Objective To explore the effect of the knockdown of transmembrane 9 superfamily protein member 2 (TM9SF2) on the replication of vesicular stomatitis virus (VSV), and investigate its role in the mechanism of antiviral innate immunity. Methods Small interfering RNA (siRNA) was used to knock down the TM9SF2 gene in human non-small cell lung cancer A549 cells. The CCK-8 method was used to assess cell proliferation. A VSV-green fluorescent protein (VSV-GFP) infected cell model was established. The plaque assay was used to measure the viral titer in the supernatant. RT-qPCR and Western blotting were employed to quantify the mRNA and protein levels of VSV genome replication in A549 cells following VSV infection, as well as the expression of interferon β (IFN-β) mRNA and interferon regulatory factor 3 (IRF3) protein phosphorylation following polyinosinic-polycytidylic acid (poly(I:C)) stimulation. Results Compared to the negative control, the knockdown of TM9SF2 exhibited a significant effect, with no observed impact on A549 cell proliferation. The VSV-GFP infected A549 cell model was successfully established. After viral stimulation, fluorescence intensity was reduced following TM9SF2 knockdown, and the mRNA and protein levels of VSV were significantly downregulated. The viral titer of VSV was decreased. After poly(I:C) stimulation, TM9SF2 knockdown significantly upregulated the mRNA level of IFN-β and the phosphorylation level of IRF3 protein. Conclusion The knockdown of TM9SF2 inhibits the replication of vesicular stomatitis virus, and positively regulates the type I interferon signaling pathway, thus enhancing the host's antiviral innate immune response.
Humans ; Virus Replication/genetics* ; Signal Transduction ; Membrane Proteins/metabolism* ; A549 Cells ; Vesiculovirus/physiology* ; Interferon-beta/metabolism* ; Interferon Regulatory Factor-3/genetics* ; Interferon Type I/metabolism* ; Vesicular Stomatitis/immunology* ; Gene Knockdown Techniques ; Vesicular stomatitis Indiana virus/physiology* ; RNA, Small Interfering/genetics*

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Objective:To investigate the clinical value of adjuvant therapy after conversion resection for pancreatic cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 173 patients with pancreatic cancer who underwent surgical resection after neoadjuvant and/or induction therapy in The First Affiliated Hospital of Naval Medical University from January 2019 to December 2021 were collected. There were 107 males and 66 females, aged (59±9)years. Observation indicators: (1) comparison of clinicopathological data between patients with and without adjuvant therapy after conversion resection for pancreatic cancer; (2) analysis of influencing factors for prognosis of pancreatic cancer after conversion resection; (3) follow-up and prognosis; (4) survival benefit of adjuvant therapy in subgroup populations. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the non-parameter rank sum test. The Graphpad prism 8 software was used to draw survival curves, the Kaplan-Meier method was used to calculate survival time and survival rates, and the Log-Rank test was used for survival analysis. The COX proportional hazards regression model was used for univariate and multivariate analyses. Interaction analysis was used to determine the benefit of adjuvant therapy in subgroup populations. Results:(1) Comparison of clinicopathological data between patients with and without adjuvant therapy after conversion resection for pancreatic cancer. Of the 173 pancreatic cancer patients, there were 108 cases with adjuvant therapy after conversion resection and 65 cases without adjuvant therapy after conversion resection, respectively. Age and body mass index were (58±9)years and (23.2±2.8)kg/m 2 in patients with adjuvant therapy, versus (61±8)years and (22.2±2.8)kg/m 2 in patients without adjuvant therapy, showing significant differences in the above indicators between them ( t=-2.036, 2.200, P<0.05). (2) Analysis of influencing factors for prognosis of pancreatic cancer after conversion resection. Results of multivariate analysis showed that CA19-9 normalization, pathological N staging, degree of tumor differentiation and postoperative adjuvant therapy were independent factors influencing overall survival time in pancreatic cancer patients receiving conversion resection ( hazard ratio=1.598, 1.541, 2.004, 2.571, 95% confidence interval as 1.041-2.453, 1.021-2.327, 1.288-3.118, 1.721-3.843, P<0.05). (3) Follow-up and prognosis. All 173 patients were followed up for 24.5(5.0,52.0)months. The postoperative median overall survival time of 173 patients was 28.9(5.7,51.9)months, and the 1-, 2-, 3-year overall survival rates were 90%, 59%, 40%, respectively. Of 2019, 2020, 2021, the proportions of patients receiving adjuvant therapy after conversion resection were 62.8%(27/43), 57.7%(30/52) and 65.4%(51/78) respectively. The postoperative median overall survival time was 42.2(8.8,49.7)months in patients with adjuvant therapy after conversion resection, versus 20.4(5.7,51.9)months in patients without adjuvant therapy after conversion resection, showing a significant difference between them ( χ2=29.893, P<0.05). (4) Survival benefit of adjuvant therapy in subgroup populations. Results of interaction analysis showed that in subgroup populations with CA19-9 normalization, pathological stage N0, pathological stage N1-2, moderate to well differentiated tumors, adjuvant therapy after conversion resection can bring a better survival benefit for patients with pancreatic cancer ( adjustment hazard ratio=0.220, 0.300, 0.410, 0.340, 95% confidence interval as 0.120-0.400, 0.170-0.560, 0.240-0.690, 0.210-0.690). Conclusions:Postoperative adjuvant therapy is an independent factor influencing overall survival time in pancreatic cancer patients receiving conversion resection. Adjuvant therapy after conversion resection can bring additional survival benefits for pancreatic cancer, particularly for patients who respond favorably to neoadjuvant and/or induction therapy.

