Bis (2-butoxyethyl) Phthalate Delays Puberty Onset by Increasing Oxidative Stress and Apoptosis in Leydig Cells in Rats / 生物医学与环境科学（英文）

OBJECTIVE@#This study investigated the effects of bis (2-butoxyethyl) phthalate (BBOP) on the onset of male puberty by affecting Leydig cell development in rats.@*METHODS@#Thirty 35-day-old male Sprague-Dawley rats were randomly allocated to five groups mg/kg bw per day that were gavaged for 21 days with BBOP at 0, 10, 100, 250, or 500 mg/kg bw per day. The hormone profiles; Leydig cell morphological metrics; mRNA and protein levels; oxidative stress; and AKT, mTOR, ERK1/2, and GSK3β pathways were assessed.@*RESULTS@#BBOP at 250 and/or 500 mg/kg bw per day decreased serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels mg/kg bw per day (P < 0.05). BBOP at 500 mg/kg bw per day decreased Leydig cell number mg/kg bw per day and downregulated Cyp11a1, Insl3, Hsd11b1, and Dhh in the testes, and Lhb and Fshb mRNAs in the pituitary gland (P < 0.05). The malondialdehyde content in the testis significantly increased, while Sod1 and Sod2 mRNAs were markedly down-regulated, by BBOP treatment at 250-500 mg/kg bw per day (P < 0.05). Furthermore, BBOP at 500 mg/kg bw per day decreased AKT1/AKT2, mTOR, and ERK1/2 phosphorylation, and GSK3β and SIRT1 levels mg/kg bw per day (P < 0.05). Finally, BBOP at 100 or 500 μmol/L induced ROS and apoptosis in Leydig cells after 24 h of treatment in vitro (P < 0.05).@*CONCLUSION@#BBOP delays puberty onset by increasing oxidative stress and apoptosis in Leydig cells in rats.@*UNLABELLED@#The graphical abstract is available on the website www.besjournal.com.

Efficacy of Chinese Medicinal Formulae for Antimicrobial-resistant Pneumonia: A Systematic Review and Meta-analysis / 中国实验方剂学杂志

Objective:To evaluate the efficacy and safety of Chinese medicinal formulae in the treatment of antimicrobial-resistant pneumonia. Method:Following article retrieval from eight databases and data extraction by two reviewers， the methodological quality of the included trials was assessed and the outcome indicators were subjected to Meta-analysis using RevMan 5.3. Result:A total of 24 randomized controlled trials （RCTs） were included， involving 1 818 cases. Meta-analysis showed that Chinese medicinal formulae combined with western routine intervention was superior to the western routine intervention in improving the overall response rate （ORR） ［relative risk （RR）=1.27， 95% confidence interval （CI） （1.21， 1.34）， <inline-formula><alternatives><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M5"><mml:mi>P</mml:mi></mml:math><graphic specific-use="big" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/27038DAF-2FF7-4d58-8001-0E6465A33408-M005.jpg"><?fx-imagestate width="2.28600001" height="2.62466669"?></graphic><graphic specific-use="small" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/27038DAF-2FF7-4d58-8001-0E6465A33408-M005c.jpg"><?fx-imagestate width="2.28600001" height="2.62466669"?></graphic></alternatives></inline-formula><0.000 01］， the bacterial clearance rate ［RR=1.49，95% CI （1.33， 1.66）， <inline-formula><alternatives><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M6"><mml:mi>P</mml:mi></mml:math><graphic specific-use="big" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/27038DAF-2FF7-4d58-8001-0E6465A33408-M006.jpg"><?fx-imagestate width="2.28600001" height="2.62466669"?></graphic><graphic specific-use="small" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/27038DAF-2FF7-4d58-8001-0E6465A33408-M006c.jpg"><?fx-imagestate width="2.28600001" height="2.62466669"?></graphic></alternatives></inline-formula><0.000 01］， and the clinical pulmonary infection score （CPIS） ［mean difference （MD）=-1.64， 95% CI （-1.87， -1.41）， <inline-formula><alternatives><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M7"><mml:mi>P</mml:mi></mml:math><graphic specific-use="big" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/27038DAF-2FF7-4d58-8001-0E6465A33408-M007.jpg"><?fx-imagestate width="2.28600001" height="2.62466669"?></graphic><graphic specific-use="small" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/27038DAF-2FF7-4d58-8001-0E6465A33408-M007c.jpg"><?fx-imagestate width="2.28600001" height="2.62466669"?></graphic></alternatives></inline-formula><0.000 01］. There was no significant difference in the incidence of adverse reactions ［RR=0.72， 95% CI （0.48， 1.07），<inline-formula><alternatives><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M8"><mml:mtext> </mml:mtext><mml:mi>P</mml:mi></mml:math><graphic specific-use="big" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/27038DAF-2FF7-4d58-8001-0E6465A33408-M008.jpg"><?fx-imagestate width="3.04799986" height="2.62466669"?></graphic><graphic specific-use="small" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/27038DAF-2FF7-4d58-8001-0E6465A33408-M008c.jpg"><?fx-imagestate width="3.04799986" height="2.62466669"?></graphic></alternatives></inline-formula>=0.1］. The comparison with the western routine intervention also revealed that Chinese medicinal formulae better improved the ORR and CPIS. Conclusion:According to the current research results， the Chinese medicinal formulae alone or combined with western routine intervention yielded more favorable clinical outcomes than western routine intervention in the treatment of antimicrobial-resistant pneumonia， without increasing the incidence of adverse events. Due to limited quality and quantity of the included RCTs， more high-quality trials are required to verify the above conclusions.

