Efficacy and safety of fluzopril in the treatment of platinum-sensitive recurrent epithelial ovarian cancer / 新乡医学院学报

Objective To investigate the efficacy and safety of fluzopril in the treatment of platinum-sensitive recurrent epithelial ovarian cancer.Methods A total of 107 patients with platinum-sensitive recurrent epithelial ovarian cancer admitted to the First Affiliated Hospital of Henan University of Science and Technology from January 2019 to December 2020 were selected as the subjects.According to treatment methods,the patients were divided into control group(n=50)and observation group(n=57).The patients in the control group received a first-line chemotherapy regimen of paclitaxel combined with platinum:on the first day,intravenous infusion with paclitaxel injection 135 mg·m-2 was administered;on day 1-3,intravenous drip with cisplatin 50-60 mg·m-2 was administered;21 days was one chemotherapy cycle.On the basis of the treatment in the control group,the patients in the observation group were given fluzoparide capsules orally,150 mg each time,twice a day,and the treatment continued until disease progression or unacceptable toxic reactions occurred;21 days was one chemotherapy cycle.The patients in both groups received three consecutive chemotherapy cycles.The clinical efficacy,prognosis within 2 years after chemotherapy,Karnofsky Performance Status(KPS)score before and after chemotherapy,and incidence of adverse reactions during chemotherapy of patients between the two groups were compared.Results After 3 cycles of chemo-therapy,the disease control rate and objective remission rate of patients in the observation group were significantly higher than those in the control group(x2=5.420,4.220;P＜0.05).Following up to 24 months,the progression free survival of patients in the observation group was significantly longer than that in the control group(t=6.702,P＜0.05);there was no statistically significant difference in 1-year survival rate of patients between the two groups(x2=0.415,P＞0.05);the 2-year survival rate of patients in the observation group was significantly higher than that in the control group(x2=5.420,P＜0.05).Before chemotherapy,there was no statistically significant difference in KPS scores of patients between the two groups(t=0.537,P＞0.05);the KPS scores of patients in the two groups after three cycles of chemotherapy were significantly higher than those before chemotherapy(t=5.604,9.378;P＜0.05);after three cycles of chemotherapy,the KPS score of patients in the observation group was significantly higher than that in the control group(t=2.608,P＜0.05).The patients in both groups experienced hematological and non-hematological adverse reactions during chemotherapy;the main hematological adverse reactions was bone marrow suppression,most of which were Ⅲ ° and Ⅳ ° adverse reactions;the non-hematological adverse reactions included alo-pecia,gastrointestinal reactions,and liver and kidney dysfunction,most of which were Ⅰ°and Ⅱ°adverse reactions.There were no chemotherapy related deaths of patients in both groups.The incidence rates of anemia,thrombocytopenia,neutropenia,leuko-penia,lymphopenia,nausea,vomiting,fatigue,loss of appetite,hair loss,elevated serum creatinine,and elevated alanine amino-transferase(ALT)of patients during chemotherapy in the control group were 68.00％(34/50),72.00％(36/50),58.00％(29/50),68.00％(34/50),22.00％(11/50),26.00％(13/50),24.00％(12/50),46.00％(23/50),30.00％(15/50),50.00％(25/50),20.00％(10/50),10.00％(5/50),respectively;the incidence rates of anemia,thrombocytopenia,neutropenia,leukopenia,lymphopenia,nausea,vomiting,fatigue,loss of appetite,hair loss,elevated serum creatinine,and elevated ALT of patients during chemotherapy in the observation group were 61.40％(35/57),63.16％(36/57),49.12％(28/57),52.63％(30/57),21.05％(12/57),22.81％(13/57),24.56％(14/57),42.11％(24/57),29.82％(17/57),47.37％(27/57),21.05％(12/57),10.53％(6/57),respectively.There was no statistically significant difference in the incidences of anemia,thrombocytopenia,neutropenia,leukopenia,lymphopenia,nausea,vomiting,fatigue,loss of appetite,hair loss,elevated serum creatinine,and elevated ALT of patients during chemotherapy between the control group and the observation group(x2=0.047,0.000,0.041,0.694,0.056,0.000,0.208,0.041,0.184,0.160,0.233,0.102;P＞0.05).Conclusion For patients with platinum-sensitive recurrent ovarian cancer,the combination of paclitaxel and platinum chemo-therapy combined with fluzopril can effectively improve the anti-tumor effect,prolong the progression-free survival,improve survival rate and quality of life,and the adverse reactions are controllable.

