Evolution and development of potent monobactam sulfonate candidate IMBZ18g as a dual inhibitor against MDR Gram-negative bacteria producing ESBLs

A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria. Compound 33a (IMBZ18G) is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant (MDR) Gram-negative strains, with a highly druglike nature. The checkerboard assay reveals its significant synergistic effect with β-lactamase inhibitor avibactam, and the MIC values against MDR enterobacteria were reduced up to 4-512 folds. X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and C β-lactamases. Accordingly, preclinical studies of 33a alone and 33a‒avibactam combination as potential innovative candidates are actively going on, in the treatment of β-lactamase-producing MDR Gram-negative bacterial infections.

Establishment of a mouse model of vascular endothelial-mesenchymal transdifferentiation genetic tracing and its role in liver fibrosis studies / 临床肝胆病杂志

Objective To establish Cdh5-Cre ERT /Acta2-tdTomato-STOP floxed -eGFP knockin genetic tracing mice, and to investigate its application in studies on vascular endothelial cell transition in liver fibrosis. Methods Cdh5-Cre ERT mice were mated with Acta2-KI mice, and the Cdh5-Cre ERT /Acta2-KI genetic tracing mice were obtained and identified by PCR genotyping. Primary liver sinusoid endothelial cells (LSECs) were isolated and cultured, and a model of CCl 4 -induced liver fibrosis was established. LSECs and liver tissue were collected for immunofluorescent staining to observe the expression of the fluorescent proteins tdTomato and eGFP. Results After being induced by tamoxifen, LSECs and liver tissue of Cdh5-Cre ERT /Acta2-KI genetic tracing mice expressed eGFP under the conditions for epithelial-mesenchymal transdifferentiation established in vivo and in vitro, while the control group without induction expressed tdTomato alone. Conclusion The successfully established Cdh5-Cre ERT /Acta2-KI genetic tracing mice can realize the effective labeling of epithelial-mesenchymal transdifferentiation, which provides a genetic tracing basis for the diverse sources of mesenchymal myofibroblasts in liver fibrosis.

Effects of FcγRIIb gene modified dendritic cells on immune tolerance of rat orthotopic liver transplantation / 中华普通外科杂志

Objective:To study the effects of FcγRIIb gene modified dendritic cells on liver function and rejection after orthotopic liver transplantation in rats.Methods:The recombinant lentivirus expression vector TRE-FcγRIIb containing Lewis rat FcγRIIb gene was constructed by gene cloning technique. TRE-FcγRIIb expression virus and TET-on regulatory virus were packaged and co-infected with immature dendritic cells derived from DA rat bone marrow. The expression of FcγRIIb was detected. Donor rats DA and recipient Lewis were paired according to body weight and then randomly divided into three groups. The control group (group A) did not receive any pretreatment. The Lewis rats in group B were treated with cyclosporin A on the 2nd day after liver TX. Immature dendritic cells derived from bone marrow of DA rats were injected intravenously one day before liver TX in FcγRIIb gene modified immature dendritic cells (1×10 6 cells)group (group C). Blood and liver tissue were biopsied 7 days after operation to detect liver function and pathological changes. Results:The abnormal liver function in FcγRIIb gene modified immature dendritic cells group (group C) was significantly lower than that of control group 7 days after operation ( P<0.05), and the liver pathological rejection of FcγRIIb gene modified immature dendritic cells group (group C) was significantly lower than that of control group 7 days after operation ( P<0.05). The average survival days of rats in the control group was 12.8 days; the average survival days of rats in the cyclosporin A group was 65.3 days; the average survival days of rats in the FcγRIIb gene-modified immature dendritic cell group was 58.5 days. Conclusion:FcγRIIb gene modified immature dendritic cells can ameliorate liver dysfunction and acute liver rejection after orthotopic liver transplantation.

