Inosine 5'-monophosphate dehydrogenase (IMPDH) is a key enzyme of de novo GMP biosynthesis. The expression and activity of IMPDH can be affected by diseases and physiological process. It is the drug target for anticancer, antiviral, antimicrobial and immunosuppressive therapeutics. Not only catalytic action but the other biological functions of IMPDH also play an important role in diseases. The basic functions, mechanism of catalysis, classification of inhibitors, biological functions and the latest advances to IMPDH will be illustrated in this review. It is expected to be helpful to the discovery of new inhibitors and biological functions of IMPDH.
Animals ; Binding Sites ; Catalysis ; Drug Design ; Drug Discovery ; Enzyme Inhibitors ; classification ; pharmacology ; Humans ; IMP Dehydrogenase ; antagonists & inhibitors ; genetics ; metabolism ; Inosine Monophosphate ; metabolism ; Molecular Structure ; NAD ; metabolism ; Polymorphism, Genetic

?AIM: To evaluate the clinical effects, corneal surface shape and corneal thickness variation after treated by Danzhi Xiaoyao Capsule combined with hypromellose 2910, dextran 70 and glycerol eye drops for dry eye in menopausal patients.?METHODS: Eighty menopausal patients ( 160 eyes ) diagnosed as dry eye were randomly divided into groups A and B ( 40 patients each ) . Group A was treated with hypromellose 2910,dextran 70 and glycerol eye drops only and group B was treated with Danzhi Xiaoyao Capsule and eye drops. Before and 1mo after treatment, the clinical effects were evaluated by symptom scores, fluorescein staining ( FL ) , tear film breakup time ( BUT ) and Schirmer Ⅰ test. While the corneal surface regularity index (SRI), surface asymmetry index (SAI) and central corneal thickness ( CCT) were observed.? RESULTS: At 1mo after treatment, the symptoms scores and FL scores of the 2 groups decreased significantly( P<0. 05 ); BUT and SⅠt were significantly increased (P<0. 05). SRI and SAI gradually increased with dry eye exacerbations, after treatment the two parameters significantly reduced than those before treatment. SRI of group B improved significantly more than group A. CCT gradually got thinning with the dry eye condition worsened, which also significantly increased after treatment (P<0. 05);but there was no difference between 2 groups before and after treatment(P>0. 05).?CONCLUSION: Combination therapy of Danzhi Xiaoyao Capsule and hypromellose 2910, dextran 70 and glycerol eye drops for menopausal patients with dry eye is more effective than single eye drops, and can improve the symptoms and signs.

Objective To evaluate the causes,prevention and treatment ot laparoscopic comphca- tions in urologic surgery.Methods From May 2000 to May 2004,135 urologic laparoscopies were per- formed,including 17 transperitoneal laparoscopies and 118 retroperitoneal laparoscopies.Of the135 cases,26 had adrenal adenoma extirpation;31 had roof-removal and decompression of renal cyst;25 had radical ne- phrectomy;6 had pyeloplasty;2 had partial resection of renal capsula and encapsulation of the great omen- tum;2 had partial nephrectomy;4 had pelviureteral resection;13 had ligation of renal pedicle lymphatic ves- sel;2 had ureterolysis;7 had ureterolithotomy;12 had ligation of spermophlebectasis;5 had exploration,re- duction and fixation of undescended testis.The intra-and post-operative complications were retrospectively reviewed and clinically analyzed.Results Overall,14 cases(10.4%)had complications.Intraoperative complications occurred in 10 cases,including 6 cases of peritoneal injuries,which were clamped during oper- ation;4 of vascular injuries,which resulted in conversion to open surgery.Postoperative complications oc- curred in 4 cases,including 2 of subcutaneous emphysema,which was spontaneously absorbed at 5 and 7 d after operation;1 of incision seepage,which was drained for 40 d and then disappeared;and 1 of urine reten- tion,for which urethral catheterization was kept for 3 d and then the patient had voluntary voiding.No death occurred in this series.Conclusions Understanding the characteristics of laparoscopic complications in u- rologic surgery and systematic training of the surgeons can reduce the occurrence of complications.

