Background/Aims: Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients. Methods: This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks. Results: 68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported. Conclusions 48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.

BACKGROUND: Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction. OBJECTIVE: This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale. METHODS: This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment. DISCUSSION This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411).
Humans ; ST Elevation Myocardial Infarction/therapy* ; Stroke Volume ; Ventricular Remodeling ; Prospective Studies ; Microcirculation ; Ventricular Function, Left ; Myocardial Infarction/etiology* ; Treatment Outcome ; Percutaneous Coronary Intervention/adverse effects* ; Heart Failure/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic

Tumors are new organisms formed by uncontrollable cell proliferation of local tissues driven by various oncogenic factors. The cause of tumors is unknown with life-threating outcome. Tumors can be classified into benign tumors， borderline tumors， and malignant tumors according to their pathological properties. Among them， malignant tumor is commonly known as cancer， with no specific medicines or reliable cure means， so this is a hot spot and difficult point in current medical research. In ancient literatures， there are many records about the efficacy of Chinese herbal medicine in treating tumor， and modern pharmacological researches have shown that more and more active ingredients of traditional Chinese medicine（TCM） have gradually highlighted their inhibitory effect on various types of tumor. Caulis sinomenii has been used for treatment of rheumatic diseases in TCM for a long history. Sinomenine is a major bioactive alkaloid presented in C. sinomenii， which has demonstrated a wide range of pharmacological activities such as anti-inflammation， immunosuppression， analgesia and sedation， and due to its slightly soluble in water， it is commonly used in clinic in the form of hydrochloride， with its commercial name of Zhengqing Fengtongning. Recent studies show that sinomenine alone or combined with chemoradiotherapy can inhibit growth of several tumors significantly or in a synergistic way， so it is termed as an inhibitor of tumors. Anti-tumor effect of sinomenine involve inhibition of tumor cell proliferation， induction of tumor cell apoptosis， blockade of tumor cell cycle， suppression of tumor invasion and metastasis， induction of autophagy of tumor cells， and reversal of multidrug resistance of tumor cells. Upon combination with nanomaterials， it can enhance efficiency and reduce toxicity. Here we summarized and reviewed recent advances on basic anti-tumor research of sinomenine， and then made a classification and description according to its in vivo and in vitro pharmacological action and mechanism of action， so as to elucidate the great potential of sinomenine as a promising anti-tumor drug， and provide reference for further research on its anti-tumor mechanism.

PURPOSE: The International Study Group on Pancreatic Fistula's definition of postoperative pancreatic fistula (POPF) has recently been updated. This study aimed to identify risk factors for POPF in patients having pancreaticoduodenectomy (PD) and to generate a nomogram to predict POPF. METHODS: Data on 298 patients who underwent PD from March 2012 to October 2017 was retrospectively reviewed and POPF statuses were redefined. A nomogram was constructed using data from 220 patients and validated using the remaining 78 patients. Independent risk factors for POPF were identified using univariate and multivariate analyses. A predictive nomogram was established based on the independent risk factors and was compared with existing models. RESULTS: Texture of the pancreas, size of the main pancreatic duct, portal vein invasion, and definitive pathology were the identified risk factors. The nomogram had a C-index of 0.793 and was internally validated. The nomogram performed better (C-index of 0.816) than the other most cited models (C-indexes of 0.728 and 0.735) in the validation cohort. In addition, the nomogram can assign patients into low- (less than 10%), intermediate- (10% to 30%), and high-risk (equal or higher than 30%) groups to facilitate personalized management. CONCLUSION The nomogram accurately predicted POPF in patients having PD.

