BACKGROUND:Bone marrow mesenchymal stem cells (BMSCs) transplantation can promote cardiac repair after myocardial infarction, but it has been limited by the low cellsurvival rate.
OBJECTIVE:To study the effect of hydrogen sulfide (H 2 S) on the BMSCs transplantation for treatment of myocardial infarction.
METHODS:BMSCs were separated and cultivated form Sprague-Dawley rats weighing (100±20) g. The 4th generation cells were used for later experiment, and marked by DAPI at 2 hours before use. Fifty male Sprague-Dawley rats, weighing (200±20) g had been divided into five groups:Sham group (n=10) and four transplantation groups:BMSCs (n=10), H 2 S-BMSCs (n=10), H 2 S (n=10), normal saline (n=10). The myocardial infarction model of four groups was established except of sham group (only thread without ligation). The cardiac function was measured by echocardiogram at 4 weeks after celltransplantation. The col agen in the infarction area was tested by Masson staining.
RESULTS AND CONCLUSION:Severe myocardial fibrosis was found in the normal saline group, with no myocardial regeneration in the infarct area. H 2 S-BMSCs group had less col agen and more cardiac muscle tissue than BMSCs or H 2 S groups. Left ventricular ejection fraction and left ventricular fractional shortening of the H 2 S-BMSCs group were significantly higher than those of the BMSCs or H 2 S groups (P<0.05). The cells survival rate and cardiac function of myocardial infarction rats can be promoted by H 2 S-preconditioned BMSCs transplantation, which is superior to BMSCs or H 2 S alone.

Objective To investigate the prognosis and adverse reactions of patients with acute-on-chronic liver failure (ACLF) receiving artificial liver support therapy stratified by international normalized ratio (INR). Methods A total of 515 ACLF patients who received artificial liver support therapy in Department of Severe liver Disease, The Ninth Hospital of Nanchang, from January 2010 to May 2020 were enrolled, and according to the level of INR, they were divided into group A with 20 patients (INR < 1.5), group B with 115 patients (1.5≤INR < 1.9), group C with 179 patients (1.9≤INR < 2.6), group D with 61 patients (2.6≤INR < 3.2), group E with 75 patients (3.2≤INR < 4.2), and group F with 65 patients (INR≥4.2). All patients received multimodality medical treatment combined with artificial liver support therapy. The one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups。The chi-square test was used for comparison of categorical data between groups. Bonferroni correction was used for further comparison between two groups. and the receiver operating characteristic (ROC) curve was used to evaluate the value of INR and MELD scoring system in predicting the prognosis of ACLF patients. Results As for 90-day mortality rate, there was a significant difference between the six groups stratified by INR ( χ 2 =124.84, P < 0.001); there was no significant difference between groups A(25%), B(25.2%), and C(39.7%) ( P > 0.05), and there was a significant difference between groups D/E/F(65.6%, 82.7%, and 92.3%, respectively) and groups A/B/C (all P < 0.05); there was no significant difference between groups D and E and between groups E and F ( P > 0.05), and there was a significant difference between groups D and F ( P < 0.05). There was no significant difference in the incidence rate of intraoperative adverse reactions between the six groups ( χ 2 =8.956, P =0.111). INR had an area under the ROC curve of 0.786 (95% confidence interval: 0.746-0.825, P < 0.001) in predicting the prognosis of patients with ACLF receiving artificial liver support therapy, with a sensitivity of 66.7% and a specificity of 79.8%. Conclusion INR has a good value in predicting the prognosis of ACLF patients receiving artificial liver support therapy, and the artificial liver has good safety.

