ObjectiveTo investigate the risk factors for bleeding within 5 days and 2 weeks after endoscopic variceal ligation （EVL） or endoscopic cyanoacrylate injection （ECI） for the treatment of esophagogastric varices in patients with liver cirrhosis， as well as the safety of EVL/ECI in patients with thrombocytopenia. MethodsA total of 489 patients with liver cirrhosis and esophagogastric varices who underwent EVL/ECI in Guangzhou Eighth People’s Hospital， Guangzhou Medical University， from January 2018 to December 2023 were enrolled as subjects， and according to the presence or absence of bleeding after surgery， they were divided into bleeding group and non-bleeding group. The risk factors for bleeding within 5 days and 2 weeks after surgery were analyzed. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between groups， and the chi-square test or the continuity-corrected chi-square test was used for comparison of categorical data between groups； the receiver operating characteristic （ROC） curve was plotted to determine the cut-off value of MELD score； a multivariate logistic regression analysis was used to identify the independent risk factors for postoperative bleeding. ResultsThere were no significant differences in the bleeding rates within 5 days and 2 weeks after EVL/ECI between the 386 patients with a platelet count of ≥50×10⁹/L and the 103 patients with a platelet count of （25 — 49）×10⁹/L （5 days： 1.94% vs 2.85%， P=0.870； 2 weeks： 2.91% vs 4.92%， P=0.544）. The overall bleeding rate was 2.66% （13/489） and 4.50% （22/489）， respectively， within 5 days and 2 weeks after EVL/ECI. The multivariate logistic regression analysis showed that MELD score was an independent risk factor for bleeding within 5 days （odds ratio ［OR］=3.726， 95% confidence interval ［CI］： 1.214 — 11.429， P=0.021） and 2 weeks （OR=5.760， 95%CI： 1.779 — 18.651， P=0.003） after EVL/ECI， while hemoglobin （Hb） was a protective factor against bleeding within 5 days （OR=0.972， 95%CI： 0.948 — 0.996， P=0.025） and 2 weeks （OR=0.976， 95%CI： 0.957 — 0.995， P=0.016） after surgery； portal vein tumor thrombus （OR=2.667， 95%CI： 1.000 — 7.117， P=0.050） was an independent risk factor for bleeding within 2 weeks after surgery， while platelet count ［（25 — 49）×10⁹/L］ was not a risk factor for postoperative bleeding （P>0.05）. ConclusionBoth EVL and ECI have good safety in patients with liver diseases and grade 3 thrombocytopenia. MELD score is an independent risk factor for bleeding within 5 days and 2 weeks after EVL/ECI， while Hb is a protective factor； portal vein tumor thrombus is an independent risk factor for bleeding within 2 weeks after surgery.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

Esophagogastric variceal bleeding is a common complication and the leading cause of death in advanced liver cirrhosis， and endoscopic variceal ligation （EVL） and endoscopic cyanoacrylate injection （ECI） are commonly used treatment strategies. Thrombocytopenia is one of the most common hematological complications in liver cirrhosis， and patients with severe thrombocytopenia have the potential risk of bleeding， which may affect treatment decision-making by clinicians and endoscopists. This article reviews the evolution of guidelines and clinical research advances regarding EVL/ECI in China and globally， in order to provide a basis for decision making among clinicians.

