OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway.

ObjectiveTo investigate the mechanism by which Notoginsenoside R1 （NGR1） ameliorates hypoxia/reoxygenation （H/R）-induced injury in AC16 human cardiomyocyte cell lines through the regulation of mitophagy. MethodsCommon genes linked to hypoxia/reoxygenation injury and mitophagy were identified by intersecting data from GeneCards and MitoCarta databases. AC16 cell viability was assessed via CCK-8 assay under varying NGR1 concentrations （0， 6.25， 12.5， 25， 50， 100， 200， 300， 400， 500 μmol/L）. AC16 cells were divided into the following groups： control group （Control）， model group （H/R）， and treatment groups （H/R + NGR1 at 100， 200 and 300 μmol/L）. Mitochondrial membrane potential （ΔΨm） was measured using 5，5'，6，6'-tetrachloro-1，1'，3，3'-tetraethylbenzimidazolylcarbocyanine iodide （JC-1） staining. Transcriptional levels of mitophagy-related genes （Parkin， Pink1， P62） were quantified by reverse transcription-quantitative PCR （RT-qPCR）. Protein expression of mitophagy-related markers （Parkin， Pink1， P62， and LC3BⅡ） was evaluated via Western blot analysis. Mitochondrial ultrastructure was visualized by transmission electron microscopy （TEM）. ResultsCompared to the control group， cell viability in the H/R group significantly decreased （P<0.01）. Treatment with NGR1 at concentrations above 100 μmol/L significantly enhanced the cell viability of AC16 cells compared to the H/R group （P<0.01）. H/R induced a significant decrease in mitochondrial membrane potential （P<0.01）， which was restored by NGR1 treatment （P<0.01）. The mRNA levels of Parkin， Pink1， and P62 in the H/R group were upregulated compared to the control group （P<0.05）， while NGR1 intervention downregulated their expression （P<0.05）. Protein expression levels of Parkin， Pink1， and LC3BⅡ in the H/R group significantly increased， while P62 expression decreased compared to the control group （P<0.01）. In contrast， different doses of NGR1 treatment significantly reduced the expression of Parkin， Pink1， and LC3BⅡ while increasing P62 expression （P<0.05）. TEM revealed that the mitochondrial structure in the H/R group was severely disrupted， with fragmented and disorganized cristae， which was alleviated by NGR1. ConclusionNGR1 ameliorates H/R-induced AC16 cell injury， and its mechanism may be associated with modulating the Pink1/Parkin pathway to suppress excessive mitophagy.

ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.

Objective:To explore the current status of self-management behavior in patients with inflammatory bowel disease and to construct a structural equation model to explore the mediating role of health literacy between discharge readiness and self-management behavior.Methods:From March to September 2023, 310 hospitalized patients with inflammatory bowel disease in the Tenth People ′s Hospital Affiliated to Tongji University were selected as the research subjects by the convenience sampling method. A cross-sectional survey was conducted using the general information questionnaire, the Health Literacy Management Scale, the Discharge Readiness Scale, and the Self-management Behavior Scale. Results:Eventually, 303 valid questionnaires were retrieved. Among the 303 patients, there were 190 males and 113 females, with an average age of (35.63 ± 16.41) years old. The total score of health literacy of patients with inflammatory bowel disease was (94.35 ± 10.78) points, indicating a health literacy compliance rate of 74.3%(225/303). The total score of discharge readiness was (79.52 ± 9.16) points, and the total score of self-management behavior was (135.22 ± 17.36) points. In patients with inflammatory bowel disease, the discharge readiness was positively correlated with the total score of health literacy ( r=0.748, P<0.01), the discharge readiness was positively correlated with the total score of self-management behavior ( r=0.821, P< 0.01), and the health literacy was positively correlated with the total score of self-management behavior ( r=0.767, P<0.01). Health literacy may serve as a mediating variable, partially explaining the relationship between discharge readiness and self-management behavior in patients with inflammatory bowel disease. The mediating effect accounted for 47.5% of the total effect. Conclusions:Discharge readiness not only positively impacts self-management behavior among patients with inflammatory bowel disease but also indirectly influences this behavior through health literacy. It is essential for clinical healthcare professionals to prioritize the assessment of discharge readiness and health literacy among these patients. By improving discharge readiness and enhancing health literacy, clinical healthcare professionals can effectively support patients with inflammatory bowel disease in their self-management efforts.