Objective:To evaluate the drug-drug interactions and the tolerability of combined medication between yimitasvir phosphate capsules with sofosbuvir tablets, omeprazole magnesium enteric-coated tablets, and rosuvastatin calcium tablets in healthy volunteers.Methods:A randomized, open, and continuous administration design was used in trial 1 (yimitasvir phosphate capsules with sofosbuvir tablets). 28 subjects were randomly divided into two groups. A non-randomized, open design was used in trial 2 (yimitasvir phosphate capsules with omeprazole magnesium enteric-coated tablets), and included 42 subjects divided into three groups. The open design method was used in trial 3 (yimitasvir phosphate capsules with rosuvastatin calcium tablets), and included 14 subjects. The plasma concentrations of yimitasvir phosphate, sofosbuvir and their main metabolites GS-331007, omeprazole and rosuvastatin were validated by a liquid chromatography/tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters were calculated by Phoenix winNonlin software.Results:(1) in trial 1, after single and co-administration, the 90% CI of sofosbuvir C max and AUC 0-tau geometric mean ratio (GMR) were 152.0% (118.0% ~ 197.0%) and 230.0% (184.0% ~ 287.0%), with an increase of 52.0% and 130.0% compared to single dose of sofosbuvir, respectively. The 90% CI of GS-331007 C max GMR was 74.0% (67.5% ~ 81.2%) and reduced by 26% compared to single dose of sofosbuvir. (2) in trial 2, the 90% CI of C max GMR after yimitasvir single or co-administration at the same time, with a 4-hours interval, or with a 12- hours interval were 68.9% (44.5% ~ 106.7%) , 64.0% (43.8% ~ 93.6%) and 56.4%(38.9% ~ 81.9%), and the 90% CI of AUC 0-t GMR were 68.6% (46.5% ~ 101.2%), 68.3% (47.6% ~ 98.0%) and 60.5% (41.8% ~ 87.5%), respectively. Compared with single dose of yimitasvir, the C max and AUC 0-t were decreased by 31.1% and 31.4%, 36.0% and 31.7%, 43.6% and 39.5%, respectively. (3) In trial 3, after single and co-administration, the 90% CI of rosuvastatin C max and AUC 0-72 GMR were 172.4% (153.6% ~ 193.5%) and 158.0% (144.3% ~ 172.9%), respectively, with an increase of 74.9% and 60.5% compared to single dose of rosuvastatin. There were no serious adverse events and adverse events leading to withdrawal from the trial. Conclusion:Yimitasvir phosphate capsules have drug-drug interactions with sofosbuvir tablets, omeprazole magnesium enteric-coated tablets, and rosuvastatin calcium tablets.

Wernekink commissure syndrome (WCS) is very rare. Four patients with WCS, admitted to our hospital from April to May 2018, were chosen for this study, and their clinical manifestations, imaging features, and etiology were retrospectively analyzed based on the literatures. All patients with WCS manifested as bilateral cerebellar ataxia such as symmetrical limb and trunk ataxia, but the degree of ataxia was asymmetrical distribution based on the anatomy. Dysarthria was the main and constant clinical manifestation of the syndrome. Ophthalmoplegia had great variability, and WCS with oculomotor nerve palsy may be considered as atypical WCS. The incidence of olivary degeneration and palatine myoclonus is relatively low, which may be related to the difference in the reported time intervals of cases. Changes in consciousness and emotion may be the characteristic of neglected WCS, which should be paid more attention. Cerebral infarction is the main etiology of WCS. We reported that cerebral infarction and WCS was the first symptom in a patient with systemic lupus erythematosus (SLE). We should pay more attention to special etiology in diagnosis and treatment of WCS.
Cerebellar Ataxia ; Cerebral Infarction ; Humans ; Lupus Erythematosus, Systemic ; Retrospective Studies ; Syndrome