The analysis of risk factors for cerebral microbleeds in cerebral infarction patients / 中国神经精神疾病杂志

Objective To analyze the risk factors of cerebral microbleeds (CMBs) in acute cerebral infarction patients. Methods We consecutively included 255 acute cerebral infarction patients who were admitted in Neurology Department of the First Affiliated Hospital of Fujian Medical University from January 2014 to December 2016. According to the number and location of CMBs, the patients were divided into infratentorial, cortical and deep cerebral groups, each of which included non-mild and moderate-severe subgroups. The differences of the level of glomerular filtration rate (eGFR) and some common arteriosclerotic risk factors were analyzed between subgroups, and the multiple logistic regression analysis was performed. Results A total of 140 subjects (54.9%) had CMBs. In the infratentorial group, the proportion of patients who were with low eGFR level in the moderate-severe CMBs subgroup was higher than in the non-mild CMBs subgroup (P=0.024). The low eGFR level (OR=3.874, 95% CI:1.261～11.901, P=0.018) and the long duration of hypertension (OR=2.128, 95%CI: 1.004～4.510, P=0.018) were the independent risk factors of the moderate-severe infratentorial CMBs. Conclusion The low eGFR level and long duration of hypertension are risk factors for the moderate and severe infratentorial CMBs after acute ischemic stroke.

Phenotypic spectrum of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy in Fujian, China: a study based on screening scale / 中华神经科杂志

Objective To summarize the phenotypic spectrum of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in Fujian population,evaluate the efficiency of the scale and try to adjust it.Methods Thirty-eight CADASIL patients and 64 CADASIL-like patients were recruited based on the CADASIL scale and gene tests,who visited the First Affiliated Hospital of Fujian Medical University and Fujian Neurology Research Institute from May 2011 to November 2017.Their clinical and neuroimaging characteristics were analyzed.Results The migraine,migraine with aura,transient ischemic attack / stroke,early onset age,psychiatric disturbances,cognitive decline,leukoencephalopathy,subcortical infarcts showed no statistically significant differences between the two groups.Instead,compared with CADASIL-like patients (10/64,15.6％;47/64,73.4％;10/64,15.6％),CADASIL patients demonstrated higher percentages of temporal pole involvements (13/38,34.2％;x5=4.716,P=0.030),external capsule involvements (36/38,94.7％;P=0.008) and family history in at least two generations (13/38,34.2％;x2=4.716,P=0.030).According to the scale,the scores showed statistically significant difference between CADASIL (14.84 ± 3.03) and CADASIL-like patients (13.34 ± 3.31;t=2.282,P=0.025) with an area under receiver operating characteristic curve of 0.622.Conclusions CADASIL showed no specific symptoms in Fujian population.The neuroimaging features were proposed to be focused on,especially the external capsule involvements.CADASIL scale could improve diagnostic efficiency,but still needs to be adjusted for Fujian population.The weight value of migraine,migraine with aura and cognitive decline was suggested to be decreased.

A clinical study of 135 patients with cerebral vascular fenestrations / 中华神经科杂志

Objective To characterize the imaging features of cerebral vascular fenestrations and the clinical features of patients with cerebral infarction.Methods We retrospectively analyzed the magnetic resonance or CT imaging data of 135 cases of cerebral vascular fenestrations from January 2015 to July 2017 in the First Affiliated Hospital of Fujian Medical University.The location,morphology and the other associated vascular diseases were described.The patients who had cerebral infarction were also analyzed.Results One hundred and thirty-five fenestrations were noted at our institution,129 in arteries,and six in veins,the detection rate being 1.1％ (135/12 232).Basilar arteries were most common,which accounted for 53.3％ (72/129) of the fenestrations.Twenty-eight (20.7％) of these patients had other vascular malformations,with a total of 15 aneurysms,two moyamoya diseases,five venous malformations,two arteriovenous fistulas,and four cavernous hemangiomas.Nine patients had cerebral infarctions,of which five patients had fenestration-relevant cerebral infarctions,and no risk factors for cerebral infarctions were found except fenestration in one patient who was diagnosed with cryptogenic stroke.No acute cerebral infarctions or transient ischemic attack occurred in patients with fenestration-relevant cerebral infarctions who had long-term antiplatelet and statin therapy during follow-up.Conclusions Cerebral vascular fenestrations occur most frequently in the basilar artery and may combine with other malformations.Long-term antiplatelet and statin therapy can be used for cerebral infarctions patients with cerebral vascular fenestrations.

