ObjectiveTo investigate whether Shenmai injection （SMI） improves cisplatin resistance in non-small cell lung cancer （NSCLC） by modulating lipid metabolism and inducing ferroptosis. MethodsHuman lung adenocarcinoma cisplatin-resistant A549/DDP cells were divided into the following groups： Blank group， cisplatin group （23.3 μmol·L^-1 cisplatin）， SMI group （20 g·L^-1 SMI）， cisplatin combined with SMI group （23.3 μmol·L^-1 cisplatin + 20 g·L^-1 SMI）， cisplatin combined with ferroptosis inhibitor/inducer Ferrostatin-1/Erastin group （23.3 μmol·L^-1 cisplatin + 10 μmol·L^-1 Ferrostatin-1/5 μmol·L^-1 Erastin）， and cisplatin combined with SMI and Ferrostatin-1/Erastin group （23.3 μmol·L^-1 cisplatin + 20 g·L^-1 SMI + 10 μmol·L^-1 Ferrostatin-1/5 μmol·L^-1 Erastin）. Network pharmacology， transcriptomics and metabolomics， Cell Counting Kit-8 （CCK-8） assay， transmission electron microscopy （TEM）， colorimetric assays， and Western blot analysis were employed to evaluate the effects of these treatments on A549/DDP cell viability， lipid droplet formation， lipid metabolite levels， mitochondrial function， lipid peroxidation， glutathione （GSH） content， total and ferrous iron content， and effects on ferroptiosis and autophagy related protein expression levels. ResultsSMI improved cisplatin resistance in NSCLC mainly by targeting lipid metabolism-related pathways in A549/DDP cells， affecting tumor cell lipid metabolism via autophagy， ferroptosis， and glycerophospholipid metabolism pathways. Compared with the cisplatin group， the cisplatin combined with SMI group showed significantly decreased cell viability （P<0.01）， increased lipid droplet accumulation （P<0.01）， and reduced mitochondrial maximal respiration， basal respiration， mitochondrial membrane potential， GSH content， total iron， and ferrous iron （all P<0.01）. Mitochondrial reactive oxygen species （ROS） was significantly elevated（P<0.01）， and lipid peroxidation levels were significantly increased. Protein expression analysis showed significant downregulation of solute carrier family 7 member 11 （SLC7A11） and p62 （P<0.05，P<0.01） and upregulation of ferritin heavy chain （FTH） and microtubule-associated protein 1 light chain 3Ⅱ （LC3Ⅱ） （P<0.05，P<0.01）. Compared with the cisplatin combined with SMI group， addition of Ferrostatin-1 significantly increased cell viability （P<0.05）， decreased mitochondrial ROS levels （P<0.05）， alleviated mitochondrial shrinkage， and reduced lipid peroxidation. Conversely， addition of Erastin further decreased cell viability （P<0.01）. ConclusionSMI improves cisplatin resistance in NSCLC by inducing oxidative stress， which may trigger ferroptosis through upregulation of lipophagy.

ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

[Objective] To investigate the infection and characteristics of hepatitis E virus among blood donors in Hangzhou. [Methods] A total of 5 075 blood samples of blood donors from Zhejiang Provincial Blood Center from September to November 2023 were collected, including 5 037 samples with normal ALT and 38 samples with elevated ALT (>50 U/L). Enzyme-linked immunosorbent assay (ELISA) was used to detect anti-HEV IgM, anti-HEV IgG and HEV-Ag. The Fisher test and Chi-square test were used to evaluate the difference in the reactivity rates of anti-HEV IgM and anti-HEV IgG among different levels of ALT. The distribution characteristics of HEV screening in blood donors were analyzed. Univariate and multivariate logistic regression were used to analyze the susceptibility factors of anti-HEV IgM and anti-HEV IgG seropositivity, and the anti-HEV IgM-reactive blood donors were followed up by telephone. [Results] The reactivity rates of anti-HEV IgM, anti-HEV IgG and HEV-Ag in 5 075 blood samples were 0.45%, 22.98% and 0%, respectively. There was no difference in the reactivity rates of anti-HEV IgM and anti-HEV IgG among different levels of ALT (P>0.05), and the results of univariate and multivariate logistic regression analysis showed that age was a risk factor for anti-HEV IgM and anti-HEV IgG reactivity in blood donors (P<0.05), while no difference in the reactivity rates of anti-HEV IgM and anti-HEV IgG among blood donors was noticed in gender, occupation and education level (P>0.05). [Conclusion] There is a potential risk of transfusion-transmitted HEV (TT-HEV) in Hangzhou, and a cost-effective HEV screening strategy needs to be established to continue regular HEV surveillance in Hangzhou to assess the risk of infection.

