Expected Eight-Week Prenatal Versus Twelve-Week Perinatal Tenofovir Alafenamide Prophylaxis to Prevent Mother-To-Child Transmission of Hepatitis B Virus: A Multicenter, Prospective, Open-label, Randomized Controlled Trial.

INTRODUCTION: The course of maternal antiviral prophylaxis to prevent mother-to-child transmission of hepatitis B virus (HBV-MTCT) varies greatly, and it has not been demonstrated in a randomized controlled study. METHODS: In this multicenter, open-label, randomized controlled trial, eligible pregnant women with HBV DNA of 5.3-9.0 log10 IU/mL who received tenofovir alafenamide fumarate (TAF) from the first day of 33 gestational weeks to delivery (expected eight-week) or to four-week postpartum (expected twelve-week) were randomly enrolled at a 1:1 ratio and followed until six-month postpartum. All infants received standard immunoprophylaxis (hepatitis B immunoglobulin and vaccine). The primary endpoint was the safety of mothers and infants. The secondary endpoint was infants' HBV-MTCT rate at seven months of age. RESULTS: Among 119 and 120 intention-to-treat pregnant women, 115 and 116 women were followed until delivery, and 110 and 112 per-protocol mother-infant dyads in two groups completed the study. Overall, TAF was well tolerated, no one discontinued therapy due to adverse events (0/239, 0%, 95% confidence interval [CI] 0%-1.6%), and no infant had congenital defects or malformations at delivery (0/231, 0%, 95% CI 0%-1.6%). The infants' physical development at birth (n=231) and at seven months (n=222) were normal. Furthermore, 97.0% (224/231, 95% CI 93.9%-98.5%) of women achieved HBV DNA <5.3 log10 IU/mL at delivery. The intention-to-treat and per-protocol infants' HBV-MTCT rates were 7.1% (17/239, 95% CI 4.5%-11.1%) and 0% (0/222, 95% CI 0%-1.7%) at seven months of age. Comparatively, 15.1% (18/119, 95% CI 9.8%-22.7%) versus 18.3% (22/120, 95% CI 12.4%-26.2%) of women in the two groups had mildly elevated alanine aminotransferase levels at three-month and six-month postpartum, respectively (P=0.507); notably, no one experienced alanine aminotransferase flare (0% [0/119, 95% CI 0%-3.1%] versus 0% [0/120, 0%-3.1%]). DISCUSSION: Maternal TAF prophylaxis to prevent HBV-MTCT is generally safe and effective, and expected eight-week prenatal duration is feasible. ClinicalTrials.gov, NCT04850950.

Expert consensus on the diagnosis and treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children.

BACKGROUND: Mycoplasma pneumoniae (M. pneumoniae) is a significant contributor to community-acquired pneumonia among children. Since 1968, when a strain of M. pneumoniae resistant to macrolide antibiotics was initially reported in Japan, macrolide-resistant M. pneumoniae (MRMP) has been documented in many countries worldwide, with varying incidence rates. MRMP infections lead to a poor response to macrolide antibiotics, frequently resulting in prolonged fever, extended antibiotic treatment, increased hospitalization, intensive care unit admissions, and a significantly higher proportion of patients receiving glucocorticoids or second-line antibiotics. Since 2000, the global incidence of MRMP has gradually increased, especially in East Asia, which has posed a serious challenge to the treatment of M. pneumoniae infections in children and attracted widespread attention from pediatricians. However, there is still no global consensus on the diagnosis and treatment of MRMP in children. METHODS: We organized 29 Chinese experts majoring in pediatric pulmonology and epidemiology to write the world's first consensus on the diagnosis and treatment of pediatric MRMP pneumonia, based on evidence collection. The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, CNKI, Medline, and the Cochrane Library. We used variations in terms for "macrolide-resistant", "Mycoplasma pneumoniae", "MP", "M. pneumoniae", "pneumonia", "MRMP", "lower respiratory tract infection", "Mycoplasma pneumoniae infection", "children", and "pediatric". RESULTS: Epidemiology, pathogenesis, clinical manifestations, early identification, laboratory examination, principles of antibiotic use, application of glucocorticoids and intravenous immunoglobulin, and precautions for bronchoscopy are highlighted. Early and rapid identification of gene mutations associated with MRMP is now available by polymerase chain reaction and fluorescent probe techniques in respiratory specimens. Although the resistance rate to macrolide remains high, it is fortunate that M. pneumoniae still maintains good in vitro sensitivity to second-line antibiotics such as tetracyclines and quinolones, making them an effective treatment option for patients with initial treatment failure caused by macrolide antibiotics. CONCLUSIONS: This consensus, based on international and national scientific evidence, provides scientific guidance for the diagnosis and treatment of MRMP in children. Further studies on tetracycline and quinolone drugs in children are urgently needed to evaluate their effects on the growth and development. Additionally, developing an antibiotic rotation treatment strategy is necessary to reduce the prevalence of MRMP strains.