Effect of Lidan Ruanjian Prescription on Lipid-lowering and Antiobesity andMetabolic Profile of Bile Acid / 中国实验方剂学杂志

Objective:To investigate the pharmacodynamics effects of antiobesity, lipid-lowering and the regulations of serum bile acid profiles of Lidan Ruanjian prescription (LDRJ) in obesity rats induced by high-fat diet. Method:The 42 rats were fed high-fat diet for 9 weeks to establish model of obese rats，24 rats were randomly divided into model group, high and low-dose LDRJ group (30,15 g·kg-1). Another 8 normal rats were selected as the normal group.The model group and normal group were given normal saline, and drug group was given the corresponding dose of drug for 4 weeks. Body weight, liver weight, white adipose tissue (WAT) weight were determined after administration medicine for 4 weeks. The bile flow of the rats was measured by bile duct intubation and fasting serum lipid levels of total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) were detected by automatic biochemical analyzer. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay was used to test serum bile acid profile of each group rats. Result:Compared with the control group, the average body weight, liver weight, WAT weight of the model group were significantly increased (P<0.01), while the fasting serum TC, TG and LDL-C levels were elevated (P<0.05，P<0.01). The total bile secretion and bile flow at each test point within 2 h were decreased and the proportion of primary bile acids was decreased (P<0.05).The serum total bile acid content decreased significantly（P<0.01），levels of cholic acid (CA), deoxycholic acid (DCA), chenodeoxycholic acid (CDCA), hyodeoxycholic acid (HDCA), taurocholic acid (TCA), taurodeoxycholic acid (TDCA), taurochenodeoxycholic acid (TCDCA), taurohyodeoxycholic acid (THDCA) and glycodeoxycholic acid (GDCA) were significantly reduced (P<0.05，P<0.01). Compare with model group, body weight, liver weight in high and low-dose LDRJ groups reduced significantly(P<0.05，P<0.01). Fasting serum TC, TG and LDL-C levels were decreased in high-dose group(P<0.05，P<0.01), so did as TG levels in low-dose group(P<0.05). The bile flow rate increased significantly in high-dose group 1~1.5 h after administration (P<0.05). All dose treatment groups increased the proportion of primary bile acids (P<0.05) and changed the bile acid profile, especially elevated the bile acid levels of TCA, DCA, glycocholic acid (GCA), GDCA in high-dose LDRJ group (P<0.05，P<0.01), while TCA and TCDCA in low-dose group (P<0.05). Conclusion:LDRJ has significant lipid-lowering and antiobesity effects and the mechanism might involve the increase of bile secretion, the stimulation of primary bile acid synthesis and the regulation of bile acid profile.

