Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Gallbladder cancer is the most common cause of hilar biliary obstruction; however, it rarely causes combined biliary, duodenal, and colon triple obstruction. In this case, the quality of life for a patient with recurrent gallbladder cancer with combined duodenal, colonic, and biliary obstruction was improved by endoscopic and endosonographic palliation, despite its technical difficulty and complexity. Seven metal stents were implanted one by one using only endoscopic methods. Successful stent-in-stent placement and endoscopic ultrasound-guided stenting after failed ERCP improved the patient’s quality of life to the extent that there was no need for any external drainage.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Objective: To analyze the clinical characteristics, laboratory examination, diagnosis, treatment, and outcome of hereditary factor Ⅹ (FⅩ) deficiency. Methods: Clinical data of 11 patients with congenital FⅩ deficiency were retrospectively analyzed from July 2009 to February 2021. Results: There were 3 males and 8 females. Median age was 39 (5-55) years. The media duration of follow-up was 81.67 (1.87-142.73) months. Of the 11 patients, 10 had bleeding symptoms, 7 had ecchymosis or hemorrhage after skin bump, 7 had nosebleed, 6 had gingival hemorrhage, and 1 had muscle hematoma. Among the female patients, 6 had menorrhagia and 1 experienced bleeding after vaginal delivery. Family history of FⅩ deficiency was found in one case. Eight patients had a history of surgery, and four had postoperative bleeding. Laboratory findings were characterized by significantly prolonged activated partial thromboplastin time, prothrombin time, and decreased FⅩ activity (FⅩ∶C) . Four cases underwent gene mutation analysis and five new mutations were found. Four cases were treated with prothrombin complex concentrates (PCC) and seven cases with fresh frozen plasma (FFP) . One female patient had significantly reduced menstrual volume after PCC prophylactic therapy. One patient received FFP for prophylactic infusion with no bleeding during and after the operation. Conclusion: Most patients with congenital FⅩ deficiency had bleeding symptoms and there was no significant correlation between severity of bleeding symptoms and FⅩ∶C. Prophylaxis should be applied in patients with severe bleeding tendencies. Gene mutation test is significant for screening, diagnosis, and prognosis prediction of congenital FX deficiency.
Adolescent ; Adult ; Blood Coagulation Factors/therapeutic use* ; Blood Coagulation Tests ; Child ; Child, Preschool ; Factor X Deficiency/genetics* ; Female ; Hemorrhage/drug therapy* ; Humans ; Male ; Middle Aged ; Plasma ; Retrospective Studies ; Young Adult

OBJECTIVE: To compare the analgesic effect of Jin Ling Zi Powder (JLZ) and its two single herbs. METHODS: The hot plate method was used to induce pain. Totally 36 mice were randomly divided into 6 groups by a complete random design, including control, model, aspirin (ASP, 0.14 g/kg body weight), JLZ (14 g/kg body weight), Corydalis yanhusuo (YHS, 14 g/kg body weight), and Toosendan Fructus (TF, 14 g/kg body weight) groups, 6 mice in each group. The mice in the control and model groups were given the same volume of saline, daily for 2 consecutive weeks. At 30, 60, 90, and 120 min after the last administration, the pain threshold of mice in each group was measured, and the improvement rate of pain threshold was calculated. Serum endogenous metabolites were analyzed by gas chromatography-mass spectrometry (GC-MS). RESULTS: There was no statistical difference in pain threshold among groups before administration (P>0.05). After 2 weeks of administration, compared with the model group, the pain threshold in JLZ, YHS, TF and ASP groups were increased to varying degrees (P<0.05). JLZ had the best analgesic effect and was superior to YHS and TF groups. A total of 14 potential biomarkers were screened in serum data analysis and potential biomarkers levels were all reversed to different degrees after the treatment with JLZ and its single herbs. These potential biomarkers were mainly related to glyoxylate and dicarboxylate metabolism, glycine, serine and threonine metabolism, valine, leucine and isoleucine biosynthesis, aminoacyl-tRNA biosynthesis and inositol phosphate metabolism. CONCLUSIONS The analgesic mechanism of JLZ and YHS was mainly due to the combination of glycine and its receptor, producing post-synaptic potential, reducing the excitability of neurons, and weakening the afferent effect of painful information.
Animals ; Mice ; Analgesics/therapeutic use* ; Aspirin/pharmacology* ; Biomarkers ; Body Weight ; Drugs, Chinese Herbal/therapeutic use* ; Glycine ; Glyoxylates ; Inositol Phosphates ; Isoleucine ; Leucine ; Metabolomics/methods* ; Powders ; RNA, Transfer ; Serine ; Threonine ; Valine