Knockdown of fibrillin-1 suppresses retina-blood barrier dysfunction by inhibiting vascular endothelial apoptosis under diabetic conditions.

AIM: To investigate the effects of fibrillin-1 (FBN1) deletion on the integrity of retina-blood barrier function and the apoptosis of vascular endothelial cells under diabetic conditions. METHODS: Streptozotocin (STZ)-induced diabetic mice were used to simulate the diabetic conditions of diabetic retinopathy (DR) patients, and FBN1 expression was detected in retinas from STZ-diabetic mice and controls. In the Gene Expression Omnibus (GEO) database, the GSE60436 dataset was selected to analyze FBN1 expressions in fibrovascular membranes from DR patients. Using lentivirus to knock down FBN1 levels, vascular leakage and endothelial barrier integrity were detected by Evans blue vascular permeability assay, fluorescein fundus angiography (FFA) and immunofluorescence labeled with tight junction marker in vivo. High glucose-induced monkey retinal vascular endothelial cells (RF/6A) were used to investigate effects of FBN1 on the cells in vitro. The vascular endothelial barrier integrity and apoptosis were detected by trans-endothelial electrical resistance (TEER) assay and flow cytometry, respectively. RESULTS: FBN1 mRNA expression was increased in retinas of STZ-induced diabetic mice and fibrovascular membranes of DR patients (GSE60436 datasets) using RNA-seq approach. Besides, knocking down of FBN1 by lentivirus intravitreal injection significantly inhibited the vascular leakage compared to STZ-DR group by Evans blue vascular permeability assay and FFA detection. Expressions of tight junction markers in STZ-DR mouse retinas were lower than those in the control group, and knocking down of FBN1 increased the tight junction levels. In vitro, 30 mmol/L glucose could significantly inhibit viability of RF/6A cells, and FBN1 mRNA expression was increased under 30 mmol/L glucose stimulation. Down-regulation of FBN1 reduced high glucose (HG)-stimulated retinal microvascular endothelial cell permeability, increased TEER, and inhibited RF/6A cell apoptosis in vitro. CONCLUSION: The expression level of FBN1 increases in retinas and vascular endothelial cells under diabetic conditions. Down-regulation of FBN1 protects the retina of early diabetic rats from retina-blood barrier damage, reduce vascular leakage, cell apoptosis, and maintain vascular endothelial cell barrier function.

Cold-hot Janus electrochemical aptamer-based sensor for calibration-free determination of biomolecules.

Real-time, high-frequency measurements of pharmaceuticals, metabolites, exogenous antigens, and other biomolecules in biological samples can provide critical information for health management and clinical diagnosis. Electrochemical aptamer-based (EAB) sensor is a promising analytical technique capable of achieving these goals. However, the issues of insufficient sensitivity, frequent calibration and lack of adapted portable electrochemical device limit its practical application in immediate detection. In response we have fabricated an on-chip-integrated, cold-hot Janus EAB (J-EAB) sensor based on the thermoelectric coolers (TECs). Attributed to the Peltier effect, the enhanced/suppressed current response can be generated simultaneously on cold/hot sides of the J-EAB sensor. The ratio of the current responses on the cold and hot sides was used as the detection signal, enabling rapid on-site, calibration-free determination of small molecules (procaine) as well as macromolecules (SARS-CoV-2 spike protein) in single step, with detection limits of 1 µM and 10 nM, respectively. We have further demonstrated that the J-EAB sensor is effective in improving the ease and usability of the actual detection process, and is expected to provide a universal, low-cost, fast and easy potential analytical tool for other clinically important biomarkers, drugs or pharmaceutical small molecules.

