Development and prospects of predicting drug polymorphs technology / 药学学报

Most chemical medicines have polymorphs. The difference of medicine polymorphs in physicochemical properties directly affects the stability, efficacy, and safety of solid medicine products. Polymorphs is incomparably important to pharmaceutical chemistry, manufacturing, and control. Meantime polymorphs is a key factor for the quality of high-end drug and formulations. Polymorph prediction technology can effectively guide screening of trial experiments, and reduce the risk of missing stable crystal form in the traditional experiment. Polymorph prediction technology was firstly based on theoretical calculations such as quantum mechanics and computational chemistry, and then was developed by the key technology of machine learning using the artificial intelligence. Nowadays, the popular trend is to combine the advantages of theoretical calculation and machine learning to jointly predict crystal structure. Recently, predicting medicine polymorphs has still been a challenging problem. It is expected to learn from and integrate existing technologies to predict medicine polymorphs more accurately and efficiently.

High-throughput screening of novel TFEB agonists in protecting against acetaminophen-induced liver injury in mice

Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

Neutralizing Antibody Responses against Five SARS-CoV-2 Variants and T Lymphocyte Change after Vaccine Breakthrough Infections from the SARS-CoV-2 Omicron BA.1 Variant in Tianjin, China: A Prospective Study / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate whether Omicron BA.1 breakthrough infection after receiving the SARS-CoV-2 vaccine could create a strong immunity barrier.@*METHODS@#Blood samples were collected at two different time points from 124 Omicron BA.1 breakthrough infected patients and 124 controls matched for age, gender, and vaccination profile. Live virus-neutralizing antibodies against five SARS-CoV-2 variants, including WT, Gamma, Beta, Delta, and Omicron BA.1, and T-lymphocyte lymphocyte counts in both groups were measured and statistically analyzed.@*RESULTS@#The neutralizing antibody titers against five different variants of SARS-CoV-2 were significantly increased in the vaccinated population infected with the Omicron BA.1 variant at 3 months after infection, but mainly increased the antibody level against the WT strain, and the antibody against the Omicron strain was the lowest. The neutralizing antibody level decreased rapidly 6 months after infection. The T-lymphocyte cell counts of patients with mild and moderate disease recovered at 3 months and completely returned to the normal state at 6 months.@*CONCLUSION@#Omicron BA.1 breakthrough infection mainly evoked humoral immune memory in the original strain after vaccination and hardly produced neutralizing antibodies specific to Omicron BA.1. Neutralizing antibodies against the different strains declined rapidly and showed features similar to those of influenza. Thus, T-lymphocytes may play an important role in recovery.

DHM improves cognitive dysfunction in T2DM rats by inhibiting hippocampal endoplasmic reticulum stress / 中国药理学通报

Aim To investigate the effeet of dihydro- myricetin ( DHM ) on cognitive dysfunction in type 2 diabetes mellitus ( T2DM) rats and its mechanism.Methods SD rats were randomly divided into the normal control group ( n = 56) : normal diet and citrate buffer solution (30 mg • kg 1 ) ; T2DM model group (n =60) : high glucose, fat and low dose STZ ( 30 mg • kg 1 ) ( Four unsuccessful rats were eliminated ).Then rats in the above two groups were treated with or without DHM (250 mg • kg 1 • d intragastric).After 12 weeks, eight rats in each group were randomly selected to perform Morris water maze and Y maze test to observe the effect of DHM on cognitive function of rats.The remaining rats in each group were injected ERS antagonist tauroursodeoxycholic acid ( TUDCA ) 10 jxg • d 1 or ERS activator tunicamycin (TUN) 10 jxL, respectively.After the behavioral analysis, the hippocampal tissues of rats were taken out.The expressions of EH stress related proteins GRP78 and P- PERK were detected by Western blot.Results Both DHM and TUDCA could improve cognitive dysfunction in T2DM rats.On the contrary, TIJN reduced the effect of DHM on cognitive dysfunction in T2DM rats.TUDCA decreased the expression of GRP78 and p- PERK proteins in T2DM rats, while TUN increased the expression of GRP78 and p-PERK proteins in T2DM rats treated by DHM.Conclusion DHM improves cognitive dysfunction in T2DM rats, and the mechanism may be related to the inhibition of endoplasmic reticulum stress.

