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.

To investigate the intervention effect and mechanism of Zhenwu Decoction on diabetic nephropathy(DN) mice of spleen-kidney Yang deficiency syndrome based on the Rho-associated coiled-coil kinase(ROCK)/IκB kinase(IKK)/nuclear factor-κB(NF-κB) pathway. Ninety-five 7-week-old db/db male mice and 25 7-week-old db/m male mice were fed adaptively for one week. The DN model of spleen-kidney Yang deficiency syndrome was induced by Dahuang Decoction combined with hydrocortisone by gavage, and then the model was evaluated. After modeling, they were randomly divided into a model group, high-dose, medium-dose, and low-dose Zhenwu Decoction groups(33.8, 16.9, and 8.45 g·kg~(-1)·d~(-1)), and an irbesartan group(25 mg·kg~(-1)·d~(-1)), with at least 15 animals in each group. The intervention lasted for eight weeks. After the intervention, body weight and food intake were measured. Serum crea-tinine(Scr), blood urea nitrogen(BUN), fasting blood glucose(FBG), urinary albumin(uALb), and urine creatinine(Ucr) were determined. The uALb/Ucr ratio(ACR) and 24 h urinary protein(UTP) were calculated. Renal pathological morphology was evaluated by HE staining and Masson staining. The levels of key molecular proteins in the ROCK/IKK/NF-κB pathway were detected by Western blot. Enzyme-linked immunosorbent assay(ELISA) was used to detect interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-8(IL-8), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α). Compared with the blank group, the model group showed increased content of BUN, uALb, and SCr, increased values of 24 h UTP and ACR, decreased content of Ucr(P<0.05), enlarged glomeruli, thickened basement membrane, mesangial matrix proliferation, inflammatory cell infiltration, and collagen fiber deposition. The protein expression of ROCK1, ROCK2, IKK, NF-κB, phosphorylated IKK(p-IKK), phosphorylated NF-κB(p-NF-κB), and phosphorylated inhibitor of NF-κB(p-IκB) increased(P<0.05), while the protein expression of inhibitor of NF-κB(IκB) decreased(P<0.05). The levels of inflammatory factors IL-1β, IL-6, IL-8, and TNF-α increased(P<0.05), while the level of IL-10 decreased(P<0.05). Compared with the model group, the groups with drug treatment showed decreased levels of BUN, uALb, SCr, 24 h UTP, and ACR, increased level of Ucr(P<0.05), and improved renal pathological status to varying degrees. The high-and medium-dose Zhenwu Decoction groups and the irbesartan group showed reduced protein expression of ROCK1, ROCK2, IKK, NF-κB, p-IKK, p-NF-κB, and p-IκB in the kidneys(P<0.05), increased protein expression of IκB(P<0.05), decreased levels of serum inflammatory factors IL-1β, IL-6, IL-8, and TNF-α(P<0.05), and increased level of IL-10(P<0.05). Zhenwu Decoction can significantly improve renal function and renal pathological damage in DN mice of spleen-kidney Yang deficiency syndrome, and its specific mechanism may be related to the inhibition of inflammatory response by down-regulating the expression of key molecules in the ROCK/IKK/NF-κB pathway in the kidney.
Mice ; Male ; Animals ; NF-kappa B/metabolism* ; Interleukin-8 ; Interleukin-10 ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6 ; I-kappa B Kinase ; Spleen ; Irbesartan ; Uridine Triphosphate ; Yang Deficiency/drug therapy* ; Kidney/pathology*

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

Through resources investigation and sample collection,a total number of 392 Dendrobium officinale from 38 different populations,9 provinces were processed for measuring and observing.Fourteen agronomy characterizations like stem height,stem diameter,number of node in stem were selected for further classification.The cluster analysis was performed using Ward and Euclidean method.The results showed that the threshold of genetic distance was 2.77.Thirtyeight populations were divided into 6 groups.The factor analysis showed that,the leaf shape,stem shape,pitch length and leaf color were very important factors for classification.This study establish the foundation for analyzing the genetic relationship of D.officinale from different populations.
Cluster Analysis ; Dendrobium ; anatomy & histology ; classification ; Plant Leaves ; Plants, Medicinal ; anatomy & histology ; classification