Pediatric high-altitude pulmonary edema and acute mountain sickness: Clinical features and risk determinants.

OBJECTIVE: This investigation aimed to delineate the clinical manifestations associated with high-altitude pulmonary edema (HAPE) and acute mountain sickness (AMS) in pediatric populations and find the risk factors of HAPE. METHODS: We conducted a retrospective analysis of clinical data from children under 18 years diagnosed with HAPE and AMS at an average altitude of 3000 m. The clinical data between these two groups were compared. RESULTS: The study encompassed 74 pediatric patients, 27 with AMS and 47 with HAPE. HAPE presentations included classic HAPE (55.3%), reentry HAPE (27.7%), and high-altitude resident pulmonary edema (HARPE, 17.0%). Notably, 87.2% of HAPE cases were male, and 68.1% had a high body mass index (BMI). HARPE instances followed viral infections, prominently SARS-CoV-2. HAPE cases exhibited higher BMI, respiratory tract infections within 1 week preceding symptom onset, an increase in white blood cell counts (WBCs), lower peripheral arterial oxygen saturation (SpO2), and higher heart rate compared to the AMS group. Multivariate logistic regression pinpointed high BMI as an independent HAPE risk factor (odds ratio = 19.389, 95% confidence interval: 1.069-351.759, p = .045). CONCLUSION: HAPE occurs predominantly in males, with high BMI identified as a critical independent risk factor. The study underscores the need for heightened awareness and preventive strategies against HAPE in children at high altitudes.

Enantioselective Synthesis of Planar-Chiral Sulfur-Containing Cyclophanes by Chiral Sulfide Catalyzed Electrophilic Sulfenylation of Arenes.

An efficient catalytic asymmetric electrophilic sulfenylation reaction for the synthesis of planar-chiral sulfur-containing cyclophanes has been developed for the first time. This was achieved by using a new Lewis base catalyst and a new ortho-trifluoromethyl-substituted sulfenylating reagent. Using the substrates with low rotational energy barrier, the transformation proceeded through a dynamic kinetic resolution, and the high rotational energy barrier of the substrates allowed the reaction to undergo a kinetic resolution process. Meanwhile, this transformation was compatible with a desymmetrization process when the symmetric substrates were used. Various planar-chiral sulfur-containing cyclophanes were readily obtained in moderate to excellent yields with moderate to excellent enantioselectivities (up to 97 % yield and 95 % ee). This approach was used to synthesize pharmaceutically relevant planar-chiral sulfur-containing molecules. Density functional theory calculations showed that π-π interactions between the sulfenyl group and the aromatic ring in the substrate play a crucial role in enantioinduction in this sulfenylation reaction.

Expert consensus on the diagnosis, treatment, and prevention of respiratory syncytial virus infections in children.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5 years, representing a major global healthcare burden. There is a great unmet need for new agents and universal strategies to prevent RSV infections in early life. A multidisciplinary consensus development group comprising experts in epidemiology, infectious diseases, respiratory medicine, and methodology aims to develop the current consensus to address clinical issues of RSV infections in children. DATA SOURCES: The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, and the Cochrane Library, using variations in terms for "respiratory syncytial virus", "RSV", "lower respiratory tract infection", "bronchiolitis", "acute", "viral pneumonia", "neonatal", "infant" "children", and "pediatric". RESULTS: Evidence-based recommendations regarding diagnosis, treatment, and prevention were proposed with a high degree of consensus. Although supportive care remains the cornerstone for the management of RSV infections, new monoclonal antibodies, vaccines, drug therapies, and viral surveillance techniques are being rolled out. CONCLUSIONS: This consensus, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of RSV infections. Further improvements in the management of RSV infections will require generating the highest quality of evidence through rigorously designed studies that possess little bias and sufficient capacity to identify clinically meaningful end points.

[Review on the Long-term and Short-term Effects of Biochar Addition on Soil Greenhouse Gas Emissions].

