Objective Through integrative bioinformatics analysis of multi-source transcriptomic data, potential biomarkers to asthma epithelial cells were identified. The expression of these candidate target was subsequently validated in lung tissues and epithelial cells from asthma models. Methods The gene expression profile data of epithelial cells from three asthma patient cohorts and corresponding healthy controls were integrated from the Gene Expression Omnibus (GEO) database. Differential expression analysis and gene co-expression network analysis were performed to identify key genes and biological pathways associated with asthma. The key genes were validated in lung tissues and epithelial cells in asthma animal models. Results Differential gene expression analysis revealed 1121 upregulated and 1484 downregulated genes in epithelial cells from asthma patients compared with healthy controls. The biological pathway enrichment analysis revealed that the upregulated genes were mainly involved in glycosylation processes, whereas the downregulated genes were mainly associated with immune cell differentiation process. The gene co-expression network analysis revealed that module 9, enriched in glycosylation-related pathways, was significantly positively correlated with asthma, whereas module 17, associated with insulin and other signaling pathways, showed a significant negative correlation with asthma. We identified the genes of polypeptide N-acetylgalactosaminyltransferase 5 (GALNT5), pyrroline-5-carboxylate reductase 1 (PYCR1), and carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as key genes within module 9, all of which were significantly upregulated in asthma. Finally, we validated that the expression levels of GALNT5, PYCR1, and CEACAM5 were significantly upregulated in epithelial cells from asthmatic lung tissue. Additionally, using a rat asthma model, we further confirmed that the protein levels of these three genes were significantly upregulated in lung tissues of the model group. Conclusion Through data integration and experimental validation, this study identified key genes and biological pathways closely associated with asthma pathogenesis. These findings provide a novel theoretical basis and potential targets for the diagnosis and treatment of asthma.
Asthma/metabolism* ; Humans ; Epithelial Cells/metabolism* ; Animals ; Biomarkers/metabolism* ; Gene Expression Profiling ; Transcriptome ; Gene Regulatory Networks ; Rats ; Computational Biology

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As a novel neuromodulation technology,the application of deep brain stimulation(DBS)in treatment-resistant psychiatric disorders has received widespread attention in recent years.Based on the current research frontiers,this review puts forward several unique and insightful issues of DBS in psychiatric disorders,including therapeutic targets,stimulation modes,closed-loop modulation,and long-term efficacy in order to provide suggestions and perspectives for future research directions.

Objective:To determine the median effective dose (ED 50) of sufentanil in inhibiting responses to tracheal intubation when combined with ciprofol in patients with Parkinson′s disease. Methods:This was a prospective study. American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients with Parkinson′s disease, aged 18-64 yr, with body mass index of 18.5-30.0 kg/m 2, of Mallampati grade Ⅰ or Ⅱ, undergoing elective deep brain stimulator implantation with tracheal intubation in the Brain Hospital Affiliated to Nanjing Medical University from July 2022 to January 2024, were selected. Sufentanil, ciprofol 0.40 mg/kg and rocuronium 0.60 mg/kg were administrated intravenously and sequentially, and endotracheal intubation was performed after onset of muscle relaxation. A positive response was defined as an increase in heart rate or mean arterial pressure by more than 20% of the baseline value within 2 min after tracheal intubation. The initial dose of sufentanil was set at 0.36 μg/kg, the dose in the next patient was determined according to the response to tracheal intubation, and the ratio between the two successive doses was 1.2. The ED 50 and 95% confidence interval of sufentanil in inhibiting responses to tracheal intubation were calculated using the Dixon-Mood method. Results:The ED 50 (95% confidence interval) of sufentanil in inhibiting responses to tracheal intubation was 0.335 (0.298-0.378) μg/kg when combined with ciprofol. Conclusions:When combined with ciprofol 0.40 mg/kg, the ED 50 of sufentanil in inhibiting responses to tracheal intubation is 0.335 μg/kg in patients with Parkinson′s disease.