Objective　To investigate the association between neutrophil-to-lymphocyte ratio (NLR) and the state of sustained immune response after hepatitis B vaccination, to explore the possibility to predict the effect of hepatitis B vaccination.Methods　Data were analysed from 10 153 individuals aged 18 years and older who had received three doses of hepatitis B vaccine and met the inclusion criteria in the National Health and Nutrition Examination Survey (NHANES) 1999-2018. They were divided into seropositive and seronegative groups based on the results of post-vaccination hepatitis B marker testing. The association between NLR and sustained immune response status after hepatitis B vaccination was assessed using a variety of methods, including multivariate weighted logistic regression models, generalised linear analysis, and smoothed curve fitting.Results　This study included 10 153 subjects with a mean age of 35.36 years, 42.82% male and 57.18% female. Adjusted multivariate weighted logistic regression models showed that for each unit increase in NLR level, the odds of a sustained immune response after hepatitis B vaccination decreased by 7% (OR=0.93, 95%CI: 0.88-0.97). Stratified analysis of NLR levels showed that the odds of a sustained immune response were 37% lower in the group with the highest NLR levels (T4) compared with the lowest group (T1) (OR=0.63, 95%CI: 0.47-0.85), and the odds of a sustained immune response were 30% lower in the T3 group compared with the T1 group (OR=0.70, 95%CI: 0.53-0.91). Restricted cubic spline analysis showed a non-linear relationship between NLR and sustained immune response status after hepatitis B vaccination (P non-linear<0.05), approximating an 'L' curve. Inflection point analysis showed that when NLR <2.16, elevated NLR significantly reduced the occurrence of sustained immune response status after hepatitis B vaccination; when NLR >2.16, the effect of its elevation on the production of sustained immune response after vaccination leveled off.Conclusion　NLR levels were negatively associated with the development of a sustained immune response after hepatitis B vaccination. Lower NLR levels have a strong positive correlation with sustained immune response after hepatitis B vaccination, whereas higher NLR levels may attenuate the effect of hepatitis B vaccination.

BACKGROUND: Cluster of differentiation 8 positive (CD8 + ) T cells play a crucial role in the response against tumors, including hepatocellular carcinoma (HCC), where their dysfunction is commonly observed. While the association between elevated peroxisome proliferator-activated receptor alpha (PPARα) expression in HCC cells and exosomes and unfavorable prognosis in HCC patients is well-established, the underlying biological mechanisms by which PPARα induces CD8 + T cell exhaustion mediated by HCC exosomes remain poorly understood. METHODS: Bioinformatics analyses and dual-luciferase reporter assays were used to investigate the regulation of microRNA-27b-3p ( miR-27b-3p ) and thymocyte selection-associated high mobility group box ( Tox ) by Pparα . In vitro and in vivo experiments were conducted to validate the effects of HCC-derived exosomes, miR-27b-3p overexpression, and Pparα on T cell function. Exosome characterization was confirmed using transmission electron microscopy, Western blotting, and particle size analysis. Exosome tracing was performed using small animal in vivo imaging and confocal microscopy. The expression levels of miR-27b-3p , Pparα , and T cell exhaustion-related molecules ( Tox , Havcr2 , and Pdcd1 ) were detected using quantitative reverse transcription polymerase chain reaction analysis, Western blotting analysis, immunofluorescence staining, and flow cytometry analysis. RESULTS: Pparα expression was significantly increased in HCC and negatively correlated with prognosis. It showed a positive correlation with Tox and a negative correlation with miR-27b-3p . The overexpressed Pparα from HCC cells was delivered to CD8 + T cells via exosomes, which absorbed miR-27b-3p both in vitro and in vivo , acting as "miRNA sponges". Further experiments demonstrated that Pparα can inhibit the negative regulation of Tox mediated by miR-27b-3p through binding to its 3'untranslated regions. CONCLUSIONS HCC-derived exosomes deliver Pparα to T cells and promote CD8 + T cell exhaustion and malignant progression of HCC via the miR-27b-3p /TOX regulatory axis. The mechanisms underlying T-cell exhaustion in HCC can be utilized for the advancement of anticancer therapies.
MicroRNAs/metabolism* ; PPAR alpha/genetics* ; Carcinoma, Hepatocellular/genetics* ; Humans ; Liver Neoplasms/genetics* ; CD8-Positive T-Lymphocytes/immunology* ; Exosomes/metabolism* ; Animals ; Cell Line, Tumor ; Mice ; High Mobility Group Proteins/genetics* ; Male ; T-Cell Exhaustion