BACKGROUND: Severe acute pancreatitis (SAP) can result in intestinal mucosal barrier (IMB) dysfunction. This study was undertaken to demonstrate the effect of IGF-I on the intestinal mucosal barrier in rats with SAP and its possible mechanisms. METHODS: Seventy-two male Wistar rats were randomly divided into three groups: a sham operation (SO group,n=24), a SAP group not treated with IGF-I (SAP group,n=24), and a SAP group treated with IGF-I (IGF-I group,n=24). SAP was induced in the rats by injecting 5.0％ sodium taurocholate into the biliary-pancreatic duct. The SO rats were given an infusion of normal saline instead. The rats in the IGF-I group underwent the SAP procedure and were given a subcutaneous injection of IGF-I at 30 minutes before the operation and at 3 hours after the operation. Eight rats in each group were sacrificed at 6, 12 and 24 hours after operation. Apoptosis of mucosal cells in the small intestine was determined by TUNEL. The levels of endotoxin and DAO and serum amylase were also measured. Pathologic changes in the small intestine were monitored. Changes of bax and bcl-2 mRNA expression in the small intestine were determined by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The levels of serum amylase were lower in the IGF-I group than in the SAP group at all three time points (P<0.05). The levels of endotoxin in the IGF-I group were higher than those in the SAP group at 6 hours, but lower in the IGF-I group than in the SAP group at 12 and 24 hours (P<0.05). The levels of diamine oxidase were higher in the IGF-I group at 6 hours but lower than those in the SAP group at 12 and 24 hours. The pathological score of the small intestine was lower in the IGF-I group than in the SAP group, and the difference was statistically significant at 12 and 24 hours. The pathologic changes observed under electron microscopy were better in the IGF-I group than those in the SAP group. The apoptosis index of intestinal epithelial cells was significantly decreased in the IGF-I group compared with the SAP group. Compared with the SO group, the mRNA expression levels of bax were increased at each time point in the SAP group, and were significantly decreased in the IGF-I group as compared with the SAP group at each time point (P<0.05). The expression levels of bcl-2 were weak and not different between the SO group and the SAP group (P>0.05). They were significantly increased in the IGF-I group versus the SO and SAP groups (P<0.05). The ratio of bax and bcl-2 mRNA expression levels at each time point in the SAP group were significantly higher than those in the SO group, but they were obviously decreased in the IGF-I group. CONCLUSIONS: Exogenous IGF-I seems to protect mucosal cells in the small intestine against SAP-induced apoptosis and could alleviate SAP-induced injury of the intestinal mucosa. The underlying mechanisms include enhanced mRNA expression of bcl-2 and inhibition of bax mRNA expression.

ObjectiveToinvestigatetheinflammatoryresponseandapoptosisof peripheral blood mononuclear cells(PBMCs) and their regulation by triptolide(TP) in IgA nephropathy(IgAN) patients.MethodsBlood samples were collected from 29 IgAN patients and 16 healthy individuals.TNF-α and IL-6 concentrations were measured by ELISA and NO concentration by Griess reagent in the plasma of samples.PBMCs were isolated from IgAN patients and cultured in vitro,and subsequently activated by PHA(10 mg/L).The cytotoxicity of different TP concentrations was assayed by MTT and two non-toxic concentrations (12.5 μg/L or 25.0 μg/L)were selected for treatment.TNF-α,IL-6 and NO concentrations were measured in the culture media collected from PBMCs cultures activated by PHA (10 mg/L) and treated with TP (12.5 μg/L or 25.0 μg/L).The PHA-activated,TP-treated cells apoptotic rate was analyzed by FACS using Annexin V-FITC staining.The expression of Bcl-2,Bax,caspase-9 and caspase-3 were detected by RT-PCR and Western blotting from lyses of PHA-activated with or without TP-treated cells.ResultsThe serum concentrations of TNF-α[(131.57±50.61) ng/L vs(30.24±18.93) ng/L,P＜0.01],IL-6[(76.36±25.21) ng/L vs(35.08±16.59) ng/L,P＜0.01] and NO[(46.36±12.93) μmol/Lvs (26.61 ±10.87) μmol/L,P＜0.01] were significantly increased in IgAN patients compared to healthy individuals.PBMCs viability in culture decreased after TP treatment in a dose-dependent manner.TP also inhibited TNF-α,IL-6 and NO levels in the media of PHA-activated PBMCs in culture and induced PBMCs apoptosis.The expression of Bcl-2 decreased markedly and Bax,caspase-9 and caspase-3 increased significantly after TP treatment (all P＜0.05).Conclusions The PBMCs from IgAN patients are in a highly activated state,and have a high apoptotic rate.TP treatment induces benificial effects in IgAN patients by inhibiting the activation of PBMCs by activating pro-apoptotic pathway.

