Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.

Objective To summarize the experience of integrative palliative care at Peking Union Medi-cal College Hospital and provide a reference for promoting the integrative palliative care model.Methods Twenty cases receiving integrative palliative care at Peking Union Medical College Hospital were collected.The clinical characteristics,reasons for initiating integrative palliative care,the process of integrative palliative care,and feedback from these cases were summarized.Results Insomnia(11 cases,55％)and pain(9 cases,45％)were the most common symptoms requiring control in the 20 cases.The integrative palliative care team assisted in medical decision-making for 17 cases(85％),prepared end-of-life for 9 cases(45％),assisted in the transfer for 3 cases(15％),and provided comfort care for all the 20 cases(100％).Conclusions The integrative palliative care model can help alleviate suffering in end-of-life patients and provide support to patients'families and the original medical teams.This model is worth further promotion within class A tertiary hospitals.

Objective:To analyze the risk factors for aspiration pneumonia (AP) among stroke survivors with dysphagia and construct a prediction model.Methods:The records of one hundred and forty-eight stroke survivors with dysphagia admitted since 2021 were retrospectively analyzed. They were divided into an AP group ( n=46) and a non-AP group ( n=102). Univariate and multivariate logistic regressions were evaluated seeking independent risk factors for AP. the receiver-operating characteristic (ROC) curves were used to analyze predictive power. Results:The incidence of AP was 31%. Multivariate logistic regression analysis showed that age, Barthel index, Kubota′s water drinking test grading, nutritional support methods and the neutrophil/lymphocyte ratio (NLR) could be useful independent predictors of AP. The areas under the ROC curves suggested that Kubota grading, nutritional support methods, the NLR and the Barthel index could be used to prepare a prediction nomogram with good sensitivity and specificity.Conclusions:Age, Barthel index, Kubota water drinking test grades, nutritional support methods and NLR are independent predictors of AP for stroke survivors with dysphagia. Combining them in a nomogram gives better predictive power than using the factors alone.

Objective:To explore the clinical efficacy of endoscopic sleeve gastrectomy (ESG) in the treatment of obesity.Method:A 26 year old female patient was admitted on October 20, 2022 due to a progressive increase in weight for 2 years. Her body mass index (BMI) was 30.04 kg/m 2, body fat percentage was 39.2%, and visceral fat grade was 15. ESG was performed using the OverStitch SX endoscopic suture system. Result:The surgery was successful, with approximately 5 ml of intraoperative bleeding.The patient discharged on the first day after surgery. Two weeks after surgery, small bowel follow-through showed a tubular shape of the stomach. At 6 months after surgery, the BMI was 25.2 kg/m 2, body fat percentage was 32%, visceral fat grade was 10. The total body weight loss rate (%TBWL) at 6 months after surgery was 16%, and the excess weight loss rate (%EWL) was 54.5%. Conclusion:ESG is effective for the treatment of obesity.

Objective:To explore the clinical efficacy of endoscopic sleeve gastrectomy (ESG) in the treatment of obesity.Method:A 26 year old female patient was admitted on October 20, 2022 due to a progressive increase in weight for 2 years. Her body mass index (BMI) was 30.04 kg/m 2, body fat percentage was 39.2%, and visceral fat grade was 15. ESG was performed using the OverStitch SX endoscopic suture system. Result:The surgery was successful, with approximately 5 ml of intraoperative bleeding.The patient discharged on the first day after surgery. Two weeks after surgery, small bowel follow-through showed a tubular shape of the stomach. At 6 months after surgery, the BMI was 25.2 kg/m 2, body fat percentage was 32%, visceral fat grade was 10. The total body weight loss rate (%TBWL) at 6 months after surgery was 16%, and the excess weight loss rate (%EWL) was 54.5%. Conclusion:ESG is effective for the treatment of obesity.

Objective:To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.