OBJECTIVE: To investigate the factors affecting the chronicity of childhood primary immune thrombo-cytopenia (ITP) and compare the efficiency of different first-line treatment regimens. METHODS: Children with ITP hospitalized in our hospital from September 2013 to October 2018 were retrospectively analyzed. RESULTS: Three hundred and one children (150 males and 151 females) were included in this study, with a median age of 8 (0.17-17) years old, and 110 (36.5%), 92 (30.6%), and 99 (32.9%) cases were grouped into newly diagnosed, persistent, and chronic ITP, respectively. The median of follow-up was 41.92 (1.07-74.03) months. At the end of the follow-up (October 2019), among the 202 newly diagnosed/persistent ITP children, 79 cases (59 newly diagnosed and 20 persistent ITP) achieved remission within 1 year after initial diagnosis, with a remission rate of 39.3%; 122 cases (50 newly diagnosed and 72 persistent ITP) developed chronic disease, with a chronicity rate of 60.7%; one case underwent splenectomy. In 99 cases with chronic ITP, 5 cases underwent splenectomy. Multivariable logistic regression analysis showed that, the insidious onset of symptoms (OR=3.754, 95%CI: 1.882-7.488, P=0.000) increased the risk of chronicity, while the positive antibody to anti-platelet membrane glycoprotein (OR=0.446, 95%CI: 0.224-0.888, P=0.021) might reduce the risk of chronicity. And no difference was found by the analysis of subtype of anti-platelet membrane glycoprotein (P=0.305). The efficacy of the first-line treatment of intravenous immunoglobulin (IVIG) alone or combined with steroid was better than that of steroid alone (P=0.028, 0.028), however, the efficiency was not significantly different between IVIG alone and combined with steroid (P=0.086). CONCLUSION Insidious onset of symptoms in pediatric ITP increases the risk of chronicity, while the positive titer of anti-platelet membrane glycoprotein may reduce the risk. In the first-line treatment for the newly diagnosed/persistent children. The efficacy of IVIG alone or combined with steroid is better than that of steroid alone.
Adolescent ; Child ; Child, Hospitalized ; Female ; Humans ; Immunoglobulins, Intravenous ; Male ; Purpura, Thrombocytopenic, Idiopathic ; Retrospective Studies ; Splenectomy

OBJECTIVE: To evaluate whether the efficacy of Getong Tongluo Capsule (, GTC, consisted of total flavone of Radix Puerariae) on improving patients' quality of life and lowering blood pressure are superior to the extract of Ginkgo biloba (EGB) for patients with convalescent-phase ischemic stroke and primary hypertension. METHODS: This randomized, positive-drug- and placebo-controlled, double-blind trial was conducted from September 2015 to October 2017. Totally 477 eligible patients from 18 hospitals in China were randomly assigned in a 2:1:1 ratio to the following interventions, twice a day for 12 weeks: (1) GTC 250 mg plus EGB-matching placebo 40 mg (237 cases, GTC group), (2) EGB 40 mg plus GTC-matching placebo 250 mg (120 cases, EGB group) or (3) GTC-matching placebo 250 mg plus EGB-matching placebo 40 mg (120 cases, placebo group). Moreover, all patients were orally administered aspirin enteric-coated tablets 100 mg, once a day for 12 weeks. The primary outcome was the Barthel Index (BI). The secondary outcomes included the control rate of blood pressure and National Institutes of Health Stroke Scale (NIHSS) scores. The incidence and severity of adverse events (AEs) were calculated and assessed. RESULTS: The BI relative independence rates, the clinical recovery rates of NIHSS, and the total effective rates of NIHSS in the GTC and EGB groups were significantly higher than the placebo group at 12 weeks after treatment (P<0.05), and no statistical significance was found between the GTC and EGB groups (P>0.05). The control rate of blood pressure in the GTC group was significantly higher than the EGB and placebo groups at 12, 18 and 24 weeks after treatment (P<0.01). There were no statistically significant differences in the incidences of AEs, adverse drug reactions, or serious AEs among the 3 groups (P>0.05). CONCLUSION GTC exhibited significant efficacy in improving patients' quality of life as well as neurological function and controlling hypertension. (Registration No. ChiCTR1800016667).