Effect of controlled low central venous pressure with milrinone on laparoscopic hepatectomy / 中华麻醉学杂志

Objective:To evaluate the effect of controlled low central venous pressure with milrinone on laparoscopic hepatectomy in the patients.Methods:Fifty American Society of Anesthesiologists physical statusⅠ-Ⅲ patients of both sexes, aged 18-64 yr, with body mass index of 18-30 kg/m 2, of Child-Pugh grade A or B, undergoing elective laparoscopic hepatectomy, were divided into 2 groups ( n=25 each) using a random number table method: milrinone group (group M) and nitroglycerin group (group NG). After the start of surgery, milrinone 0.5 μg·kg -1·min -1 was continuously infused in group M, and nitroglycerin was continuously infused with the initial dose of 0.5 μg·kg -1·min -1 to maintain central venous pressure (CVP)≤5 mmHg in group NG.Mean arterial pressure and heart rate were recorded on admission to the operation room (T 0), at skin incision (T 1), at the beginning of liver resection (T 2), at completion of liver resection (T 3), at the end of operation (T 4), and CVP, cardiac index and stroke volume variation were recorded at T 1-4.Internal jugular vein blood samples were collected to determine the concentrations of hemogloblin, blood lactate at T 1 and T 4, and serum alanine aminotransferase, aspartate aminotransferase and creatinine concentrations at 1, 3 and 7 days after surgery.The score of blood oozing in hepatic surgical field, amount of norepinephrine used, blood loss, postoperative recovery and occurrence of complications within 7 days after operation were recorded. Results:Compared with group NG, cardiac index was significantly increased at T 2, 3, the CVP was decreased at T 2, the blood oozing score, blood loss, consumption of norepinephrine, and concentrations of blood lactate were decreased, and the postoperative drainage indwelling time was shortened in group M ( P<0.05). There was no significant difference in the serum alanine aminotransferase, aspartate aminotransferase and creatinine concentrations and incidence of postoperative complications at 1, 3 and 7 days after operation between the two groups ( P>0.05). Conclusions:Milrinone is better than nitroglycerin in decreasing central venous pressure, reducing blood loss, maintaining stable circulatory function and tissue perfusion in laparoscopic hepatectomy.

Study on Sustainable Development Ability Evaluation Index System for Ethnomedicine Enterprises in Guizhou Province / 中国药房

OBJECTIVE：To establish sustainable development ability evaluation index system for ethnomedicine enterprises in Guizhou province ，and to promote the sustainable development of the ethnomedicine industry. METHODS ：The draft of evaluation index system had been made by documents collection and a meeting of focus group discussion ，the final indexes and weight had been determined by Delphi method for conducting 2 rounds expert questionnaire survey ；the index system was used to measure and compare the results with the evaluation results of the drug regulatory department and the authoritative experts of the industry. RESULTS：The draft of evaluation index system included 6 indexes in the first level indicators and 49 indexes in the second. The expert’s positive coefficients was 100％ after 2 rounds of consultation ；the authoritative coefficients on the opinions of experts for the levels of indicators were 0.86，the coordination coefficient of experts was 0.22 in the first round and 0.48 in the second. After 2 rounds of expert consultation ，the final established evaluation index system contained 6 indexes in the first level indicators and 33 indexes in the second. Fifteen ethnomedicine enterprises in Guizhou province were selected for on-site testing. The evaluation results were not much different from those of the drug regulatory department and the authoritative experts of the industry. CONCLUSIONS：Established sustainable development ability evaluation index system for ethnomedicine enterprises is scientific ， reasonable and feasible ，and can provide standardized reference for regular monitoring and evaluation.

Enlightenment of Micro-lecture Teaching on Medical Ethics Teaching under the Background of Big Data Era / 中国医学伦理学

With the arrival of big data era,the micro-lecture teaching as a new teaching mode arises at the right moment.The micro-lecture teaching has three characteristics of video-based,short and compact,studying and learning jointly by teachers and students,and students'self-study,and is of significant reference for the med-ical ethics teaching.The traditional medical ethics teaching faces with some challenges: the teaching contents at-tach importance to theory and despise timeliness; the teaching methods attach importance to teaching and despise application; the teaching evaluations attach importance to knowledge assessment and despise ability training.Therefore,the enlightenment of micro-lecture teaching on medical ethics teaching was manifested in three as-pects: combining theory with practice and paying attention to the timeliness of content; situational teaching and fo-cusing on the application of knowledge; taking students as the center,paying attention to the improvement of ethical decision-making ability.

