Background/Aims: Acetyl coenzyme A (acetyl-CoA) is one of the most essential metabolites in cell metabolism but its function and concentration in hepatocellular carcinoma (HCC) remain elusive and controversial. Methods: A comprehensive analysis of acetyl-CoA levels and acetyl-CoA synthetase 2 (ACSS2) expression across a range of samples, including patient specimens from both hepatitis B virus (HBV) positive and HBV negative HCC individuals, HBV-transgenic mouse HCC models, and multiple cell lines. Furthermore, to evaluate the functional significance of ACSS2 in HBV-related HCC, we implemented both genetic and pharmacological inhibition strategies targeting ACSS2. Molecular mechanism and mitophagy assessment were revealed by cleavage under target and tagmentation sequencing, RNA sequencing, bioinformatic analyses, transmission electron microscopy and JC-1 staining. Results: Our study revealed a distinct metabolic signature of HBV-related HCC, marked by elevated acetyl-CoA, which was driven by ACSS2. ACSS2 was upregulated by the carbohydrate response element-binding protein in HBV-related HCC. Furthermore, ACSS2 improved tumor cell proliferation, an effect that was dependent on its enzymatic activity. Mechanistically, ACSS2-induced acetyl-CoA accumulation activated voltage-dependent anion channels 1 transcription through increased H3K27ac occupancy, which subsequently promoted mitophagy and HBV-related HCC tumorigenesis. Notably, targeting ACSS2 by depletion or inhibition with a catalytic inhibitor significantly suppressed tumor growth. Conclusions These findings not only illustrate the interplay between metabolic reprogramming, epigenetic modification, and tumorigenesis in the context of HBV infection, but also highlight ACSS2 as a novel metabolic vulnerability in HBV-related HCC. Therefore, targeting ACSS2 could be a novel strategy against HBV-related HCC.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Objective To explore the outcome of improved percutaneous kyphoplasty(IPKP)for the treatment of thoracolumbar osteoporotic vertebral compression fracture(OVCF),and analyze the risk factors of postoperative bone cement leakage.Methods A total of 115 patients with thoracolumbar OVCF admitted to our hospital from March 2020 to March 2022 were included and divided into the IPKP group(n=64)and the percutaneous kyphoplasty(PKP)group(n=51)according to different surgical methods.The surgery related condition and postoperative complications of patients were recorded.The visual analogue scale(VAS)scores,Oswestry disability index(ODI)scores,anterior vertebral height,middle vertebral height and Cobb angle of patients before surgery and 3 months and 1 year after surgery were compared.The influencing factors of postoperative bone cement leakage were analyzed.Results The operation time of patients in the IPKP group was longer than that in the PKP group(P<0.05),while there was no statistically significant difference in the injected amount of bone cement during the operation between the two groups(P>0.05).The VAS and ODI scores of patients in the two groups decreased 3 months and 1 year after surgery compared with those before surgery(P<0.05),while there was no statistically significant difference in VAS or ODI scores after surgery between the two groups(P>0.05).Three months and 1 year after surgery the anterior and middle vertebral heights of patients in the IPKP and PKP groups increased and the Cobb angle decreased compared with those before surgery(P<0.05).One year after surgery,the anterior and middle vertebral heights in the IPKP group were significantly higher than those in the PKP group(P<0.05),and the Cobb angle was significantly smaller than that in the PKP group(P<0.05).Among the 115 patients with thoracolumbar OVCF,there was no complications such as infection,re-fracture,or vascular embolism occurred after surgery,and there were 13 cases with bone cement leakage,whose risk factor was incomplete endplate/posterior wall(P<0.05).Conclusion Compared with PKP,IPKP in the treatment of thoracolum-bar OVCF has better effect and better recovery of vertebral structure.Incomplete endplate/posterior wall can increase the risk of postopera-tive bone cement leakage,which requires reasonable and effective intervention measures.

