Alkyne Insertion Enabled Vinyl to Acyl 1,5-Palladium Migration: Rapid Access to Substituted 5-Membered-Dihydrobenzofurans and Indolines.

"Through space" palladium/hydrogen shift is an efficient strategy to achieve selective functionalization of a specific remote C-H bond. Compared with relatively extensive exploited 1,4-palladium migration process, the relevant 1,5-Pd/H shift was far less investigated. We herein report a novel 1,5-Pd/H shift pattern between a vinyl and an acyl group. Through the pattern, rapid access to 5-membered-dihydrobenzofuran and indoline derivatives has been achieved. Further studies have unveiled an unprecedented trifunctionalization (vinylation, alkynylation and amination) of a phenyl ring through 1,5-palladium migration relayed decarbonylative Catellani type reaction. A series of mechanistic investigations and DFT calculations have provided insights into the reaction pathway. Notably, it was unveiled that the 1,5-palladium migration in our case prefers a stepwise mechanism involving a PdIV intermediate.

MiR-122-5p knockdown protects against APAP-mediated liver injury through up-regulating NDRG3.

MiR-122-5p serves as a novel biomarker for drug-induced liver injury (DILI), but its function in DILI remains unclear. The present study, therefore, explored the function and potential mechanism of miR-122-5p in DILI. Sprague-Dawley (SD) rats were treated with miR-122-5p antagomir, and then DILI was induced in the rats by acetaminophen (APAP). To determine the effect of miR-122-5p on DILI in vivo, liver injury was examined by HE staining and TUNEL assays, and the levels of serum ALT and AST were determined using an automated clinical chemistry analyzer. To further reveal the mechanism of miR-122-5p in DILI, THLE-2 (normal liver cell line) cells were transfected with miR-122-5p mimic and inhibitor, NDRG3, and siNDRG3, and then injured by APAP. The relationship between miR-122-5p and NDRG3 was determined by TargetScan, luciferase reporter assay, and Western blot. The viability and apoptosis of THLE-2 cells were detected by CCK-8 and flow cytometry, respectively. The levels of mRNA and protein in vivo and in vitro were measured by qRT-PCR and Western blot, respectively. APAP induced liver injury and increased the levels of ALT, AST, and miR-122-5p in DILI rats. However, these effects of APAP were attenuated by miR-122-5p antagomir. MiR-122-5p negatively regulated NDRG3 expression. APAP decreased cell viability, apoptosis resistance, and Bcl-w and Bcl-2 levels whereas increased Bax level in THLE-2 cells. However, these effects of APAP on THLE-2 cells were promoted by miR-122-5p up-regulation but inhibited by miR-122-5p knockdown. MiR-122-5p knockdown protects against APAP-mediated liver injury through up-regulating NDRG3.

COVID-19 in a designated infectious diseases hospital outside Hubei Province, China.

BACKGROUND: The clinical characteristics of novel coronavirus disease (COVID-2019) patients outside the epicenter of Hubei Province are less understood. METHODS: We analyzed the epidemiological and clinical features of all COVID-2019 cases in the only referral hospital in Shenzhen City, China, from January 11, 2020, to February 6, 2020, and followed until March 6, 2020. RESULTS: Among the 298 confirmed cases, 233 (81.5%) had been to Hubei, while 42 (14%) did not have a clear travel history. Only 218 (73.15%) cases had a fever as the initial symptom. Compared with the nonsevere cases, severe cases were associated with older age, those with underlying diseases, and higher levels of C-reactive protein, interleukin-6, and erythrocyte sedimentation rate. Slower clearance of the virus was associated with a higher risk of progression to critical condition. As of March 6, 2020, 268 (89.9%) patients were discharged and the overall case fatality ratio was 1.0%. CONCLUSIONS: In a designated hospital outside Hubei Province, COVID-2019 patients could be effectively managed by properly using the existing hospital system. Mortality may be lowered when cases are relatively mild, and there are sufficient medical resources to care and treat the disease.

Divergent synthesis of 1,3,5-tri and 1,3-disubstituted pyrazoles under transition metal-free conditions.

Pyrazole cores are common structural motifs existing in various agrochemicals and pharmaceuticals. Herein, a transition metal-free, three-component reaction of arylaldehydes, ethyl acrylate and N-tosylhydrazones is described, which leads to the formation of 1,3,5-trisubstituted and 1,3-disubstituted pyrazoles divergently under slightly different conditions.

Discussion on treatment courses of brucellosis with spondylitis - a report of two cases.