Increasing concentrations of greenhouse gases in the atmosphere caused by human activities are the main cause of climate warming. Global warming is a severe challenge confronted by human society today. Reducing greenhouse gas emissions and increasing carbon sinks are the keys to addressing climate warming. Biochar addition is considered to be a promising way to reduce greenhouse gas emissions and increase carbon sinks, due to its unique physical, chemical, and biological properties. Therefore, it is of great significance to study the effects of biochar on soil greenhouse gas emissions to mitigate the greenhouse effect and achieve "carbon neutrality." The long-term and short-term effects of biochar on soil greenhouse gas emissions and their influencing mechanism were reviewed. It was found that the effects of biochar on soil greenhouse gas emissions varied with the types of biochar feedstock, pyrolysis temperature, application ratio, and soil and vegetable types. In addition, due to the different aging times and modes and cultivation methods, the mitigation effect of aged biochar on soil greenhouse gas could be enhanced or weakened or even disappeared. Further, based on the deficiencies of the previous research, the direction and focus of future research on the effects of biochar on soil greenhouse gas emissions were analyzed and prospected. It was proposed to strengthen simultaneous research on the effects of biochar on CO2, N2O, and CH4 emissions; reducing greenhouse gas emissions and carbon sequestration; different aging modes and cultivation methods of biochar; and revealing the influencing mechanism at the process level, through exploring the effects of biochar on soil carbon and nitrogen dynamics and tracing the source of greenhouse gases using 13C and 15N tracer technology.

[Effect of processing with vinegar on efficacy of Curcuma longa in treatment of dysmenorrhea in rats with syndrome of liver depression and Qi stagnation].

This study compared the effects of Curcuma longa before and after processing with vinegar on the rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation to reveal the mechanism of vinegar processing in improving the role of C. longa in soothing liver and relieving pain. The rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation was established according to the Preparation of the Animal Model of Dysmenorrhea(Draft) and the chronic unpredictable stress me-thod. The changes in the body weight, organ indexes, writhing latency, writhing score, and serum levels of six liver function indicators, sex hormones, pain factors, and blood rheological indicators were measured to evaluate the efficacy of C. longa processed with vinegar or not in treating dysmenorrhea in the rats with syndrome of liver depression and qi stagnation. Compared with the model group, the C. longa group(processed with vinegar or not) showed slow weight loss, increase in writhing latency, and decrease in writhing response(P<0.05). The inhibition rates on writhing in raw C. longa, vinegar-processed C. longa, and positive groups were 33.780%, 64.611%, and 62.466%, respectively. The significantly higher inhibition rate of the vinegar processing group indicated that vinegar-processed C. longa demonstrated more significant therapeutic effect. The vinegar-processed C. longa group showed lower levels of alanine aminotransferase(ALT), alkaline phosphatase(ALP), aspartate aminotransferase(AST), direct bilirubin(DBIL), and total bilirubin(TBIL) and higher level of albumin(ALB)(P<0.05), which indicated that vinegar processing enhanced the therapeutic effect of C. longa on liver injury. The serum levels of estradiol(E_2) and oxytocin(OT) were lower in the vinegar-processed C. longa group(P<0.05), indicating that the vinegar-processed C. longa could regulate the sex hormone levels, reduce the activity of uterine smooth muscle and contraction of uterus, and alleviate the symptoms of dysmenorrhea in rats. Moreover, the vinegar-processed C. longa group showed lower interleukin-6(IL-6) and arginine vasopressin(AVP) levels and higher beta-endorphin(ß-EP) level(P<0.05), which indicated that vinegar-processed C. longa regulated the levels of pain factors to exert the pain-relieving effect. Drug intervention decreased the whole blood viscosity low-cut, medium-cut and high-cut values, plasma viscosity, whole blood reduction viscosity low-cut and high-cut values, erythrocyte cumulative pressure, and equation K value of erythrocyte sedimentation rate(P<0.05), and the vinegar-processed C. longa group outperformed other groups. This result indicated that vinegar processing enhanced the function of C. longa in improving the local blood rheology. C. longa processed with vinegar can enter the liver to relieve the da-mage to the heart, liver, kidney, and uterus, repair the liver function, and recover the sex hormone levels and immune function by regulating the levels of sex hormones and pain factors and improving the blood rheology. It activates the pain-relieving mechanism to relieve the pain, protect the liver, and fight inflammation, which is consistent with the theory that vinegar processing facilitates C. longa entering the liver to sooth liver and relieve pain.