Objective:To investigate the current status of bedside teaching at pediatric bases and existing problems in pediatric bedside teaching, and to discuss how to improve bedside teaching in pediatrics.Methods:A questionnaire on pediatric bedside teaching was administered to 475 instructors who had participated in the backbone teacher training course of pediatric standardized residency training bases in 2022. The instructors were divided into two groups according to their medical professional titles: attending physician group and associate chief physician/chief physician group. The general information, bedside teaching rate, bedside teaching difficulties, and abilities that need to be strengthened were compared between the two groups of instructors. SPSS 21.0 was used to perform the chi-square test.Results:A total of 475 instructors responded to the questionnaire. Among them, 96.84% (460/475) were from tertiary class-A hospitals; 54.11% (257/475) had more than 10 years of clinical teaching practice; and 97.26% (462/475) conducted bedside teaching, but the proportion of bedside teaching time in routine clinical teaching was low, with only 30.11% (143/475) reaching >50.00%. The main difficulties in bedside teaching in pediatrics included noisy environments at pediatric wards or clinics (75.58%, 359/475), the lack of teaching time (71.16%, 338/475), intense clinical pressure (64.63%, 307/475), poor cooperation with children (54.95%, 261/475), the presence of parents at pediatric wards or clinics (44.84%, 213/475), varying levels of qualifications of residents (41.68%, 198/475), and high pressure of scientific research (30.11%, 143/475). There were 41.20% (96/233) of the attending physicians and 28.57% (68/238) of the associate chief physicians/chief physicians spending less than 30.00% of their teaching time at the bedside, respectively, which were significantly different ( P<0.05). Conclusions:The low proportion of time spent on bedside teaching among pediatric instructors is driven by various factors such as noisy pediatric environments and the great clinical pressure of pediatric teachers.

Objective To identify the factors associated with frailty in lung transplant patients by a meta-analysis.Methods Computerized search was performed for studies on the influencing factors of frailty in lung transplant patients in the CNKI,WanFangData,VIP,CBM,PubMed,Web of Science,Embase,Elsevier ScienceDirect and CINAHL databases.The search was conducted from the time of database construction to November 2023.Literature screening,quality assessment,and data extraction were performed independently by 2 investigators,and Meta-analysis was performed using Stata 17.0 software.Results 10 cohort studies,including 1 999 patients,were finally included,and 13 influencing factors were extracted,including advanced age(OR=1.05),female(OR=2.50),BMI(OR=0.38),diagnosis of primary pulmonary disease(OR=2.90),6MWD(OR=0.34),and lung allocation score(OR=0.69),FVC(OR=0.60),pre-transplant frailty(OR=0.81),hypoproteinemia(OR=4.12),hemoglobin(OR=0.50),anemia(OR=4.37),length of ICU stay(OR=1.24),and total length of stay(OR=1.05).Short Physical Performance Battery is an assessment tool for frailty in lung transplant patients,with an incidence of frailty in 24％before transplantation and 50％in post-transplantation.Fried Frailty Phenotype is an assessment tool for frailty in lung transplant patients,with a pre-transplant frailty incidence of 30％.Conclusion There are many factors involved in the incidence of frailty in lung transplant patients,and nursing staff should dynamically evaluate the frailty of lung transplant patients,and give individualized and precise interventions in combination with a multidisciplinary model to improve or delay the progression of frailty.

