Hepatitis B-related compensated liver cirrhosis is related to a higher risk of hepatocellular carcinoma, and antiviral therapy is the preferred method. As the pathological mechanisms of liver ...fibrosis are complex, drugs developed for a single target are difficult to be effective in clinical practice, so there are no chemical drugs or biological drugs with clear efficacy available for clinical application at present. Traditional Chinese medicine is a kind of medical science that has been gradually formed during thousands of years and continuously enriched by the people of all ethnic groups in China. Traditional Chinese medicine shows curative effects in the treatment of liver diseases, especially in the field of liver fibrosis prevention and treatment. This study aims to test the integrative medicine (Chinese medicine plus antiviral therapy) effective on lowing hepatocellular carcinoma risk among patients with hepatitis-related compensated liver cirrhosis.
This is a multi-center randomized controlled trial, and a total of 5 hospitals and 802 patients will be involved in. All the subjects are randomly allocated to the YinQiSanHuang Jiedu decoction (YQSHD) group (n = 401) or the placebo group (n = 401). The YQSHD group receives YQSHD granule with entecavir (ETV), and the placebo group receives YQSHD placebo with ETV. The treatment period will last for 52 weeks, and the follow-up period for 52 ± 2 weeks. The primary outcome measure is the annual incidence of HCC. Outcomes will be assessed at baseline and after treatment. The objective of this trial is "the integrative of YQSHD with ETV reduce the annual incidence of HCC to 1%."
The protocol has been approved by the Medical Ethics Committee of Guang'anmen Hospital, China (No.2019-006-KY), and the other centers in the trial will not begin recruiting until the local ethical approval has been obtained. Trial final results will be disseminated via publication.
Chinese Clinical Trial Registry ChiCTR1900021532 . Registered on February 26, 2019.
Nalbuphine has been suggested to be used for post-cesarean section (CS) intravenous analgesia. However, ideal concentration of nalbuphine for such analgesia remains unclear. The present study was ...conducted to explore an ideal concentration of nalbuphine for post-CS intravenous analgesia by evaluating the analgesic effects and side-effects of three different concentrations of nalbuphine combined with hydromorphone for post-CS intravenous analgesia in healthy parturients.
One-hundred-and-fourteen parturients undergoing elective CS were randomly allocated to one of three groups (38 subjects per group) according to an Excel-generated random number sheet to receive hydromorphone 0.05 mg/mL + nalbuphine 0.5 mg/mL (group LN), hydromorphone 0.05 mg/mL + nalbuphine 0.7 mg/mL (group MN), and hydromorphone 0.05 mg/mL + nalbuphine 0.9 mg/mL (group HN) using patient-controlled analgesia (PCA) pump. Visual analog scale (VAS) for pain, PCA bolus demands, cumulative PCA dose, satisfaction score, Ramsay score, and side-effects such as urinary retention were recorded.
The number of PCA bolus demands and cumulative PCA dose during the first 48 h after CS were significantly higher in group LN (21 ± 16 bolus, 129 ± 25 mL) than those in group MN (15 ± 10 bolus, 120 ± 16 mL) (both P < 0.05) and group HN (13 ± 9 bolus, 117 ± 13 mL) (both P < 0.01), but no difference was found between group HN and group MN (both P > 0.05). VAS scores were significantly lower in group HN than those in group MN and group LN for uterine cramping pain at rest and after breast-feeding within 12 h after CS (all P < 0.01) and VAS scores were significantly higher in group LN than those in group MN and group HN when oxytocin was intravenously infused within 3 days after CS (all P < 0.05), whereas VAS scores were not statistically different among groups for incisional pain (all P > 0.05). Ramsay sedation scale score in group HN was significantly higher than that in group MN at 8 and 12 h after CS (all P < 0.01) and group LN at 4, 8, 12, 24 h after CS (all P < 0.05).
Hydromorphone 0.05 mg/mL + nalbuphine 0.7 mg/mL for intravenous PCA could effectively improve the incisional pain and uterine cramping pain management and improve comfort in patients after CS.
ChiCTR1800015014, http://www.chictr.org.cn/ Chinese Clinical Trial Registry.
Penicillin-binding proteins (PBPs) include transpeptidases, carboxypeptidases, and endopeptidases for biosynthesis of peptidoglycans in the cell wall to maintain bacterial morphology and survival in ...the environment. Streptococcus pneumoniae expresses six PBPs, but their enzymatic kinetic characteristics and inhibitory effects on different β-lactam antibiotics remain poorly understood. In this study, all the six recombinant PBPs of S. pneumoniae displayed transpeptidase activity with different substrate affinities (Km = 1.56-9.11 mM) in a concentration-dependent manner, and rPBP3 showed a greater catalytic efficiency (Kcat = 2.38 s
) than the other rPBPs (Kcat = 3.20-7.49 × 10
s
). However, only rPBP3 was identified as a carboxypeptidase (Km = 8.57 mM and Kcat = 2.57 s
). None of the rPBPs exhibited endopeptidase activity. Penicillin and cefotaxime inhibited the transpeptidase and carboxypeptidase activity of all the rPBPs but imipenem did not inhibited the enzymatic activities of rPBP3. Except for the lack of binding of imipenem to rPBP3, penicillin, cefotaxime, and imipenem bound to all the other rPBPs (K
= 3.71-9.35 × 10
M). Sublethal concentrations of penicillin, cefotaxime, and imipenem induced a decrease of pneumococcal pbps-mRNA levels (p < 0.05). These results indicated that all six PBPs of S. pneumoniae are transpeptidases, while only PBP3 is a carboxypeptidase. Imipenem has no inhibitory effect on pneumococcal PBP3. The pneumococcal genes for encoding endopeptidases remain to be determined.