ObjectiveTo determine the syndrome of a rat model of follicular dysplasia induced by Tripterygium glycosides based on prescriptions and investigate the mechanism of traditional Chinese medicine intervention via the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR）/hypoxia-inducible factor-1 （HIF-1）/vascular endothelial growth factor （VEGF） pathway. MethodForty-eight rats with regular estrous cycles were randomly assigned into a normal group （n=8） and a modeling group （n=40）. The rats in the modeling group were administrated with Tripterygium glycoside suspension （75 mL·kg^-1） by gavage for 30 days. The modeled rats were assigned into model， Siwutang （3.69 g·kg^-1）， Youguiyin （3.11 g·kg^-1）， Zuoguiyin （7.29 g·kg^-1）， and Guishenwan （10.35 g·kg^-1） groups， with 8 rats in each group. The drug intervention lasted for 14 days. The changes of estrous cycle were detected by Pap staining， and a stereoscope was used to observe the morphology of the ovarian tissue. Hematoxylin-eosin staining was employed to observe the pathological changes and follicle count in the ovarian tissue. Enzyme-related immunosorbent assay （ELISA） was used to measure the levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and estradiol （E₂） in the serum. Real-time fluorescence quantitative polymerase chain reaction and Western blot were employed to determine the mRNA and protein levels， respectively， of AMPK， mTOR， HIF-1， and VEGF in the ovarian tissue. ResultCompared with the normal group， the model group had a disordered estrous cycle， reduced secondary and mature follicles， increased atretic follicles， elevated FSH and LH levels， lowered E₂ level， up-regulated mRNA and protein levels of AMPK， and down-regulated mRNA and protein levels of mTOR， HIF-1， and VEGF （P<0.01）. Compared with the model group， Guishenwan increased secondary and mature follicles， decreased atretic follicles， lowered the FSH and LH levels， elevated the E₂ level， down-regulated the mRNA and protein levels of AMPK， and up-regulated the mRNA and protein levels of mTOR， HIF-1， and VEGF （P<0.01）. Compared with Guishenwan group， Siwutang， Youguiyin， and Zuoguiyin decreased mature follicles， increased atretic follicles （P<0.01）， elevated the LH （P<0.01） and FSH （P<0.05） levels， and lowered the E₂ level （P<0.05）. In addition， Youguiyin up-regulated the protein level of AMPK （P<0.05） and down-regulated the mRNA levels of mTOR and HIF-1 （P<0.01） as well as the mRNA and protein levels of VEGF （P<0.01）. Siwutang down-regulated the mRNA levels of mTOR and HIF-1 as well as the mRNA and protein levels of VEGF （P<0.05）. Zuoguiyin down-regulated the mRNA level of mTOR and the protein and mRNA levels of VEGF （P<0.05）. ConclusionGuishenwan may improve the ovarian function and promote follicle maturation in a rat model of follicular dysplasia by inhibiting the AMPK/mTOR/HIF-1/VEGF pathway， with the therapeutic effect superior to Zuoguiyin， Youguiyin， and Siwutang. It was hypothesized that this model presented the syndrome of kidney-essence deficiency.

Bibenzyls, a kind of important plant polyphenols, have attracted growing attention for their broad and remarkable pharmacological activities. However, due to the low abundance in nature, uncontrollable and environmentally unfriendly chemical synthesis processes, these compounds are not readily accessible. Herein, one high-yield bibenzyl backbone-producing Escherichia coli strain was constructed by using a highly active and substrate-promiscuous bibenzyl synthase identified from Dendrobium officinale in combination with starter and extender biosynthetic enzymes. Three types of efficiently post-modifying modular strains were engineered by employing methyltransferases, prenyltransferase, and glycosyltransferase with high activity and substrate tolerance together with their corresponding donor biosynthetic modules. Structurally different bibenzyl derivatives were tandemly and/or divergently synthesized by co-culture engineering in various combination modes. Especially, a prenylated bibenzyl derivative ( 12) was found to be an antioxidant that exhibited potent neuroprotective activity in the cellular and rat models of ischemia stroke. RNA-seq, quantitative RT-PCR, and Western-blot analysis demonstrated that 12 could up-regulate the expression level of an apoptosis-inducing factor, mitochondria associated 3 (Aifm3), suggesting that Aifm3 might be a new target in ischemic stroke therapy. This study provides a flexible plug-and-play strategy for the easy-to-implement synthesis of structurally diverse bibenzyls through a modular co-culture engineering pipeline for drug discovery.