Objective To evaluate the impact of hospital-wide cultural initiatives on the prevention and control of noso-comial infections.Methods This study retrospectively analyzed a series of hospital-wide cultural activities related to infection control conducted at a specialized cancer hospital from 2021 to 2023.These included a video-based-show contest of personal pro-tective equipment operation,"Hand Hygiene Star""Piercing Eye"initiatives for propagating the prevention and control of noso-comial infection,and a micro-video contest on infection control.Changes of various nosocomial infection monitoring indicators from 2020 to 2023 were also analyzed to evaluate the effect of these activities.Results The monitoring indicators of nosocomial infection prevention and control in 2023 were significantly improved compared with that in 2021.Specifically,the hand hygiene compliance rate increased from 84.13％to 94.46％,the incidence of nosocomial infection decreased from 1.53％to 0.70％,the infection rate of multi-drug-resistant bacteria dropped from 0.21％to 0.11％,and the correct implementation rate of prevention and control measures of multi-drug-resistant bacteria increased from 52.50％to 88.19％,all with statistical significance(all P＜0.05).Over 3 000 individuals passed assessments for the proper use of personal protective equipment.Conclusion Hospital-wide initiatives on nosocomial infection prevention and control can effectively improve a hospital's infection control capabilities.

Objective:To investigate the application value of virtual reality laparoscopic simulator training in laparoscopic transabdominal preperitoneal hernioplasty (TAPP).Methods:The prospective cohort study was conducted. Twenty young physicians from The First Affiliated Hospital of Harbin Medical University with ≥3 years of clinical experience in general surgery and no foundation in laparoscopy were selected for training during July to August 2023. Physicians were divided into two groups based on random number table method. Physicians undergoing virtual reality laparoscopic simulator training were divided into the virtual reality group, and physicians undergoing regular laparoscopic simulator training were divided into the regular group. Two groups of physicians were trained using laparoscopic simulator for 10 days (2 hours for each skill, with a total of 6 hours per day for 3 skills), and the training covered basic laparoscopic surgical skills such as clamping, cutting and suturing and knotting. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups were conducted using the independent sample t test and the paired ttest was used for intra group comparison. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups were conducted using the chi-square test. Results:(1) Physicians situation before training. A total of 20 physicians were selected for eligibility. There were 13 males and 7 females, aged 31(range, 30?34)years. There are 7 males and 3 females in the virtual reality group, with age of (31.5±1.4)years and the TAPP simulation surgery time of (42±4)minutes before training. There are 6 male and 4 female students in the regular group, with age of (31.2±1.0)years and the TAPP simulation surgery time of (42±4)minutes before training. There was no significant difference in gender, age, TAPP simulation surgery time between the two groups of physicians ( P>0.05), confounding bias ensured comparability. (2) Basic skills of physicians before and after training. For physicians in the virtual reality group, the clamping score was 5.1±1.0, the cutting score was 4.9±1.0, the suturing and knotting score was 4.7±1.5 before training. The clamping score was 8.0±1.3, the cutting score was 7.9±1.5, the suturing and knotting score was 6.6±1.3 after training. There were significant differences in the above indicators before and after training ( t=?5.75, ?5.21, ?3.07, P<0.05). For physicians in the regular group, the clamping score was 5.3±1.0, the cutting score was 5.0±1.2, the suturing and knotting score was 4.3±1.5 before training. The clamping score was 7.1±1.2, the cutting score was 6.7±1.3, the suturing and knotting score was 5.7±1.1 after training. There were significant differences in the above indicators before and after training ( t=?3.73, ?3.16, ?2.42, P<0.05). (3) Completion of simulated surgical situations before and after training. The time of completing TAPP simulation surgery for virtual reality group after training was (29±3)minutes, versus (42±4)minutes before training, showing a significant difference before and after training ( t=7.69, P<0.05). The time of completing TAPP simulation surgery for regular group after training was (36±4)minutes, versus (42±4)minutes before training, showing a significant difference before and after training ( t=3.75, P<0.05). The time of completing TAPP simulation surgery of virtual reality group after training was shorter than that of regular group, showing a significant difference between the two groups ( t=?3.89, P<0.05). Conclusion:Both of virtual reality and regular laparoscopic simulator can enhance the basic laparoscopic surgical skills and the proficiency of TAPP simulation surgery of physicians, and the training effect of virtual reality laparoscopic simulators is better.