S100A7 promotes the metastasis and epithelial-mesenchymal transition on HeLa and CaSki cells / 中华妇产科杂志

Objective To elucidate the impact of over-expression of S100A7 on migration,invasion,proliferation, cell cycle, and epithelial-mesenchymal transition (EMT) in human cervical cancer HeLa and CaSki cells.Methods(1)Immunohistochemistry of SP was used to examine the expression of S100A7 in 40 cases of squamous cervical cancer tissues and 20 cases of normal cervical tissues.(2)The vectors of pLVX-IRES-Neo-S100A7 and pLVX-IRES-Neo were used to transfect human cervical cancer HeLa and CaSki cells, and the positive clones were screened and identified. Next, transwell migration assay, cell counting kit-8(CCK-8)assay and fluorescence activating cell sorter(FACS)were used to detect the effect of S100A7-overexpression on the migration, invasion, proliferation and cell cycle of cervical cancer cells. Furthermore, western blot was performed to observe the expression of epithelial marker(E-cadherin)and mesenchymal markers(N-cadherin,vimentin,and fibronectin)of EMT. Results(1)S100A7 expression was significantly higher in cervical squamous cancer tissues(median 91.6)than that in normal cervical tissues(median 52.1;Z=-2.948,P=0.003).(2)Stable S100A7-overexpressed cells were established using lentiviral-mediated gene delivery in HeLa and CaSki cells. S100A7 was detected by real-time quantitative reverse transcription PCR,S100A7 mRNA of S100A7-overexpressed cells were 119 ± 3 and 177 ± 16, increased significantly compared with control groups of median(P<0.01).Compared with the control cells, the number of S100A7-overexpressed HeLa and CaSki cells that passed the transwell membrane assay were increased significanatly(572 ± 51 vs 337 ± 25, P<0.01;100 ± 8 vs 41 ± 4, P<0.01).Matrigel invasion assay showed that the number of S100A7-overexpressed HeLa and CaSki cells that passed the transwell membrane were respectively 441±15 and 110±14,elevated significantly compared with control cells(156±21 and 59±7;P<0.05). However, S100A7 overexpression didn′t influence the proliferation and cell cycle progression of HeLa and CaSki cells(P>0.05). Expression of E-cadherin was dramatically decreased, while N-cadherin, vimentin, and fibronectin increased in S100A7-overexpressed cells. Conclusion S100A7 enhances the migration, invasion and EMT of HeLa cells and CaSki cells, and may be plays an important role in the development of cervical cancer.

The distribution of CTX-M drug resistance genotypes in Escherichia coli isolated from urethra in children and the influence of pH changes on its drug resistance / 临床儿科杂志

Objectives To explore the distribution of CTX-M drug resistance genotypes in Escherichia coli isolated from urethra in children and the influence of pH changes on its drug resistance. Methods A total of 113 strains of Escherichia coli isolated from clean midstream urine in children with urinary tract infection were cultured from October 2013 to May 2014. The drug sensitivity of ESBL-producing Escherichia coli was detected and counted. The distribution of CTX-M drug resistance genotypes were analyzed by PCR and gene sequencing. Different pH environment was established in vitro to evaluate the effect of pH on drug resistance of CTX-M resistant Escherichia coli. Results In 113 Escherichia coli strains, there were 68 ESBL-producing strains (60.18％), in which rate of drug resistance to meropenem and imipenem were 1.47％ and 2.94％ respectively. There were 41 strains carried CTX-M drug resistance genotype, which mainly were type CTX-M-14 and type CTX-M-15, 18 strains each. Compared with neutral environment of the pH value at 6 or 6.5, the rate of Escherichia coli resistant to cefuroxime, cefotaxime, ceftazidime and ceftriaxone had no difference (P>0.05), while the resistance to cefepime was significantly increased when pH was 6.0 (P<0.01). With the pH value at 8 or 8.5, the rate of Escherichia coli resistance to ceftazidime and cefepime was significantly decreased, and with the pH value at 8.5 the rate of Escherichia coli resistance to cefotaxime also significantly decreased (P<0.01). Conclusions The rate of ESBL-producing Escherichia coli resistance to carbapenem antibiotic is low. The rate of Escherichia coli carrying CTX-M drug resistance genotype is high with CTX-M-14 and CTX-M-15 being the most prevalent genotypes. Properly alkalization of urine may contribute to the treatment of CTX-M resistant Escherichia coli in children with urinary tract infection.