Objective:To evaluate the cumulative live birth rate (CLBR) and cost-effectiveness of fixed versus adjusted follicle-stimulation hormone (FSH) dosages in infertile women with different ovarian responses during their first assisted reproductive technology (ART) cycle.Methods:A retrospective real-world cohort study was conducted on 5 419 infertile women who underwent their first ART treatment at the Department of Reproductive Medicine of the First Affiliated Hospital of Nanjing Medical University between January 2013 and December 2017. All patients received an individualized starting dosage of gonadotropin. Based on whether FSH dosages were adjusted during controlled ovarian stimulation (COS), patients were divided into fixed-dosage group ( n=2 061) and adjusted-dosage group ( n=3 358). Clinical outcomes and FSH cost-effectiveness were compared between the two groups across different ovarian response groups, with CLBR as the primary outcome. Propensity score matching (PSM) and multivariable logistic regression were used to adjust for potential confounders. Results:FSH dosage adjustments were found in 62.0% (3 358/5 419) of cycles during COS. After PSM, baseline characteristics were comparable between the two groups (all P>0.05). After adjusting for confounders using multivariable logistic regression, FSH dosage adjustment was not significantly associated with CLBR ( OR=1.06, 95% CI: 0.94-1.20, P=0.332). Compared with the adjusted-dosage group, the fixed-dosage group showed no significant differences in CLBR in poor-, normal-, and high-responder groups (all P>0.05). The incidence of ovarian hyperstimulation syndrome (OHSS) did not differ significantly between the two groups ( P>0.05). In poor-, normal-, and high-responder groups, the total FSH dosages in the fixed-dose group [1 350 (375, 1 825) U, 1 200 (375, 1 500) U and 525 (375, 1 128) U, respectively] were significantly lower than those in the adjusted-dose group [1 875 (1 425, 2 294) U, P=0.001; 1 425 (450, 1 875) U, P<0.001; 600 (375, 1 425) U, P=0.020]. Similarly, average FSH costs in different ovarian response groups in the fixed-dosage group [4 725.0 (1 312.5, 6 387.5) yuan, 4 200.0 (1 312.5, 5 250.0) yuan and 1 837.5 (1 312.5, 3 947.3) yuan, respectively] were significantly lower than those in the adjusted-dosage group [6 562.5 (4 987.5, 8 028.1) yuan, P=0.001; 4 987.5 (1 575.0, 6 562.5) yuan, P<0.001; 2 100.0 (1 312.5, 4 987.5) yuan, P=0.020]. For normal-responders, the FSH cost per high-quality embryo in the fixed-dosage group [1 365.0 (875.0, 2 537.5) yuan] was significantly lower than that in the adjusted-dosage group [2 056.3 (1 268.8, 3 412.5) yuan, P<0.001]. Conclusion:FSH dosage adjustment during COS is not associated with CLBR or the incidence of OHSS. However, the fixed-dose group exhibited lower total FSH dosages and costs across different ovarian response populations. In the context of ART being covered by medical insurance, fixed FSH dosage may represent a more cost-effective ovarian stimulation protocol.

Objective To investigate whether successful percutaneous coronary intervention(PCI)could improve symptoms and quality of life(QOL)in left main disease and/or 3-vessel disease patients with diabetes.Methods Patients with left main disease and/or 3-vessel disease who underwent PCI in the First Affiliated Hospital of Air Force Medical University from April 2018 to May 2021 were consecutively enrolled and subdivided into 2 groups:diabetes and no diabetes.Detailed baseline characteristics,symptoms,including dyspnea and angina,assessed with the Rose dyspnea scale(RDS),Seattle angina questionnaire(SAQ),the European quality of life-5 dimensions(EQ-5D)and 12-item short-form health survey(SF-12)questionnaire respectively,procedural details,and 1 month and 1 year follow-up data were collected.Results Among 440 left main disease and/or 3-vessel disease patients,disease was present in 176(40.00％),who had more hypertension,peripheral artery disease,and LCX lesion(all P＜0.05).The incidence of major adverse cardiovascular events(MACE)and all-cause mortality were similar between the two groups(both P＞0.05)at 1 month follow-up,while all-cause mortality in diabetes patients was significantly higher than those without diabetes at 1 year follow-up(P=0.013).Low left ventricular ejection fraction was an independent risk factor for MACE and all-cause mortality at 1 month and 1 year follow-up after successful revascularization(all P＜0.05).Most importantly,symptoms,including dyspnea and angina,and QOL were markedly improved regardless of diabetes both at 1 month and 1 year follow-up(all P＜0.05).Diabetes patients showed improved dyspnea and QOL at similar degree to the non-diabetes patients(all P＞0.05)and a more significantly relieved angina(P=0.013).Additionally,the number of chronic total occlusion(CTO)per patient was identified as an independent risk factor of dyspnea(OR 0.723,95％CI 0.525～0.997,P=0.048)and angina relief(OR 0.686,95％CI 0.473～0.995,P=0.047),and the contrast volume(OR 0.995,95％CI 0.992～0.999,P=0.008)as an independent risk factor of QOL improvement in diabetic patients.Conclusions Successful PCI is beneficial for relieving symptoms and improving quality of life in patients with diabetes who have left main disease and/or 3-vessel disease.