Atroposelective Sulfenylation of Biaryl Anilines Catalyzed by Chiral SPINOL-Derived Selenide.

The atroposelective electrophilic sulfenylation of biaryl anilines has been realized for the first time. The reaction is enabled by a new chiral 6,6'-dianisole substituted SPINOL-derived selenide. A variety of axially chiral sulfur-containing biaryl aniline compounds were obtained in moderate to excellent yields with moderate to excellent enantioselectivities. The experimental results suggest that catalyst rigidity is important for the high atroposelectivity.

[Material basis and mechanism of Curcuma longa tuberous roots with and without vinegar processing in treating primary dysmenorrhea].

Liquid chromatography-mass spectrometry was employed to analyze the chemical components in Curcuma longa tuberous roots(HSYJ), C. longa tuberous roots processed with vinegar(CHSYJ), and rat serum after the administration. The active components of HSYJ and CHSYJ absorbed in serum were identified based on the secondary spectrum of database and literature. The targets of primary dysmenorrhea was screened out from database. The protein-protein interaction network analysis, gene ontology(GO) functional annotation, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed for the common targets shared by the drug active components in serum and primary dysmenorrhea, and the component-target-pathway network was constructed. AutoDock was used to conduct molecular docking between the core components and targets. A total of 44 chemical components were identified from HSYJ and CHSYJ, including 18 absorbed in serum. On the basis of network pharmacology, we identified 8 core components(including procurcumenol, isobutyl p-hydroxybenzoate, ferulic acid, and zedoarondiol) and 10 core targets \[including interleukin-6(IL-6), estrogen receptor 1(ESR1), and prostaglandin-endoperoxide synthase 2(PTGS2)\]. The core targets were mainly distributed in the heart, liver, uterus, and smooth muscle. The molecular docking results showed that the core components were well bound to the core targets, indicating that HSYJ and CHSYJ may exert therapeutic effect on primary dysmenorrhea via estrogen, ovarian steroidogenesis, tumor necrosis factor(TNF), hypoxia-inducible factor-1(HIF-1), IL-17 and other signaling pathways. This study clarifies the HSYJ and CHSYJ components absorbed in serum, as well as the corresponding mechanism, providing a reference for further elucidating the therapeutic material basis and clinical application of HSYJ and CHSYJ.

In-syringe dispersive solid phase filter extraction cleanup followed by liquid chromatography-triple quadrupole mass spectrometry for fast determination of colchicine in plasma/urine.

As an effective treatment for acute gouty arthritis and cardiovascular disease, colchicine is also a toxic alkaloid and may cause poisoning or even death in overdose. The study of colchicine elimination and the diagnosis of poisoning etiology need the rapid and accurate quantitative analysis method in biological matrix. An analytical method was developed for colchicine in plasma and urine by in-syringe dispersive solid phase extraction (DSPE) followed by liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS). Sample extraction and protein precipitation were proceeded with acetonitrile. The extract was cleaned by in-syringe DSPE. An XBridge™ BEH C18 column（100 mm × 2.1 mm, 2.5 µm）was used to separate colchicine by gradient elution with mobile phase of 0.01% (v/v) ammonia-methanol. The amount and filling sequence of magnesium sulfate (MgSO4) and primary secondary amine (PSA) suitable for in-syringe DSPE were studied. Scopolamine was screened as the quantitative internal standard (IS) for colchicine analysis according to the consistency of recovery rate, chromatographic retention time and matrix effects. The limits of detection for colchicine in plasma and urine were both 0.06 ng mL-1 and the limits of quantitation were both 0.2 ng mL-1. The linear range was 0.04 - 20 ng mL-1 (Equivalent to 0.2-100 ng mL-1 in plasma or urine) with a correlation coefficient r > 0.999. By IS calibration, the average recoveries at three spiking levels in plasma and urine were 95.3-102.68% and 93.9-94.8% with the relative standard deviations (RSDs) of 2.9-5.7% and 2.3-3.4%, respectively. The matrix effects, stability, dilution effects and carryover for determination of colchicine in plasma and urine were also evaluated. The elimination of colchicine within 72-384 h post-ingestion was studied for a poisoning patient with the doses of 1 mg d-1 for 39 days and then 3 mg d-1 for 15 days).