Clinical research on Huang Bai capsules combined with Chinese medicine fumigation on the treatment of chronic anal fissure / 中国生化药物杂志

Objective To research the effect of Huang Bai capsules combined with Chinese medicine fumigation on treatment of chronic anal fissure.Methods 84 patients with chronic anal fissure from the second hospital of Shandong from January 2014～June 2016 were divided into two groups randomly.The control group was treated with Nitroglycerin and Lining gel and the observation group was treated with Huang Bai capsules combined with Chinese medicine fumigation.Treatment efficacy,symptom improvement,VAS score,gap healing time,ARP and RRP were compared between the two groups.Results The total effective rate in the observation group 95.24％is higher than that in the control group 78.57％(P<0.05).The proportion of bleeding and constipation after treatmen were lower than that before treatment(P<0.05).The proportion of bleeding and constipation in the observation group(9.52％and 11.90％)were lower than those in the control group(28.57％and 33.33％)(P<0.05).③ VAS score and gap healing time in the observation group were(1.18±0.20)points and(14.92±2.05)days,which were better than those in the control group(2.39±0.22)points and(19.16±2.28)days(P<0.05).④ARP and RRP in the observation group were(7.88±0.40)kPa and(2.61±0.31)kPa,which were lower than those in the control group(8.59±0.55)kPa and(3.09±0.45)kPa(P<0.05).Conclusion It can speed up crack healing and improve the effect of patients with anal fissure which Huang Bai capsules combined with Chinese medicine fumigation were used in the treatment.

Clinical analysis of 7 cases of varicella-zoster virus myelitis / 中国神经精神疾病杂志

Objective To investigate the clinical characteristics, diagnosis, treatment and prognosis of varicella zoster virus myelitis. Methods The clinical data of 7 varicella zoster virus myelitis patients were retrospectively analyzed and clinical follow-up was conducted. Results Seven patients had characteristic skin rash and symptoms of spinal cord injury. The initial symptoms including rash in 5 cases and spinal cord damage symptoms in 2 cases. The affected skin sections were consistent with the spinal cord segment in 4 cases, and below the level of spinal cord injury in 3 cases. All 7 cases were confirmed by spinal MRI with segmental spinal cord lesions as evidenced by long T1and long T2signals in the affected spinal cord including enhancing lesion in 2 cases. Lesions located in thoracic cord in 5 cases and in cervical cord in two cases.All patients received steroid hormone treatment.Among them,5 patients received additional antiviral treatment. After 12~36 months follow-up, 5 cases were cured, 1 case left with sphincter dysfunction and 1 case with slight numbness of hands. Conclusion Varicella zoster virus myelitis is characterized by characteristic rash and spinal cord symptoms.Antiviral drugs and corticosteroid therapy can yield better prognosis.

Construction Practice of Modern Pharmaceutical Logistics and Dispensing System in Outpatient Pharmacy / 中国药房

OBJECTIVE:To introduce the experience on how to build modern pharmaceutical logistics and dispensing system in outpatient pharmacy,and to provide reference for the construction of modern outpatient pharmacy. METHODS:The pharmaceuti-cal logistics system could be constructed by setting up secondary warehouse,pharmaceutical supply chain management system (PSCMS) and electronic drug storage system (EDSS);pharmaceutical dispensing system could be constructed through allocating automatic drug dispensing machine with different functions reasonably to carry out dispensing way of different modes combination, building automated pharmacy management system and developing emergency plan for the system fault of the automated pharmacy. The effects of logistics and dispensing system in our hospital were evaluated through comparing related index before and after the application of the systems. RESULTS:With the aid of PSCMS,the drug purchase information could be collected and calculated au-tomatically,the frequency and working time of the purchase were reduced by 50% and 75% respectively,and the accuracy of the purchase plan was increased by 12.5%;with the EDSS,the position and number information of the drugs could be acquired imme-diately,and the complementation and inventory time were decreased by 67% and 58% respectively;the time for manual dispens-ing was reduced by 68%,and the incidence of internal mistakes was decreased by 76.7%;under new dispensing system,the pre-scription could be distributed automatically and intelligently,the rate of automatic prescription processing was increased to 72.7%, and the average waiting time to pick up drugs was controlled to below 10 min. CONCLUSIONS:The pharmacists’working effi-ciency and the quality of pharmaceutical care have been improved by the modern pharmaceutical logistics and dispensing system, which settle the foundation for the transformation of the pharmaceutical care mode.