Effect of ulinastatin on activity of JAK2/STAT3 signaling pathway during focal cerebral ischemia-reperfusion in rats / 中华麻醉学杂志

Objective To evaluate the effect of ulinastatin on the activity of Janus kinase 2/signaling transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway during focal cerebral ischemia-reperfusion (I/R) in rats.Methods Forty-eight clean-grade healthy adult male Sprague-Dawley rats,aged 6-8 weeks,weighing 230-280 g,were divided into 3 groups (n=16 each) using a random number table:sham operation group (S group),cerebral I/R group (I/R group) and ulinastatin group (U group).Focal cerebral I/R was induced by occlusion of the middle cerebral artery for 2 h followed by reperfusion.Ulinastatin 100 000 U/kg was injected via the femoral vein immediately after beginning of cerebral ischemia in group U.Neurologic deficit was evaluated and scored (NDS) at 24 h of reperfusion.The rats were then sacrificed and brains were removed for measurement of the cerebral infarct size (by TTC staining) and for determination of the expression of total JAK2,total STAT3 and phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) in the cerebral cortex.Results Compared with S group,NDS and cerebral infarct size were significantly increased,and the expression of p-STAT3 and p-JAK2 in the cerebral cortex was up-regulated in I/R group and U group (P＜0.05).Compared with I/R group,NDS and cerebral infarct size were significantly decreased,and the expression of p-STAT3 and p-JAK2 in the cerebral cortex was down-regulated in U group (P＜0.05).There was no significant difference in the expression of total JAK2 and total STAT3 in the cerebral cortex between three groups (P＞0.05).Conclusion Ulinastatin can inhibit the activity of JAK2/STAT3 signaling pathway during cerebral I/R,which may be involved in the brain protective mechanism of ulinastatin in rats.

Clinical Study on Zi Wu Liu Zhu Na Jia Needling for Spastic Hemiplegia after Cerebral Stroke / 上海针灸杂志

Objective To evaluate the clinical efficacy ofZi Wu Liu Zhu Na Jia needling (acupuncture based on midnight-noon ebb-flow theory) in treating spastic hemiplegia after cerebral stroke by using surface electromyography (sEMG).Method Fifty-two patients with spastic hemiplegia due to cerebral stroke were randomized into a treatment group and a control group, 26 cases each. The two groups were both intervened by conventional rehabilitation training. In addition, the treatment group was givenZi Wu Liu Zhu Na Jia needling and the control group was given ordinary acupuncture. The two groups were treated once a day, 15 sessions as a course. The ambulation ability, muscle tension, neurological deficit score (NDS), Fugl-Meyer Assessment Scale (FMA), and Berg Balance Scale (BBS) were evaluated before the intervention and after 2 treatment courses, and the sEMG signals were also collected and analyzed.Result The Holden's Functional Ambulation Classification (FAC) and Modified Ashworth Scale scores were significantly changed in the two groups after the intervention (P<0.01). After the intervention, the FAC and MAS scores in the treatment group were significantly different from those in the control group (P<0.05). The NDS, FMA and BBS scores were significantly changed in the two groups after the treatment (P<0.05). The NDS, FMA and BBS scores in the treatment group were significantly different from those in the control group after the treatment (P<0.05). Of the sEMG signals, H/M max in the treatment group was significantly different from that in the control group after the intervention (P<0.01).Zi Wu Liu Zhu Na Jia needling with rehabilitation training can significantly mitigate the muscle tension and promote the activities of daily living in patients with spastic hemiplegia after cerebral stroke.

Effect of intrathecal dexmedetomidine on expression of GIRK1 in dorsal root ganglia of rats with diabetic neuropathic pain / 中华麻醉学杂志

Objective To evaluate the effect of intrathecal dexmedetomidine on the expression of G-protein-coupled inwardly rectifying K+ channel 1 (GIRK1) in dorsal root ganglia of rats with diabetic neuropathic pain (DNP).Methods A total of 144 healthy adult male SPF Sprague-Dawley rats,aged 8-10 weeks,weighing 200-220 g,were randomly divided into 4 groups (n =36 each) using a random number table:control group (group C),dexmedetomidine group (group D),group DNP,and DNP + dexmedetomidine group (group DD).DNP model was established by single intraperitoneal injection of streptozotocin (STZ) 60 mg/kg.In D and DD groups,dexmedetomidine 1.5 μg/kg was injected intrathecally at 14 days after citrate buffer or STZ injection,while the equal volume of normal saline was given in group C.The mechanical pain threshold was measured before STZ injection (T0),at 14 days after STZ injection (T1),and at 2,4 and 6 h after intrathecal injection (T:2-4).After measurement of the mechanical pain threshold at T2-4,the rats were sacrificed,and the dorsal root ganglia of the lumbar segment (L4-6) were removed for determination of the number of GIRK1 positive cells and expression of GIRK1 protein by immunofluorescence and Western blot,respectively.Results Compared with group DNP,the mechanical pain threshold was significantly increased,the number of GIRK1 positive cells in dorsal root ganglia was significantly increased,and the expression of GIRK1 was significantly up-regulated at T2-4 in group DD (P＜0.05).Compared with group D,the number of GIRK1 positive cells in dorsal root ganglia was significantly increased,and the expression of GIRK1 was significantly up-regulated at T2-4 in group DD (P＜0.05).Compared with group C,the mechanical pain threshold was significantly decreased at T1-4 in group DNP (P＜0.05).Conclusion Intrathecal dexmedetomidine attenuates DNP through up-regulating the expression of GIRK1 in dorsal root ganglia of rats.