Human Brucellosis is a zoonotic contagious disease caused by Brucella infection and is common throughout the world, which can travel through the bloodstream to various organs. Brucellar spondylitis(BS) is the foremost cause of brucellosis's debilitating and disabling complications. We report two sisters with brucellosis complicated by lumbar spondylodiscitis accompanied by cold abscess formation. The diagnosis was based on their symptoms, epidemiological characteristics, laboratory and magnetic resonance imaging(MRI) results. Our therapeutic strategy in these two cases indicate that drug combination and prolongation of the use of antibiotics is a therapeutic strategy worthy of popularizing to reach a greater clearance rate of the infection.

Palladium-Catalyzed Three-Component Selective Aminoallylation of Diazo Compounds.

We describe a Xantphos-containing dinuclear palladium complex-enabled geminal aminoallylation of diazocarbonyl compounds, which selectively provides a range of quaternary α-amino esters. Direct N-H insertion, allylic alkylation of amino nucleophiles, and diene formation were not observed under standard conditions. Mechanistic studies indicated that a relayed pathway via allylation of the N-H insertion product or [2,3]-sigmatropic rearrangement of an ylide intermediate was unlikely.

Palladium-Catalyzed Three-Component Coupling Reaction of o-Bromobenzaldehyde, N-Tosylhydrazone, and Methanol.

A ligand-controlled palladium-catalyzed three-component reaction of o-bromobenzaldehyde, N-tosylhydrazone, and methanol is described. This reaction uses readily available compounds as starting materials while displaying a broad substrate scope and good functional group compatibility.

Gynura Segetum Related Hepatic Sinusoidal Obstruction Syndrome: A Liver Disease with High Mortality and Misdiagnosis Rate.

BACKGROUND AND AIM: Gynura segetum (Tusanqi or Jusanqi) is widely used in China as a herbal remedy, however, it has often been associated with hepatic sinusoidal obstruction syndrome (HSOS). Its extent in inducing hepatotoxicity is not sufficiently understood. Hence, we aimed to identify the characteristic features of Gynura segetum associated HSOS. METHODS: A total of 64 patients diagnosed with HSOS induced by gynura segetum were enrolled from eight Chinese tertiary care hospitals between 2008 and 2018. General information regarding diagnosis, disease history, suspected drug use, symptoms and signs, biochemical index, imaging data, liver histology, treatment methods, severity and prognosis were collected and analyzed. RESULTS: The mean age of the enrolled patients were 58.07±11.44 years. Male patients accounted for 64.1% of HSOS patients. The median latency period was 75 days. The number of patients with a definite diagnosis from the eight hospitals was 5 (7.81%), with a misdiagnosis rate of 92.18%. Hepatomegaly, splenomegaly, ascites and lower limbs edema were present in 89.1%, 76.6%, 81.3% and 43.8% of the patients, respectively. The imaging characteristic changes were liver parenchyma echo thickening, uneven density, and hepatic vein stenosis and occlusion. Liver biopsies had characteristic pathological changes. Except for ALT and D-Dimer, liver function and coagulation index at admission and before discharge were not significantly different (p>0.05). The 6-month mortality rate was 77.55%, with upper-gastrointestinal bleeding being the leading cause of death (42.11%). The second leading cause of death was a secondary infection (36.84%), while the third was hepatorenal syndrome (21.05%). CONCLUSION: Gynura segetum related HSOS often presents as progressive hepatic congestion, portal hypertension and liver failure, and has a high mortality and misdiagnosis rate.

Causes, clinical features and outcomes of drug-induced liver injury in hospitalized patients in a Chinese tertiary care hospital.

Drug-induced liver injury (DILI) is an important liver disease in China, owing to the country's huge population and the availability of a multitude of drugs. Consequently, DILI is becoming an increasingly serious health problem. However, there is not enough relevant epidemiological data, and the clinical features of these patients are not clear. We conducted this study to report the causes and clinical features of DILI in hospitalized patients, and identify the mortality and predictive factors. We retrospectively collected and analyzed the data of all hospitalized patients whose discharge diagnosis was DILI at the Second Xiangya Hospital between January 2011 and December 2014. The data analyses were performed using SAS version 9.2. Among the 469 patients who were diagnosed with DILI at discharge, 361 met the criteria for DILI on re-evaluation. The crude annual incidence rate of DILI was 92.95 cases per 100,000 patients. Chinese herbal medicine was identified as the primary cause of DILI in 36.01 % of the patients. The overall mortality was 8.59 %. Alcohol consumption, use of antituberculosis drugs, serum total bilirubin, direct bilirubin, total protein, albumin, thrombinogen time, international normalized ratio, and the model for end-stage liver disease (MELD) score were significantly correlated with DILI-associated mortality. Among them, the MELD score and albumin were found to be independent predictors of outcome in patients with DILI. Chinese herbal medicine was the primary cause of DILI in the identified patients. The MELD score and albumin were independent predictors of outcome in patients with DILI.