•An automatic data analysis strategy for UPLC-HRMS-based metabolomics is provided.•Underlying component information can be accurately and efficiently extracted.•Significantly expressed metabolites ...can be rapidly screened.•Performance of our method is comparable for several state-of-the-art methods.•A Matlab GUI for UPLC-HRMS is developed for users freely on our website.
Data analysis for ultra-performance liquid chromatography high-resolution mass spectrometry-based metabolomics is a challenging task. The present work provides an automatic data analysis workflow (AntDAS2) by developing three novel algorithms, as follows: (i) a density-based ion clustering algorithm is designed for extracted-ion chromatogram extraction from high-resolution mass spectrometry; (ii) a new maximal value-based peak detection method is proposed with the aid of automatic baseline correction and instrumental noise estimation; and (iii) the strategy that clusters high-resolution m/z peaks to simultaneously align multiple components by a modified dynamic programing is designed to efficiently correct time-shift problem across samples. Standard compounds and complex datasets are used to study the performance of AntDAS2. AntDAS2 is better than several state-of-the-art methods, namely, XCMS Online, Mzmine2, and MS-DIAL, to identify underlying components and improve pattern recognition capability. Meanwhile, AntDAS2 is more efficient than XCMS Online and Mzmine2. A MATLAB GUI of AntDAS2 is designed for convenient analysis and is available at the following webpage: http://software.tobaccodb.org/software/antdas2.
Background
c‐MET has recently been identified as a promising novel target in non‐small cell lung cancer (NSCLC). We detected the consistency of c‐MET gene amplification in metastatic lymph nodes and ...tumor tissues of NSCLC patients and discuss the clinical application value of c‐MET gene amplification in metastatic lymph nodes.
Methods
Real‐time fluorescent quantitative PCR was used to test tumor tissues in 368 NSCLC patients and 178 paired metastatic lymph node samples. The amplification consistency in metastatic lymph nodes and tissue samples were compared and the correlation between c‐MET gene amplification and the clinical characteristics of patients was analyzed.
Results
The c‐MET gene amplification rate was 8.97% (33/368) in tumor tissues. Of the 178 paired cases, c‐MET gene amplification was positive in 7.95% (15/178) of cancerous tissues and 18.54% (33/178) of metastatic lymph nodes. c‐MET gene amplification was detected more frequently in metastatic lymph nodes than in primary cancerous tissue. When metastatic lymph nodes were used as surrogate samples of primary cancerous tissues, the sensitivity was 86.67% (13/15) and the specificity was 87.69% (143/163).
Conclusions
Screening for c‐MET gene amplification in lymph node metastases could determine which patients are eligible for tyrosine kinase inhibitor therapy. Lymph node metastasis can predict c‐MET gene amplification in a primary tumor and guide the clinical use of c‐MET gene targeted drugs.
Abstract Emerging evidence has demonstrated that postconditioning with sevoflurane provided neuroprotection. In this study, we investigated the neuroprotective effect of different concentrations of ...sevoflurane in rats with middle cerebral artery occlusion (MCAO). Furthermore, we tested the hypothesis that the neuroprotective effect of postconditioning with sevoflurane is associated with inhibition of apoptosis and mediated by activation of the phosphoinositide-3-kinase/Akt (PI3K/Akt) pathway. Adult male Sprague–Dawley rats were subjected to MCAO for 90 min and then treated with sevoflurane at the beginning of reperfusion. The infarct volume, neurological deficit scores and brain edema were evaluated at 24 hours. Spatial learning and memory was examined by Morris water maze. Apoptosis and apoptosis-related proteins were studied by TUNEL, immunohistochemistry and western blot. The neuroprotective effect and the amount of p-Akt after sevoflurane administration with or without wortmannin were analyzed. Postconditioning with sevoflurane 1.0 minimum alveolar concentration (MAC) and 1.5 MAC significantly decreased neurological deficit scores, infarct volume and brain edema and markedly improved spatial learning and memory. Postconditioning also reduced apoptotic cells, upregulated Bcl-2 and downregulated P53 and Bax. Wortmannin abolished the neuroprotective effect and prevented the increasing of p-Akt. Our data suggest postconditioning with sevoflurane (1.0 MAC and 1.5 MAC) not only reduced infarct volume but also improved learning and memory. Our study further showed that this neuroprotective effect may be partly due to the activation of PI3K/Akt pathway and inhibiting neuronal apoptosis.