Dual roles of p62/SQSTM1 in the injury and recovery phases of acetaminophen-induced liver injury in mice

Acetaminophen (APAP) overdose can induce liver injury and is the most frequent cause of acute liver failure in the United States. We investigated the role of p62/SQSTM1 (referred to as p62) in APAP-induced liver injury (AILI) in mice. We found that the hepatic protein levels of p62 dramatically increased at 24 h after APAP treatment, which was inversely correlated with the hepatic levels of APAP-adducts. APAP also activated mTOR at 24 h, which is associated with increased cell proliferation. In contrast, p62 knockout (KO) mice showed increased hepatic levels of APAP-adducts detected by a specific antibody using Western blot analysis but decreased mTOR activation and cell proliferation with aggravated liver injury at 24 h after APAP treatment. Surprisingly, p62 KO mice recovered from AILI whereas the wild-type mice still sustained liver injury at 48 h. We found increased number of infiltrated macrophages in p62 KO mice that were accompanied with decreased hepatic von Willebrand factor (VWF) and platelet aggregation, which are associated with increased cell proliferation and improved liver injury at 48 h after APAP treatment. Our data indicate that p62 inhibits the late injury phase of AILI by increasing autophagic selective removal of APAP-adducts and mitochondria but impairs the recovery phase of AILI likely by enhancing hepatic blood coagulation.

Recommendations for the use of the acetaminophen hepatotoxicity model for mechanistic studies and how to avoid common pitfalls

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, which is safe at therapeutic doses but can cause severe liver injury and even liver failure after overdoses. The mouse model of APAP hepatotoxicity recapitulates closely the human pathophysiology. As a result, this clinically relevant model is frequently used to study mechanisms of drug-induced liver injury and even more so to test potential therapeutic interventions. However, the complexity of the model requires a thorough understanding of the pathophysiology to obtain valid results and mechanistic information that is translatable to the clinic. However, many studies using this model are flawed, which jeopardizes the scientific and clinical relevance. The purpose of this review is to provide a framework of the model where mechanistically sound and clinically relevant data can be obtained. The discussion provides insight into the injury mechanisms and how to study it including the critical roles of drug metabolism, mitochondrial dysfunction, necrotic cell death, autophagy and the sterile inflammatory response. In addition, the most frequently made mistakes when using this model are discussed. Thus, considering these recommendations when studying APAP hepatotoxicity will facilitate the discovery of more clinically relevant interventions.

Autophagy and liver cancer

Autophagy is a highly conserved catabolic process that degrades cytosolic proteins and organelles via formation of autophagosomes that fuse with lysosomes to form autolysosomes, whereby autophagic cargos are degraded. Numerous studies have demonstrated that autophagy plays a critical role in the regulation of liver physiology and homeostasis, and impaired autophagy leads to the pathogenesis of various liver diseases such as viral hepatitis, alcohol associated liver diseases (AALD), non-alcoholic fatty liver diseases (NAFLD), and liver cancer. Recent evidence indicates that autophagy may play a dual role in liver cancer: inhibiting early tumor initiation while promoting progression and malignancy of already formed liver tumors. In this review, we summarized the progress of current understanding of how hepatic viral infection, alcohol consumption and diet-induced fatty liver diseases impair hepatic autophagy. We also discussed how impaired autophagy promotes liver tumorigenesis, and paradoxically how autophagy is required to promote the malignancy and progression of liver cancer. Understanding the molecular mechanisms underlying how autophagy differentially affects liver cancer development and progression may help to design better therapeutic strategies for prevention and treatment of liver cancer.