Knowledge, attitudes and practices of enhanced recovery after surgery among paediatric surgical nurses in China: A Cross-Sectional study.

AIM: To investigate paediatric surgical nurses' knowledge, attitudes and practices (KAP) regarding enhanced recovery after surgery (ERAS). DESIGN: A cross-sectional study. METHODS: A 34-question survey was developed. An electronic version of the questionnaire was distributed to nurses working in paediatric surgical departments of 22 tertiary hospitals from 14 provinces of China by means of convenience sampling from February to April 2021. A total of 855 nurses' data was used as the final sample. The statistical analysis included nonparametric test, Spearman's correlation and multiple linear regression. RESULTS: There is still room for improvement regarding the KAP of paediatric surgical nurses, especially in the knowledge of "postoperative recovery" and "preoperative preparation". The influencing factors of KAP were educational level, geographical region (South, Central, North, Northwest), years of work experience, hospital category (general hospital, women and children's hospital), and familiarity with ERAS.

Electrophilic Thiocyanation of Tryptamine Derivatives: Divergent Synthesis of SCN-Containing Indole Compounds.

A tandem dearomative electrophilic thiocyanation/cyclization/acylation of indoles was developed for the first time, which is enabled by acyl chloride. A variety of 3-SCN pyrroloindolines were obtained with moderate to excellent yields. Interestingly, following replacement of acyl chloride with methanesulfonic acid, 2-SCN tryptamines were obtained using the same starting substrates and reagents. Furthermore, catalytic enantioselective manner of thiocyanation/cyclization/acylation reaction was also studied. An enantiomer self-disproportionation effect of 3-SCN pyrroloindolines was discovered. A series of chiral 3-SCN pyrroloindolines were obtained with high enantioselectivities.

Atroposelective Electrophilic Sulfenylation of N-Aryl Aminoquinone Derivatives Catalyzed by Chiral SPINOL-Derived Sulfide.

Atroposelective electrophilic sulfenylation of N-aryl aminoquinone derivatives has been achieved for the first time. This transformation is enabled by a new chiral 6,6'-disubstituted SPINOL-derived sulfide catalyst, which was first synthesized and then successfully explored for catalyzing enantioselective reactions. Various axially chiral sulfur-containing diarylamine derivatives were readily obtained in moderate to excellent yields with moderate to excellent enantioselectivities. A class of relatively flexible stereogenic C-N axes was easily constructed. The experimental results and a computational study suggested that an intramolecular N-H⋅⋅⋅S hydrogen bond is important for the stability of the C-N axis, which is consistent with our hypothesis. Density functional theory calculations revealed the origin of atroposelectivity and underscored the importance of catalyst rigidity in this sulfenylation reaction.

The Alkynylative Difunctionalization of Alkenes.

Given alkynyl group is an important functional unit, a variety of efficient methods have been developed to construct alkynyl-containing compounds. Among them, the alkynylative difunctionalization of alkenes is one of the most straightforward and efficient strategies for preparing these compounds and so has made great progress in recent years, including the catalytic asymmetric manner. However, there is no comprehensive review to summarize these studies. This review is aimed at comprehensively summarizing the alkynylative difunctionalization of alkenes, which is presented in terms of alkynylation-initiated and alkynylation-terminated difunctionalizations of alkenes. We hope that this review will help to encourage more researchers to further explore in this field.

Palladium-Catalyzed Three-Component Cross-Coupling of Conjugated Dienes with Indoles Using Ethynylbenziodazolones as Electrophilic Alkynylating Reagents.

A palladium-catalyzed regioselective 1,2-alkynyl-carbonalization of conjugated dienes with ethynylbenziodazolone (EBZ) and indoles has been developed for the first time. Various molecules containing alkenyl, alkynyl, and indole groups were readily obtained. Moreover, the resulting products can be applied to various derivatizations. This protocol uses EBZ as an electrophilic alkynylating reagent, avoiding the byproduct of dimerization of alkynes.