Objective: To investigate the dose-response relationship between hemoglobin concentration and preterm birth, during pregnancy. Methods: With Zhuang ethnicity, a total of 12 780 pregnant women and their infants that admitted to Wuming、Pingguo、Jingxi、Debao、Longan and Tiandong hospitals, were recruited, in Guangxi Zhuang Autonomous Region, from January 2015 to December 2017. Non-conditional logistic regression method was used to analyze the effect of anemia on preterm birth during pregnancy. Dose-response relationship between hemoglobin concentration and preterm birth was explored, using the restrictive cubic spline model. Results: After excluding 2 053 pregnant women with hypertension or aged 35 years and over, results from the non-conditional logistic regression analysis showed that the risk of preterm birth in the anemia group was 1.29 times (OR=1.29, 95%CI: 1.04-1.59, P=0.019) of the non-anemia group in the first trimester. Data from the restricted cubic sample showed that there appeared nonlinear "L" dose-response relationship between hemoglobin concentration and preterm birth in the first trimester and "U" shape in the third trimester (non-linearity test P<0.001). Conclusion There appeared nonlinear dose-response relationship between the hemoglobin concentration and preterm birth, both in the first and third trimesters.

OBJECTIVE: To investigate whether craving and demographic factors to predict relapse in alcohol dependence. METHODS: This study was a prospective cohort study. From August 2017 to August 2018, 158 Han male inpatients who met the diagnositic and statistical manual disorders-fourth version(DSM-IV) alcohol dependence diagnostic criteria were recruited from three mental hospitals in China. The participants were interviewed at baseline and followed up by telephone after 3 months for assessment. The baseline assessment after the acute withdrawal period included demographic data and alcohol-related data, clinical institute withdrawal assessment-advanced revised (CIWA-Ar), withdrawal and cue-induced craving on visual analog scale (VAS), Michigan alcoholism screening test (MAST), self-rating anxiety scale (SAS), self-rating depression scale (SDS) and alcohol urge questionnaire (AUQ). According to the follow-up results, "relapse" was defined as the consumption of beverages containing ethanol at any time during the follow-up study, and "time to relapse" was defined as the number of days from the first drinking to the baseline. Whether relapse occurred and the time to relapse were the primary endpoints. Cox proportional hazard regression model was used to analyze the factors affecting the relapse of alcohol dependence. RESULTS: In the study, 158 alcohol dependence patients were finally included, age from 21 to 60 years, with the mean age of (40.31±9.14) years. The relapse rate was 63.7% three months after baseline assessment. According to Cox univariate analysis and multivariate analysis, the age (OR=0.975, P=0.030) and CIWA-Ar scores (OR=1.126, P=0.010) significantly predicted relapse. And there was no significant difference in education level, marital status, withdrawal and cue-induced craving on VAS, SAS and SDS between the relapse group and the non-relapse group (P>0.05). CONCLUSION Age and severity of alcohol-dependent withdrawal symptoms during hospitalization are significantly related to relapse for alcohol in alcohol-dependent patients. To be exact, the older age is a protective factor, that is to say, the younger patients are prone to relapse, while the risk of relapse is raised by the higher severity of withdrawal symptoms. However, neither cue-induced nor withdrawal craving can predict relapse of alcohol-dependent patients.
Adult ; Alcoholism ; China ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prospective Studies ; Recurrence ; Young Adult

It is recognized that prenatal care plays an important role in reducing adverse birth.Chinese pregnant women with medical condition were required to seek additional health care based on the recommended at least 5 times health care visits.This study was to estimate the association between prenatal care utilization (PCU) and preterm birth (PTB),and to investigate if medical conditions during pregnancy modified the association.This population-based case control study sampled women with PTB as cases;one control for each case was randomly selected from women with term births.The Electronic Perinatal Health Care Information System (EPHCIS) and a questionnaire were used for data collection.The PCU was measured by a renewed Prenatal Care Utilization (APNCU) index.Logistic regression models were used to estimate odds ratios (OR) and the 95％ confidence interval (95％ CI).Totally,2393 women with PTBs and 4263 women with term births were collected.In this study,695 (10.5％) women experienced inadequate prenatal care,and 5131 (77.1％) received adequate plus prenatal care.Inadequate PCU was associated with PTB (adjusted OR:1.41,95％ CI:1.32-1.84);the similar positive association was found between adequate plus PCU and PTB.Among women with medical conditions,these associations still existed;but among women without medical conditions,the association between inadequate PCU and PTB disappeared.Our data suggests that women receiving inappropriate PCU are at an increased risk of having PTB,but it does depend on whether the woman has a medical condition during pregnancy.

