Search

We report a method for the synthesis of a universal deuterated methylthiolating reagent through a one-pot gram-scale operation under mild conditions. This reacts with various nucleophiles to give SCD3 analogues with high deuterium levels (>99% D).

A new type of organocatalyzed 1,3-thiosulfonylation has been developed to straightforwardly access highly functionalized vinyl sulfones, which features mild conditions, atom- and step-economy, practicability, conciseness, and environmental friendliness. Moreover, these valuable products can be transformed to vinyl sulfides

Purpose: To conduct a systematic analysis on data from randomized controlled trials (RCTs) on different doses of guselkumab, and provide high-quality evidence for its use in the treatment of patients with moderate-to-severe plaque psoriasis (PsO). Methods: Related studies were searched using online search engines including MEDLINE, PubMed, and central registry of Cochrane controlled trials from January 2001 to October 2017. Only randomized, placebo-controlled, double-blind clinical trials involving guselkumab- and placebo-treated PsO subjects were included. Results: Five eligible double-blind, randomized, and placebo-controlled trials involving patients with moderate-to-severe PsO subjects treated with guselkumab were included. Compared with the placebo groups, the proportion of patients with improvements in Psoriasis Area and Severity Index (PASI) 75 (RR= 12.14; 95% CI= 9.11-16.16; p < 0.001); PASI 90 (RR= 23.26; 95% CI =14.57-37.13; p < 0.001), and PASI 100 (RR = 37.66; 95% CI = 15.81-89.69; p < 0.001) were significantly higher than those in guselkumab-treated groups. Furthermore, the guselkumab-treated groups showed significant decreases in Physician’s Global Assessment (PGA) score (RR = 10.46; 95% CI = 7.96-13.83; p < 0.001) and the Dermatology Life Quality Index (DLQI) score (SMD = -1.3; 95% CL = -1.4 to -1.19; p < 0.001), when compared with the placebo groups. However, there were no significant differences in adverse events (AEs) (RR = 1.01; 95% CL = 0.93-1.11; p > 0.05); severe adverse events (SAEs) (RR = 1.32; 95% CI =0.69-2.54; p > 0.05) and study discontinuations (RR = 0.79; 95% CI = 0.42-1.48; p > 0.05) between the two groups. Conclusion: This meta-analysis summarizes available evidence for the use of guselkumab in psoriasis. The results suggest that guselkumab is superior to placebo in moderate-to-severe psoriasis, and is welltolerated, effective, and safe in improving the severity of disease and quality of life. Keywords: Guselkumab, Effectiveness, Safety, Plaque psoriasis, Meta-analysis, Quality of life

We have developed a high-efficiency and practical Cu-catalyzed cross-coupling to directly construct versatile α-aryl-esters by utilizing readily available aryl bromides (or chlorides) and malonates. These gram-scale approaches occur with turnovers of up to 1560 and are smoothly conducted by the usage of a low catalyst loading, a new available ligand, and a green solvent. A variety of functional groups are tolerated, and the application occurs with α-aryl-esters to access nonsteroidal anti-inflammatory drugs (NSAIDs) on the gram scale.

Background: Currently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, causing an unprecedented pandemic However, there is st

Aconiti Lateralis Radix Praeparata ("Fuzi" in Chinese) in combination with Zingiberis Rhizoma ("Ganjiang" in Chinese) is commonly applied for the treatment of heart failure for thousands of years in China. However, its therapeutic mechanism is still poorly defined. This study aimed to investigate whether the compatibility of Fuzi and Ganjiang can protect rats with acute heart failure by enhancing mitochondrial biogenesis via Sirt1/PGC-1α signaling pathway. Hemodynamic parameters, including heart rate and left ventricular maximal rate of pressure rise and decline, were recorded in rats with acute heart failure induced by Propafenone hydrochloride. The serum levels of cardiac enzymes, including creatine kinase, lactate dehydrogenase, brain natriuretic peptide and cardiac troponin T, were also determined. The gene and protein levels of Sirtuin 1 (Sirt1), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and their downstream transcription factors were measured as well. The results indicated that Fuzi-Ganjiang herbal couple provided more significant benefits by restoring the left ventricular function and cardiac enzyme activities in comparison with their single use. Moreover, this herbal couple possessed a significant cardio-protection by increasing both gene and protein levels of Sirt1 and PGC-1α. In conclusion, the compatibility of Fuzi and Ganjiang had better therapeutic effect than their single use against failing heart, and the underlying mechanisms were partially through increasing mitochondrial biogenesis via Sirt1/PGC-1α pathway.

