intragastric administration of letrozole in positive control group and 0.05,0.2 and 0.8 g/kg grape seed extract in low-,medium-and high-dose groups,respectively,once a day until over 2/3 of the epiphyseal plate in the model control group was closed.The length of the tibia was then observed.Another 18 Sprague-Dawley rats were randomly divided into model control group,positive control group,and medium-dose group,with 6 rats in each group,treated as above for 1.5 continuous months.The expression of Caspase-9 protein in rat growth plate cartilage was detected by western blot. RESULTS AND CONCLUSION:(1)In vitro experiment:17β-estradiol could induce apoptosis in growth plate chondrocytes,and letrozole,grape seed extract,and caspase-9 inhibitors could all inhibit apoptosis in growth plate chondrocytes.(2)In vivo experiment:When more than 2/3 of the epiphyseal plate in the model control group was closed,the number of rats with epiphysis closure in the positive control and medium-dose groups was less than that in the model control group(P＜0.05),and the tibial length was longer than that in the model control group(P＜0.05),and the Caspase-9 protein expression in the tibial growth plate was lower than that in the model control group(P＜0.05).To conclude,the appropriate dose of grape seed extract can effectively inhibit the apoptosis of growth plate chondrocytes and delay epiphyseal closure,which has the potential to promote bone growth.

ObjectiveTo observe the clinical efficacy of Shengmaisan combined with polymyxin B in the treatment of carbapenem-resistant gram-negative bacillus infection with sepsis complicated with severe acute respiratory distress syndrome. MethodA total of 90 patients suffering from carbapenem-resistant gram-negative bacillus infection with sepsis complicated with severe acute respiratory distress syndrome were randomly divided into a control group and an observation group， with 45 cases in each group. The control group was treated with polymyxin B， and the observation group was treated with Shengmaisan combined with polymyxin B. The treatment course of both groups was seven days. The infection-related indicators ［white blood cell （WBC） count， procalcitonin （PCT）， neutrophil apolipoprotein （HNL）］， inflammatory factors ［interleukin-6 （IL-6）， serum chemokine ligand 2 （CXCL2）］， and T lymphocyte subpopulations （CD3⁺， CD4⁺， CD8⁺， and CD4⁺/ CD8⁺ value）， acute physiological and chronic health Ⅱ （APACHE Ⅱ） score before and after treatment， as well as bacterial clearance rate and 28-day survival rate after treatment were observed. Result① The experiment was completed， and 81 cases were included， including 41 cases in the observation group and 40 cases in the control group. The general data of the two groups were comparable. ② The bacterial clearance rate of the observation group and the control group was 75.6% （31/41） and 52.5% （21/40）， respectively， and the observation group was higher than the control group （χ²=4.7， P<0.05）. ③ The WBC count， PCT， HNL， IL-6， CXCL2， and APACHE Ⅱ scores of the observation group and the control group all decreased after treatment （P<0.05）. Except for the WBC count， the PCT， HNL， IL-6， CXCL2， and APACHE Ⅱ scores of the observation group were lower than those of the control group （P<0.05）. ④ The values of CD3⁺， CD4⁺， and CD4⁺/CD8⁺ in the observation group were increased after treatment （P<0.05）， and CD8⁺ was decreased （P<0.05）. In the control group， only CD3⁺ value was increased （P<0.05）. The values of CD3⁺， CD4⁺， and CD4⁺/CD8⁺ in the observation group were higher than those in the control group， and the value of CD8⁺ was lower than that in the control group （P<0.05）. ⑤ The 28-day survival rate in the observation group was higher than that in the control group （χ²=4.3， P<0.05）. ConclusionShengmaisan combined with polymyxin B in the treatment of carbapenem-resistant gram-negative bacillus infection with sepsis complicated with severe acute respiratory distress syndrome can better clear bacteria， control infection， reduce the level of inflammatory factors， regulate the immune state of the body， and improve the short-term prognosis.

Nosocomial infection control personnel are crucial in ensuring the nosocomial infection management and the implementation of prevention and control measures. The level of their job competency directly determines the quality and standard of nosocomial infection management. This article reviews the research progress of competency requirements and evaluation indicators of nosocomial infection personnel domestically and internationally. It also summarizes the current gaps and primary reasons behind these gaps in China’s research， so as to offer insights for the future development and improvement of the comprehensive capabilities of these professionals.