[Objective]To explore if the enhanced recovery after surgery (ERAS) protocol for pregnant women with gestational diabetes mellitus (GDM) who are undergoing elective cesarean delivery could cause perioperative glycemic abnormalities and heighten the risk of neonatal hypoglycemia.[Methods]A retrospective analysis was conducted on a cohort of pregnant women with singleton pregnancies who underwent elective cesarean sections and received ERAS between May 1,2022,and October 31,2023,at the Third Affiliated Hospital of Sun Yat-sen University. A total of 150 patients were included in this study,comprising the GDM group (n=75) and the non-GDM group (n=75). The study included pregnant women with good glycemic control (GDM) and maternal age (18-30 years;30-35 years;35-40 years;>40 years),BMI (<18.5 kg/m2;18.5-24.9 kg/m2;25-30 kg/m2;>30 kg/m2),and gestational age (within 7 days). We used these criteria to match 1∶1 non-GDM women as the control group. After administering preoperative oral carbohydrates,we observed the trends of maternal glycemic changes,including hyperglycemia and hypoglycemia,at any time of the day. We also evaluated the incidence of hypoglycemic low Apgar scores in newborns,abnormal pH values in blood gases,and the rate of transfer to the pediatric unit immediately after delivery.[Results]No significant difference was observed in fasting blood glucose levels on the day of surgery between the two groups of pregnant women[(4.4±0.5) mmol/L vs. (4.3±0.5) mmol/L,t=1.395,P=0.165]. The blood glucose peak was reached 30 minutes after consuming 300 mL (42.6 g of low-dose carbohydrate) of a light drink[(7.2±0.9) mmol/L vs. (6.4±0.8) mmol/L,t=5.773,P<0.001],with a subsequent decline in blood glucose levels. At the 120-minute mark,blood glucose had returned to the pre-oral carbohydrate level. The blood glucose levels in GDM groups was significantly higher than those in the non-GDM group (P<0.005). Although the incidence of hyperglycemia was significantly higher in the GDM group than in the non-GDM group at the 30-minute peak blood glucose level after oral carbohydrate intake,and the difference was statistically significant (17.3％ vs. 1.3％,x2=11.354,P<0.001),severe hyperglycemia (≥10 mmol/L) did not occur. The incidence of hypoglycemia was not significantly higher in neonates in the GDM group than in the non-GDM group (22.7％ vs. 28％,x2=0.564,P=0.453). The incidence of neonatal hypoglycemia in the GDM group was not significantly elevated in comparison to the non-GDM group after adjusting for age and BMI (Model 1),primiparity and gestational week of delivery (Model 2),hypertensive disorders of pregnancy (Model 3),cesarean section indications,time of cesarean section,and intraoperative hemorrhage (Model 4),and neonatal weight (Model 5).[Conclusion]In GDM patients with excellent glycemic control,an ERAS regimen with a low oral dose of carbohydrates prior to elective cesarean section does not increase the risk of preoperative serious hyperglycemia in mothers,nor does it increase the incidence of neonatal hypoglycemia.

Abstract: Objective　To investigate the impacts of vaccination with inactivated SARS-COV-2 vaccine on the clinical manifestations and serological responses of COVID-19 patients infected by Delta and Alpha variants. Methods　Clinical and experimental data of 341 confirmed SARS-COV-2 patients were collected from The Eighth Affiliated Hospital of Guangzhou Medical University May 1- September 30, 2021. The subjects were divided into Delta and Alpha variant group according to virus variants, and were divided into vaccinated group and unvaccinated group according to whether they had received inactivated COVID-19 vaccine or not. The clinical manifestations and serological responses of patients with Delta and Alpha variant, and vaccinated and unvaccinated patients with Delta and Alpha variants were compared. Results　Totally 253 patients were infected with Delta variant (103 vaccinated and 150 unvaccinated patients), and 88 patients were infected with Alpha variant (21 vaccinated and 67 unvaccinated patients). The proportion of asymptomatic infection in Delta variants group was significantly lower than that in Alpha variants group (P<0.01). Delta variant group of vaccination rates and vaccine breakthrough infection rate was 40.7% (103/253) and 22.9% (58/253), were higher than Alpha variant group was 23.9% (21/88) and 8.0% (7/88), difference was statistically significant (χ2= 8.009, 9.484, P<0.01). The proportion of cough and fever in Delta variant group was higher than that in Alpha variant group (both P<0.01), the peak viral load was higher than that of Alpha variant group (P<0.01), the virus duration was longer than that of Alpha variant group (P<0.01), the levels of SAA, CRP and IFN were higher than those of Alpha variant group (all P<0.05), CD4+T cell count was lower than that of Alpha variant group (P<0.05), IgG and IgM levels were lower than those of Alpha variant group (both P<0.01). The proportion of moderate COVID-19 in the vaccinated group was lower than that in the unvaccinated group (P<0.01). In these two variants, the peak viral load of vaccinated group was lower than that of the unvaccinated group (both P<0.01), the duration of virus was shorter than that of unvaccinated group (both P<0.01). The levels of SAA, CRP and IL-6 in the vaccinated group were lower than those in the unvaccinated group (all P<0.05), CD4+T cell level was higher than that of unvaccinated group (both P<0.05), IgG and IgM level were higher than those in unvaccinated group (both P<0.05). Conclusions　Delta variant can lead to higher viral load and more severe disease course, which is associated with vaccine breakthrough infection. Inactivated vaccines for COVID-19 can reduce severe illness and death by reducing viral load, disease duration and inflammatory response through humoral and cellular immune mechanisms.