Background: To investigate whether TDF-containing regimens significantly benefited efficacy, safety, and tolerability in TAF-containing regimens in virologically suppressed HIV-infected patients. Methods: PubMed, Embase, Web of Science, and the Cochrane Trial Registry were systematically searched for eligible studies. We extracted and evaluated the pooled data from available randomized controlled trials (RCTs). Results: Eight eligible RCTs were included. In the intention-to-treat (ITT) analysis, patients who switched to TAF-containing regimens had significantly better viral suppression than those continuing TDF-containing regimens at weeks 48 and 96 (RR, 1.02; 95CI, 1.00–1.03; p 0.05). Compared with those receiving the TDF-containing regimens, virologically suppressed HIV-infected patients on the TAF-containing regimens had significant increases in CD4 cell counts (SMD, 0.12; 95CI, 0.08 to 0.17; p

Objective Currently, powdered Chinese herbal medicines (CHMs) were mainly evaluated through physical property, chemical dissolution, and bioactivity independently. It could not reflect the quality comprehensively. This paper was to explore and establish a comprehensive evaluation method for powdered CHMs. Methods Isatidis Radix was chosen as an exemple. Firstly, powdered Isatidis Radix in different particle size was prepared. Then, their physical properties were characterized. The dissolution of index component epigoitrin was determined, and their antiviral activities were evaluated by neuraminidase-based bioassay. Results As the particle size decreased, powder distribution tended to be uniform, and the dissolution of epigoitrin increased, antiviral activity enhanced. According to cluster analysis of above results, the sequence of evaluation consequence was ultrafine powder S2 (D90: 32.80 ± 0.29) > ultrafine powder S1 (D90: 52.08 ± 0.53) > fine powder S0 (D90: 118.16 ± 0.76) (from the superior to the inferior). Conclusion Overall, the comprehensive evaluation for powdered CHMs based on the physical characterization, chemical dissolution, and bioassay could not only be used to evaluate powdered herbs, but also guide the screening and optimization of the particle size of powder.

Zingiberis Rhizoma is a typical Chinese herb in ‘hot’ property. Nowadays, increasing attention has been aroused for its essential role in both health care and treatment of ‘cold’ syndrome. And research about characteristics of Zingiberis Rhizoma is able to provide an important reference for its deeper understand and successful clinic application. However, cognition level about the ‘hot’ property of Zingiberis Rhizoma is superficial, and mechanism behind the ‘hot’ presentation is still elusive and unclear. In this study, the ‘hot’ property of Zingiberis Rhizoma was investigated at a monomer level with assistance of microcalorimetry, an objective and sensitive method in evaluating biological activity. Three bioactive compounds including 6-gingerol, 8-gingerol and 6-shogaol were selected, and their thermal activities were explored with mitochondria as target. The power–time curves were recorded, and five thermal parameters (k, P max, T max, Q and P av) were obtained. With PCA, P av was calculated to be the main parameter to measure the bioactivities of 6-gingerol, 8-gingerol and 6-shogaol. Finally, the bioactivities of three subjects were compared with sequence to be 6-gingerol > 8-gingerol > 6-shogaol. Generally, our study is promising to offer a reference to the research about characteristics of Zingiberis Rhizoma or other herbs and is of great interest for clinic practice.

BACKGROUND Toxoplasma encephalitis (TE) is one of the main opportunistic infections in acquired immunodeficiency syndrome (AIDS) patients, and represents a social burden due to its high prevalence and morbidity. Concomitant antiretroviral therapy (ART), together with effective anti- toxoplasma combination therapy, is an effective strategy to treat AIDS-associated TE (AIDS/TE) patients. However, the timing for the initiation of ART after diagnosis of TE remains controversial. We therefore designed the present study to determine the optimal timing for ART initiation in AIDS/TE patients. METHODS/DESIGN This trial is a 17-center, randomized, prospective clinical study with 2 parallel arms. A total of 200 participants will be randomized at a 1:1 ratio into the 2 arms: the early ART initiation (≤14 days after TE diagnosis) arm and the deferred ART (>14 days after TE diagnosis) arm. The primary outcome will be the difference of mortality between the 2 arms at 48 weeks. The secondary outcomes will be the differences between the 2 arms in the changes of CD4+ counts from baseline to week 48, the rate of virologic suppression (HIV ribonucleic acid

