OBJECTIVETo investigate the mechanism of epididymal hypofunction of rats with varicocele (VC) by observing the changes in the epididymal index, motility of epididymal sperm, expressions of hypoxia-inducible factor 1 alpha (HIF-1 alpha) and the tumor suppressor protein p53, and epididymal epithelial cells.

METHODSNinety SD rats were equally randomized to a VC model (A), a sham operation (B), and a normal control group (C). At 49 days after surgery, all the rats were executed after weighing. Then the volume of the left epididymis was obtained, the epididymal sperm motility was detected by computer-assisted sperm analysis (CASA), the expressions of HIF-1 alpha and p53 in the epididymal tissue were determined by Western-blot, and the epididymal epithelial cells were observed by HE staining.

RESULTSVC models were successfully established in 27 of the rats. One-way ANOVA test showed no statistically significant differences in the epididymis index among groups A ([40.53 +/- 1.76] x 10 (-5)) , B ([43.31 1.58] x 10( -5)) , and C ( [44. 10 +/- 2.62] x 10 -5) (P > 0.05). Sperm motility and the percentage of progressively motile sperm were significantly lower in group A ([71.86 +/- 5.07]% and [42. 26 +/-4.45]%) than in B ([78.51 4.50]% and [49.08 +/-4. 19]% ) and C ( [79.24 +/- 2.70] % and [52. 23+/- 2. 23] % ) (both P <0.05) , while the expressions of HTF-1 a and p53 were remarkably higher in A (1.74 +/- 0. 16 and 1.71 +/- 0. 11) than in B (0.32 +/- 0. 08 and 0.56 +/- 0.13) and C (0.12 +/- 0. 03 and 0.25 +/-0.06) (both P < 0.05). The epididymal epithelial cells in group A were obviously decreased in number and arranged in loose and disorderly patterns as compared with those in B and C.

CONCLUSIONVaricocele can cause hypoxia in the epididymal tissue, which in turn may lead to epididymal hypofunction.

Animals ; Disease Models, Animal ; Epididymis ; metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Sperm Motility ; Tumor Suppressor Protein p53 ; metabolism ; Varicocele ; metabolism

In this paper,the background,present situation,problem and tactics of GAP(Good Agricultural Practice)of chinese materia medica are discussed.The main problems of the yielding of chinese materia medica are as followings:(1)Lack of close controlling standards and scientific detecting methods.(2)Decentralized management.low benefit and low controllability.(3)The pesticide residue and heavy metal content exceeding the provided standard.(4)Production and marketing disjointed,supervising and controlling intensity in the whole yielding process not enough.Thus,3 measures are put forward:(1)Strengthening the management of the quality of chinese materia medica,formulating strict and unitary quality controlling standards,setting up scientific checking methods.(2)Developing genuine drugs,establishing famous brands.(3)Establishing green chinese meateria medica yielding bases,to make the Chinese Materia Medica utilization sustainable.

OBJECTIVETo study the effect of the sphingosine kinase 1 (SphK1) inhibitor N,N-dimethylsphingosine (DMS) in combination with chemotherapeutic drugs (DDP, 5-Fu, MMC) on the proliferation of gastric cancer cells (SGC7901) in vitro, and to evaluate whether SphK1 inhibitors could be used as synergetic agents in chemotherapy.

METHODSSGC7901 cells were incubated in vitro with DMS (1 micromol/L) and 5-Fu, DDP, MMC at different concentrations in combination or separately for 24 h. The effects on the growth and survival of SGC7901 cells were determined by MTT assay. The inhibition rates were assessed by response surface analysis and the interactive relationships between the combined drugs were evaluated on the basis of positive/negative values of the cross product coefficients in the response surface equation.