This study adopted the 4 pairs of simple sequence repeats(SSR) primers selected by National Resource Center for Chinese Meteria Medica (CACMS) to detect 29 populations of Dendrobium officinale samples from 9 main places of production; 5,7,4 and 3 polymorphism bands were amplified from these 4 pairs of SSR primers. The DNA identities of different populations were constructed by SSR. The 29 D. officinale populations could be divided into 4 classes. The clustering result was related to the places of production. Samples from Yunnan,Guizhou,Sichuan provinces were classified into one category,while samples from Anhui and Guangxi provinces were classified into another category. Samples from Guangdong Danxia,Zhejiang Yongkang,Zhejiang Leqing and Taining belonged to a category. PopGene (version 1.32) software was applied to calculate the genetic similarity of the 29 D. officinale populations. The similarities was between 0.403 4 and 1.0.Based on the genetic similarity,the genetic consistency included three classes,A,B and C. Samples with a similar geographical location and landform environment have higher genetic similarities,which indicate the same genetic background. This paper provides reference information to study the identification, selection and breeding of good varieties.

The anhydrite and gypsum are the main sulfate minerals during evaporation of seawater or lake.They record the information about relative hydrogeology and the composition of mother liquor.Boron is diffluent element, and often occurs in all kinds of evaporites.Presently, the boron isotope has been applied widely in mineral deposits forming, geochemistry and palaeoenvironment.However, there is little research about characteristic of boron isotope in anhydrite and gypsum minerals, because of the low content of boron and micro-solubility in water and hydrochloric acid.This study developed a method of extracting and purifying boron in anhydrite and gypsum by phase transformation and ion-exchange.Firstly, the samples were mixed with ammonium hydrogen carbonate to transform the calcium sulfate to calcium carbonate.And diluted hydrochloric acid (1 mol/L) was added to resolve calcium carbonate.The percent conversion was about 85%in the first stage, and up to complete resolution by repeating this process.Secondly, boron specific ion-exchange resin ( Amberlite IRA 743 ) was used to gather the boron ions fully and further refined the samples with more than 1 μg of boron by anionic and cationic resin mixed by Ion Exchange Ⅱ and Dowex 50 W × 8.Finally, according to the modified method by He, the values of boron isotope were determined by TIMS.The boron content is analytically pure gypsum was 3.501 ± 0.128 μg/g ( n=12 , RSD=3.6%) and the average recovery was 100.47%.Besides, the δ11B value of analytically pure gypsum added with NIST SRM 951 was 17.98‰±0.21‰ (n=3, RSD=1.2%).This method has good repeatability and can meet the requirements of boron isotopic measurement of anhydrite and gypsum.

Objective: To observe the lumen structural changes of radial artery (RA) in patients with transradial coronary intervention and the impact of nitroglycerin on the structure by optical coherence tomography (OCT). Methods: A total of 20 patients with transradial coronary intervention were enrolled for OCT imaging to observe and compare the lumen structures of RA between the basic condition and nitroglycerin treated condition. Results: OCT imaging found that 15/20 patients had radial spasm and 1 had intimal tear. Compared to basic condition, with nitroglycerin treatment, the mean lumen diameter, lumen area and total vascular area were increased in the distal, middle and proximal portion of RA, all P<0.001; the intima-media thickness was decreased in the distal, middle and proximal portion of RA, all P<0.001; while the cross section area of tunica media, intimal thickness and extravascular membrane thickness were similar between the basic condition and nitroglycerin treated condition, all P>0.005. Conclusion: Vasodilatation drug may obviously enlarge RA lumen area and total vascular area in patients after transradial coronary intervention.

The study aims to explore the main differential characteristics of Phragmites Rhizoma and its counterfeits (rhizomes of Arundo donax, Triarrhena lutarioriparia and Miscanthus sinensis) and provide experimental basis for the reasonable applications of gramineous plants through system research and comparison of plant morphogenesis, character, transverse organization characteristics and powder microscopic characteristics.

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.

OBJECTIVETo investigate the effect of FCGR3A polymorphisms on the antibody-dependent cell-mediated cytotoxicity (ADCC) activity induced by cetuximab against A549 cells.

METHODSA549 cell line was used as target cells and NKTm cells as effector cells. FCGR3A polymorphisms were detected by direct sequencing. The ADCC activity mediated by cetuximab was assessed by CCK-8 assay.

RESULTSThree genotypes of FCGR3A were detected:V/V,V/F,and F/F. The ADCC activity of NKTm cells with these three different genotypes mediated by cetuximab were significantly different (P=0.0015). NKTm cells with FCGR3A-158V/V genotypes had significantly higher ADCC activity than FCGR3A-V/F or F/F genotypes (P<0.01),whereas the ADCC activity between V/F and F/F genotype showed no statistical significance(P>0.05).

CONCLUSIONFCGR3A polymorphisms have an impact on ADCC activity mediated by cetuximab in NKTm cells.