OBJECTIVE: To evaluate the the effect and prognosis of transcatheter device closure for perimembranous ventricular septal defects(PmVSDs)with aortic valve prolapse(AVP). METHODS: The clinical data of 1108 patients who underwent percutaneous closure from January 2011 to January 2017 were collected to conduct this retrospective study,mainly including transthoracic echocardiography,digital subtraction angiography data,occluder type and sociodemographic information(age,weight and gender). T-test and Mann-Whitney U test were used to compare group measurement data. Wilcoxon signed rank test was used for the nonnormal distribution of paired design data. Fisher exact test was used for the four fold table. Monte Carlo approximation exact probability method was used for the R×C table.Multiple Logistic-regression analysis was used to estimate the risk factors of AR. RESULTS: Compared with 10(0.9%)of1053 patients without AVP,8(14.5%)of the 55 children with preoperative AVP presented aggravated postoperative aortic regulation(AR)and AR usually occurred in the long-term follow-up(>1 year). None of the AR progressed to moderate or severe. There were no significant changes in left ventricular ejection fraction,left ventricular shortening rate or AR before and after interventional operation in PmVSDs with AVP. CONCLUSION: Percutaneous closure for ventricular septal defect combined with AVP is an effective alternative to surgery when using appropriate occluders,meeting related standards and operated in an experienced cardiovascular center.

Objective: To better understand the economic burden of patients with epilepsy receiving outpatient services in China and to analyze potential factors influencing epileptic economic burden through a cross-sectional study. Methods: Using a self-designed questionnaire, we collected information retrospectively from 754 patients with epilepsy evaluated in neurology clinics in Shanghai Municipality, Shanxi Province and Sichuan Province. Descriptive analyses were used after cost variables were presented as logarithms, and multiple linear regressions were performed to explore influencing factors. Results: Fifty percent of the investigated patients experienced an epilepsy attack before the age of 15, and 51.3% had suffered from epilepsy for more than five years. In the past year, 87.9% of patients had visited different hospitals multiple times for evaluation (40.3%) and maintenance treatment (40.7%). The total economic burden of epilepsy was US$ 1 143.2. The average direct economic burden and indirect economic burden were US$ 939.0 and US$ 110.2, respectively. Multiple linear regressions showed that patients had to bear greater economic burden if they were hospitalized, using multiple antiepileptic drugs, experiencing illness for less than 5 years, in severe seizure index or active epilepsy with drug resistance, which was statistically significant. Totally only 14.3% of patients could get reimbursement in outpatient services. Conclusions: Patients with epilepsy must present to hospitals regularly for satisfactory prognosis, which results in economic burden. Patients bear greater economic burden, especially direct medical costs, if they are newly diagnosed, experience severe seizures, or undergo multiple drug treatments that require more frequent monitoring. However, current insurance policy for outpatient services do not help reduce economic burden of patients efficiently.

BackgroundIn the current society, infertility related to age has become a social problem. The in vitro fertilization (IVF) success rate in women with poor ovarian response (POR) is very low. Dandelion extract T-1 (DE-T1) is an effective component of the extract from the leaves and stems of Taraxacum officinale, which is one of the medicines used in some patients with POR, but its molecular mechanism remains unclear.

MethodsFollowing IVF, ovarian granulosa cells (GCs) of sixty patients were extracted and divided into normal ovarian response (NOR) and POR groups. GCs were cultured in a dose-dependent and time-dependent manner with DE-T1, proliferation of GCs was determined by Cell Counting Kit-8 assay, and mRNA levels of insulin-like growth factor 1 receptor (IGF-1R), luteotropic hormone receptor (LHR), follicle-stimulating hormone receptor (FSHR), LHR, and CYP19A1 (aromatase) were determined by quantitative polymerase chain reaction. Progesterone and estradiol (E2) concentrations were determined by enzyme-linked immunosorbent assay.

ResultsThe cell viability gradually increased with the progressive increase in the DE-T1 concentration. Compared with the control group (without DE-T1), the mRNA expressions of FSHR, LHR, IGF-1R, and CYP19A1 were upregulated after the addition of DE-T1, especially in the 2.5% DE-T1 group (P < 0.01). The expression of IGF-1R was upregulated approximately 25 times (24.97 ± 4.02 times) in the POR group with 2.5% DE-T1. E2 and progesterone levels increased with the increasing DE-T1 concentration. There were highly significant differences in the E2 and progesterone secretion between the NOR and POR groups (P < 0.01).

ConclusionDE-T1 may promote steroid hormone synthesis by promoting GC proliferation and upregulating GC receptor expression, thereby improving ovarian endocrine function.