RESULTSThe growth inhibition rate of the gastric cancer cells by treatment with DMS (1 micromol/L) was (10.23 +/- 0.74)%. The growth inhibition rates of the gastric cancer cells treated with 5-Fu (1, 5 and 25 microg/ml) for 24 h were (9.95 +/- 3.24)%, (21.04 +/- 2.19)%, and (45.49 +/- 3.60)%, respectively. The growth inhibition rates of the gastric cancer cells treated with DDP (0.5, 2.5 and 12.5 microg/ml) for 24 h were (9.38 +/- 0.79)%, (19.61 +/- 0.90)%, and (29.83 +/- 0.54)%, respectively. The growth inhibition rates of the gastric cancer cells treated with MMC (0.1, 0.5 and 2.5 microg/ml) for 24 h were (15.35 +/- 0.77)%, (24.72 +/- 0.83)%, and (30.68 +/- 0.28)%, respectively. There were significant differences among the inhibition rates caused by different concentrations of the drugs (P < 0.05). When 1 micromol/L DMS was used in combination with 5-Fu (1, 5, and 25 microg/ml) for 24 h, the growth inhibition rates of the cancer cells were (16.76 +/- 0.41)%, (27.28 +/- 0.29)% and (52.56 +/- 3.60)%, respectively. When 1 micromol/L DMS was used in combination with DDP (0.5, 2.5, and 12.5 microg/ml) for 24 h, the growth inhibition rates of the cancer cells were (15.35 +/- 0.86)%, (25.57 +/- 0.27)%, (36.37 +/- 0.51)%, respectively. When 1 micromol/L DMS was used in combination with MMC (0.1, 0.5, and 2.5 microg/ml) for 24 h, the growth inhibition rates of the cancer cells were (21.02 +/- 0.28)%, (32.10 +/- 0.27)%, (36.36 +/- 0.28)%, respectively. There were also significant differences among the growth inhibition rates caused by different concentrations of the drugs alone and in combination groups (P < 0.05).

CONCLUSIONSDMS can suppress the proliferation of SGC7901 cells in vitro, and there are evident synergetic effects when it is used in combination with chemotherapeutic drugs. The results of this study indicate that SphK1 inhibitors may become novel and promising chemotherapeutic sensitizers.

Antibiotics, Antineoplastic ; pharmacology ; Antimetabolites, Antineoplastic ; pharmacology ; Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cisplatin ; pharmacology ; Drug Synergism ; Enzyme Inhibitors ; pharmacology ; Fluorouracil ; pharmacology ; Humans ; Mitomycin ; pharmacology ; Phosphotransferases (Alcohol Group Acceptor) ; antagonists & inhibitors ; Sphingosine ; analogs & derivatives ; pharmacology ; Stomach Neoplasms ; pathology

OBJECTIVETo elucidate the roles of JAK/STATs signal pathway on anti-proliferative effects induced by IFN-alpha in MHCC97.

METHODSAn IRF9 expression vector was transfected into MHCC97 with Dosper. The expression of IRF9, cycle regulating proteins and the forming of ISGF3 complex were detected using Western blot and EMSA, respectively. Cell proliferation and distribution were monitored using MTT and flow cytometry.

RESULTSHigh expression of IRF9 restored the anti-proliferative response of MHCC97 on IFN-alpha treatment and delayed the cell transition from S phase to G2 phase induced by IFN-alpha.

CONCLUSIONThe integrity and functions of JAK/STATs signal pathway played an important role in mediating the anti-proliferative effects of IFN-alpha in MHCC97.

Carcinoma, Hepatocellular ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Interferon-Stimulated Gene Factor 3, gamma Subunit ; genetics ; Interferon-alpha ; metabolism ; pharmacology ; Janus Kinases ; genetics ; physiology ; Liver Neoplasms ; genetics ; metabolism ; pathology ; STAT Transcription Factors ; genetics ; physiology ; Signal Transduction ; Transfection

OBJECTIVETo evaluate the long-term survival of multidisciplinary treatment based on thoracic surgery for cervical esophageal squamous cell carcinoma.

METHODSThe clinical characters and follow-up data of forty-one cervical esophageal cancer patients who accepted multidisciplinary treatment based on surgery with preservation of pharynx and larynx were retrospectively reviewed, and the long-term survival was compared with 480 non-cervical esophageal cancers who accepted surgery in the same period done by the same surgical team.