Mechanism of Traditional Chinese Medicine in Treating Drug-resistant Bacterial Infection / 中国实验方剂学杂志

The discovery of penicillin has effectively controlled the infection caused by Gram-positive bacteria. Afterwards, the research and development of antibacterial drugs has entered the golden age, and made a great contribution to human health. However, in recent years, with the increasing use of antibiotics around the world, pathogenic bacteria drive gene mutation to obtain drug resistance to ensure its survival advantage, and promote the transfer of drug-resistant genes, resulting in a sharp increase of drug-resistant bacteria. In addition, the current development speed of new antibiotics is far slower than the growth and spread speed of drug-resistant bacteria, which makes the drug-resistant crisis more serious and becomes one of the biggest threats to the global community. Compared with the same type of bacterial infection, drug-resistant bacterial infection has the characteristics of complexity and refractoriness, which causes worse clinical outcome and higher risk of death in patients, and brings severe challenges to clinical work. If the trend of bacterial drug resistance is not controlled, the crisis of no drug available will come. Therefore, it is urgent to explore effective alternative means to fight against bacterial drug resistance and reduce the harm of drug-resistant bacterial infection. Traditional Chinese medicine（TCM） has unique advantages in the treatment of infectious diseases. Compared with modern antibacterial drugs, it has the characteristics of wide sources, rich active ingredients, and is not easy to produce drug resistance. It may be an important source for screening and developing new anti-infective drugs. Therefore, it is promising to develop and utilize TCM to solve the problem of drug-resistant bacteria infection. This paper will review relevant studies in recent years in terms of interfering with the biochemical metabolism of drug-resistant bacteria to directly inhibit or kill drug-resistant bacteria, improving bacterial drug resistance to indirectly inhibit bacteria and kill bacteria, and maintaining the balance of the body and regulating the treatment of drug-resistant bacteria infection as a whole, so as to provide references for guiding clinical medication and research and development of new traditional Chinese medicines.

Mechanism of Chinese Material Medica in Treatment of Diabetes Mellitus Cerebral Infarction / 中国实验方剂学杂志

Diabetes mellitus complicated with cerebral infarction is the commonest and most serious vascular complication of diabetes mellitus. With a high disability and mortality rate, it seriously threatens human health. Because the pathogenesis is still unclear, more and more scholars have focused on the research of diabetic cerebral infarction at home and abroad. Traditional Chinese medicine(TCM) compounds have a remarkable curative effect in the treatment of diabetic cerebral infarction. Its mechanisms of action mainly include anti-hypertension, reduction of blood sugar and lipid, promotion of vascular regeneration and vascular endothelial function, anticoagulation, anti-thrombosis, improvement of nerve function defect, reduction of infarct volume, improvement of hemorheological, inhibition of inflammation and platelet aggregation, and promotion of collateral circulation. Through literature search, this paper summarizes the research progress of the mechanisms of TCM compounds in treating diabetic cerebral infarction in recent five years at home and abroad, in order to provide reference for clinical treatment.

Functional polymorphisms in CYP2C19 & CYP3A5 genes associated with decreased susceptibility for paediatric tuberculosis.

Background & objectives: Tuberculosis (TB) bacilli ingested by macrophages evade host immune responses by multiple mechanisms including the inhibition of apoptosis. As the cytochrome-P-450 system (CYP) contributes to apoptosis it has been suggested that genetic variation in CYP may be associated with susceptibility to TB infection. This study was carried out to evaluate cytochrome P-450 polymorphisms in Chinese Han children and to investigate the effect of these polymorphisms in paediatric TB. Methods: Frequencies for the CYP2C19, CYP3A4, CYP3A5 and CYP2E1 mutated alleles and genotypes were compared between 142 Chinese paediatric TB patients and 150 non-infected controls by real time PCR genotyping on peripheral leukocyte DNA. Results: CYP2C19 (636 G>A, rs4986893) A allele and AG genotype were associated with decreased susceptibility to TB (P = 0.006, OR= 0.33, 95% CI: 0.15-0.76; and P = 0.005, OR =0.31, 95% CI: 0.14-0.72 respectively), as were the CYP3A5 (6986A>G, rs776746) G allele and particularly homozygous GG (recessive mode) genotype (P = 0.004, OR=0.61, 95% CI: 0.43-0.85; and P=0.002, OR=0.47, 95% CI: 0.29-0.76). Interpretation & conclusions: The data suggested that CYP2C19 and CYP3A5 polymorphisms affect susceptibility to paediatric TB. Further studies are indicated to confirm and elucidate these observations.

Littoral cell angioma of the spleen: report of three cases and a review of the literature / 中华医学杂志(英文版)

Littoral cell angioma is a recently described rare vascular tumor of the spleen. The clinical course of this benign tumor is asymptomatic in most patients. Herein, we described three patients with littoral cell angioma detected during physical examination. A brief discussion and review of a handful of cases of splenic littoral cell angioma, which have been previously reported in the English language literature, are performed in this paper.