Chiral Lewis Base Catalyzed Enantioselective Selenocyclization of 1,1-Disubstituted Alkenes: Asymmetric Synthesis of Selenium-Containing 4H-3,1-Benzoxazines.

An enantioselective selenocyclization of 1,1-disubstituted alkenes was achieved for the first time, which is enabled by a novel combination of a chiral BINAM-derived sulfide and an achiral Lewis acid. Various selenium-containing 4H-3,1-benzoxazines, which are widely present in a range of medicinally relevant molecules, were readily obtained in moderate to good yields and good to excellent enantioselectivities. A series of tetrasubstituted carbon stereocenters were facilely constructed.

Efficacy and safety of Chinese herbal medicine Qirui Weishu capsule in treating chronic non-atrophic gastritis: A multicentre, double-blind, randomized controlled clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: QiruiWeishu capsule is an herbal preparation from a herbal formula prescribed by an experienced doctor at Guang'anmen Hospital of China Academy of Chinese Medical Sciences. It has been used clinically for more than 30 years. Abdominal pain, distension, and nausea are common symptoms of chronic non-atrophic gastritis with erosion dampness and heat stasis syndrome, and this herbal medicine has been used to treat them. AIM OF THE STUDY: To verify the clinical efficacy and safety of QiruiWeishu capsule in the treatment of chronic non-atrophic gastritis with damp-heat stasis syndrome. MATERIALS AND METHODS: This study was a multicenter randomized double-blind clinical trial with positive herbal drug SanjiuWeitai capsule as control and superiority test of main efficacy. A total of 477 subjects with chronic non-atrophic gastritis with erosion diagnosed by gastroscopy and pathological biopsy were randomly divided into QiruiWeishu capsule and SanjiuWeitai groups respectively in a ratio of 3:1. During the trial, subjects were required to complete medication for 28 days. The primary outcome was the disappearance rate of epigastric pain from baseline to 4weeks. At baseline, treatment at 1, 2, and 4 weeks, and follow-up at 8 and 16 weeks, the epigastric pain and traditional Chinese medicine (TCM) symptom scores were evaluated; gastroscopy, histopathology, and the helicobacter pylori test were evaluated at baseline and after 4 weeks of treatment. The safety assessment included blood routine, liver and kidney function, coagulation of laboratory tests, and electrocardiogram (ECG). RESULTS: Both groups of subjects had a high level of medication adherence (defined as treatment completion for over 80%) (346/357, 96.9% in Qirui Weishu group vs 118/120, 98.3% in Sanjiu Weitai group; p > 0.05). The QiruiWeishu capsule was significantly better than SanjiuWeitai capsule in disappearance rate of epigastric pain (64.2%, 229/357vs 46.7%, 56/120; p < 0.001)，especially subgroupsubjects with moderate epigastric pain (65.0%, 89/137 vs 30.4%, 14/46; p < 0.001), grade1 erythema (67.7%, 149/220 vs 51.9%, 42/81; p = 0.011) and grade 2 erythema (57.6%, 70/121 vs37.1%, 13/35; p = 0.050) of gastroscopy, grade 2 erosion (66.7%, 118/177 vs43.9%, 25/57; p = 0.002) of gastroscopy and Helicobacter pylori negative (65.4%, 155/237 vs 42.7%, 35/82; p < 0.001) at baseline. For the scores of TCM symptoms in QiruiWeishu group were significantly lower than those in SanjiuWeitai group after 28 days of treatment (p = 0.002). The number and incidence of adverse events related to the trial drug were 14/355 (3.9%) in QiruiWeishu group, 6/118 (5.1%) in SanjiuWeitai group (p > 0.05). No serious adverse reactions occurred in the two groups. According to laboratory tests and ECG, there was no discernible effect on heart, liver, kidney, or blood coagulation function. CONCLUSION: Qirui Weishu capsule appears to be more effective in terms of symptoms than the SanjiuWeitai capsule, and its use is both safe and effective for the treatment of chronic non-atrophic gastritis. A further randomized, double-blind, placebo-control trial is warranted to verify its benefit.