To compare the prognosis and adverse effects of induction or adjuvant chemotherapy (IC or AC) plus concurrent chemoradiotherapy (CCRT) versus CCRT alone in paediatric nasopharyngeal carcinoma (NPC) ...patients in the intensity-modulated radiotherapy (IMRT) era.
549 patients diagnosed from 2005 to 2021 were enrolled. Our primary endpoint was progression-free survival (PFS). The recursive partitioning analysis (RPA) was applied to derive a risk stratification system. Kaplan–Meier survival curves were used to assess the cumulative survival rates, and cox analysis was applied to evaluate the relationship between variables and endpoints.
The RPA-based risk stratification identified three different risk groups. In the intermediate-risk (stage IVa and EBV<4000 copies/ml) group, patients who received IC followed by CCRT achieved a significantly better 3-year PFS rate than those treated with CCRT alone (87.35% versus 75.89%; P = 0.04). But survival benefit was not obtained from the additional IC or AC in the low-risk (stage II-III and EBV<4000 copies/ml) or high-risk (stage II-IVa and EBV≥4000 copies/ml) group. The most common grade 3 or 4 adverse events in patients treated with CCRT, IC + CCRT, and CCRT + AC were neutropenia (8.1%, 33.0% versus 36.9%, respectively) and leukopenia (14.1%, 26.8% versus 32.3%, respectively) with statistically significant difference.
Paediatric NPC patients in the intermediate-risk group treated with IC followed by CCRT had significantly better PFS compared with patients treated with CCRT alone. And the overall incidence of acute adverse events in patients treated with IC or AC plus CCRT was higher than in patients treated with CCRT alone.
•EBV DNA was independently associated with risk stratification in paediatric NPC.•Paediatric NPC patients with intermediate-risk could benefit from the additional IC.•Overall incidence of AE in paediatrics receiving IC/AC + CCRT was significantly higher.
Zika virus (ZIKV) is an emerging flavivirus that causes congenital syndromes including microcephaly and fetal demise in pregnant women. No commercial vaccines against ZIKV are currently available. We ...previously generated a chimeric ZIKV (ChinZIKV) based on the Chaoyang virus (CYV) by replacing the prME protein of CYV with that of a contemporary ZIKV strain GZ01. Herein, we evaluated this vaccine candidate in a mouse model and showed that ChinZIKV was totally safe in both adult and suckling immunodeficient mice. No viral RNA was detected in the serum of mice inoculated with ChinZIKV. All of the mice inoculated with ChinZIKV survived, while mice inoculated with ZIKV succumbed to infection in 8 days. A single dose of ChinZIKV partially protected mice against lethal ZIKV challenge. In contrast, all the control PBS-immunized mice succumbed to infection after ZIKV challenge. Our results warrant further development of ChinZIKV as a vaccine candidate in clinical trials.
Chronic hepatitis B (CHB) is a global public health problem. Antiviral therapy is the primary treatment. Studies have shown that a combined therapy of traditional Chinese medicine (TCM) and ...conventional antiviral drugs has better efficacy than conventional antiviral for treatment of CHB. YinQiSanHuang-antiviral decoction (YQSH) is a TCM compound preparation that has shown an effect on anti-hepatitis B virus and on slowing progression of hepatitis B-related liver diseases. To evaluate the efficacy and safety of YQSH combined with entecavir and its preventive effect on hepatitis B cirrhosis, we designed this randomized, double-blind and placebo-controlled trial. The objective is that the combination of YinQiSanHuang-antiviral decoction with entecavir will reduce the annual incidence of liver fibrosis/cirrhosis to 1%.
This is a multicenter, randomized, placebo-controlled, double-blinded trial involving five hospitals. A total of 802 patients are randomly allocated to two groups: the YQSH group (n = 401) or the placebo group (n = 401). The YQSH group receives YQSH with entecavir; the placebo group receives granules of placebo with entecavir. Patients receive treatment for 52 weeks and then are followed up for 52 ± 2 weeks. The primary outcome measure is the annual incidence of cirrhosis. The secondary outcome measures are hepatitis B virus DNA negative rate, hepatitis B surface antigen negative rate, hepatitis B e antigen seroconversion rate, liver function (alanine aminotransferase, aspartate aminotransferase , gamma-glutamyl transferase , alkaline phosphatase , serum albumin, and total bilirubin), spleen thickness, evaluation scores of patients' clinical symptoms, and safety assessment. Outcomes will be assessed at baseline and after treatment.
Combination therapy could become a trend for treatment of CHB, and this trial expects to provide credible clinical evidence for the future combination of TCM and conventional antiviral drugs for the treatment of CHB.
Chinese Clinical Trial Registry: ChiCTR1900021521. Registered on 25 February 2019.
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