BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

ObjectiveTo investigate the effect of Yiqi Yangyin Jiedu Huayu prescription on minimal hepatic encephalopathy in liver cirrhosis based on intestinal metabolomics. MethodsA total of 11 patients with liver cirrhosis who were hospitalized in Beijing Ditan Hospital， Capital Medical University， from March to May 2024， and were diagnosed with MHE based on psychometric hepatic encephalopathy score were enrolled as subjects， and 11 healthy family members of the patients were enrolled as control group. Fecal samples were collected for metabolomics analysis from the control group and the patients with MHE before and after treatment with Yiqi Yangyin Jiedu Huayu prescription， and a population cohort study was conducted to investigate the effect of Yiqi Yangyin Jiedu Huayu prescription on intestinal metabolism of patients with MHE. The Fisher’s exact test was used for categorical data between two groups； the independent samples t-test was used for comparison of normally distributed continuous data between two groups， the paired t-test was used for comparision before and after treatment within the same group， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups. ResultsA total of 29 differentially expressed metabolites were detected between the MHE group and the control group， mainly amino acids， organic acids， organic amines， carbohydrates， fatty acids， and vitamins， and there were 12 upregulated metabolites and 17 downregulated metabolites in the MHE group， which were mainly enriched in the metabolic pathways of ornithine， branched-chain amino acid， and aromatic amino acid. After the treatment with Yiqi Yangyin Jiedu Huayu prescription， 80 differentially expressed metabolites were detected in the patients with MHE， mainly carbohydrates， organic acids， and amino acids， and there were 56 upregulated metabolites and 24 downregulated metabolites， which were mainly enriched in the metabolic pathways of ornithine， branched-chain amino acid， and aromatic amino acid. ConclusionYiqi Yangyin Jiedu Huayu prescription can exert a therapeutic effect on patients with MHE by regulating intestinal metabolism.

Liver cirrhosis is the terminal stage of chronic liver disease. Minimizing complications of liver cirrhosis and the occurrence of liver cancer has become an important goal for liver cirrhosis treatment. The primary etiology leading to liver cirrhosis is chronic hepatitis B infection. "Dual-anti therapy" refers to the combination of anti-viral and anti-fibrosis treatment, which is the characteristic and advantage of the integration of Chinese and Western medicine. The article elaborates on the concept and strategies of "dual antibody therapy" based on evidence-based medicine and introduces the research progress in terms of representative anti-fibrotic Chinese patent medicines for reversing liver cirrhosis, reducing the occurrence of hepatocellular carcinoma, and loweri ng portal hypertension and its complications and others, revealing that dual antibody therapy can clinically facilitate dual reduction" (reducing both liver cancer and complications of cirrhosis). Additionally, it analyzes and summarizes the mechanism of action of anti-fibrotic Chinese patent medicines and prospects of a new model of liver cirrhosis treatment combining Chinese and Western medicine, thereby providing novel ideas for the prevention and treatment of clinical liver diseases.

ObjectiveTo investigate the impact of anticentromere antibody （ACA） on the clinical features and prognosis of patients with primary biliary cholangitis （PBC） by comparing clinical classification， ursodeoxycholic acid （UDCA） response， GLOBE score， and UK-PBC score between ACA-positive PBC patients and ACA-negative PBC patients. MethodsA total of 749 patients who were admitted to Beijing Ditan Hospital， Capital Medical University， from August 2013 to December 2022 and were diagnosed with PBC were enrolled and divided into ACA-positive group with 147 patients and ACA-negative group with 602 patients. According to their conditions on admission， the two groups were compared in terms of the distribution of clinical types， i.e.， chronic progression-type PBC， portal hypertension-type PBC， and standard jaundice/liver failure-type PBC. There were 261 patients with complete data after 1-year follow-up， among whom there were 53 patients with positive ACA and 208 with negative ACA. A statistical analysis was performed， and propensity score matching was performed based on sex and age at a ratio of 1∶2. The two groups were compared in terms of 1-year UDCA response rate， GLOBE score， and UK-PBC score before and after matching. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. ResultsCompared with the ACA-negative group， the ACA-positive group had a significantly higher age （61.28±10.35 years vs 56.74±12.17 years， t=4.164， P<0.001）， a significantly higher proportion of female patients （93.9% vs 77.6%， χ²=20.221， P<0.001）， a significantly higher proportion of patients with portal hypertension （48.3% vs 27.6%， χ²=23.289， P<0.001）， and a significantly lower proportion of patients with jaundice/liver failure （24.5% vs 38.5%， χ²=10.205， P<0.001）. After 1-year follow-up， for the 261 PBC patients with complete data， there was no significant difference in UDCA response rate before propensity score matching between the ACA-positive group and the ACA-negative group （41.5% vs 41.8%， P>0.05）， and there was a significant difference in the proportion of patients with a GLOBE score of >0.3 between the ACA-positive group and the ACA-negative group （92.5% vs 80.3%， χ²=3.935， P=0.047）. There were 53 patients in the ACA-positive group and 106 patients in the ACA-negative group after propensity score matching， and there were no significant differences between the two groups in UDCA response rate， GLOBE score， and UK-PBC score （all P>0.05）. ConclusionACA-positive patients tend to have an older age， with a higher proportion of female patients or patients with portal hypertension， while there is a relatively low proportion of patients with jaundice/liver failure. Positive ACA has no significant impact on UDCA response rate， GLOBE score， and UK-PBC score.