Objective To analyze the characteristics of clinical manifestations, risk factors, therapies and acute outcomes in patients with cerebral venous sinus thrombosis complicated by cerebral hemorrhage. Methods Seventy-five patients with cerebral venous sinus thrombosis were included in the study. According to the radiological findings on the brain image, patients were divided into two subgroups:cerebral hemorrhage group and non-hemorrhage group. The demo?graphic data, potential risk factors, clinical manifestations, radiological features, therapeutic strategies and acute out?comes were compared between two subgroups, and high risk factors were also analyzed. Results There were seventy-five patients with cerebral venous sinus thrombosis in the present study. Twenty-eight patients of them (37.2%) had cerebral hemorrhage whereas the remaining forty-seven patients (62.7%) did not have cerebral hemorrhage. Pregnancy/puerperi?um were significantly higher in patients with cerebral hemorrhage (with vs without;28.6%vs. 6.4%, P=0.015), while in?fection was markedly higher in patients without cerebral hemorrhage (with vs without;7.1% vs. 29.8%, P=0.021). Head?ache (92.9% vs. 70.2%, P=0.021), unconsciousness (25.0% vs. 6.4%,P=0.034), seizures (53.6% vs. 19.1%, P=0.002) and motor deficits (35.7% vs. 12.8%, P=0.019) were more common in patients with cerebral hemorrhage. Moreover, mul?tiple sinus involvement (1.4% vs. 44.7%, P=0.024) was significantly higher and the acute outcomes(mRS≥3: 46.4%vs.17.0%, P=0.006)were poorer in patients with cerebral hemorrhage. Binary Logistic analysis showed that pregnancy/pu?erperium (P=0.004) and multiple sinus involvement were positively, whereas infection was negatively correlated with cere?bral venous sinus thrombosis and hemorrhage ( P=0.007;P=0.03). Conclusions Pregnancy/puerperium, headache, uncon?sciousness, seizures, motor deficits and multiple sinus involvement are more frequently in patients with cerebral venous sinus thrombosis and hemorrhage, and the acute outcomes are poorer in patients with cerebral venous sinus thrombosis complicated by cerebral hemorrhage.

OBJECTIVETo inquire the characteristic proteins in chronic myocardial ischemia by testing twodimensional electrophoresis (2-DE) map to explore the possible inherent pathological mechanism and the therapeutic intervention of qi deficiency and blood stasis syndrome.

METHODSAmeroid constrictor ring was placed on the first interval of left anterior descending coronary artery to prepare chronic myocardial ischemia model on Chinese miniature swine. Animals were randomly divided into sham group and model group with 10 animals in each group, respectively. The dynamic symptoms observation of the four diagnostic information was collected from 0 to 12 weeks. Echocardiography was employed to evaluate cardiac function and the degree of myocardial ischemia, 2-DE and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) were used to carry out proteomics research on animals. Enzyme-linked immunosorbent assay was applied to identify the relevant differential proteins on chronic myocardial ischemia with qi deficiency and blood stasis syndrome.

RESULTSThe preliminary study found that at the 12th week, chronic myocardial ischemia with qi deficiency and blood stasis syndrome model was established stably. Compared with the sham group, there were 8 different proteins down-regulated, 22 proteins up-regulated significantly. After validated by MALDITOF-MS/MS, 11 protein spots were identified. Distinct proteins were mainly associated with energy metabolism and myocardial structural injury, including isocitrate dehydrogenase 3 (NAD+) alpha, NADH dehydrogenase (NAD) Fe-S protein 1, chain A (crystal structure of aldose reductase by binding domain reveals a new Nadph), heat shock protein 27 (HSP27), oxidoreductase (NAD-binding protein), antioxidant protein isoform, cardiac troponin T (cTnT), myosin (myosin light polypeptide), cardiac alpha tropomyosin, apolipoprotein A-I and albumin.

CONCLUSIONDown-regulated energy metabolism disorder mediated by NADH respiratory chain and myocardial injury may be the pathogenesis of myocardial ischemia with qi deficiency and blood stasis syndrome. These proteins may be the potential diagnostic marker(s) for qi deficiency and blood stasis syndrome, finally provided new clues for new therapeutic drug target of Chinese medicine.

Animals ; Blood Coagulation Disorders ; complications ; metabolism ; Electrophoresis, Gel, Two-Dimensional ; Energy Metabolism ; physiology ; Metabolic Diseases ; etiology ; metabolism ; Myocardial Ischemia ; complications ; metabolism ; Myocardial Reperfusion Injury ; etiology ; metabolism ; Proteomics ; methods ; Qi ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Swine ; Swine, Miniature ; Syndrome