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.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

Objective To evaluate the safety and efficacy of total arterial off-pump coronary artery bypass grafting (OPCABG) using a left internal thoracic artery (LITA) combined with bilateral radial arteries (RAs). Methods We retrospectively analyzed the clinical data of patients with severe multi-vessel coronary artery disease who underwent total arterial OPCABG with a LITA and bilateral RAs at Sichuan Provincial People’s Hospital from November 2020 to April 2023. Results A total of 24 patients were included, comprising 23 males and 1 female, with a mean age of (53.63±4.33) years. The New York Heart Association (NYHA) functional class was Ⅱ to Ⅲ. The mean number of distal anastomoses was 3.17±0.38. A Y-graft was constructed in 12 patients and sequential grafting was performed in 4 patients. Concomitant procedures included coronary endarterectomy in 1 patient, intra-aortic balloon pump (IABP) implantation in 10 patients, and thymoma resection in 1 patient. The mean operative time was (308.13±30.39) min, mechanical ventilation time was (15.42±7.42) h, ICU stay was (46.08±27.32) h, and postoperative hospital stay was (11.71±1.90) d. There were no in-hospital deaths. Postoperative complications included one patient of acute renal failure and one patient of cerebral infarction. Pre-discharge color Doppler echocardiography revealed that the left ventricular end-diastolic diameter was significantly smaller than before surgery (P<0.05), while the left ventricular ejection fraction and fractional shortening were significantly higher (P<0.05). Coronary computed tomography angiography (CTA) showed that all arterial grafts were patent. During a mean follow-up of (14.58±8.75) months, no patients experienced angina recurrence or mortality. Repeat coronary CTA or angiography in 16 patients one year postoperatively confirmed that all arterial grafts remained patent. Conclusion Total arterial OPCABG using a LITA and bilateral RAs is a safe and effective treatment for patients with severe multi-vessel coronary artery disease. For high-risk patients, intraoperative IABP support is recommended.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Objective To analyze the relationship between different degrees of cerebral venous sinus stenosis and the trans-stenotic pressure gradient using a 3D-printed hemodynamic simulation system for cerebral venous sinuses.Methods Based on the double elastic cavity model,a complete morphological model of the superior sagittal sinus,transverse sinus,and sigmoid sinuses was constructed using 3D printing technology.An in vitro hemodynamic simulation system incorporating pulsatile blood flow was established to simulate the hemodynamic environment of cerebral venous sinus stenosis.Using this system,both unilateral dominant drainage and bilateral balanced drainage were simulated.The degree of stenosis and the pressure upstream and downstream of the stenosis were measured.The pressure difference and pressure ratio were calculated to analyze the correlation between stenosis degree and the trans-stenotic pressure gradient.Results In the unilateral dominant drainage model,as the stenosis severity increased,the upstream pressure increased,whereas the downstream pressure remained relatively stable,leading to an increased pressure gradient between the two ends.The regression equation for stenosis degree(X)and pressure gradient(pressure difference ΔP)was:YΔP=1.962X-1.417(R=0.867,R2=0.753,P<0.001).In the bilateral balanced drainage model of cerebral venous sinuses,when the stenosis degree on one side of the model increased,the pressure gradient between the two ends changed slightly and eventually reached a stable state.The regression equation between X and ΔP was:YΔP=0.62X+1.047(R=0.98,R2=0.96,P<0.001).Conclusions Stenosis in cerebral venous sinuses with unilateral dominant drainage has a more significant impact on the pressure gradient,while unilateral stenosis in bilateral cerebral venous sinuses with balanced drainage has a smaller impact on the pressure gradient.This result suggests that for bilateral venous sinus stenosis,stent implantation can be prioritized in one side of the cerebral venous sinuses.