Objective To evaluate the effect of remote interventions with digital health technologies in lung transplant patients.Methods Databases,including CKNI,Wangfang,VIP,CMB,Cochrane Library,PubMed,Embase,Web of Science,Scopus and BMJ Best Practice were searched from their inception to July 2023.There were 2 researchers who independently screened and extracted the literature,and then evaluated quality of the included studies.Meta-analysis was performed using RevMan 5.2.Results 10 studies with 1 262 patients were included.The results of meta-analysis showed that compared with conventional intervention,remote intervention based on digital health technology could improve self-monitoring compliance of lung transplant patients[0R=0.64,95％CI(0.46,0.88),P=0.006],improve quality of life including mental health status[OR=3.08,95％CI(0.41,5.74),P=0.020]and physical health status[OR=3.81,95％CI(1.19,6.43),P=0.004].In terms of the intervention forms,the application-based remote intervention had better self-monitoring compliance,and the difference was statistically significant(P=0.007).However,in terms of the comparison of readmission rate[OR=1.73,95％CI(0.98,3.04),P=0.060],anxiety[OR=-0.12,95％CI(-1.36,1.11),P=0.850],and depression[OR=0.62,95％CI(-0.80,2.03),P=0.390],the effect of intervention was unclear.Conclusion Remote intervention based on digital health technology can improve self-monitoring compliance and quality of life in lung transplant patients;applications are the optimal form of intervention.Limited by the quality and quantity of included studies and the heterogeneity of study results,more high-quality studies are needed to further verify the effects of digital health technology on readmission rates,anxiety and depression of lung transplant patients.

Objective To investigate the incidence and risk factors of post-transplant diabetes mellitus(PTDM)in adult lung transplant recipients.Methods Conducting a convenience sampling method,we retrospectively analyzed the clinical data of lung transplant recipients from January 2020 to December 2022 at a tertiary A hospital in Hangzhou,Zhejiang Province.According to the PTDM diagnostic criteria,lung transplant recipients are divided into a PTDM group and a non-PTDM group.The incidence rate of PTDM is calculated,and the influencing factors for PTDM occurrence are analyzed using both univariate and multivariate logistic regression methods.Results A total of 140 patients were included in this study,and 54 lung transplant recipients developed PTDM within 6 months,with an incidence of 38.57％.Univariate analysis showed that there were significant differences in age,gender,BMI,smoking history,pre-operative glycated albumin,pre-operative fasting blood glucose,early post-operative blood glucose and pre-operative creatinine between the 2 groups(P＜0.05).Multivariate Logistic analysis showed that gender(OR=5.283),BMI(OR=6.122),pre-operative glycated albumin(OR=1.330),and early post-operative blood glucose(0R=1.444)were the influencing factors.Conclusion Lung transplant recipients who were male,BMI ≥24.0,with high levels of glycated albumin before surgery,and high blood sugar early after surgery had a higher risk of developing PTDM.Clinical nurses can formulate relevant nursing measures according to the influencing factors to prevent the occurrence of PTDM.