Introduction of pertussis surveillance system and evaluation of its operational effect in Tianjin / 中国当代儿科杂志

The pertussis surveillance system has been established since 2009 in Tianjin, and continuously improved over the past 10 years. This system determines the definition and classification of pertussis, establishes simple and feasible sampling methods and laboratory detection methods in clinical practice, standardizes the report management of pertussis cases and the treatment of epidemic situations. After the implementation of the surveillance system, the number of reported pertussis cases increased from 26 in 2009 to 802 in 2017, the number of diagnosed cases increased from 19 in 2009 to 662 in 2017, the reported incidence rate of pertussis increased from 0.16/100 000 in 2009 to 4.28/100 000 in 2017, and the number of medical institutions of reporting perutssis cases increased from 2 in 2009 to 53 in 2017. The specimen collection rate of the reported cases reached up to 93.66%. These results show that the sensitivity of pertussis surveillance has been improved and show that the data from the surveillance system may reflect more precisely the epidemical characteristics of perutssis in Tianjin.

Level of copeptin for early prediction of cardiorenal syndrome in rats / 中国病理生理杂志

AIM:To study the value of copeptin(CPP)level for the prediction of cardiorenal syndrome (CRS)in the rats with subtotal nephrectomy(SNX)combined with myocardial infarction(MI).METHODS: Male SD rats(n=60)were divided into blank control group(Con group), renal failure group(SNX group), heart failure group (MI group)and heart failure+renal failure group(CRS group).The concentrations of CPP in the serum and urine,hemo-dynamic indexes,blood pressure and renal function indexes were measured 1~5 weeks after modeling.The predictive val-ue of CPP for CRS in the rats was evaluated by the receiver operating characteristic(ROC)curve.RESULTS:Compared with Con group,left ventricular systolic pressure(LVSP)at 9 d in CRS group was significantly decreased(P<0.05),left ventricular end-diastolic pressure(LVEDP)at 9 d in CRS group was significantly increased(P<0.05), and the differ-ence of blood pressure at each time point was not statistically significant.The levels of blood urea nitrogen(BUN)and uri-nary creatinine(Ucr)in CRS group were significantly increased at 1 and 3 weeks(P<0.05).Compared with Con group, serum CPP level was significantly increased at 1,3 and 5 weeks(P<0.05), and urine CPP level was significantly in-creased at 3 weeks in CRS group.Serum brain natriuretic peptide(BNP)level was significantly increased at 1 and 3 weeks,while urine BNP level was significantly increased at 5 weeks after modeling in CRS group(P<0.05).No correla-tion between serum or urine CPP and BNP or BUN levels at 1 week in CRS group was observed.The results of ROC curve analysis indicated that the area under the curve(AUC)of serum CPP was 0.908(95%CI:0.789~1.028),and the cut-off value was 56.59 ng/L(sensitivity 0.875,specificity 0.800).CONCLUSION:The combination of SNX and MI estab-lishes a CRS rat model with both heart and kidney injury,and serum CPP can be used as a sensitive and specific biomarker for early prediction of CRS.

Low expression of lncRNA-GAS5 promotes epithelial-mesenchymal transition of breast cancer cells in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the role of long non-coding RNA growth arrest-specific transcript 5 (lncRNA-GAS5) in breast cancer progression and epithelial-mesenchymal transition (EMT) of the cancer cells.</p><p><b>METHODS</b>Real-time quantitative PCR (qRT-PCR) was used to detect the expression of lncRNA-GAS5 in 37 pairs of breast cancer and adjacent non-tumor tissues and in parental MCF-7 cells and paclitaxel-resistant MCF-7 (MCF-7/PR) cells, and the correlation of lncRNA-GAS5 expression with the clinical stage and lymph node metastasis of breast cancer was investigated. The expressions of the genes related with cell cycle and EMT at both the mRNA and protein levels were detected using qRT-PCR, Western blotting and immunohistochemistry. The changes in the biological behaviors and morphology of breast cancer cells with either lncRNA-GAS5 knockdown or overexpression were observed. Nude mouse models were established bearing breast cancer xenografts derived from MCF-7/PR cells or MCF-7/PR cells over-expressing lncRNA-GAS5, and the inhibitory effect of paclitaxel on tumor growth was evaluated.</p><p><b>RESULTS</b>The transcriptional levels of lncRNA-GAS5 were significantly lower in breast cancer tissues than in the adjacent non-tumor tissues (P<0.05), and decreased lncRNA-GAS5 expression was significantly correlated with TNM stage and lymph node metastasis of breast cancer (P<0.05). lncRNA-GAS5 expression was also significantly lowered in paclitaxel-resistant breast cancer cells and showed a positive correlation with P21 expression and a negative correlation with CDK6. MCF-7 cells during EMT presented with a lowered expression of lncRNA-GAS5, whereas lncRNA-GAS5 over-expression strongly suppressed MCF-7/PR cell migration and invasion, and increased the susceptibility of the cells to paclitaxel. In the tumor-bearing nude mouse models, lncRNA-GAS5 overexpression in the tumor cells obviously enhanced the inhibitory effect of paclitaxel on tumor growth and lung metastasis by reversing the EMT marker proteins.</p><p><b>CONCLUSION</b>A decreased expression of lncRNA-GAS5 promotes lung metastasis of breast cancer by inducing EMT, suggesting the potential of lncRNA-GAS5 as a therapeutic target in breast cancer.</p>