Background and purpose:The Shanghai Municipal Center for Disease Control and Prevention provides annual updates on cancer statistics in Shanghai.Breast cancer is one of the common malignant tumors among women.In recent years,the incidence of female breast cancer was increasing,while its trend of mortality showed declining.This study aimed to investigate the survival rates of new female breast cancer cases in Shanghai from 2002 to 2017.Methods:Data of new cases and deaths of female breast cancer patients with follow-up information from 2002 to 2017 were obtained from the Population-based Cancer Registry and Vital Statistics System of Shanghai Municipal Center for Disease Control and Prevention.Numbers,proportions,and survival rates were stratified by year of diagnosis,age,histological type and stage at diagnosis for analysis.The 5-year observed survival rates were calculated based on the life table method.The probabilities of surviving from 0 to 99 years were estimated with the Elandt-Johnson model,and then cumulative expected survival rates were calculated using the Ederer Ⅱ method.Finally,the 5-year relative survival rates were calculated.The annual percent change(APC)of survival rates was estimated by Joinpoint Regression Program.Results:A total of 73 600 new female breast cancer cases were diagnosed from 2002 to 2017 in Shanghai.Among them,67 681 cases were morphological verification,accounting for 91.96%.By December 31,2022,23 745(32.26%)cases had died,and 19 466(26.45%)cases had died of cancer.A total of 68 332(92.84%)cases,who were either dead or followed for over 5 years,were considered to have complete follow-up.The remaining 5 268(7.16%)cases were lost to follow-up.73 538(99.92%)cases were included in the observed cohort for survival analysis.The number of observed cases nearly doubled from 3330 in 2002 to 6095 in 2017.The 5-year observed survival rate changed from 78.77%in 2002 to 84.55%in 2017 dynamically,showed a low increasing trend with an average rate of 0.50%per year(APC=0.50%,t=8.75,P＜0.001).The 5-year relative survival rate also increased from 83.46%to 89.24%slowly,with an average rate of 0.47%(APC=0.47%,t=9.80,P＜0.001).The overall 5-year observation survival rate of female cancer was 83.24%(82.96%-83.52%),and the 5-year relative survival rate was 87.58%(87.29%-87.87%)in Shanghai from 2002 to 2017.It was increasing over time,decreasing with aging and advanced stage at diagnosis continuously.There was no significant difference in the 5-year relative survival rates between the groups aged 15 to 64(P＞0.05).The group with an unknown stage had the highest number of cases,followed by the stage Ⅱ group,and then the stage Ⅰ group.The 5-year relative survival rate of cases with stage Ⅰ disease reached 99.10%(98.78%-99.42%),but these cases only accounted for 25.51%of the total.The 5-year relative survival rate of cases with stage Ⅳ disease was 52.54%(50.98%-54.11%),and these cases accounted for 6.13%of the total.The 5-year relative survival rate of cases with s unknown stage was 82.04%(81.42%-82.65%),and these cases accounted for 31.05%of the total.Conclusion:The diagnostic levels and survival rates of female breast cancer in Shanghai were relatively high and continue to improve.However,the proportions of cases with unknown histological type and unknown stage remain relatively high,and the proportion of stage Ⅰ cases is not very large.The survival rates of stage Ⅳ cases are relatively low.This study provides evidence for further research,prevention and control efforts for female breast cancer.