Objective To discuss the clinical application of controlling nutritional status(CONUT)score in predicting the prognosis of hepatocellular carcinoma(HCC)patients who are treated with transarterial chemoembolization(TACE),and to construct a nomogram model integrated with multiple prognostic factors which help clinicians to accurately predict the prognosis of each patient.Methods The clinical data of 155 primary HCC patients,who were treated with TACE at the Third Affiliated Hospital of Soochow University of China between January 2017 and June 2020,were retrospectively analyzed.The optimal cutoff point of CONUT score was identified by receiver operation characteristics(ROC)curve and its prognostic significance was analyzed by Kaplan-Meier curve.The univariate and multivariate Cox survival analysis was performed to determine the independent prognostic factors for HCC patients treated with TACE.A nomogram model was constructed based on the significant variables which were obtained from the multivariate analysis,and its ability in predicting overall survival(OS)in HCC patients receiving TACE treatment was evaluated by using the consistency index(C-index).The calibration curves were plotted to evaluate the consistency between the predicted probability and the actual probability.Results The optimal cutoff point of CONUT score for predicting OS was 4,with an AUC value of 0.766(95％CI=0.691-0.841).The patients of high CONUT score group(≥4)had larger tumor diameter(P=0.014),higher serum AFP level(P=0.002),poorer hepatic function(P＜0.01),poorer response to TACE treatment(P＜0.01),and shorter median OS(P＜0.01).Child-Pugh grade,maximum tumor diameter,serum AFP level,BCLC stage,therapeutic response to TACE,and CONUT score were the independent predictors of OS in HCC patients after TACE treatment(all P＜0.05).Based on the above variables,the nomogram model was constructed,and its C-index was 0.785(95％CI=0.691-0.879).The calibration curves showed that a good consistency existed between the predicted probability of the model and the actual probability.Conclusion CONUT score is a simple and feasible tool for predicting the prognosis of HCC patients who are treated with TACE.The nomogram model integrated with tumor biological characteristics,therapeutic response to TACE treatment and CONUT score carries a reliable predictive ability,therefore,this model is worth further promotion and verification.(J Intervent Radiol,2023,32:1190-1196)

Objective:To compare the prognoses of salvage liver transplantation fulfilling the Criteria of Milan, University of California San Francisco(UCSF)and Hangzhou.Methods:Clinical data were retrospectively reviewed for 256 patients with recurrent hepatocellular carcinoma(HCC)undergoing donation after citizen death(DCD)liver transplantation(LT)from January 2015 to October 2019.They were divided into two groups of primary(PLT, n=175)and salvage(SLT, n=81). General profiles, tumor pathological characteristics and postoperative complications of two groups were compared by T-test, rank-sum or χ2 test.Kaplan-Meier method and Log rank test were employed for comparing overall survival rate(OS)and recurrence-free survival rate(RFS)between two groups.In SLT group, 31 cases fulfilled Milan criteria, 45 cases UCSF criteria and 69 cases Hangzhou criteria.OS/RFS of three groups were compared.According to there was downstaging or bridging treatment pre-LT, SLT group was divided into downstaging group(n=32)and non-downstaging group(n=49). OS/RFS of two groups were compared.According to the Rescit1.1 criteria, downstaging group were divided into remission group(n=14)and non-remission group(n=18)and OS/RFS of two groups were compared. Results:The operative durations of PLT and SLT groups were(439.5±74.9)and(475.1±83.4)min respectively.There was significant inter-group difference( P<0.05); However, no significant inter-group difference existed in amount of intraoperative bleeding, blood transfusion, postoperative hospital stay or incidence of postoperative complications(all P>0.05). No significant difference existed in OS/RFS between PLT and SLT groups( P>0.05). No significant difference existed in OS at 1/3/5 years post-SLT among Milan, UCSF and Hangzhou criteria groups(all P>0.05); However, RFS in Milan criteria group at 1/3/5 years post-SLT were 93.5%, 81.7% and 81.7% respectively.They were significantly higher than 68.9%, 59.7% and 59.7% in UCSF criteria group and 78.3%, 58.8% and 55.5% in Hangzhou criteria group(all P<0.05). For patients on downstaging therapy, OS in the Remission group at 1, 3 and 5 years post-SLT were 100%, 73% and 73% respectively, which was significantly higher than 83.3%, 49.4% and 0 in non-Remission group( P=0.042). RFS in the Remission group at 1, 3 and 5 years post-SLT were 100%, 62.5% and 46.9% respectively, which was significantly higher than 52.9%, 0 and 0 in no-Remission group( P=0.001). Conclusions:The survival outcome of SLT recipients is similar to that of PLT recipients.The overall survival of SLT recipients shows no significant difference between Milan, UCSF and Hangzhou criteria.However, SLT recipients fulfilling Milan criteria have the longest recurrence-free time.The prognosis of patients with remission after preoperative descending treatment is superior to that of patients without remission.