Thalidomide-based Regimens for Elderly and/or Transplant Ineligible Patients with Multiple Myeloma: A Meta-analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Thalidomide is an immunomodulatory and anti-angiogenic drug that has shown promise in patients with myeloma. Trials comparing efficacy of standard melphalan and prednisone (MP) therapy with MP plus thalidomide (MPT) in transplant-ineligible or elderly patients with multiple myeloma (MM) have provided conflicting evidence. This meta-analysis aimed to determine the efficacy and toxicity of thalidomide in previously untreated elderly patients with myeloma.</p><p><b>METHODS</b>Medline, the Cochrane Controlled Trials register, conference proceedings of the American Society of Hematology (1995-2014), the American Society of Clinical Oncology (1995-2014), and CBM, VIP, and CNKI databases were searched for randomized control trials with the use of the medical subject headings "MM " and "thalidomide ". Trials were assessed by two reviewers for eligibility. Meta-analysis was conducted using a fixed effects model. Sensitivity analysis was performed to test the robustness of the findings.</p><p><b>RESULTS</b>Overall, seven trials were identified, covering a total of 1821 subjects. The summary hazard ratio (thalidomide vs. control) was 0.82 (95% confidence interval [CI]: 0.72-0.94) for overall survival (OS), and 0.65 (95% CI: 0.58-0.73) for progression-free survival, in favor of thalidomide treated group. The risk ratio of complete response with induction thalidomide was 3.48 (95% CI: 2.24-5.41). A higher rate of III/IV adverse events were observed in MPT arm compared with the MP arm. However, analysis of sub-groups administering anticoagulation as venous thromboembolism prophylaxis suggested no difference in relative risk of thrombotic events between two arms (RR = 1.47, 95% CI: 0.43-5.07, P = 0.54). Further analysis of trials on the treatment effects of MPT versus MP on adverse events-related mortality showed no statistical difference between two arms (RR = 1.24, 95% CI: [0.95-1.63], P = 0.120).</p><p><b>CONCLUSION</b>Thalidomide appears to improve the OS of elderly and/or transplant-ineligible patients with MM when it is added to standard MP therapy.</p>

Laparoscopic anterior resection with doubling-stapling technique anastomosis for rectal cancer / 中华胃肠外科杂志

Double-stapling technique (DST) has brought a revolutionary change for rectal cancer surgery. It has overcome the shortcomings of manual intestinal anastomosis operational difficulties caused by the narrow space of pelvic surgery, shortened the operation time, improved anal sphincter preservation rate, and reduced the risk of anastomotic leakage. The author gives a comprehensive and detail description of laparoscopic DST based on his ten years experience of laparoscopic colorectal resection for colorectal cancer.