Expression of connexin 43 in spinal cord dorsal horn of rats with acute incisional pain / 南方医科大学学报

<p><b>OBJECTIVE</b>To examine the effect of acute incisional pain on the expression of connexin 43 in rat spinal cord dorsal horn.</p><p><b>METHODS</b>Eighty rats were assigned into control group without any treatment and incisional pain group with incision surgery. For paw incisions, a 1-cm longitudinal incision was made through the skin and fascia of the plantar aspect of the right hind paw. After surgery, the 50% paw withdrawal threshold (PWT) was assessed in response to a tactile stimulus with calibrated von Frey monofilaments at 1, 2, 4 and 24 h, respectively. The spinal cord dorsal horn of rats was isolated at 1, 2, and 4 h after the surgery to assess the expression of connexin 43 using Western blotting and immunofluorescence assay.</p><p><b>RESULTS</b>The 50% PWT of the rats was significantly decreased after the incision surgery, and this decrement was the most obvious at 2 and 4 h. Western blotting and immunofluorescence assay showed that the expression of connexin 43 in the spinal cord dorsal horn was significantly increased in rats receiving the surgery especially at 2 and 4 h after the surgery.</p><p><b>CONCLUSION</b>Incision surgery induces an significant increase in connexin 43 expression in rat spinal cord dorsal horn, suggestting an potential role of connexin43 in postoperative incisional pain.</p>

The effect of etomidate on the gap junctional intercellular communication between human malignant glioma cells / 中国癌症杂志

Background and purpose:Gap junctions (GJ) could enhance cytotoxicity induced by chemo-therapeutic agents. Previous studies have showed that some of anesthetics exerted effect on GJ and thereby affected the cytotoxicity of X-ray. However, it is still unclear whether etomidate, a commonly used anesthesia adative agent, could alter GJ intercellular communication in tumor cells. This study explored the effect of etomidate on GJ composed of connexin 43 in U87 malignant glioma cells to provide mechanism clues for studies on the effect of anesthetics on the toxicity induced by chemotherapeutic agents.Methods:Sulforhodamine B was used to examine the toxicity of etomidate on U87 malignant gli-oma cells. The effect of etomidate on GJ function was determined by parachute dye-coupling assay.Results:Pretreatment of etomidate at the concentration of 0.1, 0.5, 1 or 5 μmol/L for 4 h did not induce cytotoxicity in U87 cells. So etomidate at these concentrations would not reduce the amount of GJ on U87 cell membranes. Parachute dye-coupling assay had showed that treatment with 0.5 and 1 μmol/L etomidate for 4 h significantly decreased the dye spread through GJ in U87 cells, while 0.1 μmol/L etomidate had no effect on dye spread of U87 cells through GJ.Conclusion:Etomidate inhibits GJ function in glioma cells.

Role of mTOR signaling pathway in dexmedetomidine-induced reduction of renal ischemia-reperfusion injury in rats: the relationship with HIF-1α / 中华麻醉学杂志