Clinical features of sporadic Creutzfeldt-Jakob disease / 中国神经精神疾病杂志

Objective We characterized the clinical features of sporadic Creutzfeldt-Jakob disease(sCJD)in or?der to diagnose it at the early stage. Methods Seventeen patients with sCJD were enrolled in the study. The clinical data, symptoms at the early stage, result of auxiliary examinations and survival time were analyzed. Results The ratio of male to female was 1:1.83 and the average age of onset was 60 ± 8.8 years old. Most of them presented with walking unstable (82.4%)and hypomnesia (64.7%) as the initial symptom. The occurrence rate was 82.4%, 76.5%and 58.8%for myoclo?nus, colored-ribbon-shaped high signals in cerebral cortex and high signals in basal ganglia of MRI. Periodic synchro?nous discharge (PSD) of electroencephalography(EEG) was seen in 82.4% cases, while cerebrospinal fluid analysis re?vealed positive results for 14-3-3 protein in 70%cases. Twelve patients had been dead in our study. The median surviv?al time was 12±7.7 months. Conclusions sCJD is more frequently occurred in mid-aged and older without specific symp?toms in early stage and positive rate of high signals in cerebral cortex of MRI and PSD of EEG is high.

Research on exposure to polycyclic aromatic hydrocarbons during pregnancy and risk of preterm birth / 中华预防医学杂志

Polycyclic aromatic hydrocarbons (PAH) are a group of toxic pollutants existing in the environment widely, and can be taken into the body through various ways containing the digestive tract, respiratory tract and so on. Pregnant women and newborn infants are important and susceptive populations. Relevant study evidences indicate that exposure to PAH during pregnancy may be a important risk factor of preterm delivery, but the special mechanism isn't very clear and may be related with DNA damage, oxidative stress, systemic inflammation, endocrine disruption and so on. This paper reviewed related contents including the influences and evaluation methods of exposure to PAH during pregnancy, increasing risk and potential mechanism for preterm delivery of exposure to PAH during pregnancy.

Relationship and the underlying mechanism of cholesterol metabolism with colorectal cancer / 中华内分泌代谢杂志

Recent meta-analysis based on both clinical trials and epidemiological studies has revealed the relationship of dietary cholesterol,blood cholesterol level and cholesterol lowering drugs (statins) with colorectal cancer.This review summarises the advances in current evidences of linking cholesterol metabolism and risk of colorectal cancer and the underlying molecular mechanisms based on pharmacogenetics and molecular pathology.

Prevalence of macrosomia and its risk factors in China: a national survey in 2011 / 中华围产医学杂志

Objective To investigate the prevalence of macrosomia in China and the risk factors.Methods By stratified cluster random sampling,the medical records of 101 723 singleton term infants born in 37 hospitals nation wide (in 14 provinces) from January 1,2011 to December 31,2011 were reviewed.Adjusted odd ratio (aOR) and 95％ confidence interval (CI) were used to describe the risk factors.Population attribute risk (PAR) was used to quantitatively describe the associations between risk factors and the prevalence of macrosomia.Results The general prevalence of macrosomia was 7.3％ (7403/101 723).The prevalence varied among provinces (4.1％ to 13.4 ％).Logistic regression analysis showed that macrosomia were positively associated with living in northern China (aOR =1.4,95 ％ CI:1.2 ～ 1.6,PAR =19.9 ％),maternal age ≥ 35 (aOR =1.1,95％ CI:0.9～1.3,PAR=8.7％),pre-pregnant BMI≥28 (aOR=3.6,95％ CI:2.9～4.5,PAR=15.1％),gravidity＞1 (aOR=1.2,95％ CI:1.1～1.4,PAR=10.8％),parity＞1 (aOR=1.8,95％ CI:1.5～ 2.1,PAR=10.1％),maternal height≥160 cm (aOR =1.6,95％ CI:1.4～ 1.9,PAR=29.5％),gestational weight gain (GWG) ≥16 kg (aOR=2.2,95％ CI:1.9～2.4,PAR=25.2％),gestational diabetes mellitus (aOR=1.2,95％ CI:1.0～ 1.3,PAR =3.2％),gestational weeks≥40(aOR=2.4,95％ CI:2.1～ 2.7,PAR=34.4％)and baby boy (aOR=l.6,95％ CI:1.4～1.8,PAR=25.4％).Maternal BMI,gestational week and GWG were most strongly associated with macrosomia.Conclusions The prevalence of macrosomia varied dramatically between different areas in China.Pre-pregnancy BMI,gestational week and GWG,as the main modifiable risk factors for macrosomia,need more attention from health care providers.