Construction of pBIFC-VN173-CXCR4 and pBIFC-VC155-NT21MP eukaryotic expression plasmids and their interaction in living cells / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To construct pBIFC-VN173-CXCR4 and pBIFC-VC155-NT21MP eukaryotic expression plasmids and to investigate the interaction of chemokine receptor 4 (CXCR4) and viral macrophage inflammatory protein-II(vMIP-II) N terminal 21 peptides (NT21MP) in living cells.</p><p><b>METHODS</b>DNA fragment encoding NT21MP was chemically synthesized and inserted into BiFC eukaryotic expression vector pBIFC-VC155. The full length of CXCR4 DNA fragment was amplified by RT-PCR from SKBR (3) cells and inserted into BiFC eukaryotic expression plasmid pBIFC-VN173. Two recombinant vectors were identified by restriction enzyme digestion and DNA sequencing. The recombinant vectors were cotransfected into Africa green monkey kidney fibroblast COS-7 cells by using Lipofectamine 2000. The interaction of NT21MP and CXCR4 was detected by bimolecular fluorescence complementation (BiFC) assay.</p><p><b>RESULTS</b>The restriction enzyme digestion and DNA sequences and open read frames of two vectors were consistent with experiment design. The BiFC plasmids were successfully cotransfected into the target cells and expressed. The strong BiFC signals were detected in pBIFC-VN173-CXCR4 and pBIFC-VC155-NT21MP cotransfected cells and the fluorescence signal was located in the cytoplasm.</p><p><b>CONCLUSION</b>The eukaryotic expression plasmids for BiFC assay are successfully constructed. The interaction of NT21MP and CXCR4 in living cells can be detected by using this technology.</p>

Study and verification test on finite element materials properties of the long bone based on CT images / 医用生物力学

Objective To discuss the method for defining personalized materials properties of the fresh human long bone with alcohol treatment and the effect from the number of bone materials on finite element results. Methods Based on images from CT scans, a three dimensional solid model of the long bone was established in Mimics, which was then classified into the cortical bone, cancellous bone and marrow in Hypermesh. Based on relevant empirical formulas, material parameters of the cortical bone and cancellous bone were given, respectively, and 5 finite element analysis (FEA) models with different numbers of materials were set up. The simulation for linear elasticity of the compression was carried out in Abaqus and the results were validated by in vitro verification test. Results Under the end displacement ranging from 0 to 1 mm, the average relative error between the simulation results and the experimental data for holistic force-displacement was about 10%, when the materials number was defined as 1 kind of the cancellous bone and over 10 kinds of the cortical bone. And the average relative error between the simulation results and the experimental data for the deformation of the measurement points was 14.6%. The error of holistic force displacement for 1 kind of the cortical bone was 2.83% when the end displacement ranged from 0 to 0.5 mm. Conclusions (1) Using the gray value of CT scans, materials properties of the main component of the bone could be defined accurately. (2) The simulation result was greatly affected by the material number of the cortical bone, and defining 10 kinds of the cortical bone could satisfy the FEA need. (3) The FEA model with 1 kind of the cortical bone also could satisfy the need of analysis under small deformation.

Electroacupuncture at Zhongji (CV 3) for treatment of benign hyperplasia of prostate: a multi-central randomized controlled study / 中国针灸

<p><b>OBJECTIVE</b>To assess the role of Zhongji (CV 3) in treatment of benign hyperplasia of prostate.</p><p><b>METHODS</b>Multi-central, randomized, controlled, single bland clinical method was adopted, and 276 cases were divided into an electroacupuncture (EA) group and a medication group, 138 cases in each group. The EA group were treated with EA at Zhongji (CV 3) and the medication group with oral administration of Qianliekang tablets. After treatment of 1 course, their therapeutic effects and changes of international prostate symptom (I-PSS) cumulative score, life quality index (L) cumulative score, nocturia times, urine stream state, lower abdominal symptom, maximal volume of urine flow, residual urine volume, prostatic volume, etc. Were assessed in the two groups.</p><p><b>RESULTS</b>The total effective rate was 96.4% in the EA group and 86.2% in the medication group, the former being better than the latter (P<0. 01); the two groups were effective in improvement of international prostate symptom (I-PSS) cumulative score, life quality index (L) cumulative score, nocturia times, urine stream state, hypogastrium symptom, maximal volume of urine flow, residual urine volume, prostatic volume, etc. with the former better than the latter.</p><p><b>CONCLUSION</b>Acupuncture at Zhongji (CV 3) has a significant therapeutic effect for treatment of benign hyperplasia of prostate.</p>