RESULTSThere were 28 males and 13 females with a mean age of 62 years old. In the cervical esophageal cancer group, 30 patients accepted neoadjuvant chemotherapy, 25 patients accepted adjuvant chemotherapy, and 21 patients accepted both. Six patients received postoperative radiation. Four patients underwent exploratory surgery alone, and 37 cases underwent radical surgery and cervical anastomosis. One case died during the perioperative period. The 1-, 3-, 5- and 8-year survival rates were 96.8%, 52.6%, 35.1%, and 35.1% in the 36 patients with cervical esophageal cancer who underwent radical surgery, and were 85.0%, 54.3%, 45.0%, and 36.7% respectively in the 457 non-cervical esophageal cancer patients. There was no significant difference between the cervical group and non-cervical group(P=0.91).

CONCLUSIONCervical esophageal cancer should be treated in a multidisciplinary approach to obtain satisfactory long-term outcomes.

Combined Modality Therapy ; Esophageal Neoplasms ; surgery ; Esophagectomy ; methods ; Female ; Follow-Up Studies ; Humans ; Larynx ; surgery ; Male ; Middle Aged ; Pharynx ; surgery ; Retrospective Studies ; Treatment Outcome

Objective To investigate the possible association between mother's periodontal status and preterm low birth weight(PLBW)in Beijing.Methods The periodontal status of 83 women who bore a preterm low birth weight infant(PLBW group)and 44 women who bore a normal birth weight infant(NBW group)within two years in four hospitals in Beijing were evaluated.These women were all generally healthy.The clinical periodontal parameters including plaque index(PLI),probing depth(PD),attachment loss (AL)and bleeding index(BI)recorded.Results The percentages of PD≥4 mm sites,AL≥2 mm sites and BOP(+)sites in two groups were 8.1%vs 6.9%,12.8%vs 6.1%and 70.4%vs 66.9%,respectively,which showed significantly higher in PLBW group than in NBW group(P＜0.01,P＜0.001,P＜0.01 ).Conclusions There was possible association between mother's periodontal status and preterm low birth weight in the investigated area.Poor periodontal status may be one of the risk factors of PLBW.

Objective To investigate the impact of esketamine hydrochloride in combination with ultrasound-guided transverse thoracic muscle plane block on stress response and inflammatory levels in patients undergoing cardiac valve replacement under general anesthesia.Methods A total of 120 patients who underwent elective extra-corporeal circulation-supported median open heart valve replacement were selected and randomly assigned into four groups using the random number table method:general anesthesia alone(Group G),general anesthesia with intrave-nous administration of esketamine(Group E),general anesthesia with transverse thoracic plane block(Group T),and esketamine combined with transverse thoracic muscle plane block(Group ET);each group consisted of 30 cases.Patients in group E and group ET received a continuous infusion of esketamine hydrochloride injection at a rate of 0.2 mg/kg-1?h-1 until the completion of the surgical procedure,while patients in group G and group T received an equivalent volume of saline solution until the completion of the surgical procedure.After the induction of general anesthesia,patients in group T and group ET underwent ultrasound-guided bilateral transverse thoracic muscle plane block,while patients in group G and group E did not receive any specific intervention.All four groups received identical protocols for anesthesia induction and maintenance,with self-controlled intravenous analgesic pumps administered to all patients postoperatively.The following time points were recorded:1 day prior to surgery(T0),pre-induction of anesthesia(T1),1 minute post-tracheal intubation(T2),1 minute post-median sternotomy(T3),1 minute prior to initiation of cardiopulmonary circulation(T4),1 minute after cessation of cardiopulmonary circula-tion(T5),1 minute after completion of surgery(T6),1 day post-surgery(T7),2 days post-surgery(T8),and 3 days post-surgery(T9).Mean Arterial Pressure(MAP)and Heart Rate(HR)were continuously monitored from T1 to T6.The levels of blood glucose and lactate were measured and recorded at T1,T4 to T6.The levels of White Blood Cells(WBC)and C-Reactive Protein(CRP)were assessed at T0,as well as at T7 to T9.The occurrence of postoperative adverse reactions was documented in all four groups.Results(1)Comparison of hemodynamics among the four groups:Compared with group G,there was a significant decrease in MAP and HR at T3 in group T(P<0.05).At the T5 time point,MAP was lower in group ET compared to group E,while HR was higher in group ET compared to group T(P<0.05).(2)The lactate and blood glucose levels of the four patient groups after extracorporeal circulation transfer were higher than those at the T1 time point(P<0.05).Patients in group E had lower lactate values at the T5 time point and lower blood glucose values at the T6 time point compared to group G(P<0.05).Additionally,patients in group E exhibited lower lactate and blood glucose values at both the T5 and T6 time points compared to those in group T(P<0.05).(3)Compared to T0,the levels of white blood cells(WBC)and C-reactive protein(CRP)were increased in all four groups after surgery(P<0.05).At the T7 time point,the WBC levels in group E and group T were significantly lower than those in group G(P<0.05).Furthermore,compared to group E and group T,the level of WBC in group ET was significantly lower at T7,while the level of CRP was significantly lower at T8(P<0.05).(4)There were no significant differences observed in postoperative adverse reactions among the four groups(P>0.05).Conclusion Combining low-dose esketamine hydrochloride with transverse thoracic muscle plane block under general anesthesia during open heart valve replacement surgery can effectively stabilize the patient's hemodynamics,mitigate perioperative stress response and postoperative inflammation levels,thereby demonstrating significant clini-cal utility.