Objective To explore the efficacy of semaglutide in the treatment of type 2 diabetes mellitus(T2DM)com-bined with non-alcoholic fatty liver disease(NAFLD)and its effect on oxidative stress and inflammatory factors.Methods Totally 80 patients with T2DM accompanied by NAFLD admitted to the First Affiliated Hospital of Xinxiang Medical University from July 2021 to December 2022 were selected and randomly assigned to the observation group and the control group,with 40 patients in each group.Patients in the control group were treated with pioglitazone metformin and dapagliflozin,while patients in the observation group were treated with pioglitazone metformin,dapagliflozin,and semaglutide.The levels of glycated hemoglobin(HbA1c),fasting blood glucose(FBG),2-hour postprandial blood glucose(2hPG),body mass,body mass index(BMI),waist circumference,alanine aminotransferase(ALT),aspartate aminotransferase(AST),gamma-glutamyl transferase(GGT),controlled attenuation parameter(CAP),liver stiffness measurement(LSM),malondialdehyde(MDA),glutathione peroxidase(GSH-PX),lipid peroxide(LPO),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-10(IL-10)before and after the treatment were compared.Results After 24 weeks of treatment,the overall response rate(ORR)in the observation group and control group was 92.5％(37/40)and 72.5％(29/40),respectively;and the ORR in the observation group was significantly higher than that in the control group(x2=5.541,P＜0.05).Before treatment,there was no statistically significant difference in the body mass,BMI,waist circumference,HbA1c,FBG,2hPG,ALT,AST,GGT,CAP,LSM,MDA,GSH-PX,LPO,TNF-α,IL-6,and IL-10 of patients between the 2 groups(P＞0.05);after 24 weeks of treatment,the body mass,BMI,waist circumference,HbA1c,FBG,2hPG,ALT,AST,GGT,CAP,LSM,MDA,LPO,TNF-α,IL-6,and IL-10 were significantly lower than before treatment,while GSH-PX was significantly higher than before treatment(P＜0.05);after 24 weeks of treatment,the body mass,BMI,waist circumference,HbA1c,FBG,2hPG,ALT,AST,GGT,CAP,LSM,MDA,LPO,TNF-α,IL-6,and IL-10 of patients in the observation group were significantly lower than those in the control group,and GSH-PX was significantly higher than that in the control group(P＜0.05).The incidence of adverse reactions in the observation group and the control group during the treatment period was 17.5％(7/40)and 12.5％(5/40),respectively;and the difference in the incidence of adverse reactions between the two groups was not statistically significant(P＞0.05).Conclusion Semaglutide significantly downregulates the levels of FBG,2hPG and HbA1c in patients with T2DM combined with NAFLD and reduces the body mass,waist circumference,liver enzyme level,hepatic fat content,hepatic fibrosis,oxidative stress,and inflammatory indicators.

The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling pathways.However,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited.In this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling pathway.Subsequently,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a deletion.Additionally,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)progression.Remarkably,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)model.Furthermore,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages.Notably,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical β-catenin oncogenic pathway in vivo.Specifically,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with β-catenin activity within the TME,involving macrophages and T cells.In summary,our study undergoes the po-tential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment,thereby mitigating the risk of malignancies.

Objective To explore the effect of pregabalin on sleep of patients after video-assisted thoracic surgery(VATS).Methods 120 cases of patients undergoing VATS under general anesthesia were randomly divided into 75 mg pregabalin group(group A),150 mg pregabalin group(group B),and placebo group(group C),with 40 patients in each group.On the night of the operation,the morning and evening of the first day and the second day after the operation,the patients in the three groups were given one tablet of pregabalin(75 mg),one tablet of placebo with the same shape and smell,two tablets of pregabalin(150 mg)and two tablets of placebo with the same shape and smell respectively.Athens insomnia scale(AIS)was used to evaluate the incidence of postoperative sleep disturbance(PSD)on the night of operation,and the patients'sleep quality every night from one night before operation to the 2nd day after operation was assessed using the St.Mary's Hospital sleep questionaire(SMH).Pittsburgh sleep quality index(PSQI)was used to evaluate the patients'sleep quality one day before the operation,7 days after operation,and 1 month after the operation.The digital rating scale(NRS)was used to evaluate the patients'pain at the incision and the surgical side.The remedial analgesia,incidence of adverse events in the 72 h postoperative period,and patient satisfaction score were recorded.Results The incidence of PSD in group A,group B and group C was 45.0％,42.5％and 72.5％,respectively,the incidence of group A and group B was significantly lower than in group C(group A,B and C compared in pairs,P＜0.016 7).The SMH scores in group A and group B were significantly higher than in group C on the day of operation,the first day and the second day after operation(group A,B and C compared in pairs,P＜0.016 7).The incidence of NRS scores in groups A and B at the incision and postoperative remedial analgesia was significantly lower than in group C on postoperative day 1 and postoperative day 2(group A,B and C compared in pairs,P＜0.016 7).There was no statistically significant difference in the pain scores at the incision and shoulder among the three groups at the remaining time points.The postoperative patient satisfaction scores were significantly higher in group A and group B than in group C(P＜0.01).The incidence of dizziness in group B was significantly higher than in the other two groups(P＜0.016 7).Conclusion Oral administration of pregabalin(75 mg/150 mg)for 3 days after VATS can reduce the incidence of PSD and improve the quality of sleep that night,but oral administration of 150 mg pregabalin may increase the incidence of dizziness.