Objective:A prospective, multicenter randomized controlled clinical research was conducted to explore the diagnostic value of the new optical staining technology for domestic endoscope, spectral focused imaging (SFI) and variable intelligent staining technology (VIST), for gastric precancerous lesions.Methods:Patients who intended to undergo gastroscopy between August 2020 and May 2021 were randomly divided into the white light group and the new optical staining group at the First Hospital of Hebei Medical University, Shanghai Tenth People's Hospital and the Second Affiliated Hospital of Soochow University. A sequential examination method was applied (white light to new optical staining or new optical staining to white light). The endoscopic diagnostic results and the detection results of Helicobacter pylori ( HP) of the two groups were recorded. At the same time, such five variables as gastric mucosal atrophy, intestinal metaplasia, fold enlargement, nodular gastritis and diffuse redness were evaluated for the risk of gastric cancer in the two groups. Results:A total of 419 cases were enrolled, including 208 cases in the white light group and 211 cases in the new optical staining group. Compared with pathological findings, the detection rates of gastric inflammation, atrophy, intestinal metaplasia, low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia and advanced cancer lesions in the white light group were 28.9%, 40.4%, 64.9%, 17.8%, 0.5% and 0.5% respectively; while those in the new optical staining group were 30.8%, 42.7%, 62.6%, 15.2%, 2.8% and 0.5%. There were no significant differences in the detection rates between the two groups ( P>0.05). Compared with pathology, the sensitivity, the specificity, the accuracy, the positive predictive value and the negative predictive value for gastric mucosal atrophy in the white light group were 92.9%, 61.3%, 74.0%, 61.9% and 92.7% respectively and those in the new optical staining group (SFI mode) were 94.4%, 64.5%, 77.3%, 66.4% and 94.0% respectively. The above 5 measures for gastric mucosal intestinal metaplasia were 68.1%, 72.6%, 69.7%, 82.1% and 55.2% in the white light group, and 87.1%, 89.9%, 88.2%, 93.5% and 80.7% in the new optical staining group (VIST mode), with significant difference between the two groups ( P<0.05). In terms of HP infection with 13C-urea breath test ( 13C-UBT) results as the gold standard, the above 5 measures were 90.2%, 84.3%, 87.4%, 86.8% and 88.2% in the white light group and 92.6%, 77.1%, 85.4%, 82.2% and 90.1% in the new optical staining group respectively. The proportion of high-risk gastric lesions in the new optical staining group was higher in cases of a gastric cancer risk score≥ 4 ( P<0.05). Conclusion:The new optical staining technology of domestic endoscopy has higher diagnostic value for gastric mucosal intestinal metaplasia. Gastroscopy is helpful for the detection of precancerous lesions with gastric cancer risk score as a tool. The new optical staining technology of domestic endoscopy is similar to imported endoscopy in diagnosing gastric precancerous lesions and HP infection, which is an effective means to detect gastric mucosal precancerous lesions.

Tripterygium wilfordii is a valuable medicinal plant rich in biologically active diterpenoids, but there are few studies on the origins of these diterpenoids in its secondary metabolism. Here, we identified three regions containing tandemly duplicated diterpene synthase genes on chromosomes (Chr) 17 and 21 of T. wilfordii and obtained 11 diterpene synthases with different functions. We further revealed that these diterpene synthases underwent duplication and rearrangement at approximately 2.3-23.7 million years ago (MYA) by whole-genome triplication (WGT), transposon mediation, and tandem duplication, followed by functional divergence. We first demonstrated that four key amino acids in the sequences of TwCPS3, TwCPS5, and TwCPS6 were altered during evolution, leading to their functional divergence and the formation of diterpene secondary metabolites. Then, we demonstrated that the functional divergence of three TwKSLs was driven by mutations in two key amino acids. Finally, we discovered the mechanisms of evolution and pseudogenization of miltiradiene synthases in T. wilfordii and elucidated that the new function in TwMS1/2 from the terpene synthase (TPS)-b subfamily was caused by progressive changes in multiple amino acids after the WGT event. Our results provide key evidence for the formation of diverse diterpenoids during the evolution of secondary metabolites in T. wilfordii.