Affiliated Hospital of Jiangnan University has always adhered to the public welfare orientation,with the starting point of three fusion three innovation,guided by the high-quality development strategy led by party building,strengthened top-level design,solidly implemented grassroots party building quality and efficiency improvement actions based on branch fortresses,deepened the standardization and standardization construction of party branches,adhered to the deep integration of party building business,explored the key path of the affiliated hospital's characteristics,continuously improved the level of refined management,and met the people's medical needs in all aspects,It has conducted effective exploration and practice.

Objective:To explore the surgical technique and results of three-dimensional aortic valve anatomic repair for bicuspid aortic valve (BAV) with aortic regurgitation (AR).Methods:This is a retrospective case series study. From August 2021 to December 2023, 130 consecutive patients with BAV-AR underwent aortic valve anatomic repair at the Department of Cardiothoracic Surgery, Zhongshan Hospital, Fudan University,and the data were retrospectively analyzed. There were 115 males and 15 females, aged (38.6±11.7) years (range: 15 to 67 years). All patients received modified aortic root reconstruction, to do three-dimensional root remodeling, including the basal ring, sinus of Valsalva and sino-tubular junction simultaneously. Perioperative and follow-up data were collected and analyzed. Comparisons between groups were performed using independent samples t-test, Wilcoxon paired signed-rank test, or χ2 test. Results:No patient transferred to valve replacement during the operation. The cardiopulmonary bypass time ( M(IQR)) was 109(34) minutes (range:67 to 247 minutes), and the aortic cross-clamp time was 76(26) minutes (range: 32 to 158 minutes). Preoperative transesophageal echocardiography showed 123 patients (94.6%) presented with moderate or severe regurgitation. Immediately postoperative transesophageal echocardiography showed no regurgitation in 22 patients (16.9%), trace regurgitation in 81 patients (62.3%) and mild regurgitation in 27 patients (20.8%). Follow up was completed in all patients, with a follow-up of 5.5(9.4) months (range: 0.1 to 27.6 months). No mortality was observed during follow-up. Echocardiography was obtained in 112 patients at the latest follow-up, including no regurgitation in 4 patients (3.6%), trace regurgitation in 58 patients (51.8%), mild regurgitation in 45 patients (40.2%), moderate regurgitation in 4 patients (3.6%), and severe regurgitation in 1 patient (0.9%). Conclusion:For patients with BAV-AR who have good valve quality and no severe aortic sinus dilation, the recent outcomes of three-dimensional anatomical repair technique, focusing on overall remodeling of the aortic root, are satisfactory.