Preoperative chemoradiotherapy with FOLFOX in low rectal cancer: a multicenter study / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the toxicity and safety of FOLFOX regimen concurrent with radiotherapy in neoadjuvant setting in patients with low rectal cancer.</p><p><b>METHODS</b>Fifty-six patients with stage T(3-4)N(0)M(0) and T(1-4)N(1-2)M(0) were eligible from Aug. 2004 to Jul. 2007. Upon entry the study, they received 4 cycles of chemotherapy with FOLFOX regimen. Radiotherapy was added from the second cycle of chemotherapy (CT). The total dose of radiotherapy (RT) was 46 Gy (2 Gy x 23). Total mesorectal excision (TME) was performed 4-8 weeks after RT.</p><p><b>RESULTS</b>Among them, 54 cases received 4 cycles of CT, 1 patient stopped CT after the second cycle of CT because of unrecovery from neutropenia. One patient stopped chemoradiotherapy(CRT) because of complicating with active pulmonary tuberculosis after 2 cycles of CT and 10 times of RT. Two occurred liver, lung and bone metastases after CT. Totally 220 cycles of CT were administrated. Fifty-two patients received operation after CRT, 50 with anal interior sphincter reservation, 19 with prophylactic ileac stoma. Anastomotic leakage occurred in 2 patients after operation, and rectal vaginal fistula in 2 patients 1 month after operation. According to the pathologic results, 7 patients achieved complete response, 41 partial response, 4 stable disease, and the objective response rate was 85.7%.</p><p><b>CONCLUSION</b>Concomitant treatment of FOLFOX regimen and RT in neoadjuvant setting of rectal cancer was safe and tolerable, and it suggests that protective ileostomy for anastomotic leakage following anus-preserving operation should be performed.</p>

Effects of sodium fluoride on the morphologic characteristics of primarily cultured thyroid cells of rats / 中国地方病学杂志

Objective To investigate the effects of different concentrations of sodium fluoride on the morphologic characteristics of primarily cultured thyroid cells of SD rats and in order to obtain important proof for approaehing the mechani8m of thyroid gland damage caused by fluoride.Methods Thyroid cells of SD rat were primarily culture for 96 hours,and cell density was adjusted to 5.0×108/L Cell suspension with 5 ml Wills seeded into 6 weII plates,after 12 hours,0(contr01),10.100,1000 μmol/L of sodium fluoride was added into the well, witll each well representing different level of treatment group.Finally the cultured thyroid cells were collected for morph010gic study.Results Under microscope,the transparency of the control thyroid cells Was good,and cells gathered in cluster and adhered to wall.But a lot of cells treated with fluoride suspended,and lost their transparency-under scaning delectron microscope,the control calls showed integrated membrane and tightness to each other,as well as clear boundary between cells normal proliferation.While the thyroid cells treated with 10,100 μmol/L sodium fluoride 0bviouslv shrinked and deformed,and the cells treated with 1000 μmol/L of sodium fluoride were broken-Conclusions nuoride can affect the growth and development of thyroid cell and damage the structure and morphology.Sodium fluoride affects the morphologie characteristics of thyroid cells in a dose-response manner.

Effect of total flaveos of Gymostemma pentaphyllum on protein expression of Fas/FasL genes and TNF-alpha concentration in cultured neonatal rat cardiomyocytes with hypoxia-reoxygenation / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effect of total flaveos of Gymostemma pentaphyllum on the protein expression of apoptosis-associated Fas/FasL gene and tumor necrosis factor-alpha (TNF-alpha) concentration in cultured neonatal rat cardiomyocytes with hypoxia-reoxygenation (H/R).</p><p><b>METHOD</b>A cultured primary neonatal rat cardiomyocytes model with H/R was erected, experiments were divided into six groups, (1)control group, (2)H/R group, (3)15 mg x L(-1) TFG plus H/R group, (4)45 mg x L(-1) TFG plus H/R group, (5) 105 mg x L(-1) TFG plus H/R group, (6)105 mg x L(-1) TFG group. TNF-aconcentration in cultured cardiomyocytes with H/R, was determined by ELISA method, the protein expression of Fas/FasL genes were estimated by immunohisto-chemistry.</p><p><b>RESULT</b>After cardiomyocytes were made with H/R, Compared with control group, the positive expression index (PEI) of Fas/FasL proteins in cardiomyocytes increased significantly, Compared with H/R groups, the PEI of Fas/FasL proteins were lower significantly in groups with different dosages of TFG (P < 0.05). TFG inhibited the secretion of TNF-alpha from myocardial cells and increased the survival rate of myocardial cells.</p><p><b>CONCLUSION</b>The protein expression of apoptosis-associated Fas/FasL genes increased during H/R. The TFG can protect myocardium against H/R injury by decreasing the production of TNF-alpha, downregulating the protein expression of Fas/FasL genes, and then inhibiting myocyte apoptosis.</p>