Autism spectrum disorder (ASD) is a range of neurodevelopmental diseases characterized by social dysfunction and stereotypic behaviors. The etiology of ASD remains largely unexplored, resulting in a diverse array of described clinical manifestations and varying degrees of severity. Currently, there are no drugs approved by a supervisory organization that can effectively treat the core symptoms of ASD. Childhood and adolescence are crucial stages for making significant achievements in ASD treatment, necessitating the development of drugs specifically for these periods. Based on the drug targets and mechanisms of action, it can be found that atypical psychotropic medications, anti-inflammatory and antioxidant medications, hormonal medications, ion channel medications, and gastrointestinal medications have shown significant improvement in treating the core symptoms of ASD in both children and adolescents. In addition, comparisons of drugs within the same category regarding efficacy and safety have been made to identify better alternatives and promote drug development. While further evaluation of the effectiveness and safety of these medications is needed, they hold great potential for widespread application in the clinical treatment of the principal symptoms of ASD.
Humans ; Autism Spectrum Disorder/drug therapy* ; Child ; Adolescent ; Psychotropic Drugs/therapeutic use* ; Antioxidants/therapeutic use* ; Anti-Inflammatory Agents/therapeutic use* ; Gastrointestinal Agents/therapeutic use*

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Objective: To investigate the trends in incidence of viral hepatitis in Yuxi City, Yunnan Province from 2004 to 2022, so as to provide insights into the management of viral hepatitis. Methods: Data of viral hepatitis cases in Yuxi City from 2004 to 2022 were retrieved from the China Disease Prevention and Control Information System. The temporal, human and spatial distribution of viral hepatitis cases were analyzed using a descriptive epidemiological method, and the trends in incidence of viral hepatitis were evaluated in Yuxi City from 2004 to 2022 using annual percent change (APC) and average APC (AAPC). Results: A total of 37 430 viral hepatitis cases were reported in Yuxi City from 2004 to 2022, with an average annual incidence rate of 91.27/105, and the incidence showed a tendency towards a rise (AAPC=12.686, P<0.05). There were 29 229 cases with hepatitis B, 5 796 cases with hepatitis C, 1 451 cases with hepatitis A, 520 cases with hepatitis E and 434 cases with unclassified hepatitis reported in Yuxi City, with average annual incidence rates of 71.27/105, 14.13/105, 3.54/105, 1.27/105 and 1.06/105, respectively. The average annual incidence rates of viral hepatitis were 98.24/105 and 78.94/105 among men and women, which both appeared a tendency towards a rise (AAPC=12.415% and 12.581%, both P<0.05). The highest average annual incidence of viral hepatitis was seen among residents at age of 25 to 29 years (139.89/105), with the lowest seen among residents at ages of 0 to 4 years (11.38/105), and the average annual incidence of viral hepatitis appeared a tendency towards a rise with age (P<0.05). The highest average annual incidence of viral hepatitis was seen in Huaning County (234.24/105), with the lowest seen in Chengjiang City (26.11/105), and the average annual incidence appeared a tendency towards a rise in Xinping County from 2004 to 2022 (AAPC=21.451%, P<0.05). Conclusions The reported incidence of viral hepatitis appeared a tendency towards a rise in Yuxi City from 2004 to 2022, with hepatitis B as the main type. High incidence was seen among men and adolescents. The viral hepatitis control strategy requires to be adjusted with adaptations to high-incidence hepatitis subgroups, residents and regions.

Chronic hepatitis B virus (HBV) infection remains a global health burden. Timely and effective antiviral therapy is beneficial for patients with HBV infection. With existing antiviral drugs, including nucleos(t)ide analogs and interferon-alfa, patients can achieve viral suppression with improved prognosis. However, the rate of hepatitis B surface antigen loss is low. To achieve a functional cure and even complete cure in chronic hepatitis B patients, new antivirals need to be developed. In this review, we summarized the advantages and disadvantages of existing antiviral drugs and focused on new antivirals including direct-acting antiviral drugs and immunotherapeutic approaches.
Antiviral Agents/therapeutic use* ; Hepatitis B/drug therapy* ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B, Chronic/drug therapy* ; Hepatitis C, Chronic/drug therapy* ; Humans