AIM To investigate the effects of Xuesaitong Capsules(Panax notoginseng saponins)on ischemia/reperfusion injury in a mouse model of skin frostbite.METHODS The mice were randomly divided into the control group,the model group,the dexamethasone group(1 mg/kg),and the low-dose,medium-dose,and high-dose Xuesaitong Capsules groups(0.036,0.072,and 0.144 g/kg),with eight mice in each group.A frostbite model was established using a dry ice-cooled ceramic(ferrite)magnet.On the 2nd day after modeling,each group started its corresponding dosing by gavage for 14 consecutive days.The wound healing,histopathological changes,and serum levels of high-sensitivity C-reactive protein(hs-CRP),thromboxane B2(TXB2),6-keto-prostaglandin F1α(6-K-PGF1α),nitric oxide(NO)and endothelin(ET)were assessed using ELISA.The superoxide dismutase(SOD)activity and malondialdehyde(MDA)levels in skin tissues were measured biochemically.The protein expressions of tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6,Toll-like receptor(TLR)4 and phosphorylated nuclear factor-KB p65(p-NF-κB p65)in skin tissues were determined by Western blot.Additionally,LncRNA H19 mRNA expression in skin tissues was evaluated using RT-qPCR.RESULTS After the final administration,compared with the control group,the model group exhibited partial scab detachment,wound healing,and larger wound areas;hyperkeratosis with incomplete keratinization,detachment of the dermis and subcutaneous tissue,partial loss of appendages,subcutaneous edema,and dilated,congested,and hemorrhagic stromal vessels with extensive lymphocyte infiltration revealed by the histopathological examination;elevated serum levels of hs-CRP,TXB2,and ET(P＜0.05,P＜0.01);decreased 6-K-PGF1α and NO levels(P＜0.05,P＜0.01);reduced SOD activity in skin tissues(P＜0.01);increased MDA levels(P＜0.01);and upregulated protein expressions of TNF-α,IL-1β,IL-6,TLR4 and p-NF-κB p65,as well as LncRNA H19 mRNA expression(P＜0.05,P＜0.01).Compared with the model group,the group intervened with high-dose Xuesaitong Capsules displayed reduced wound areas(P＜0.01);decreased serum levels of hs-CRP,TXB2 and ET(P＜0.05,P＜0.01);increased 6-K-PGF1α and NO levels(P＜0.05,P＜0.01);enhanced SOD activity(P＜0.05,P＜0.01);reduced MDA level in skin tissues(P＜0.05,P＜0.01);and down-regulated TNF-α,IL-1β,IL-6,TLR4 and p-NF-κB p65 protein expressions and suppressed LncRNA H19 mRNA expression in skin tissues as well(P＜0.05,P＜0.01).CONCLUSION Xuesaitong Capsules alleviate ischemia/reperfusion injury in frostbite-injured mice by exerting anti-inflammatory and anti oxidative stress effects and restoring vascular endothelial function mediated by the downregulation of LncRNA H19 expression and inhibition of the TLR4/NF-κB signaling pathway.

Medical therapy and surgical intervention are the two primary approaches for treating myocardial bridge.However,there remains controversy regarding the use of coronary artery bypass grafting(CABG)and myocardial bridge unroofing.Here,we report a case of myocardial infarction following CABG in a patient with a myocardial bridge.The patient was admitted to Lanzhou First Peopie's Hospital with persistent chest pain,chest tightness,and shortness of breath lasting 2 hours.Physical examination revealed no significant abnormalities.Electrocardiography(ECG)indicated extensive anterior wall myocardial infarction.Laboratory findings showed myoglobin levels of 140.1 ng/ml and troponin Ⅰ levels of 2.59 ng/ml,with no other significant abnormalities.The initial diagnosis was acute extensive anterior wall myocardial infarction.Emergency coronary angiography revealed a myocardial bridge in the mid-segment of the left anterior descending artery(LAD).Emergency CABG using the left internal mammary artery to the LAD was performed,leading to symptomatic improvement,and the patient was discharged in stable condition.However,the patient experienced a recurrent myocardial infarction seven years post-surgery and received secondary preventive medical therapy.The patient is currently under ongoing follow-up care.CABG is an effective treatment for myocardial bridge.However,based on the case reported in this study,we recommend careful evaluation of whether a patient may benefit from CABG.