BACKGROUND: Resting heart rate (RHR) is considered as a strong predictor of total mortality and hospitalization due to heart failure in hypertension patients. Bisoprolol fumarate, a second-generation beta-adrenoreceptor blockers (β-blocker) is commonly prescribed drug to manage hypertension. The present study was to retrospectively evaluate changes in the average RHR and its association with cardiovascular outcomes in bisoprolol-treated coronary artery disease (CAD) patients from the CAD treated with bisoprolol (BISO-CAD) study who had comorbid hypertension. METHODS: We performed ad-hoc analysis for hypertension sub-group of the BISO-CAD study (n = 866), which was a phase IV, multination, multi-center, single-arm, observational study carried out from October 2011 to July 2015 across China, South Korea, and Vietnam. Multivariate regression analysis was used to identify factors associated with incidence of composite cardiac clinical outcome (CCCO), the results were presented as adjusted odds ratio (OR) along with 95% confidence interval (CI) and adjusted P value. RESULTS: A total of 681 patients (mean age: 64.77 ± 10.33 years) with hypertension from BISO-CAD study were included in the analysis. Bisoprolol improved CCCOs in CAD patients with comorbid hypertension, with RHR <65 and <70 beats/min compared with RHR ≥65 and ≥75 beats/min, respectively, in the efficacy analysis (EA) set. In addition, it lowered RHR in both intent-to-treat (ITT) and EA groups after 6, 12, and 18 months of treatment. Further, RHR 70 to 74 beats/min resulted in significantly higher risk of CCCOs EA set of patients (adjusted OR: 4.34; 95% CI: 1.19-15.89; P = 0.03). Also, events of hospitalization due to acute coronary syndrome were higher when RHR 69 to 74 beats/min compared to RHR <69 beats/min in ITT patients. CONCLUSION Bisoprolol can effectively reduce RHR in Asian CAD patients with comorbid hypertension and hence, improve CCCO without affecting their blood pressure.

Objective: To analyze the clinical characteristics, treatment and prognosis of patients with thrombotic thrombocytopenic purpura (TTP) . Methods: 83 patients with TTP from May 1998 to May 2019 were analyzed retrospectively. Results: Among the 83 patients, there were 27 males and 56 females, with a median age of 39 (10-68) years. 41 cases (49.4%) showed pentalogy syndrome and 79 cases (95.2%) showed triad syndrome. 78.0% (46/59) of the patients had a PLASMIC score of 6 or higher. TTP gene mutations was detected in 5 of 10 patients. The activity of von Willebrand factor-cleaving protease (ADAMTS13) , which was detected in 10 patients before plasma exchange (PEX) , was less than 10% in 9 patients. 83 patients were treated with PEX/plasma infusion and glucocorticoid, 35 of which were treated combined with rituximab and/or immunosuppressant. The median follow-up was 34 (1-167) months, the effective rate was 81.9%, the remission rate was 63.9%, the relapse rate was (35.7 ±7.1) %, and the 3-year overall survival (OS) rate was (78.6 ±4.6) %. The effective rate (72.9%vs 94.3%, P=0.019) and OS rate[ (63.8±7.5) %vs (94.3±3.9) %, χ(2)=8.450, P=0.004] in the group treated with PEX/PI and glucocorticoid alone were lower than those in the group treated combined with rituximab and/or immunosuppressant. COX multivariate analysis showed that age (HR=1.111, 95%CI 1.044-1.184, P=0.001) and alanine transaminase (ALT) /aspartate aminotransferase (AST) (HR=1.353, 95%CI 1.072-1.708, P=0.011) were independent risk factors for OS. Conclusion: Most patients with TTP have triad syndrome, accompanied by a decrease in ADAMTS13 activity. Plasma infusion and glucocorticoid combined with rituximab, immunosuppressive therapy could improve overall survival. The prognosis of patients with older age and high ALT/AST ratio is poor.
ADAM Proteins ; ADAMTS13 Protein ; Adolescent ; Adult ; Aged ; Child ; Female ; Humans ; Male ; Middle Aged ; Plasma Exchange ; Purpura, Thrombotic Thrombocytopenic ; Retrospective Studies ; Rituximab ; Young Adult