Objective To evaluate the role of mammalian target of rapamycin (mTOR) signaling pathway in dexmedetomidine-induced reduction of renal ischemia-reperfusion (I/R) injury in rats and the relationship with hypoxia-inducible factor 1 (HIF-1α).Methods Seventy-two male Sprague-Dawley rats, aged 10-12 weeks, weighing 220-260 g, were randomly divided into 4 groups (n=18 each) using a random number table: sham operation group (group S), group I/R, dexmedetomidine group (group Dex) ,and rapamicyn + dexmedetomidine group (group Rpm+Dex).Renal I/R was produced by occlusion of bilateral renal pedicles for 35 min follow by reperfusion in anesthetized rats in I/R, Dex and Rpm+Dex groups.Bilateral renal pedicles were only exposed, and then the abdominal cavity was closed in group S.Dexdetomidine 50 μg/kg was injected intraperitoneally at 30 min before I/R in group Dex.In group Rpm+Dex, rapamicyn 1.5 mg/kg and dexdetomidine 50 μg/kg were injected intraperitoneally, and renal I/R model was established 30 min later.Immediately after onset of reperfusion, and at 4 and 24 h of reperfusion (T1-3) , blood samples were collected from the caudal vein for measurement of serum creatinine and blood urea nitrogen (BUN) concentrations.After blood sampling at T1-3, the rats were sacrificed, and the renal specimens were obtained for detection of HIF-1αt, erythropoietin (EPO) and mTOR expression by Western blot.Their kidneys were removed at T3, and cut into sections which were stained with haematoxylin and eosin and examined under microscope.Acute renal tubular necrosis was scored.The cell apoptosis in renal tissues was detected by TUNEL assay, and apoptosis index (AI) was calculated.Results Compared with group S,the concentrations of serum creatinine and BUN, expression of HIF-1α, EPO and mTOR at T2,3 , AI at T3 and acute renal tubular necrosis score were significantly increased in the other three groups (P＜ 0.05).Compared with group I/R, the concentrations of serum creatinine and BUN were significantly decreased, and the expression of HIF-1α, EPO and mTOR was up-regulated at T2,3 , and AI and acute renal tubular necrosis score were decreased in group Dex (P＜0.05) , and no significant change was found in the parameters mentioned above in group Rpm + Dex (P ＞ 0.05).Conclusion The mTOR signaling pathway is involved in dexmedetomidine-induced reduction of renal I/R injury, which may be related to dexmedetomidine-produced up-regulation of HIF-1α expression in renal tissues of rats.

The role of gap junctions composed of connexin 43 on the anti-tumor effect induced by etoposide / 中国癌症杂志

Background and purpose: Gap junctions(GJ) could enhance cytotoxicity induced by chemotherapeutic agents. However, whether or not GJ composed of connexin 43 (Cx43) could increase etoposide cytotoxicity remains unclear. The aim of this study was to explore the effect of GJ composed of Cx43 on etoposide cytotoxicity in testicular cancer cells. Methods: Eighteen-glycyrrhetinic acid and siRNA were used to inhibit GJ function. Retinoid acid was used to enhance GJ function.“Parachute”dye-coupling assay was used to examine dye spread through GJ composed of Cx43 in MLTC-1 cells. “Standard colony-forming assay” was used to examine cell survivals of MLTC-1 cells treated with etoposide. Results: Assayed by “parachute” dye-coupling assay, the dye spread through GJ in MLTC-1 cells was significantly decreased by 18-glycyrrhetinic acid however increased by retinoid acid. Cx43 expression and GJ function in MLTC-1 cells were inhibited by Cx43-siRNA. Results from “standard colony-forming assay” showed that etoposide cytotoxicity was decreased by 18-glycyrrhetinic acid and siRNA, however enhanced by GJ function enhancer retinoid acid. Conclusion:The function inhibition of Cx43 composed GJ in MLTC-1 cells could decrease etoposide cytotoxicity. The enhancement of GJ composed of Cx43 in MLTC-1 could increase etoposide cytotoxicity.

Progress of E.coli producing extended spectrum beta-lactameses in children with urinary tract infection / 国际儿科学杂志

Urinary tract infections (UTI)is a childhood disease.With the use of extended spectrum antibiotics,resistant strains have increased every year,especially Escherichia coli(E.coli).The mechanisms of drug resistance are as follows:hydrolase,target gene mutations,efflux pumps and membrane permeability change.Of which producing extended-spectrum β-lactamase(ESBL) is increasing.So it presents a huge challenge to clinical antibiotic selection.According to the resistance genes (blaTEM,blaSHV,blaCTX-M,etc.),the ESBL can be classified into different types (TEM type,SHV-type,CTX-M type,etc.).The drug-resistant genes play an important role in spreading and prevalence of the resistance genes.It's necessary to do a review of the currently known genotypes.It is both in favor of scientific research work and providing guidance for clinical work.