OBJECTIVEAn UPLC method was developed to evaluate the quality of Paeoniae Radix by simultaneously determining four components, paeoniflorin, albiflorin, benzoylpaeoniflorin and paeonol in Paeoniae Radix Alba decoction pieces.

METHODThe UPLC chromatographic column was ACQUITY UPLC® HSS T3. The mobile phase was acetonitrile-0.05% phosphoric acid water with gradient elution. The column temperature was 30 °C and detection wavelength was 230 nm with a flow rate of 0.4 mL · min(-1). A linear model was obtained through principal component analysis (PCA), and PCA scores were used to evaluate the quality of Radix Paeoniae Alba decoction pieces comprehensively.

RESULTPaeoniflorin, albiflorin, benzoylpaeoniflorin and paeonol could be well separated from other components, and the results of specificity, precision, repeatability, linearity, recovery rate and stability reached the standards, respectively. The content of paeoniflorin in 9 batches of Paeoniae Radix Alba decoction pieces was below the standard given by Chinese Pharmacopoeia (2010 edition). Using the comprehensive scoring method with principal component analysis, the results showed that the samples from Zhejiang province have better quality than those from Anhui and Shandong provinces.

CONCLUSIONThe method established in this study can effectively determine the content of paeoniflorin, albiflorin, benzoylpaeoniflorin and paeonol, which could be used for quality control of Paeoniae Radix Alba.

After studying the discipline of chemical components distribution in peony root, it was found that the content distribution of albiflorin, paeoniflorin, benzoylpaeoniflorin and paeonol was inhomogeneous in different parts of peony root, as same as in different roots belonging to a same plant. Therefore, in order to minimize the effects of different qualities of materials on experimental result, the content changing percentages of four chemical components was chosen as indicators to study processing method of Paeoniae Radix Alba. The processing technique of Paeoniae Radix Alba was put peony roots in the boiled water for at most ten minutes, and cut them into 2-3 mm slices after peeling the root bark, finally dry them in a oven under 55 degrees C, which was similar to the traditional processing method used in Bozhou. And the peeling, boiling and drying methods would affect the contents of albiflorin, paeoniflorin, benzoylpaeoniflorin and paeonol on several levels.
Chemistry, Pharmaceutical ; methods ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Paeonia ; chemistry ; Plant Roots ; chemistry

To ensure the stability of chemistry components and the convenience of operation, ultrasound method was chosen to study in this investigation. As the total common peaks area in chromatograms was set to be evaluation index, the influence on the technology caused by extraction time, ethanol concentration and liquid-to-solid ratio was studied by using single factor methodology, and the extraction technology of Paeoniae Radix Alba was optimized by using response surface methodology. The results showed that the extracting results were most affected by ethanol concentration; liquid-to-solid ratio came the second and extraction time thirdly. The optimum ultrasonic-assisted extraction conditions were as follow: the ultrasonic extraction time was 20.06 min, the ethanol concentration in solvent was 72.04%, and the liquid-to-solid ratio was 53.38 mL · g(-1), the predicted value of total common peaks area was 2.1608 x 10(8). Under the extraction conditions after optimization, the total common peaks area was 2.1422 x 10(8), and the relative deviation between the measured and predicted value was 0.86%, so the optimized extraction technology for Paeoniae Radix Alba is suitable and feasible. Besides, for the purpose of extracting more sufficiently and completely, the optimized extraction technology had more advantages than the extraction method recorded in the monogragh of Paeoniae Radix Alba in Chinese Pharmacopoeia, which will come true the assessment and utilization comprehensively.
Paeonia ; chemistry ; Technology, Pharmaceutical ; methods