Objective Color doppler ultrasonography of chronic Keshan disease (CKD) was evaluated to provide evidences for clinic diagnosis of the disease. Methods From September to Novermber 2009, according to "Diagnostic criteria of Keshan disease" (GB 17021-1997), 64 cases of CKD were randomly sampled from five Keshan diseased districts in Shandong province, Zoucheng, Sishui, Yishui, Wulian, Jvxian, and Pingyi as patient group. Thirty four healthy volunteers being checked up by Shandong Institute for Endemic Diseases Control and Research were put in control group. All the subjects were examined with Color doppler ultrasonography. The indexes of cardiac structure, left ventricular (LV) systolic function and LV diastolic function were measured.Results Left atrial internal diameter, LV end-diastolic internal diameter, LV end-systolic internal diameter, right ventricular diameter, aorta diameter, right atrial transverse diameter, right atrial long diameter and left ventricle mass of the patient group[(35.38 ± 6.89), (61.57 ± 8.61), (45.39 ± 10.29), (17.22 ± 3.79), (28.69 ± 2.81),(38.00 ± 6.05), (42.68 ± 8.65)mm, (283.22 ± 103.12)g] were higher than that of control group[(26.70 ± 3.27),(45.41 ± 4.93), (26.91 ± 4.35), (13.76 ± 2.27), (24.09 ± 2.89), (31.50 ± 3.32), (35.82 ± 3.14) mm, (156.03 ±39.86)g, t = 6.93, 10.09, 9.98, 4.87, 7.64, 5.81, 4.46, 6.90, all P＜ 0.05]. The LV ejection fraction and fractional shortening of the left ventricular of the patient group[(49.25 ± 14.33)%, (26.11 ± 9.17)%] were lower than that of control group[(73.88 ± 4.04)%, (42.88 ± 3.62)%, t = - 9.79, - 10.22, all P＜ 0.05]. Diffuse hypokinetic motion of the left ventricle reduced in 95% (61/64) of CKD patients, and 5% (3/64) of CKD patients had segmental LV dyskinesia. Seventy five per sent(48/64) of the patients accompanied with mitral regurgitation, and 39% (26/64) of these cases accompanied with tricuspid regurgitation. Meaningful Mitral or tricuspid regurgitation was not found out in control group. Conclusions The CKD patients' bore of atrio-ventricular cavity and LV mass are enlarged, and their motion of ventricle is reduced or partly reduced. They have poor heart function. Mitral regurgitation are more than tricuspid regurgitation. Color doppler Ultrasonography is important in diagnosis of chronic Keshan discase.

OBJECTIVE: To investigate the numbers, sizes and types distribution of diatoms in drowned and postmortem immersed rabbits' lungs. METHODS: Sixty-two rabbits were randomly divided into drowning group (n = 30), postmortem immersion group (n = 30) and land death group (n=2), and the diatoms in each lung lobe were analyzed quantitatively and qualitatively by microwave digestion and scanning electron microscopy. RESULTS: In the drowning group, the diatoms were detected in each lung lobe with Cyclotella and Melosira in the majority. In the postmortem immersion group, Cyclotella was in the majority. And the diatoms weren't detected in some lung lobes in postmortem immersion. There were significant differences in the detection rates of upper lobe of left lung, middle lobe and cardiac lobe of right lung in two groups (P < 0.05). CONCLUSION Based on the microwave digestion and scanning electron microscopy, the numbers, sizes and types distribution of diatoms in drowned and postmortem immersed rabbits' lungs can be analyzed and used as references for testing theory.
Animals ; Autopsy ; Diatoms/isolation & purification* ; Drowning ; Lung/microbiology* ; Microscopy, Electron, Scanning ; Microwaves ; Rabbits

OBJECTIVETo analyze the tendency in the incidence of malignant tumors in nutrition-intervened population of Lin County.