Objective To investigate the impact of anticentromere antibody(ACA)on the clinical features and prognosis of patients with primary biliary cholangitis(PBC)by comparing clinical classification,ursodeoxycholic acid(UDCA)response,GLOBE score,and UK-PBC score between ACA-positive PBC patients and ACA-negative PBC patients.Methods A total of 749 patients who were admitted to Beijing Ditan Hospital,Capital Medical University,from August 2013 to December 2022 and were diagnosed with PBC were enrolled and divided into ACA-positive group with 147 patients and ACA-negative group with 602 patients.According to their conditions on admission,the two groups were compared in terms of the distribution of clinical types,i.e.,chronic progression-type PBC,portal hypertension-type PBC,and standard jaundice/liver failure-type PBC.There were 261 patients with complete data after 1-year follow-up,among whom there were 53 patients with positive ACA and 208 with negative ACA.A statistical analysis was performed,and propensity score matching was performed based on sex and age at a ratio of 1∶2.The two groups were compared in terms of 1-year UDCA response rate,GLOBE score,and UK-PBC score before and after matching.The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between two groups.Results Compared with the ACA-negative group,the ACA-positive group had a significantly higher age(61.28±10.35 years vs 56.74±12.17 years,t=4.164,P<0.001),a significantly higher proportion of female patients(93.9%vs 77.6%,χ2=20.221,P<0.001),a significantly higher proportion of patients with portal hypertension(48.3%vs 27.6%,χ2=23.289,P<0.001),and a significantly lower proportion of patients with jaundice/liver failure(24.5%vs 38.5%,χ2=10.205,P<0.001).After 1-year follow-up,for the 261 PBC patients with complete data,there was no significant difference in UDCA response rate before propensity score matching between the ACA-positive group and the ACA-negative group(41.5%vs 41.8%,P>0.05),and there was a significant difference in the proportion of patients with a GLOBE score of>0.3 between the ACA-positive group and the ACA-negative group(92.5%vs 80.3%,χ2=3.935,P=0.047).There were 53 patients in the ACA-positive group and 106 patients in the ACA-negative group after propensity score matching,and there were no significant differences between the two groups in UDCA response rate,GLOBE score,and UK-PBC score(all P>0.05).Conclusion ACA-positive patients tend to have an older age,with a higher proportion of female patients or patients with portal hypertension,while there is a relatively low proportion of patients with jaundice/liver failure.Positive ACA has no significant impact on UDCA response rate,GLOBE score,and UK-PBC score.

Liver cirrhosis is the terminal stage of chronic liver disease. Minimizing complications of liver cirrhosis and the occurrence of liver cancer has become an important goal for liver cirrhosis treatment. The primary etiology leading to liver cirrhosis is chronic hepatitis B infection. "Dual-anti therapy" refers to the combination of anti-viral and anti-fibrosis treatment, which is the characteristic and advantage of the integration of Chinese and Western medicine. The article elaborates on the concept and strategies of "dual antibody therapy" based on evidence-based medicine and introduces the research progress in terms of representative anti-fibrotic Chinese patent medicines for reversing liver cirrhosis, reducing the occurrence of hepatocellular carcinoma, and loweri ng portal hypertension and its complications and others, revealing that dual antibody therapy can clinically facilitate dual reduction" (reducing both liver cancer and complications of cirrhosis). Additionally, it analyzes and summarizes the mechanism of action of anti-fibrotic Chinese patent medicines and prospects of a new model of liver cirrhosis treatment combining Chinese and Western medicine, thereby providing novel ideas for the prevention and treatment of clinical liver diseases.