Objectives:To investigate long-term clinical outcomes of renal denervation(RDN)for the treatment of resistant hypertension. Methods:This study retrospectively enrolled 58 patients with resistant hypertension who received RDN treatment via femoral artery approach at Fuwai Hospital between February 2012 and November 2019.Follow up was performed at 1,3,6 months,1 year,and annually after RDN,and the last follow-up was June 2023.The baseline data and postoperative follow-up data including office blood pressure,24-hour mean blood pressure and heart rate,types and load of antihypertensive drugs,renal function,and major adverse events(including renal artery stenosis,acute myocardial infarction,stroke,cardiovascular death,and all-cause death)were obtained and analyzed.The impact of RDN on 10-year cardiovascular and cerebrovascular events was evaluated using the Framingham risk assessment model and the Chinese model. Results:A total of 58 patients were enrolled,with 1 patient(1.72%)died from lung cancer.Forty-one patients(70.69%)were visited in the last follow-up and the average follow-up time was(10.21±1.75)years.Compared with baseline,the office systolic/diastolic blood pressure was decreased by(12.59±21.65)/(9.87±14.27)mmHg(P<0.01,1 mmHg=0.133 kPa),24-hour mean systolic/diastolic blood pressure reduced by(11.28±15.33)/(7.94±12.29)mmHg(P<0.01),24-hour mean heart rate reduced by(2.45±9.46)bpm(P>0.05),the types of antihypertensive drugs decreased by 1.17±2.25(P<0.01),the drug load reduced by 1.45±2.37(P<0.001),and the estimated glomerular filtration rate decreased by(6.83±18.37)ml/(min·1.73 m2)(P<0.05)at the last follow-up.The impact of RDN on 10-year cardiovascular events and stroke risk was as follows:Framingham risk assessment showed an absolute risk decrease of 14.25%and 2.12%,respectively,and decreased by 5.72%and 17.46%using the Chinese cardiovascular and cerebrovascular risk assessment. Conclusions:This study showed that RDN could significantly reduce blood pressure levels in patients with resistant hypertension in the long-term follow up,and was expected to further reduce cardiovascular and cerebrovascular risks.

Objective:To explore the surgical technique and results of three-dimensional aortic valve anatomic repair for bicuspid aortic valve (BAV) with aortic regurgitation (AR).Methods:This is a retrospective case series study. From August 2021 to December 2023, 130 consecutive patients with BAV-AR underwent aortic valve anatomic repair at the Department of Cardiothoracic Surgery, Zhongshan Hospital, Fudan University,and the data were retrospectively analyzed. There were 115 males and 15 females, aged (38.6±11.7) years (range: 15 to 67 years). All patients received modified aortic root reconstruction, to do three-dimensional root remodeling, including the basal ring, sinus of Valsalva and sino-tubular junction simultaneously. Perioperative and follow-up data were collected and analyzed. Comparisons between groups were performed using independent samples t-test, Wilcoxon paired signed-rank test, or χ2 test. Results:No patient transferred to valve replacement during the operation. The cardiopulmonary bypass time ( M(IQR)) was 109(34) minutes (range:67 to 247 minutes), and the aortic cross-clamp time was 76(26) minutes (range: 32 to 158 minutes). Preoperative transesophageal echocardiography showed 123 patients (94.6%) presented with moderate or severe regurgitation. Immediately postoperative transesophageal echocardiography showed no regurgitation in 22 patients (16.9%), trace regurgitation in 81 patients (62.3%) and mild regurgitation in 27 patients (20.8%). Follow up was completed in all patients, with a follow-up of 5.5(9.4) months (range: 0.1 to 27.6 months). No mortality was observed during follow-up. Echocardiography was obtained in 112 patients at the latest follow-up, including no regurgitation in 4 patients (3.6%), trace regurgitation in 58 patients (51.8%), mild regurgitation in 45 patients (40.2%), moderate regurgitation in 4 patients (3.6%), and severe regurgitation in 1 patient (0.9%). Conclusion:For patients with BAV-AR who have good valve quality and no severe aortic sinus dilation, the recent outcomes of three-dimensional anatomical repair technique, focusing on overall remodeling of the aortic root, are satisfactory.

In recent years, mRNA drugs have shown a great potential for the treatment of genetic diseases and attracted the attention of many researchers. This article has reviewed the advance in the research of mRNA drugs for the treatment of genetic diseases over the past 30 years, including their mechanisms of action and structure design, with a focus on their advantages as alternative therapies such as high specificity, low dosage, and sustained expression. Meanwhile, challenges for the effective delivery and storage methods for the mRNA drugs are discussed, with an aim to provide guidance for subsequent researches.