Primary Study on Hydrolysation of Centipedes Protein and Evaluation of Its ACE Inhibitory Activity / 世界科学技术-中医药现代化

This study was aimed to analyze the major protein composition of centipedes (Scolopendra subspinipes mutilans L.Koch.), and the ACE inhibitory activity of its hydrolysis. Albumins, gulbulins, coixins and glutelins were sequentially extracted from centipedes flour with corresponding buffer and then quantified by Kjeldahl method and Brandford. Hydrolysation of four kinds of proteins of centipedes and the residues were conducted with pepsin. The hydrolysis was ultrafiltrated (MWCO=3 000) and lyophilized. The peptides (≤3 kD) were obtained to evalu-ate the ACE inhibitory activity by RP-HPLC. The results showed that the total protein content of centipedes was (62.69±1.41)%. Among which the contents of albumins, globulins, coixins, glutelins and residual were account-ing for (6.42±0.31)%, (7.94±0.24)%, (4.31±0.34)%, (40.66±0.56)% and (25.78±0.60)%, respectively. The inhibition rate of hydrolysis of four kinds of protein and residual were 50.28%, 57.37%, 31.15%, 58.99%, 80.81%, respectively. It was concluded that centipedes were rich in protein and the hydrolyzate of all proteins manifested ACE inhibitory activity at different extent. The residual and glutelins indicated strong ACE inhibitory potential by hydrolysis. This research provided valuable sights for exploring hypotensive activity and functional food from centi-pedes.

The effect of simvastatin on the gap junction function of hepatocellular carcinoma cells / 中国癌症杂志

Background and purpose:It has been reported that gap junctional (GJ) function was signiifcantly decreased in hepatocellular carcinoma (HCC) tissues and cell lines. However, the increased GJ suppress tumorigenesis and the development of liver cancer. This study therefore aimed to examine the effect of simvastatin on GJ function between Hep3b cells. Thus, the exploition of drugs to increase GJ function between liver cancer cells will provide an efifcient approach to ifght against liver tumor as well as increase cytotoxicity of antitumor agents.Methods:SRB was used to assay the toxicity of simvastatin. The effect of simvastatin on GJ function was determined by “Parachute” dye-coupling assay and scrape loading/dye transfer assay.Results:Pretreated Hep3b cells with simvastatin at the concentration of 1, 5 or 10 μmol/L for 24 h did not induce the cytotoxicity. So simvastatin at the concentration of 5 and 10 μmol/L would not reduce the amount of GJ on cell membranes. “Parachute” dye-coupling assay showed that the treatment with 5 and 10 μmol/L simvastatin for 4 h enhanced the dye spread through GJ in Hep3b cells. Similarly, scrape loading/dye transfer assay showed that simvastatin could induce the increasing spread of lucifer yellow (Ly, Sigma) around the scoifng cells with increasing concentrations.Conclusion:Simvastatin could increase the GJ function of Hep3b cells.

Optimization on Hydrolysis Conditions of Coix Prolamin and Angiotensin-converting Enzyme Inhibitory Activity of Hydrolysates / 世界科学技术-中医药现代化

This study was aimed to optimize the hydrolysis conditions of Coix prolamin, which occupied the highest content in total protein of it, and then evaluate the angiotensin-converting enzyme (ACE) inhibitory activity of the corresponding hydrolysates. Pepsin was used to hydrolyze prolamin and OPA method was applied to determine the degree of hydrolysis. The optimum conditions of hydrolyzing prolamin were obtained by orthogonal design subse-quently. The ACE inhibitory activity of small molecular weight (less than 3 kD) peptides gained by ultrafiltration of the hydrolysates was assayed by RP-HPLC method. The result showed that the optimized hydrolysis conditions were substrate concentration of 1%, enzyme-to-substrate ratio of 1:5 and hydrolysis duration for 48 h. The hydrolysates exhibited an ACE inhibitory ratio of (83.40 ± 0.93)% at the concentration of 0.1 mg·mL-1. It was concluded that prolamin hydrolysates displayed a high ACE inhibitory activity in vitro, which provided guidance for further research of antihypertensive component and development of functional food from Coix.