Objective:To investigate and compare the clinical outcomes of the arterial pre-occlusion technique(APOT) and the traditional technique in the surgery of locally advanced pancreatic cancer with arterial involvement after conversion therapy.Methods:This is a retrospective cohort study. The clinical data of 145 patients with locally advanced pancreatic cancer with arterial involvement admitted to the Department of Hepato-Biliary-Pancreatic Surgery of the First Hospital Affiliated to Naval Medical University,from January 2020 to December 2022 were retrospectively analyzed. All patients completed neoadjuvant therapy for tumors, and the feasibility of radical surgical treatment was determined by a multidisciplinary collaborative team evaluation before surgery. According to whether the intraoperative artery was pre-occluded, 145 patients were divided into two groups, including 28 cases in the APOT group(16 males, 12 females, aged (59.0±9.4) years), and 117 cases in the routine surgery group(76 males, 41 females, aged (55.1±8.2) years). To ensure comparability of baseline data between the APOT group and the routine surgery group, a 1∶2 match was performed using the propensity score matching method, and the caliper value was 0.006 45. The t-test,the Mann-Whitney U test, χ2 test or Fisher′s exact test were used to compare the data between the two groups,respectively. Results:After matching the propensity score,there were 28 cases in the APOT group and 56 cases in the routine surgery group. There were no significant differences in gender,age,preoperative comorbidities,preoperative body mass index,surgical approaches,chemotherapy regimen,stereotactic body radiation therapy ratio,tumor markers,and type of invaded artery between the two groups (all P>0.05).The arterial occlusion time M(IQR) in the APOT group was 7.0(3.8)minutes(range:3 to 15 minutes),and no ischemic manifestations were observed in the distal target organs that blocked blood vessels after surgery. The operation time was (170.3±57.7)minutes in the APOT group and (235.0±80.2)minutes in the routine surgery group,and the difference was statistically significant ( t=-3.800, P<0.01). The APOT group also experienced less intraoperative blood loss(650(588)ml vs. 800(600)ml; U=1 026.500, P=0.021). No significant differences were found between the groups in combined vein resection and reconstruction,celiac trunk resection,early postoperative complications, readmission rates at 30 days,and postoperative length of stay(all P>0.05). Extra-arterial dissection was performed in all patients,with arterial resection and reconstruction in 3 cases: 2 cases in the APOT group(1 case involving the superior mesenteric artery and 1 case involving the common hepatic artery) and 1 case in the routine group(involving the common hepatic artery). Postoperative abdominal bleeding occurred in 4 cases,with 3 cases in the routine group,1 case in the routine group. The R0 resection rate was 85.7%(24/28) in the APOT group and 80.4%(45/56) in the routine group,without significant differences between the groups( P=0.763). The median overall survival time was 27.6 months for the APOT group and 22.5 months for the routine group,while the median disease-free survival was 11.7 months and 16.8 months,respectively,with no significant differences between the two groups( P=0.532, P=0.927). Conclusion:The arterial pre-occlusion technique can be used for extra-arterial dissection in patients with locally advanced pancreatic cancer involving the arteries,reducing surgery time and intraoperative blood loss.

Objective:This study aimed to provide basic data for the prevention, diagnosis and treatment of pediatric viral myocarditis (VMC) in China through analyzing the epidemic characteristics and disease burden of pediatric inpatients with VMC from 2016 to 2021.Methods:We performed a descriptive statistical analysis to the age, genders, seasons, regions and hospitalization cost and days of pediatric VMC inpatients and the death. All of the information was obtained from 27 Children′s hospitals or Maternal and Child Health hospitals of 23 provinces of China from 2016 to 2021.Results:A total of 7 647 599 cases including 1 646 VMC inpatients were admitted into our study. The annual numbers of hospitalizations were 173, 227, 313, 301, 295 and 337, with the hospitalized constituent ratios being 14.9/100 000, 17.9/100 000, 23.0/100 000, 20.5/100 000, 26.5/100 000 and 26.4/100 000 from 2016 to 2021. In recent 6 years, the proportion of VMC hospitalizations had increased yearly ( P<0.001), and had associated with the onset age ( P<0.001). Aged 12-≤18 years owned the highest hospitalized constituent ratio. The Northeast of China owned the largest number of VMC inpatients, and the East second to it. Among the 1 646 VMC children, there were 68 deaths, with the hospitalized case fatality rate of 4.13%. There were no significant differences between genders, age, seasons, years and fatality rate of VMC inpatients. For the diseases burden, the median of hospitalization days of all VMC inpatients was 10 days (IQR 6, 21), and the median of hospitalization cost was 1 1 842.3 RMB (IQR 6 969.22, 19 714.78). The median of hospitalization days of deceased VMC children was only 1 day (IQR 1, 3), the median cost could be 8 874.03 RMB (IQR 5 277.94, 5 6 151.59). Conclusions:In this study, we found that proportion of hospitalization of VMC children increased year by year, adolescence might be a risk factor of VMC. The fatality of VMC inpatients could be up to 4.13%, and the death led to a huge economic burden of society, family and individuals.