Objective:Based on latent profile analysis, the category characteristics of decisional dilemma of participating in thrombolysis decision-making agents of patients with acute myocardial infarction (AMI) are analyzed to reduce the decision-making difficulties of decision-making agents in AMI patients.Method:The 292 cases of decision-making agents of patients with AMI and treated by intravenous thrombolysis in emergency department of Xinjiang Uygur Autonomous Region People's Hospital were selected as respondents From January 2022 to June 2023.A cross-sectional survey was conducted using General Information Questionnaire, Perceived Social Support Scale, State-Trait Anxiety Inventory, Control Preference Scale, Wake Forest Physician Trust Scale and Decisional Conflict Scale.Selected Mplus 8.3 software to conduct potential profile analysis on the survey data.Results:The 281 valid questionnaires were ultimately collected, with 146 males and 135 females aged 35-72(55.61 ± 9.05) among 281 AMI patients; 135 acting decision-makers from the south, 146 females, aged 30-72(55.52 ± 6.74).The score of decisional dilemma of participating in thrombolysis of decision-making agents of patients with AMI was 45(41, 46). LPA analysis showed that decisional dilemma of participating in thrombolysis of decision-making agents can be divided into 4 latent profiles which were low-level decisional dilemma profile accounts for 16.01% (45/281), high-level decisional dilemma profile accounts for 16.38% (46/281), extra high-level decisional dilemma profile with social support restricting accounts for 35.23% (99/281) and extra high-level decisional dilemma profile with information restricting accounts for 32.28% (91/281). Multiple logistic regression analysis showed represented patients with AMI history, decision-making agent ′s age, gender, educational level, decision-making role, decision-making participation type were significant influencing factors of decisional dilemma of participating in thrombolysis of high-level decisional dilemma profile (all P<0.05);represented patients with AMI history, decision-making agent ′s age, gender, education level, decision-making role, assuming patient ′s treatment payment role, assuming patient ′s care role, perceived social support level, state anxiety level, decision-making participation type and trust doctors level were significant influencing factors of decisional dilemma of participating in thrombolysis of extra high-level decisional dilemma profile with social support restricting and extra high-level decisional dilemma profile with information restricting(all P<0.05). Conclusions:The level decisional dilemma of participating in thrombolysis of decision-making agents for intravenous thrombolysis treatment of AMI patients were high, and their decisional dilemma can be divided into low-level decisional dilemma profile, high-level decisional dilemma profile, extra high-level decisional dilemma profile with social support restricting and extra high-level decisional dilemma profile with information restricting.They should be purposively intervened based on their corresponding decisional dilemma profile.

Objective To investigate the effects of Yitangkang on browning of white adipose and PINK1/Parkin pathway of mitophagy in adipose tissue of db/db mice.Methods Totally 30 six-week db/db mice were randomly divided into model group,Yitangkang Group(30 g/kg)and liraglutide group(200 μg/kg),and another 10 C57BL/6 mice of the same age were set as normal group.All groups were treated with corresponding drugs or normal saline for 5 weeks.During the period of administration,the body mass and fasting blood glucose(FBG)of mice in each group were detected regularly,the samples of liver,white and brown adipose of mice were weighed,the contents of serum triglyceride cholesterol(TC),triacylglycerol(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were detected by biochemical analyzer,HE staining was used to observe the pathological changes of inguinal white adipose tissue(iWAT),immunohistochemical staining was used to detect the expression of browning marker protein uncoupling protein-1(UCP1)in iWAT,Western blot was used to detect the expressions of browning-related proteins UCP1,PRDM16,PGC-1α and mitophagy-related proteins PINK1,Parkin,Beclin-1,p62 in iWAT.Results Compared with the normal group,the body mass,liver,white adipose and brown adipose mass of the model group significantly increased(P<0.01),the FBG and serum TG,TC and LDL-C contents significantly increased(P<0.01),and the content of HDL-C significantly decreased(P<0.01);large vacuoles in iWAT adipocytes,the diameter of adipocytes increased obviously,some adipocytes were extruded and deformed,and the edge of adipocytes was not clear,the expressions of iWAT UCP1,PRDM16,PGC-1α and p62 proteins decreased(P<0.01),while the expressions of PINK1,Parkin and Beclin-1 proteins increased(P<0.01).Compared with the model group,the body mass,liver and white adipose mass significantly decreased in Yitangkang group and the liraglutide group(P<0.01),FBG and serum contents of TC,TG and LDL-C were significantly decreased(P<0.05,P<0.01),while HDL-C content significantly increased(P<0.01);the diameter of iWAT adipocytes decreased,the number increased,and the morphology was regular,the expressions of iWAT UCP1,PRDM16,PGC-1α and p62 proteins increased(P<0.01),while the expressions of PINK1,Parkin and Beclin-1 proteins decreased(P<0.05,P<0.01).Conclusion Yitangkang can improve glucose and lipid metabolism and promote browning of white adipose in db/db mice,which may be related to mitophagy mediated by PINK1/Parkin pathway.