Evaluation of pre-operative bladder contractility as a predictor of improved response rate to a staged trial of sacral neuromodulation in patients with detrusor underactivity.

PURPOSE: Sacral neuromodulation (SNM) is one of the few management options shown to improve outcomes in patients with detrusor underactivity (DU). This original research will investigate if preserved bladder contractility can predict a successful treatment with SNM. METHODS: This is a retrospective study of a prospectively collected database of consecutive patients with DU, who had a staged SNM trial from January 2013 to December 2018, with a minimum of 12 months follow-up. The primary outcome was the success of stage 1 SNM trial. RESULTS: In total, 69 patients with DU were followed. The median age was 67 [interquartile range (IQR) 74-55], median baseline bladder contractility index (BCI) 18 (IQR 67-0), and median post-void residual 200 mL (IQR 300-130). There were 35 patients (51%) that responded to a SNM trial. At a median follow-up of 23 months (IQR 39-12), three were removed for poor efficacy. In patients with detrusor acontractility (DAC), six responded (33%), compared to 29 patients (57%) with BCI > 0. This was statistically significant, p value 0.03. Younger age was also a predictive factor for SNM response, p value 0.02. There were no differences noted in those with gender, neurogenic history, previous pelvic surgery, diabetes, or pre-operative voiding history. CONCLUSION: Our study showed that patients with preserved bladder contractility are more likely to respond to a trial of SNM compared with those that have DAC. Younger age was also predictive of SNM response. UDS is the only method to accurately identify DAC patients. This information will help in patient selection and pre-operative counselling.

Randomised controlled trial for high-dose intravenous zinc as adjunctive therapy in SARS-CoV-2 (COVID-19) positive critically ill patients: trial protocol.

INTRODUCTION: SARS-CoV-2 (COVID-19) has caused an international pandemic of respiratory illness, resulting in significant healthcare and economic turmoil. To date, no robust vaccine or treatment has been identified. Elemental zinc has previously been demonstrated to have beneficial effects on coronaviruses and other viral respiratory infections due to its effect on RNA polymerase. Additionally, zinc has well-demonstrated protective effects against hypoxic injury-a clear mechanism of end-organ injury in respiratory distress syndrome. We aimed to assess the effect of high-dose intravenous zinc (HDIVZn) on SARS-CoV-2 infection. The end of study analyses will evaluate the reduction of impact of oxygen saturations or requirement of oxygen supplementation. METHODS AND ANALYSIS: We designed a double-blind randomised controlled trial of daily HDIVZn (0.5 mg/kg) versus placebo. Primary outcome measures are lowest oxygen saturation (or greatest level of supplemental oxygenation) for non-ventilated patients and worst PaO2/FiO2 for ventilated patients. Following power calculations, 60 hospitalised patients and 100 ventilated patients will be recruited to demonstrate a 20% difference. The duration of follow-up is up to the point of discharge. ETHICS AND DISSEMINATION: Ethical approval was obtained through the independent Human Research Ethics Committee. Participant recruitment will commence in May 2020. Results will be published in peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: ACTRN126200000454976.

Identification of the chemical components and metabolites of tripterygium glycoside tablets in mice by HPLC-Q/TOF MS.

Tripterygium glycosides tablets (TGT) contain the main extract of tripterygium and are widely used clinically to treat autoimmune diseases such as rheumatoid arthritis and nephrotic syndrome. However, TGT can lead to liver and renal failure in clinic. The exposed components and their metabolites of TGT in vivo were rarely researched. In this study, the components and metabolites of TGT in mice liver, kidney and plasma were profiled by high performance liquid chromatography coupled with tandem quadrupole time-of-flight mass spectrometry (HPLC-Q/TOFMS) after TGT was orally administered to mice. The components and metabolites were detected and identified based on their retention time, accurate mass data of quasi-molecular ion, characteristic fragment ions, and the fragmentation rules. Finally, 48 prototype components, including 25 diterpenoids, 11 triterpenoids and 12 alkaloids, were detected in mice, as well as 99 metabolites, undergoing hydroxylation, dehydrogenation, ester bond hydrolysis of Phase I metabolism, and glutathione, glucuronic acid binding of Phase II metabolism. The components and metabolites in mice were compared between single- and multiple- low dose groups and between high and low dose groups. Furthermore, a total of 21 components and 35 metabolites were predicted to have potential toxic risk by software. The results would provide material basis to clarify the clinical efficacy and toxicity of TGT.

Chemical identification and quality evaluation of Lycopus lucidus Turcz by UHPLC-Q-TOF-MS and HPLC-MS/MS and hierarchical clustering analysis.

