Objective To study the protection of taurine(TAU) against apoptosis of neurons induced by manganese(Mn) in vitro. Method Cortex neurons were separated from Wistar neonatal rats and cultured in vitro.The assays began when neurons grew under the best conditions. Cells were randomly divided into 7 groups: control group,Mn-added groups (Mn 0.2,0.6 and 1.0 mmol/L respectively),TAU-intervened groups (1.5mmol/L TAU with Mn). All treatments lasted 24h. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) was used to observe the morphology of apoptosic neurons. Flow cytometry (FCM) was used to quantitate neuron apoptosic rates. Results (1) Typical morphologic charateristic was found in Mn-added groups. TAU intervention could protect against the effect of 1.5mmol/l Mn on neurons. (2) FCM indicated that TAU can protect against neurons apoptosis induced by Mn. Conclusion Taurine can protect neurons from apoptosis induced by Mn in vitro.

Objective To explore the change of serum high-sensitivity cardiac troponin T(hs-cTnT),myoglobin(MYO),creatine kinase isoenzyme(CK-MB)mass(CK-MB mass)and N-terminal pro-brain natriuretic peptide(NT-proBNP)levels in the patients with renal dysfunction.Methods The inpatients with renal dysfunction(excluding cardiac and skeletal muscle diseases)in our hos-pital were collected and divided into the compensation period group(30 cases),decompensation period group(24 cases)and uremia group(22 cases)according to serum urea and creatine concentration,and 36 healthy individuals were selected as the control group. Venous blood was collected on an empty stomach and separated for obtaining serum.Serum levels of hs-cTnT,MYO,CK-MB mass and NT-proBNP were measured by the electrochemiluminescent immunoassay.Results Serum hs-cTnT levels in the compensation period group,decompensation period group,uremia group and the control group were 16.4(10.9-24.2),17.0(13.0-25.5),25.9 (16.5-33.8),13.7(9.4 -19.7 )pg/mL respectively.Serum MYO levels were 52.4 (40.0 -96.5 ),87.9 (57.7 -118.3 ),115.7 (94.2-175.8),34.8(24.3-48.1)ng/mL,respectively.Serum CK-MB mass levels were 1.03(0.82 -1.75),1.31 (1.08 -1.69), 1.66(1.01-2.46),1.88(1.63-2.43)ng/mL,respectively.Serum NT-proBNP levels were 292.5(123.3-576.2),363.3(192.3-893.3),1 357.2(536.5 -4 662.9),110.3 (70.1 -196.3)ng/mL,respectively.The serum hs-cTnT,MYO and NT-proBNP levels were increased with renal function decrease.The nonparametric Kruskal-Wallis H test showed statistically significant difference a-mong groups(H =14.46,49.81 and 35.00,P <0.05 ).The CK-MB mass level had no statistically significant difference among groups(P >0.05).Conclusion The patients with renal dysfunction have the higher risk rate for complicating the cardiovascular e-vents.Early detection of cardiac markers conduces to the diagnosis of myocardial injury,the evaluation of the risk rate of myocardial infarction occurrence in future and the diagnosis of heart failure and evaluation of the risk rate of heart failure occurrence in future.

Objective: To evaluate the therapeutic efficacy of acupuncture plus Dang Gui Bu Xue Qu Feng Tang for benign essential blepharospasm (BEB). Methods: A prospective randomized controlled trial was performed. A total of 105 participants were randomized 1:1:1 into an acupuncture group, a herbal medicine group and an acupuncture plus herbal medicine group. Participants in the acupuncture group received manual acupuncture treatment, twice a week. Participants in the herbal medicine group received Dang Gui Bu Xue Qu Feng Tang, oral administration, once a day. Participants in the acupuncture plus herbal medicine group received both treatments. The therapeutic effects of the three groups were evaluated after four weeks of treatment. The primary outcome was the Jankovic rating scale (JRS) score, and the secondary outcome was the blepharospasm disability index (BSDI) score. Results: After four weeks of treatment, the JRS total scores significantly decreased in all three groups versus baseline (P<0.05). A greater reduction in the JRS total score was reported in participants in the acupuncture plus herbal medicine group (P<0.05), but there was no significant difference between the acupuncture group and the herbal medicine group (P>0.05). The acupuncture plus herbal medicine group had a greater decrease in the JRS severity score than the herbal medicine group (P<0.05). The reduction in the JRS frequency score was not significantly different among the three groups (P>0.05). The BSDI scores significantly decreased in all three groups versus baseline (P<0.05), but the reduction in the BSDI score was insignificantly different among the three groups (P>0.05). Conclusion: It is effective in the treatment of BEB either to use acupuncture and Dang Gui Bu Xue Qu Feng Tang alone or in combination. The combination therapy shows a more significant effect than either of the treatment alone.