METHODSSubjects who had been enrolled in the General Population Trial, Lin County Nutrition Intervention Trial were followed up and the data of malignant tumors were collected with collaboration of National Cancer Institute/National Institute of Health. Incidences of malignant tumors during and after nutrition intervention were calculated and compared.

RESULTSEsophageal cancer, cardiac cancer, and stomach cancer were constantly the three leading cancers, accounting for 84.06% and 83.74% of the malignant tumors in men and women, respectively. The incidences of lung cancer and liver cancer in men showed increasing tendencies, while similar tendencies were found in those of stomach cancer, colorectal cancer, and liver cancer in women. With the prolonging of the follow-up, the incidences of upper digestive tract cancers declined (except stomach cancer in women).

CONCLUSIONSThe upper digestive tract cancers remain the leading malignant tumors, although their incidences may decline with longer-term follow-up. Prevention and control of tumors in Lin County should still be focused on the esophageal cancer, cardiac cancer, and stomach cancer, as well as lung cancer and liver cancer.

Adult ; Aged ; China ; epidemiology ; Diet ; Feeding Behavior ; Female ; Follow-Up Studies ; Humans ; Incidence ; Male ; Middle Aged ; Neoplasms ; epidemiology ; Prospective Studies ; Risk Factors

OBJECTIVETo investigate an individualized approach to the treatment of auricle keloid to maintain the normal appearance of external ear and meanwhile reduce the recurrence.

METHODSDifferent local flaps were performed according to the location of the keloid in our approach. The auricle was divided into different anatomical regions and all the patients received local postoperative radiotherapy.

RESULTSOf 68 patients with auricle keloid received the individualized approach, 3 cases suffered delayed healing due to partial flap necrosis. The remaining patients were followed up for 8-21 months(mean:11.5 months) . Recurrence occurred in one patient(1.47%) .

CONCLUSIONThe individualized approach combining local flaps with radiotherapy in treating auricle keloid can effectively maintain the normal ear appearance with low recurrence rate.

Adult ; Ear, External ; surgery ; Female ; Follow-Up Studies ; Humans ; Keloid ; radiotherapy ; surgery ; Male ; Radiotherapy, Adjuvant ; Recurrence ; Surgical Flaps ; Young Adult

Objective To study the cell toxicity of thrombin in astrocytes in vitro and the protective effect of hirudo extract liquid (HEL) on the injured astrocytes. Methods Astrocytes were isolated from Wistar rats' cerebral cortex and cultured in vitro, and observed under a phase contrast microscope for growth status. Cell activity was measured with MTT assay. The survival of astrocytes was investigated after exposed to a selected concentration of thrombin ranging from 0.1 to 100 U/mL or to HEL ranging from 0.25 to 4 mg/μL by observing cell morphology under an inverted phase-contrast microscope and measuring the lactate dehydrogenase (LDH) activity (a marker of cell death) in cell supernatant. Expressions of HSP70 and TGFβ-1 protein in astrocytes were investigated by immunohistochemistry. Results (1) Thrombin (1-100 U/mL) had toxicity on astrocytes in vitro in a dose-dependent manner (F=118.65, P=0.000). (2) HEL (0.25-4 mg/μL) could significantly reduce the cell toxicity of 10 U/mL thrombin in astrocytes (F=156.08, P=0.000). With the increasing concentration of HEL, the protection of HEL was accordingly enhanced, and it even increased the expressions of HSP70and TGFβ-1. Conclusions HEL could accelerate the proliferation of astrocytes, enhance the expressions of HSP70 and TGFβ-1 protein, so as to significantly depress the cell toxicity of thrombin to astrocytes.