Lycopus lucidus Turcz has been used as a traditional phytomedicine for menstrual disorder, amenorrhea, menstrual cramps, inflammation and cardiovascular diseases. However, there is not enough information about identification and quantification for the chemical constituents of L. lucidus Turcz. In this work, a simple, rapid and sensitive UHPLC-Q-TOF-MS method was developed for characterization and identification of the phytochemical compositions in L. lucidus Turcz in negative ion mode. A total of 37 compounds, including 15 phenolic acids, 12 flavonoids, three triterpenoids and seven organic acids were tentatively characterized and identified by means of the retention time, accurate mass and characteristic fragment ions. Thirteen compounds were reported for the first time in L. lucidus Turcz. Among of them, 11 compounds were further quantified by multiple reactions monitoring. The results showed good performance with respect to linearity (r > 0.9959), repeatability (RSD < 2.6%), intra- and inter-day precision (RSD < 3.2%), recovery (93.1-104.9%), and lower limit of quantification (5-50 ng/mL). Subsequently, the results were analyzed and classified by hierarchical cluster analysis. The research could be applied for identification and quality evaluation for L. lucidus Turcz.

High-Throughput Sequencing Reveals Hypothalamic MicroRNAs as Novel Partners Involved in Timing the Rapid Development of Chicken (Gallus gallus) Gonads.

Onset of the rapid gonad growth is a milestone in sexual development that comprises many genes and regulatory factors. The observations in model organisms and mammals including humans have shown a potential link between miRNAs and development timing. To determine whether miRNAs play roles in this process in the chicken (Gallus gallus), the Solexa deep sequencing was performed to analyze the profiles of miRNA expression in the hypothalamus of hens from two different pubertal stages, before onset of the rapid gonad development (BO) and after onset of the rapid gonad development (AO). 374 conserved and 46 novel miRNAs were identified as hypothalamus-expressed miRNAs in the chicken. 144 conserved miRNAs were showed to be differentially expressed (reads > 10, P < 0.05) during the transition from BO to AO. Five differentially expressed miRNAs were validated by real-time quantitative RT-PCR (qRT-PCR) method. 2013 putative genes were predicted as the targets of the 15 most differentially expressed miRNAs (fold-change > 4.0, P < 0.01). Of these genes, 7 putative circadian clock genes, Per2, Bmal1/2, Clock, Cry1/2, and Star were found to be targeted multiple times by the miRNAs. qRT-PCR revealed the basic transcription levels of these clock genes were much higher (P < 0.01) in AO than in BO. Further functional analysis suggested that these 15 miRNAs play important roles in transcriptional regulation and signal transduction pathways. The results provide new insights into miRNAs functions in timing the rapid development of chicken gonads. Considering the characteristics of miRNA functional conservation, the results will contribute to the research on puberty onset in humans.

Comprehensive two-dimensional liquid chromatography coupled with quadrupole time-of-flight mass spectrometry for chemical constituents analysis of tripterygium glycosides tablets.

Comprehensive two-dimensional liquid chromatography platform (LC×LC) coupled with quadrupole time-of-flight (QTOF) mass spectrometry (MS) is developed to separate, identify and relatively determine the chemical constituents of two types of tripterygium glycosides tablets (TGT). The types and relative contents of the constituents discovered in two kinds of TGT tablets were subsequently compared. C8 and C18 column were used for the separation of the first and second dimensional chromatography ((1)D and (2)D) respectively, and an integrated shift and full gradient mode was used in (2)D. Using this LC×LC-QTOF-MS platform, 92 and 132 constituents were detected in TGT preparations from Hubei and Hunan manufacturers respectively (HB-TGT and HN-TGT), most of which belonged to the diterpenoid, triterpenoid and alkaloid families. 50 and 90 compounds were unique in HB-TGT and HN-TGT, respectively, and their relative contents proportion were 52.0% and 54.2% of HB-TGT and HN-TGT, respectively. Furthermore, two TGT tablets could both lead to obvious change in biochemical parameters, oxidative stress related parameters and histopathological status to different degree. In all, the LC×LC-QTOF-MS platform offer a powerful and efficient method for characterizing, identifying and semi-quantifying chemical components in TGT preparations.

Integrated targeted sphingolipidomics and transcriptomics reveal abnormal sphingolipid metabolism as a novel mechanism of the hepatotoxicity and nephrotoxicity of triptolide.