Objective:To investigate the changes of cerebral blood flow before and after transfusion in neonates with anemia,and analyze the related influencing factors of neonatal middle cerebral artery blood flow.Methods:A total of 39 neonates with anemia who were hospitalized in the Department of Neonatology of Shaanxi Provincial People's Hospital from October 2021 to March 2023 and received blood transfusion treatment were selected.Basic data were collected.Transcranial Doppler ultrasound was used to collect peak systolic flow velocity(Vs),end-diastolic flow velocity(Vd)and vascular resistance index(RI)of left and right middle cerebral artery(MCA).To analyze the relationship between neonatal anemia and middle cerebral artery blood flow velocity.To explore the effects of anemia and blood transfusion on middle cerebral artery blood flow,and analyze the related factors of middle cerebral artery blood flow.Results:A total of 39 neonates were included in this study,and the Vs on both the left and right sides of the middle cerebral artery after transfusion was lower than that before transfusion[Vs on the left side after transfusion was(44.7±16.7)cm/s compared with that before transfusion(45.9±19.2)cm/s,Vs on the right side after transfusion:(49.2±18.4)cm/s Vs(52.4±25.1)cm/s before transfusion];The mean blood pressure,Vd and RI after transfusion were all higher than those before transfusion[mean pressure(after transfusion/before transfusion):(41.7±6.3)mmHg ratio(40.9±6.9)mmHg],[Vd after transfusion on the left side:(11.7±6.6)cm/s compared with that before transfusion(10.9±5.0)cm/s,Vd after transfusion on the right side:(10.5±4.0)cm/s compared with(9.6±5.5)cm/s],[left post-transfusion RI:(0.75±0.08)compared with pre-transfusion RI:(0.74±0.09),right post-transfusion RI:(0.77±0.08)compared with(0.70±0.86)before transfusion],but the difference was not statistically significant(P＞0.05);Through further correlation analysis,gestational age at birth,standard deviation of hemoglobin and normal value before and after transfusion,mean blood pressure,birth weight and blood flow of middle cerebral artery were respectively correlated,and it was found that gestational age was positively correlated with MCA Vd before transfusion,the standard deviation of hemoglobin before transfusion was negatively correlated with MCA on the left and right side,and the mean blood pressure was positively correlated with MCA blood flow.Birth weight was positively correlated with right side Vd of MCA after transfusion.Conclusion:Blood transfusion in anemic neonates can affect blood flow velocity in middle cerebral artery.The blood flow velocity of middle cerebral artery was correlated with gestational age,anemia degree,mean blood pressure and birth weight.

Aim To explore the therapeutic effects of resveratrol(Res)on hepatic inflammation and oxida-tive stress in rheumatoid arthritis(RA),and to eluci-date the relationship of the regulatory mechanism of the Nrf2/Keap1 signaling pathway in it.Methods A mouse model of arthritis was induced using chicken type Ⅱ collagen in combination with complete Freund's adjuvant,and Res was administered by tube feeding for treatment.Serum liver function indices and levels of hepatic inflammation and oxidative stress were detected in mice.An in vitro cellular model of hepatic inflam-mation and oxidative stress was established by treating mouse primary hepatocytes(MPHs)with TNF-α(5μg·L-1),cell proliferation inhibition was detected by CCK-8,and inflammation and oxidative stress-relat-ed indices were detected by protein blotting.The in-trinsic mechanisms by which Res attenuated hepatic in-flammation and oxidative stress in rheumatoid arthritis were explored by treating MPHs with Nrf2 inhibitor and Keap1 overexpression plasmid.Results Res signifi-cantly reduced the levels of inflammation and oxidative stress in hepatic tissues of collagen-induced arthritis mice as well as TNF-α-treated MPHs,and activated the Nrf2/Keap1 signaling pathway.Inflammation and oxidative stress levels in MPHs were exacerbated by the use of Nrf2 inhibitors and Keap1 overexpression,which promoted apoptosis.Conclusion Res attenuates he-patic inflammation and oxidative stress in rheumatoid arthritis via the Nrf2/Keap1 pathway.