Objective To investigate clinical efficacy of Xiaotan Tongluo Gel combined with mecobalamin tablets in treating chemotherapy-induced peripheral neuropathy (CIPN). Methods Totally 67 cases of CIPN were divided into the treatment group (36 cases) and the control group (31 cases). Both groups were given mecobalamin tablets, 0.5 mg each time, three times a day, orally. Patients in the treatment group were treated with Xiaotan Tongluo Gel for external use at the same time. The patients in control group were treated with placebo gel for external use, 1 mL/cm2, rubbed on the skin 1 cm more than sensory obstruction in diameter. The treatment for both groups lasted for 14 d as a treatment course, and the treatment lasted for 2 courses. The changes of peripheral nerve toxicity, TCM syndrome scores and the nerve conduction velocity were observed in the two groups. Results On the 14th and 28th days of treatment, the total effective rates of peripheral nerve toxicity were 75.00% and 91.67% in the treatment group, and 38.71% and 67.74% in the control group, and the treatment group was significantly better than those of the control group (P=0.002, P=0.005); On the 14th and 28th days of treatment, the total effective rate of TCM efficacy in the treatment group was 75.00% and 94.44% respectively, and that in the control group was 45.16% and 64.52% respectively, and the treatment group was significantly better than the control group (P=0.018, P=0.005). Compared with before treatment, the TCM syndrome scores in both groups were significantly reduced on the 14th and 28th days (P＜0.01); The TCM syndrome scores in the treatment group were significantly lower than those in the control group at the same time points after treatment (P＜0.01). Compared with before treatment, the sensory and motor nerve conduction speeds of the peroneal and median nerves in the two groups at 14th and 28th days were significantly increased (P＜0.01); Comparing the two groups at the same time point after treatment, the sensory and motor nerve conduction velocity of the peroneal and median nerves in the treatment group was significantly better than that in the control group (P＜0.05, P＜0.01). Conclusion Xiaotan Tongluo Gel combined with mecobalamin tablets can effectively improve the peripheral neurotoxicity induced by chemotherapy, TCM syndrome scores, and the nerve conduction velocity.

OBJECTIVETo study the protective effects of naja naja atra venom (NNAV) in a rat model of diabetic nephropathy (DN).