Apoptosis induced by the bile acids in the liver is considered to play a pivotal role in the pathogenesis of cholestatic disease. Increasing evidence has demonstrated that Paeoniflorin (PF) exerts therapeutic effect on severe cholestatic liver diseases. However, whether PF could protect against alpha-naphthylisothiocyanate (ANIT)-induced cholestasis by inhibiting apoptosis remains unclear. In this study, we mainly investigated the effect and anti-apoptosis mechanism of PF on cholestasis. Experimental results indicated that PF pretreatment could attenuate liver damage and cholestasis by ANIT in rats, lift the biliary excretion in addition to decrease serum indices (ALT, AST, DBIL, TBIL, TBA, ALP and ϒ-GT) and conspicuous neutrophil infiltration and cell apoptosis in liver evidenced by TUNEL staining. Furthermore, the pro-apoptosis genes expression of Bax, Caspase-9 and Caspase-3 increased by ANIT were prominently reduced after PF treatment. The increase of anti-apoptosis gene and main regulator Bcl-2 in mitochondria by ANIT was largely reversed by PF pre-treatment. In summary, our study demonstrated that PF pre-treatment not only significantly attenuated ANIT-induced cholestasis and liver injury, but also largely reduced cell apoptosis in liver, thus may act as a potential therapeutic agent for cholestasis disease.

Background Simplifying antiretroviral therapy (ART) enhances tolerability, decreases toxicities, and reduces costs. However, more evidence is still needed to show the benefit and risk of simplified ART regimens. Therefore, we aimed to evaluate the efficacy and safety of simplified ART regimens based on raltegravir for people living with HIV infection. Methods We did a systematic review and meta-analysis of randomised controlled trials (RCTs). We systematically searched PubMed, MEDLINE, Web of Science, and Embase from their inception to Jan 31, 2018, using the following search terms: “HIV”, “protease inhibitor”, and “raltegravir” in English. We identified raltegravir-based RCTs containing only two drugs; we subsequently compared the efficacy and safety between raltegravir-based simplified regimens with traditional protease inhibitor-based three-drug or four-drug regimens. Primary measures included viral suppression, CD4 cell counts, and adverse events. We pooled data across studies and estimated summary effect sizes using an intention-to-treat (ITT) analysis and per-protocol (PP) analysis. The included data were analysed with Review Manager (version 5.3). Findings We identified and included eight RCTs involving 4420 patients with HIV-1 infection, of whom 2187 (49·5%) patients who were receiving raltegravir plus ritonavir-boosted protease inhibitors were compared with 2144 (48·5%) patients receiving ritonavir-boosted protease inhibitors plus two or three nucleoside reverse-transcriptase inhibitors (NRTIs). The proportion of viral suppression of raltegravir-based simplified regimens was 77% (95% CI 73–80 for the ITT analysis) and 81% (95% CI 71–91 for the PP analysis) at 24 weeks, 79% (71–87; ITT) and 75% (70–81; PP) at 48 weeks, and 74% (61–86; ITT) and 82% (70–93; PP) at 96 weeks. The proportion of viral suppression of ritonavir-boosted protease inhibitors plus two or three NRTIs was 69% (95% CI 65–74 for the ITT analysis) and 70% (95% CI 53–88 for the PP analysis) at 24 weeks, 78% (70–86; ITT) and 73% (68–79; PP) at 48 weeks, and 71% (61–82; ITT) and 80% (71–89; PP) at 96 weeks. At 24 weeks, the efficacy of raltegravir-based two-drug regimens was greater than that of ritonavir-boosted protease inhibitors plus two or three NRTIs (ITT analysis: risk ratio 1·11, 95% credible interval 1·02–1·21; p=0·01). Patients had significantly higher CD4 cell counts than those receiving NRTIs-based three-drug or four-drug regimens at 48 weeks and 96 weeks. Raltegravir-based simplified regimens had less grade 3 or 4 adverse events than traditional NRTIs-based regimens at 48 week (p=0·007). Interpretation The results of this systematic review and meta-analysis supported that regimens containing raltegravir plus ritonavir-boosted protease inhibitors were non-inferior to regimens containing ritonavir-boosted protease inhibitors plus two or three NRTIs in viral suppression. However, simplified regimens resulted in better CD4 cell count concentrations and lower numbers of adverse events. Funding The National Science and Technology Major Project of China During the 13th Five-year Plan Period (2018ZX10302104001), Chinese Medicine Science and Technology Project (number ZY201702047), Chinese Government 13th Five-year Plan (2017ZX10201101), Major Project of Beijing Municipal Science and Technology Committee (D161100000416003), and The National Natural Science Foundation of China (81701984).