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective:To explore the predictive value of electrocardiogram repolarization related parameters combined with serum brain natriuretic peptide(BNP)and 25 hydroxyvitamin D3[25-(OH)-D3]for malignant arrhythmia(MA)after percutaneous coronary intervention(PCI)in patients with acute myocardial infarction.Methods:This study was a prospective single-center study,120 patients with acute myocardial infarction who underwent PCI in our hospital from June 2022 to June 2024 were selected,they were divided into combined group(n=25)and non combined group(n=95)based on whether MA occurred within 72 h after PCI.All patients underwent routine electrocardiogram examination,the mean R wave to R wave(RR)interval,QRS start to T end(QT)interval,T wave time,corrected QT(QTc)interval,T wave peak to T wave end(Tp-e)interval,T wave amplitude,and other electrocardiogram repolarization related parameters between two groups were measuredand compared.The serum BNP and 25-(OH)-D3 levels between two groups were detected and compared.Influencing factors were analyzed by single and multiple logistic regression analysis.Predict value was analyzed by receiver operating characteristic(ROC)curve.Results:The mean QT interval and QTc interval in the combined group were significantly lower than those in the non combined group(P＜0.05).The serum BNP levels in the combined group was significantly higher than that in the non combined group,and the serum 25-(OH)-D3 level was significantly lower than that in the non combined group(both P＜0.05).Univariate analysis showed that there were statistically significant differences in terms of age,number of vascular lesions,cardiac troponin I(cTnI),and creatine kinase MB(CK-MB)(P＜0.05).Multiple logistic regression analysis showed that serum CK-MB and BNP were independent risk factors for MA after PCI in patients with acute myocardial infarction,while mean QT interval,mean QTc interval,and elevated 25-(OH)-D3 were independent protective factors(P＜0.05).Draw ROC curves,and the results show that the mean QT interval,mean QTc interval,serum BNP,and 25-(OH)-D3 levels alone predict the area under curve(AUC)for postoperative MA after PCI was 0.762(0.706-0.817),0.822(0.772-0.871),0.809(0.757-0.862),and 0.709(0.642-0.775),respectively,the AUC for combined prediction was 0.882(0.843-0.920).Conclusion:Electrocardiogram repolarization related parameters such as mean QT interval and QTc interval for MA after PCI in patients with acute myocardial infarction were lower,serum BNP is increased,and 25-(OH)-D3 is decreased,the combined detection of these indicators has high predictive value for postoperative MA after PCI.

Objective:To investigate the correlation of epithelial lesions among different biopsy sites in the female lower genital tract and the relationship between age and lesion distribution.Methods:A total of 406 148 patients with cervical biopsy specimens archived at the Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University from January 2010 to December 2021 were analyzed. Among them, 70 309 cases (17.31%) had concurrent vaginal biopsies, and 16 073 cases (3.96%) had concurrent vulvar biopsies. (1) Cases were divided into four 3-year intervals to compare vaginal or vulvar biopsy rates and high-grade squamous intraepithelial lesion (HSIL) or worse (HSIL +) detection rates across time periods. (2) Correlations between cervical lesions and vaginal or vulvar lesions were assessed. (3) Patients were stratified into three age groups (<30, 30-49, and ≥50 years) to compare vaginal or vulvar HSIL + detection rates. Results:Mean ages of patients with cervical, vaginal, and vulvar biopsies were (41.3±11.0), (47.4±12.5), and (41.9±13.2) years, respectively. Patients with vaginal biopsy were significantly older than cervical or vulvar groups (all P<0.001). (1) Vaginal biopsy rates increased markedly from 7.37% (2010—2012) to 22.76% (2019—2021; χ2=9 205.01, P<0.001); vulvar biopsy rates increased slightly from 2.80% to 5.69% ( χ2=1 777.25, P<0.001). Correspondingly, vaginal HSIL + detection rates rose from 0.28% to >0.5% (0.56% in 2013—2015, 0.59% in 2016—2018, 0.51% in 2019—2021; χ2=134.70, P<0.001), while vulvar HSIL + rates increased from 0.03% to 0.33% ( χ2=56.54, P<0.001). (2) Weak correlation existed between cervical and vaginal lesions ( r=0.28; P<0.001; n=70 309), while cervical-vulvar correlation was weaker ( r=0.22, P<0.001; n=16 073). (3) Vaginal HSIL + detection rates were higher in cervical HSIL + patients aged 30-49 years (26.65%) and ≥50 years (26.79%) versus <30 years (14.63%; both P<0.001). Conversely, vulvar HSIL + detection rates were higher in the <30 years group (23.08%) versus 30-49 years (13.83%) and ≥50 years (12.89%; both P<0.05). Conclusions:Vaginal or vulvar lesion detection rates increase with biopsy frequency. Vaginal lesions correlate with cervical abnormalities, whereas vulvar lesions are relatively independent. In cervical HSIL + patients, those <30 years are more prone to have vulvar HSIL +, while those ≥30 years show higher vaginal HSIL + incidence. These age-specific distribution patterns inform optimized biopsy strategies.