METHODSThe rat diabetes model was induced by intraperitoneal injection of streptozotocin (STZ). Thirty-two model rats were randomly divided into one DN group (n=8) and three treatment groups (n=8 each) that received NNAV at doses of 30, 90, or 270 μg/(kg·day) via oral gavage, another eight rats as normal controls. After 12 weeks, all rats were sacrificed and the changes in serum and urine biological index levels were determined by colorimetric assay. Microalbumin (mALB), N-acetyl-β- glucosaminidase (NAG) and cystatin C (CysC) concentrations were measured by ELISA. Renal tissues were sliced for pathological and immunohistochemical observations.

RESULTSComparied with the DN group, serum glucose was decreased by 31.04%, total cholesterol 21.96%, triglyceride 23.78%, serum creatinine 19.83%, blood urea nitrogen 31.28%, urinary protein excretion 45.42%, mALB 10.42%, NAG 20.65%, CysC 19.57%, whereas albumin increased by 5.55%, high-density lipoprotein-cholesterol 59.09%, creatinine clearance 19.05% in the treatment group by NNAV administration at dose of 90 μg/(kg·day). NNAV also reduced the levels of malondialdehyde in serum (22.56%) and kidney tissue (9.79%), and increased superoxide dismutase concentration in serum (15%) and decreased it in renal tissue (8.85%). In addition, under light microscopy kidney structure was improved and glomerular hypertrophy decreased by 8.29%. As shown by immunohistochemistry, NNAV inhibited transforming growth factor-β1 by 6.70% and nuclear actor-κB by 5.15%.

CONCLUSIONNNAV improves biological indexes in DN, and it may exert renoprotective effects in rats with STZ-induced diabetes.

Animals ; Body Weight ; Diabetes Mellitus, Experimental ; complications ; Diabetic Nephropathies ; drug therapy ; pathology ; Dose-Response Relationship, Drug ; Elapid Venoms ; administration & dosage ; pharmacology ; Elapidae ; physiology ; Kidney ; drug effects ; pathology ; Male ; Malondialdehyde ; Organ Size ; Rats ; Rats, Wistar ; Superoxide Dismutase

Objective To evaluate the discriminatory efficiency of multiple loci of variable numbers of tandem repeats (VNTR) in Mycobacterium tuberculosis genome.Genotyping and identification on Chinese M.tuberculosis clinical strains were used to locate a series of high discriminated loci,so as to provide the basis for creating a standardized multiple loci VNTR analysis (MLVA) to distribute fast typing and identification on Chinese M.tuberculosis.Methods VNTR loci which were chosen from the website http://minisatellites.u-psud.fr/ and referenced to the genome sequence of M.tuberculosis standard strain H37Rv were tested in Chinese M.tuberculosis clinical strains and H37Rv by means of PCR.The primers were designed by DNAStar software.The repeat member of VNTR unit was estimated by the result of PCR.The discrimination power of single locus or multiple loci was confirmed by the Hunter-Gaston index.Results 45 VNTR loci were tested in 135 Chinese M.tuberculosis clinical strains and H37Rv.The discrimination power of these loci appeared different from each other,with the biggest Hunter-Gaston index as 0.814 (0.797-0.830),the smallest one as 0.015 (0.001-0.028),and there were 13 loci with which the Hunter-Gaston index was bigger than 0.5.Results showed that the discrimination power was increasing by different loci that associated with each other.The more loci that were combined,the bigger the Hunter-Gaston index was,For example,the Hunter-Gaston index of Qub11-b associated with Qub 18 was 0.936,by which 136 strains could be divided into 44 groups.With the combination of 9 loci including Qub11-b,Qub18,Mtub21,Rv2372,MIRU26,Qub26,Qub4156c,Qub11-a and Qub15,the HunterGaston index could have reached 1 and by which the 136 strains could be divided into 136 groups,also showing that the biggest discrimination power to strain identification,viz.strain level genotype were reached.Conclusion The discrimination power of different locus was different.The discrimination power of multiple loci was much more satisfied than that of single locus.It was satisfied the combine discrimination power of 9 loci including Qubll-b,Qubl8,Mtub21,Rv2372,MIRU26,Qub26,Qub4156c,Qub11-a and Qubl5,by which the qualified typing method could gain to facilitate research on molecular epidemiology with the Hunter-Gaston index analysis.