Objective Based on the endoplasmic reticulum stress(ERS)inositol-requiring enzyme-1α(IRE1α)/apoptosis signal-regulated kinase 1(ASK1)/c-Jun N-terminal kinase(JNK)pathway to investigate the intervention effect of Ziziphi Spinosae Semen(ZSS)-Albiziae Flos(AF)on the depression model of rats,which were prepared by solitary rearing combined with chronic unpredictable mild stress(CUMS).Methods A total of 144 rats were randomly divided into normal group,model group,high-,medium-and low-dose groups of ZSS-AF,and Venlafaxine group.In addition to the normal group,the rats in other groups were isolated for 21 days combined with CUMS to prepare the depression model.The behavioral changes of rats were observed by open field test and Morris water maze test.The ultrastructural changes of hippocampal neurons were observed by transmission electron microscope.TUNEL staining was used to observe the apoptosis of nerve cells in hippocampus.The protein expression levels of IRE1α,phosphorylated(P)-IRE1α,ASK1,P-ASK1,JNK,P-JNK,B cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax)and cysteme aspartate specific protease-3(Caspase-3)in hippocampus were detected by Western Blot.The mRNA expression levels of IRE1α,ASK1,JNK,Bax,Bcl-2 and Caspase-3 in hippocampus were detected by Real-Time PCR.Results Compared with the normal group,the scores of horizontal movement and vertical movement in the open field test of rats in the model group were decreased(P＜0.01).In the water maze test,the escape latency was increased and the number of crossing the original platform was decreased(P＜0.01).The number of hippocampal apoptosis was increased(P＜0.01).The protein expression levels of P-IRE1 α/IRE1 α,P-ASK1/ASK1,P-JNK/JNK,Bax,Caspase-3 and mRNA expressions of IRE1α,ASK1,JNK,Bax,Caspase-3 in hippocampus were increased,while the protein and mRNA expression levels of Bcl-2 were decreased(P＜0.01).Compared with model group,the scores of horizontal movement and vertical movement in the open field test of rats in each dose ZSS-AF groups and Venlafaxine group were increased(P＜0.01).In the water maze test,the escape latency was decreased and the times of crossing the original platform was increased(P＜0.01).The number of hippocampal apoptosis was decreased(P＜0.01).The mRNA expression levels of P-IRE1α/IRE1α,P-ASK1/ASK1,P-JNK/JNK,Bax,Caspase-3 protein and IRE1α,ASK1,JNK,Bax,Caspase-3 in hippocampus were decreased,while the protein and mRNA expression levels of Bcl-2 were increased(P＜0.05,P＜0.01).The effect of medium-dose ZSS-AF group was better than that of high-and low-dose groups.Conclusion ZSS-AF may play an antidepressant role by regulating IRE1α/ASK1/JNK pathway of endoplasmic reticulum stress.

Objective: To explore the association between dietary inflammatory index (DII) and metabolic syndrome (MetS) and its components among children aged 6-14 years in Beijing, so as to provide a reference for preventing MetS. Methods: A cross sectional study was carried out in 2 086 records of 1 832 children from the 2017 and 2019 Nutrition and Health Surveillance in Primary and Secondary school students of Beijing (NHSPSB). Three day consecutive 24 hour dietary recalls combined with weighing household cooking oils and condiments were used to collect dietary intake and calculate DII. MetS was diagnosed according to "Definition and Suggestion on the Metabolic Syndrome of Chinese Children and Adolescent". The Generalized estimating equations (GEEs) models were used to analyze the association between DII and the presence of MetS and its components (abdominal obesity, high triglyceride, low high density lipoprotein cholesterol, hypertension, and hyperglycemia). Results: The mean DII score was (1.64±1.07) for the included children. No significant association was found between DII scores and the likelihood of MetS (per 1 point increment: OR =1.16, 95% CI =0.92-1.48, P >0.05). In terms of the components of MetS, DII scores were positively associated with the odds of high triglyceride (per 1 point increment: OR =1.17, 95% CI =1.01-1.36, P <0.05). There was no statistically significant difference in the association among different age groups ( P >0.05). No significant associations were observed between DII and other MetS components( P >0.05). Conclusion DII scores may not be correlated with the risk of MetS, but proinflammatory diet might increase the risk of high triglyceride. DII score in childhood should be emphasized to identify and prevent MetS as soon as possible.

OBJECTIVETacrolimus (FK506) is an immunosuppressive drug, which is widely used to prevent rejection of transplanted organs. However, chronic administration of FK506 leads to hypertension in solid organ transplantation patients, and its molecular mechanisms are much more complicated. In this review, we will discuss the above-mentioned molecular mechanisms of FK506-induced hypertension in solid organ transplantation subjects.

DATA SOURCESThe data analyzed in this review were mainly from relevant articles without restriction on the publication date reported in PubMed. The terms "FK506" or "tacrolimus" and "hypertension" were used for the literature search.

STUDY SELECTIONOriginal articles with no limitation of research design and critical reviews containing data relevant to FK506-induced hypertension and its molecular mechanisms were retrieved, reviewed and analyzed.

RESULTSThere are several molecular mechanisms attributed to FK506-induced hypertension in solid organ transplantation subjects. First, FK506 binds FK506 binding protein 12 and its related isoform 12.6 (FKBP12/12.6) and removes them from intracellular ryanodine receptors that induce a calcium ion leakage from the endoplasmic/sarcoplasmic reticulum. The conventional protein kinase C beta II (cPKCβII)-mediated phosphorylation of endothelial nitric oxide (NO) synthase at Thr495, which reduces the production of NO, was activated by calcium ion leakage. Second, transforming growth factor receptor/SMAD2/3 signaling activation plays an important role in Treg/Th17 cell imbalance in T cells which toget converge to cause inflammation, endothelial dysfunction, and hypertension following tacrolimus treatment. Third, the activation of with-no-K(Lys) kinases/STE20/SPS1-related proline/alanine-rich kinase/thiazide-sensitive sodium chloride co-transporter (WNKs/SPAK/NCC) pathway has a central role in tacrolimus-induced hypertension. Finally, the enhanced activity of renal renin-angiotensin-aldosterone system seems to play a crucial role in the pathophysiology of FK506-induced hypertension.

CONCLUSIONFK506 plays a predominant role in the pathophysiology of hypertension in solid organ transplantation subjects.

Humans ; Hypertension ; chemically induced ; Immunosuppressive Agents ; adverse effects ; therapeutic use ; Organ Transplantation ; adverse effects ; Tacrolimus ; adverse effects ; therapeutic use

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.
Humans ; Anti-Bacterial Agents/therapeutic use* ; China ; Drug Monitoring/methods* ; Polymyxin B ; Practice Guidelines as Topic