ETHNOPHARMACOLOGICAL RELEVANCE: Tripterygium wilfordii Hook F (TWHF) is a traditional herbal medicine in China. Triptolide (TP), the primary bioactive compound of TWHF, is an anti-inflammatory and immunosuppressive compound that can also injure the liver and kidney. Unfortunately, the toxicity mechanism remains unknown. AIM OF THE STUDY: The aim of this study is to understand the regulatory role of sphingolipid (SPL) pathways in the TP-induced toxic mechanism in the liver and kidney in delayed-type hypersensitivity (DTH) Balb\c mouse. MATERIAL AND METHODS: 76 core sphingolipids and 29 species of related metabolic enzymes in liver, kidney and plasma were analyzed with previous HPLC-MS/MS and real time qPCR method, respectively. Furthermore, the data generated from these two omics underwent integrated analysis to describe TP-induced abnormal sphingolipid metabolism and identify the specific biomarkers of TP toxicity using bioinformation method. RESULTS: High-dose (LD50) TP could induce severe liver and kidney injuries. Moreover, TP comprehensively influenced the enzymes involved in the sphingolipids metabolism in the liver and kidney at the mRNA expression level. Furthermore, the total levels of ceramides (Cers), sphingomyelins (SMs) and sphingosine (Sph) were all elevated, while dihydroceramides (dhCers) and hexosylceramides (HexCers) were all down-regulated. Several enzymes, including kdsr, CerS2, CerS4, CerS5 and CerS6 in the liver and Cerk in the kidney were probably responsible for the TP-induced toxic effect, identifying them as possible novel therapeutic targets. Besides, fractions of long chain SPL (C16-C20) exhibited significant increase, and fractions of unsaturated dhCer and Cer were significantly changed, both of which above may be due to the change of mRNA expression level of CerSs. Moreover, several biomarkers for the diagnosis of TP poisoning were discovered. CONCLUSION: In summary, the regulation of SPL metabolism uncovered a novel mechanism underlying TP poisoning in the liver and kidney. In addition, key biomarkers and enzymes may play an important role in reducing the clinical risk associated with the use of TP.

Clinical treatment of the stenosing tenovaginitis of flexor digitorum by micro-wound technique using hooked needle-shaped surgical knife.

OBJECTIVE: To observe the therapeutic effect and safety of using the hooked needle-shaped knife to treat the stenosing tenovaginitis of flexor digitorum. METHODS: Sixty outpatients were divided into a treatment group of 30 cases treated by using the hooked needle-shaped knife, and a control group of 30 cases treated by block therapy. 6 months later, the alleviation of pain in the affected finger during movement, under pressure, traction and finger-bending anti-resistance was compared before and after treatment. RESULTS: The alleviation of pain during movement, under pressure, traction and finger-bending anti-resistance was much better in the treatment group than that of the control group (P < 0.01), with a effective rate of 93.3% in the treatment group and 80.0% in the control group (P < 0.01). CONCLUSION: The micro-wound technique using the hooked needle-shaped knife has definite effect and safety for stenosing tenovaginitis of flexor digitorum.

[Case control study of hook needle knife for the treatment of stenosing tenovaginitis of flexor digitorum].

OBJECTIVE: To investigate the effect and safety of the hook needle knife for the treatment of stenosing tenovaginitis of flexor digitorum. METHODS: From September 2007 to September 2008, 60 outpatients with stenosing tenovaginitis of flexor digitorum were randomized divided into the treatment group and the control group, 30 cases in each group. Among the patients, 44 patients were female and 16 patients were male, aged from 34 to 69 years, averaged 56 years, the duration of disease ranged from 1 month to 1 year, averaged 3 months. All the patients were treated with hook needle knife and local-blocking respectively. The patients were followed up for 6 months, and the relief of moving-pain, tender-pain, stretching-pain and resist-ing--pain were observed respectively. All the patients were evaluated by the symptoms with numerical rating scale. RESULTS: The relief of moving-pain, tender-pain, stretching-pain and resisting-pain in the treatment group were significantly better than those of the control group; and the therapeutic effects of treatment group were better than those of the control group. CONCLUSION: The method for treating stenosing tenovaginitis of flexor digitorum with hook needle knife has advantages of definite effects, micro-invasion and safety.

High diversity of endophytic fungi from the pharmaceutical plant, Heterosmilax japonica Kunth revealed by cultivation-independent approach.

Heterosmilax japonica Kunth is well recognized for its diuretic effects in China. However, little is known about its endophytic fungi. In this study, microbial communities inhabiting the stems of H. japonica in spring and summer were investigated by light microscopy and cultivation-independent approaches, such as RFLP analysis and sequencing of rDNA ITS library. Molecular phylogenetic analysis showed that a broad spectrum of fungi, including Mycosphaerella, Phomopsis, Aureobasidium, Cladosporium, Glomerella, Botryosphaeria, Guignardia, is able to colonize the plants internally. Particularly, several rDNA sequences determined in this study like YJ4-61 are not specifically affiliated with any currently documented fungal sequences in the public database. Several sequence types, such as YJ4-9 and YJ4-70, are significantly similar to some uncultured environmental samples. Furthermore, our result also showed that the samples collected in spring harbored more abundant endophytic populations than that in summer, implying a seasonal fluctuation for the endophytes in H. japonica.