The inclusion complex of taxifolin(TAX)with hydroxypropyl-β-cyclodextrin(HP-β-CD)was prepared by saturated aqueous solution method,and the preparation conditions such as molar ratio,volume ratio of solution,inclusion temperature and inclusion time were selected by single-factor experiment.The orthogonal design of three-level four-factor L9(34)was used to screen the preparation process of the inclusion complex,and the inclusion complex was prepared with optimal preparation process.The prepared inclusion complex was characterized by scanning electron microscopy(SEM),nuclear magnetic resonance(1H NMR,2D NMR),Fourier transform infrared spectroscopy(FT-IR),ultraviolet-visible(UV-Vis)absorption spectroscopy and X-ray powder diffraction(XRD).The inclusion ratio,biostability,solubility and in vitro release of the inclusion complex were investigated.The results of orthogonal experiments showed that the optimum conditions for preparation of the inclusion complex were as follows:the molar ratio of TAX to HP-β-CD was 1:1,the volume ratio of methanol to ultra-pure water was 1:8,the inclusion time was 8 h,and the inclusion temperature was 30℃.Under the optimal conditions,the inclusion ratio between TAX and HP-β-CD was calculated to be 1:1 by Job's curve method.According to the change of UV-vis absorption spectra,the host-guest complexation constant of 4.9488×104 L/mol was obtained by Benesi-Hildebrand curve method.The solubility of TAX increased from 1.2665 mg/mL to 19.3469 mg/mL after inclusion,demonstrating that HP-β-CD could serve as an effective host molecule for TAX,which could significantly enhance the bio-stability and solubility of the formed inclusion complex.

ObjectiveTo investigate the feasibility and safety of endoscopic retrograde cholangiopancreatography （ERCP） combined with oral cholangiopancreatography in the treatment of major duodenal papilla gallbladder polyps. MethodsA retrospective analysis was performed for the clinical data of eight patients with choledocholithiasis and gallbladder polyps who underwent ERCP and combined with oral cholangiopancreatography for major duodenal papilla cholecystectomy in Center of Digestive Endoscopy， Jilin People’s Hospital， from May 2022 to June 2024， and related data were collected， including the success rate of surgery， the technical success rate of gallbladder polyp removal， the superselective method of cystic duct， the time of operation， the time of gallbladder polyp removal， and surgical complications. ResultsBoth the success rate of surgery and the technical success rate of gallbladder polyp removal reached 100%， and of all eight patients， three patients used guide wire to enter the gallbladder under direct view， while five patients received oral cholangiopancreatography to directly enter the gallbladder. The time of operation was 51.88±12.34 minutes， and the time of gallbladder polyp removal was 23.13±10.94 minutes. The diameter of gallbladder polyp was 2‍ ‍—‍ ‍8 mm， and pathological examination showed inflammatory polyps in three patients， adenomatous polyps in one patient， and cholesterol polyps in four patients. There were no complications during or after surgery. The patients were followed up for 2‍ ‍—‍ ‍27 months after surgery， and no recurrence of gallbladder polyp was observed. ConclusionOral cholangiopancreatography is technically safe and feasible in endoscopic major duodenal papilla cholecystectomy.

Objective To evaluate the efficacy and safety of a novel intravascular lithotripsy(IVL)balloon—Vesscrack shockwave balloon—for vascular preparation before stent implantation in patients with severe coronary artery calcification(CAC).Methods This was a prospective,single-arm,multicenter study conducted in China from June 2022 to October 2022.Patients with severe CAC were treated with the Vesscrack shockwave balloon for lesion preparation,followed by drug-eluting stent(DES)implantation.Of these,33 patients underwent optical coherence tomography(OCT).The primary endpoint was procedural success,defined as successful stent implantation with residual stenosis≤30％and the absence of in-hospital major adverse events,including cardiac death,target vessel-related myocardial infarction,or target lesion revascularization.Results A total of 170 patients[mean age:(65.9±7.9)years,116 males]were enrolled.After treatment with IVL and DES,the minimum lumen diameter increased significantly compared to baseline[(2.34±0.40)mm vs.(0.95±0.33)mm,P＜0.001],the degree of stenosis was significantly reduced[(13.24±6.60)％vs.(65.18±10.59)％,P＜0.001].Procedural success was achieved in 100％of cases,and device success was 98.8％.The 30-day patient-related cardiovascular clinical composite endpoint(POCE)rate was 0.0,with no target lesion failure,no confirmed or potential thrombotic events were observed.The shockwave energy generator demonstrated excellent stability and ease of use.Among the 33 patients assessed with OCT,after IVL intervention,the maximum calcified area of the lumen[(3.51±1.51)mm2 vs.(2.85±1.80)mm2,P＜0.001],and the minimum lumen area within the target lesion[(3.08±1.04)mm2 vs.(2.02±0.75)mm2,P＜0.001],and after DES intervention,the luminal area of the largest calcified site[(6.59±1.64)mm2 vs.(2.85±1.80)mm2,P＜0.001]and the minimum luminal area within the target lesion[(6.19±1.45)mm2 vs.(2.02±0.75)mm2,P＜0.001]were significantly increased,and the differences were statistically significant.Conclusions The Vesscrack shockwave balloon is effective and safe for vascular preparation in patients with severe CAC prior to stent implantation.It achieves significant calcified plaque modification,high procedural success rates,and minimal complications.