Objective To evaluate the efficacy and safety of transcatheter aortic valve implantation(TAVI)for the treatment of primary aortic valve regurgitation(NAVR)and to compare the difference in the choice of prosthetic valve size and the difference in complications with aortic stenosis(AS).Methods According to the definition of Valve Academic Research Consortium(VARC-3),143 patients with NAVR/AS treated with TAVI and patients with NAVR treated with surgical aortic valve replacement(SAVR)at Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,China,from March 2019 to September 2024 were selected,and clinical data on baseline,perioperative,and primary endpoint events were were retrospectively collected and compared.Results Forty-three patients with NAVR were treated with TAVI,with a device success rate of 86.0％and a surgical success rate of 95.3％.Subgroup comparisons:(1)NAVR-TAVI group than NAVR-SAVR group:patients in the TAVI group had a significantly shorter operative time than those in the SAVR group(P＜0.001);complete left bundle branch block was more likely to occur after TAVI(P=0.042),and complete right bundle branch block was more likely to occur after SAVR(P=0.044).SAVR postoperatively The incidence of congestive heart failure was higher(P=0.013),and the mortality rate was significantly higher in the SAVR group than in the TAVI group(P=0.019).(2)NAVR-TAVI group than AS-TAVI group:the differences in access selection,THV size[28(22,34)mm vs.24(22,32)mm,P=0.044]and proportion of THV overdiameter[14％(7％,20％)vs.7％(3％,11％),P＜0.001]were statistically significant.patients in AS and NAVR groups had 1 case of permanent pacing after TAVI treatment.In the AS and NAVR groups,there was 1 case of permanent pacemaker implantation after TAVI.2 patients in the AS group were converted to surgical treatment,and 6 patients died.Conclusions The use of"off-label"(transfemoral)and"on-label"(transapical)TAVI devices(both from domestic sources)is safer than SAVR for the treatment of NAVR,especially in elderly and high-risk patients.Compared with patients with AS treated with TAVI,larger diameter annulas are usually selected for NAVR,with higher rates of valve migration,but overall safety and efficacy are comparable to AS.

Aim To explore the therapeutic effects of resveratrol(Res)on hepatic inflammation and oxida-tive stress in rheumatoid arthritis(RA),and to eluci-date the relationship of the regulatory mechanism of the Nrf2/Keap1 signaling pathway in it.Methods A mouse model of arthritis was induced using chicken type Ⅱ collagen in combination with complete Freund's adjuvant,and Res was administered by tube feeding for treatment.Serum liver function indices and levels of hepatic inflammation and oxidative stress were detected in mice.An in vitro cellular model of hepatic inflam-mation and oxidative stress was established by treating mouse primary hepatocytes(MPHs)with TNF-α(5μg·L-1),cell proliferation inhibition was detected by CCK-8,and inflammation and oxidative stress-relat-ed indices were detected by protein blotting.The in-trinsic mechanisms by which Res attenuated hepatic in-flammation and oxidative stress in rheumatoid arthritis were explored by treating MPHs with Nrf2 inhibitor and Keap1 overexpression plasmid.Results Res signifi-cantly reduced the levels of inflammation and oxidative stress in hepatic tissues of collagen-induced arthritis mice as well as TNF-α-treated MPHs,and activated the Nrf2/Keap1 signaling pathway.Inflammation and oxidative stress levels in MPHs were exacerbated by the use of Nrf2 inhibitors and Keap1 overexpression,which promoted apoptosis.Conclusion Res attenuates he-patic inflammation and oxidative stress in rheumatoid arthritis via the Nrf2/Keap1 pathway.