Objective To investigate the differences in clinical features between the primary biliary cholangitis(PBC)patients with negative or positive anti-mitochondrial antibody(AMA)by analyzing related immune and biochemical parameters.Methods This study was conducted among the patients who attended Beijing Ditan Hospital,Capital Medical University,from January 2013 to December 2022 and were diagnosed with PBC,and they were divided into AMA negative group with 139 patients(24.5%)and AMA positive group with 428 patients(75.5%).Propensity score matching at a ratio of 1∶1 was performed with age and sex as matching factors and a matching tolerance of 0.06.Liver function,coagulation,and immune parameters on admission were analyzed,as well as the changes in liver function and other indicators after 6 months of treatment and the response to ursodeoxycholic acid(UDCA)at 6 and 12 months of treatment.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data between two groups.Results There were 139 AMA-negative PBC patients and 139 AMA-positive PBC patients after propensity score matching.Compared with the AMA positive group on admission,the AMA negative group had significantly lower levels of direct bilirubin and globulin(Glo)and significantly higher levels of albumin,albumin/globulin ratio,prealbumin,and fibrinogen(all P<0.05).After 6 months of UDCA treatment,there were significant differences in Glo and prealbumin between the AMA negative group and the AMA positive group(P<0.05).Both the AMA negative group and the AMA positive group had an increase in prealbumin after 6 months of treatment,and the AMA negative group had a significantly greater increase than the AMA positive group(U=41.00,P=0.015).After UDCA treatment for 6 and 12 months,there was no significant difference in treatment response to UDCA between the AMA negative group and the AMA positive group(all P>0.05).Conclusion After matching for age and sex,compared with the AMA-positive PBC patients,the AMA-negative PBC patients tend to have a milder degree of liver inflammation and damage,significantly greater improvements in inflammation and liver synthesis ability after UDCA treatment,and better response to UDCA.

BACKGROUND: Low-density computed tomography (LDCT) improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data. Hence, accurate diagnosis of early-stage lung cancer remains challenging. The purpose of the study was to assess the feasibility of using circulating tumour cells (CTCs) to differentiate malignant from benign pulmonary nodules. METHODS: 122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited. Peripheral blood samples were collected before surgery, and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis. Laser capture microdissection, MALBAC amplification, and whole-exome sequencing were performed on 8 samples. The diagnostic efficacy of CTCs counting, and the genomic variation profile of benign and malignant CTCs samples were analysed. RESULTS: Using 2.5 cells/5 mL as the cut-off value, the area under the receiver operating characteristic curve was of 0.651 (95% confidence interval: 0.538-0.764), with a sensitivity and specificity of 0.526 and 0.800, respectively, and positive and negative predictive values of 91.1% and 30.3%, respectively. Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples. TP53 mutations were identified in CTCs of four malignant cases; in particular, g.7578115T>C, g.7578645C>T, and g.7579472G>C were exclusively detected in all four malignant samples. CONCLUSIONS CTCs play an ancillary role in the diagnosis of pulmonary nodules. TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules.
Humans ; Lung Neoplasms ; Exome Sequencing ; Multiple Pulmonary Nodules ; Carcinoma ; DNA Repair

Objective:To study the safety and feasibility of anatomic left hemihepatectomy via cranial-dorsal approach in the treatment of left hepatolithiasis.Methods:Clinical data of 47 patients with left intrahepatic bile duct stones who underwent cranial-dorsal approach laparoscopic anatomic left hemihepatectomy in Hunan People's Hospital from October 2016 to June 2022 were retrospectively analyzed, including 15 males and 32 females, aged (56.45±1.37) years old. The operative time, intraoperative blood loss, postoperative liver function and complications were analyzed. Patients were followed up by telephone and outpatient review.Results:All 47 patients successfully underwent laparoscopic surgery without conversion. The median operative time was 260 (range, 160-440) min. The median intraoperative blood loss was 100 ml (range, 20-400 ml). The total bilirubin, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were 15.7 (11.7, 21.9) μmol/L, 126.6 (91.7, 168.5) U/L, and 151.1 (98.0, 212.4) U/L on postoperative day (POD) 1, respectively, and decreased to 12.6 (9.6, 16.2) μmol/L, 97.9 (60.7, 156.9) U/L, 54.2 (40.0, 104.1) U/L on POD 3, respectively. The median postoperative hospital stay was 7 (range, 4-24) d. Postoperative abdominal effusion and infection occurred in one patient, and the complication rate was 2.1% (1/47). Postoperative CT review found residual stones in common bile duct in one patient [2.1% (1/47)]. No stone recurrence or death occurred during postoperative follow-up.Conclusion:Anatomic left hemihepatectomy via cranial-dorsal approach is a safe and feasible surgery for the treatment of left hepatolithiasis.