Objective To explore the long-term efficacy of percutaneous pulmonary valve implantation(PPVI)and the durability of the domestic self-expanding Venus P valve.Methods A total of 8 patients with post-surgical right ventricular outflow tract(RVOT)dysfunction,who were admitted to hospital from October 2014 to July 2016 and deemed anatomically suitable for PPVI with self-expanding valve,were included prospectively.Clinical,imaging,procedural and follow-up data were analyzed.The survival rates,perioperative and long-term complication rates,long-term efficacy of PPVI,and long-term function of Venus P in 8 patients were evaluated.The immediate procedural results were evaluated by clinical implant success rate,which is defined as successful valve implantation with echocardiography-assessed pulmonary regurgitation＜moderate and peak trans-pulmonary pressure gradient＜40 mmHg.Results A total of 8 patients were included,with 7 females,aged 14 to 36 years.The initial diagnosis included post-surgical Tetralogy of Fallot(5 cases),post-surgical Trilogy of Fallot(1 case),post-surgical Quadricuspid pulmonary valve stenosis(1 case)and post-surgical Double-Outlet Right Ventricle(1 case).The indications of PPVI included RVOT-pulmonary obstruction and regurgitation(1 case)and isolated regurgitation(7 cases).Clinical implant success was achieved in all of the 8 patients with firmly fixed valve,and there were no such complications as valve detachment,displacement or stent fracture.All patients experienced significant symptom relief after the procedure.The right ventricular end-diastolic volume index(RVEDVi)measured by CMR 6 months after PPVI showed a significant decrease compared to preprocedural values[(89.99±13.85)ml/m2 vs.(144.93±11.28)ml/m2,P=0.001].Postoperative pulmonary regurgitation were significantly improved or disappeared in all patients,and there was no statistically significant difference in the average peak pressure gradient measured by echocardiogram between preoperative and the latest follow-up[(23.25±8.39)mmHg vs.(18.75±6.28)mmHg,P=0.210].Over an average follow-up period of(9.25±0.71)years,1 case of infective endocarditis occurred 5 years after PPVI.During the follow-up,no death,deterioration of heart failure,malignant arrhythmia or other serious complications were observed.All patients completed 8-year follow-up,and 3 completed 10-year follow-up.All patients were graded as NYHA functional class one at the latest follow-up.Conclusions PPVI using the domestically produced self-expanding Venus P is safe and feasible for the treatment of patients with post-surgical RVOT dysfunction and suitable anatomy.Our study confirms the long-term efficacy and durability of Venus P from multiple perspectives,and no severe stent fracture occurred without pre-stent implantation in the native RVOT.

We propose a strategy to reduce unnecessary prostate biopsies in Chinese patients with total prostate-specific antigen (tPSA) >10 ng ml -1 and Prostate Imaging Reporting and Data System (PI-RADS) scores between 1 and 3. Clinical data derived from 517 patients of The First Affiliated Hospital of USTC (Hefei, China) from January 2020 to December 2023 who met the screening criteria for the study were retrospectively collected. Independent predictors were identified via univariate and multivariate logistic regression analysis. The diagnostic capacity of clinical variables was evaluated using the receiver operating characteristic (ROC) curves and area under the curve (AUC). A prostate biopsy strategy was developed via risk stratification. Of the 517 patients, 17/348 (4.9%) with PI-RADS 1-2 were diagnosed with clinically significant prostate cancer (csPCa), and 27/169 (16.0%) patients with PI-RADS 3 were diagnosed with csPCa. The appropriate prostate-specific antigen density (PSAD) cut-off values were 0.45 ng ml -2 for PI-RADS 1-2 patients and 0.3 ng ml -2 for PI-RADS 3 patients. The appropriate prostate volume (PV) cut-off values were 40 ml for PI-RADS 1-2 patients and 50 ml for PI-RADS 3 patients. The prostate biopsy strategy based on PSAD and PV developed in this study can reduce unnecessary prostate biopsies in patients with tPSA >10 ng ml -1 and PI-RADS 1-3. In the study, 66.5% (344/517) patients did not need to undergo prostate biopsy, at the expense of missing only 1.7% (6/344) patients with csPCa.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Prostate-Specific Antigen/blood* ; Aged ; Middle Aged ; Retrospective Studies ; Prostate/diagnostic imaging* ; Unnecessary Procedures/statistics & numerical data* ; Biopsy/statistics & numerical data* ; China ; ROC Curve