Total mesorectal excision versus conventional radical surgery for rectal cancer: a meta analysis / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare treatment outcomes of total mesorectal excision (TME) with those of conventional radical surgery (CRS) for rectal cancer.</p><p><b>METHODS</b>Literature reviews were performed with key words, such as rectal cancer, total mesorectal excision, TME on all studies reported on TME versus CRS for rectal cancer between January 1986 to May 2006. According to the same screening criteria, 17 clinical studies were included in our systematic reviews. Two of our co-authors drew the details of trial design, characteristics of participants, results and so on from the studies included. Data analyses were performed by using RevMan 4.2.</p><p><b>RESULTS</b>Sample volume in this Meta analysis was 5267 rectal cancer cases. Quality and quantity analyses were performed within all included studies, prospective studies (prospective nonrandomized studies and multicenter prospective nonrandomized studies) and retrospective studies. The results showed that postoperative survival rate was significantly increased [OR 1.81 (95%CI 1.55-2.11, P<0.00001), OR 1.79 (95%CI 1.49-2.15, P<0.00001) and OR 1.84 (95%CI 1.39-2.45, P<0.00001)] and local recurrence rate was significantly reduced [OR 0.35 (95%CI 0.29-0.43, P<0.00001), OR 0.41 (95%CI 0.32-0.53, P<0.00001) and OR 0.29 (95%CI 0.22-0.39, P<0.00001)] after TME was used. The results of all study analyses agreed with those from prospective studies analyses, in which postoperative mortality was significantly reduced [OR 0.51 (95%CI 0.32-0.87, P=0.007) and OR 0.56 (95%CI 0.33-0.94, P=0.04)] after TME treatment, meanwhile the results of retrospective study analyses indicated that there was no significant difference between TME group and CRS group in postoperative mortality [OR 0.39 (95%CI 0.14-1.10, P=0.07)]. TME was a risk factor for postoperative anastomotic leak according to the results of all included studies and prospective study analyses, but no difference between TME group and CRS group had been found [OR 1.24 (95%CI 0.84-1.83, P=0.29) OR 1.98 (95%CI 0.85-4.61, P=0.11)].</p><p><b>CONCLUSIONS</b>TME is still the standard operative technique for rectal cancer. As compared with CRS, TME results in lower postoperative local recurrence rate and higher survival rate.</p>

Short-term and long-term outcomes of moxifloxacin treatment in acute exacerbations of COPD / 中国感染与化疗杂志

Objective To investigate the aetiology of acute exacerbations of COPD (AECOPD),and the effects of moxifloxacin in the treatment of AECOPD.Methods Patients with stable COPD based on GOLD criteria were included in the study.Sputum collected at first exacerbation was analyzed for bacteria count and culture.IL-6,IL-8 and TNF-?were measured by enzyme- linked immunosorbent assay (ELISA).Eligible patients were randomized to receive moxifloxacin (400 mg qd for 5 days) or ce- faclor (250 mg q8h for 7 days).Efficacy parameters were evaluated at 7 and 14 days after treatment initiation and 1 year later. Results Of the 46 patients with moderate or severe COPD (male 38,moderate 24),21 (45.65%) were microbiologically evalu- able at baseline.The main pathogen was Haemophilus influenzae (10/21).Clinical efficacy rate was 87.0% in moxifloxacin group and 82.6% in cefaclor group.Bacterial eradication rate was 80.0% and 72.7% respectively.The difference between groups was not statistically significant in terms of clinical or microbiological efficacy.In moxifloxacin arm,the frequency of ex- acerbation was 2.6?1.0,significantly lower than control arm (3.5?1.4,P