Simultaneous Determination of Silybin A and Silybin B in Rat Plasma and Pharmacokinetic Study / 中草药·英文版

Objective To investigate the bioavailability and pharmacokinetics of silybin A and silybin B in rats,respectively.Methods Following iv and ig administration of silybin to 20 Wistar rats,the plasma samples were collected at different time points up to 12 h.Sample pretreatment was involved in one-step protein precipitation with acetonitrile.Silybin A and silybin B were simultaneously determined by LC-MS/MS.Results After ig dosing silybin 28,56,and 112 mg/kg to rats,the t1/2β values were 5.48,5.08,and 5.73 h for silybin A,and 4.56,4.12,and 5.53 h for silybin B; The Cmax were 674.3,1349.4,and 2042.5 ng/mL for silybin A,and 671.0,1365.4,and 2066.2 ng/mL for silybin B; The Tmax were 0.20,0.23,and 0.20 h for silybin A,and 0.20,0.23,and 0.20 h for silybin B; The AUC were 454.4,845.9,and 1219.5 h·ng/mL for silybin A,and 432.0,817.1,and 1153.6 h·ng/mL for silybin B.The absolute bioavailabilities of silybin A and silybin B were 2.86％ and 1.93％,respectively.Conclusion Silybin A and silybin B have very low bioavailability after ig administration,and there is no significant difference in the pharmacokinetic parameters between silybin A and silybin B,which indicates that the two diastereoisomers have similar pharmacokinetic behavior in rats.

Value of Chemosensitivity Assay In Vitro on Breast Cancer / 中国普外基础与临床杂志

Objective To explore the value of chemosensitivity assay in vitro on breast cancer.MethodsIn vitro chemosensitivity of 6 species of chemotherapeutic agents applied to 38 cases of breast cancer patients were detected by tissue culture-end point staining-computer image analysis(TECIA).ResultsThe sensitivity to chemotherapeutic agents commonly used in the breast cancer level from high to low was as follow:Doxorubicin(ADM),Paclitaxel(TAX),Vinorelbine(NVB),Cyclophosphamide(CTX),Cisplatin(DDP)and Fluorouracil(FU).ConclusionDrugs sensitivity experiment of cancer in vitro by TECIA has an important value to instruct clinical medication and individual chemotherapy for breast cancer.

Applications of Multilevel Bivariate Models in Multiple Correlation / 中国卫生统计

Objective　To analyze the partial correlation problems by multilevel bivariate models.Methods　Multilevel bivariate models.Results　The results of correlation analysis with multilevel bivariate models is same with traditional methods,but the former is more quick and simple.Conclusion　Multilevel bivariate models are effective methods in analyzing the partial correlation problems.

APE/Ref-1 protein and ischemia/reperfusion injury of neurons in the brain / 中国病理生理杂志

Cerebral ischemia and the aftermath of reperfusion form a hypoxic/hyperoxic sequence of events that can trigger DNA damage in neurons of central nervous system. Neuronal apoptosis will happen without immediate DNA repair. APE/Ref-1 is a multifunctional protein involoved in DNA base excision repair pathway and in redox reguiation of DNA-binding activity of AP-1 family members, which may play an important role in protection of postischemic neuronal damage.

The Relationship Between Nitrate,Nitrite,N-Nitrosocompound and Human Congenital Malformations / 环境与健康杂志

It is well known that the nitrate and nitrite from environment is causally related to infant methemoglobinemia and esophageal cancer.In the past three decades,there was also much evidence to reveal that nitrite and nitrate from drinking water or diet were potentially related to human congenital malformations.The present paper introduced the exposure and transformation of nitrate,nitrite and N-nitrosocompound from environment and the evidences of investigation about relationship between these compounds and human congenital malformations.