Effect of duloxetine on the levels of cytokines in patients with first-episode depression / 中华行为医学与脑科学杂志

ObjectiveTo explore the changes of the levels of cytokines in patients with first-episode depression and the effect on the levels of cytokines after the treatment with duloxetine.MethodsThe serum levels of interleukin 1 ( IL-1 ),interleukin 6 ( IL-6 ),tumor necrosis factor-alpha ( TNF-αt ),interleukin4 ( IL-4 ),interleukin10(IL-10) were measured in 38 patients with depression before and after duloxetine treatment by enzyme linked immunosorbent assay(ELISA).HAMD score were assessed at pre- treatment and post-treatment to assess curative effect.The control group was 30 healthy individuals.All data were statisticaly analyzed by SPSS.ResultsBefore treatment,the HAMD score and the levels of serum IL-6,TNF-α,IL-1 in first-episode depressant patients were remarkablely higher than those in the control group( IL-6:( 10.66 ± 3.12 ) pg/ml vs (2.72 ± 0.91 ) pg/ml ;TNF-α:(77.49 ±3.12) pg/ml vs (37.48 ±5.87) pg/ml; IL-1:(39.09 ± 3.77 ) pg/ml vs ( 10.31 ± 1.05 ) pg/ml ),the levels of serum IL-4 and IL-10 in first-episode depressant patients were remarkablely lower than those in the control group(P＜0.05,P＜0.01 ).The HAMD score and the levels of serum IL-6,TNF-α,IL-1 in post-treatment were remarkablely lower than pre-treatment (P ＜ 0.05 ),but which were still higher than the control group(P＜ 0.05 ).The levels of serum IL-4 and IL-10 in post-treatment were remarkablely increased than pre-treatment(P＜0.05).The levels of serum IL-6,TNF-α,IL-1 were positively correlated with the HAMD score( r =0.667,0.486,0.727,P ＜0.01 ),but the levels of serum IL-4 and IL-10 were negatively correlated with the HAMD scorae ( r=-0.433,-0.269,P＜0.05,P＜ 0.01 ).ConclusionsThe first-episode depressant patients show immune disorder induced by cytokines.Anti-depressant activity of duloxetine may participate in the regulation of cytokines and Th1/Th2 unbalance.

Establishment of three screening models of angiotensin converting enzyme inhibitors / 中国中药杂志

<p><b>OBJECTIVE</b>To establish and compare three in vitro screening models of angiotensin converting enzyme inhibitors (ACEI), and provide methodological basis for screening ACEI drugs from Chinese herbal medicine.</p><p><b>METHOD</b>Three screening models were established using rat serum, pure angiotensin converting enzyme (ACE) and crude extract enzyme from rabbit lung as enzyme sources, respectively, with corresponding testing methods, and captopril as the positive drug.</p><p><b>RESULT</b>The IC50 of captopril was 2.30 nmol x L(-1) using rat serum as the enzyme; and 1.04 nmol x L(-1) for ACE pure enzyme; and 1.40 nmol x L(-1) for crude extract enzyme from rabbit lung.</p><p><b>CONCLUSION</b>Results from the three screening models were all in accordance with literature reports. These models can be applied to in vitro pharmaceutical screening. The selection of suitable screening model depend on the experimental situation and the inherent characters of models.</p>

Influence of plasma matrix metalloproteinase-7 levels and genetic polymorphism of -181A/G on the stability of carotid plaque / 中华神经科杂志

Objective To explore the influence of plasma matrix metalloproteinase-7 ( MMP-7 ) levels and genetic polymorphism of MMP-7 - 181 A/G on the stability of carotid plaque.Method According to carotid ultrasound examination, 503 patients with carotid atherosclerotic lesions were consecutively recruited and divided into vulnerable plaque group (n = 118) and stable plaque group (n = 385).Plasma MMP-7 levels were measured by enzyme-linked immunosorbent assay (ELISA), and MMP-7 -181 A/G genotypes were determined by polymerase chain reaction-restiction fragment length polymorphism (PCR-RFLP).Results Plasma MMP-7 levels in carotid vulnerable plaque group were significantly enhanced as compared to stable plaque group (t =5.49, P =0.00).The frequency of MMP-7 -181G allele in vulnerable plaque group was significantly higher than that in stable plaque group (11.4% vs 7.0% ,χ2 = 4.78, P= 0.029).Compared to AA genotype, the genotypes with - 181G allele (AG + GG) significantly increased susceptibility to carotid vulnerable plaque ( χ2 = 5.01, OR = 1.81, P = 0.025 ) .When further analyzing the relationship between genotype and plasma MMP-7 levels, no significant differences of plasma MMP-7 levels were observed between AA genotype and AG + GG genotype in stable plaque group.However, in vulnerable plaque group, plasma MMP-7 levels of AG + GG genotype were significantly higher than that of AA genotype( t = 2.62, P = 0.01).Conclusion The present findings suggest that plasma MMP-7 level may be a biomarker for carotid vulnerable plaque.Genetic polymorphism of - 181 A/G in MMP-7 promoter may affect the expression of MMP-7, and seems to be implicated in susceptibility to carotid vulnerable plaque.