Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

Objective To systematically review the efficacy and safety of solifenacin in the treatment of patients with bladder spasm after transurethral resection of prostate based on current evidence.Methods We searched Pubmed,EMbase,the Cochrane Library,CBM,CNKI,VIP and Wanfang Database from the establishment to October 2016 for the published literature on the treatment of patients with bladder spasm after transurethral resection of prostate with solifenacin.Two reviewers independently screened literature,extracted data and assessed the risk of bias of included studies.Then,meta-analysis was performed using RevMan 5.3 software.Results A total of 11 RCTs involving 621 patients were included.The results of meta-analysis showed that:compared with the no-solifenacin group(n=311),the numbers of bladder spasm episodes[MD=-1.38,95%CI(-1.97,-0.97)P<0.00001],duration of bladder spasm[MD=-0.26,95%CI(-0.41,-0.11),P=0.0008],the time of bladder perfusion clearance[MD=-0.59,95%CI(-0.88,-0.29),P<0.0001],indwelling catheter delivery[MD=-0.29,95%CI(-0.48,-0.11),P=0.09]in solifenacin group(n=310) reduced significantly,and there was no statistical difference in the incidence of overall adverse events between the two groups[RR=0.71,95%CI(0.17,2.98),P=0.64].Conclusion Current evidence indicates that solifenacin is more effective and safe in the treatment of patients with bladder spasm after transurethral resection of prostate.Due to the limited quantity and quality of the include studies,more high quality studies are needed to verify the above conclusion.

Objective To establish a REDE-DHPLC method for detecting the EGFR and KRAS mutations in plasma DNA from tumor patients, and investigate its clinical significance. Methods Restriction endonucleases Mse Ⅰ , Msc Ⅰ , BstN Ⅰ and Bgl Ⅰ were used to digest the wild type fragments of exon 19,exon 21 of EGFR gene and coden 12, 13 of KRAS gene for enriching the mutation fragments, and REDE-DHPLC method was established to detect EGFR and KRAS mutations. The sensitivities of REDE-DHPLC and conventional DHPLC were analyzed by using a series of plasmids containing 50%, 10%, 5%, 1% and 0. 1% mutation genes. Then, Plasma samples and paraffin-embedded tissue samples of 120 NSCLC patients and 120 colorectal cancer patients were detected by REDE-DHPLC. Compared with conventional DHPLC and sequencing, the diagnostic efficiency of REDE-DHPLC method was evaluated by detecting the mutation status of 2 genes in plasma of NSCLC and colorectal cancer patients. Results The sensitivity values of REDE-DHPLC and conventional DHPLC for detecting mutations in 4 loci were 0. 1% and 1%respectively. Plasmid DNA containing 0.1% mutation gene was detected to be positive continually for 2 to 3 times by REDE-DHPLC. EGFR mutation rates of 120 plasma from NSCLC patients detected by REDE-DHPLC, conventional DHPLC and sequencing methods were 27. 5%, 16. 7% and 12.5% respectively, and KRAS mutation rates of 120 plasma from colorectal cancer patients were 38. 3%, 25. 8% and 16. 7%,respectively. The positive rates of EGFR and KRAS mutation detected by REDE-DHPLC were significantly higher than conventional DHPLC(x2 = 4. 092, 4. 301, all P ＜ 0. 05 ) and sequencing method (x2= 8. 438,14. 127,all P ＜ 0. 05 ). In comparison with conventional DHPLC, the sensitivities of REDE-DHPLC for detecting EGFR and KRAS mutation were 100% (20/20,31/31), the specificities were 87. 0% (87/100)and 83. 2% (74/89). In comparison with sequencing method, the sensitivities of REDE-DHPLC were 100%( 15/15,20/20), the specificities were 82.9% (87/105)and 74. 0% (74/100). The coincidence rate of the two methods for detecting EGFR and KRAS mutation were 89. 2% ( 107/120, Kappa = 0. 690, P ＜ 0. 05 ) and 87.5% ( 105/120, Kappa= 0. 718, P ＜ 0. 05 ). The Consistency of EGFR and KRAS mutation status in plasma and tissues detected by REDE-DHPLC were 91.7% (33/36, Kappa =0. 939,P ＜0. 05)and 90. 2 %(46/51, Kappa = 0. 914, P ＜ 0. 05 ), respectively. Conclusions The REDE-DHPLC method is highly sensitive and specific for detecting EGFR and KRAS mutations in plasma DNA from tumor patients. The results are easy to be interpreted without missing homozygous point mutation, which indicate that the detection of EGFR and KRAS mutations in plasma DNA by REDE-DHPLC could therefore extend to be usedin clinical laboratory.

Objective To investigate the imaging features of primary clear cell carcinoma of liver and to assess the role of CT and MRI in the diagnosis of the disease. Methods Nineteen cases of primary liver clear cell carcinoma of liver were collected. All cases were confirmed by operation and pathology. Both pre-contrast and post-contrast scans with spiral CT were performed in 13 cases. MRI with T1WI, T2WI, and dynamic multi-phase contrast scanning were performed in 8 cases. Imaging findings in all cases were retrospectively reviewed. Results On pre-contrast CT scans, all 13 lesions appeared as hypodensity and among them irregular more hypodense region was found in 9 cases. On the arterial phase, all cases showed obvious enhancement, among which 9 cases were enhanced heterogeneously with central non-enhanced area.On the portal venous phase, 11 lesions were hypodense compared with normal live parenchyma and 2 lesions were isodense. The rim enhancement of tumor capsule was demonstrated in 3 cases. On MR T1WI, 5 of 8 were hypointense and 3 were slightly hyperintense. On MR T2WI, 5 of 8 cases were heterogeneously hyperintense, and 3 were iso-hypointense. On the MR arterial phase, marked enhancement was found in all 8 cases. On the portal venous phase and delayed phase, 7 of 8 cases were hypointense and 1 was isointense.The rim enhancement of tumor capsule was found in 2 cases. Conclusion CT and MRI can display the characteristic features of primary clear cell carcinoma of liver and can be helpful to improve the diagnostic accuracy.

In order to understand the situation of schistosomiasis in Fujian Province, the surveillance and field survey data of 16 counties (cities or districts) were statistically analyzed from 2003 to 2008 according to the national and provincial surveillance protocols. The snail areas were 69 400 m~2 in 2003, and 506 700 m~2 in 2004, then decreased to 57 700 m~2 in 2008 after the snail control in 2005 and 2006. Serological examinations were conducted in 18 000 people, among which 5 412 people were the mobile population from schistosome-endemic areas, and 110 persons were positive, among which 8 persons had eggs and miracidia in their stools, among 7 885 appendix samples, Schistosoma japonicum eggs were found in 8 samples of the patients who came from the o-riginal endemic areas. By the stool examination, 2 709 head of farm cattle in the region with snails were not found infected with Schistosoma japonicum. It is suggested that the areas of residual snails are large and widespread, and the imported patients are found frequently, so the danger of schistosomisis transmission still remains.

OBJECTIVETo investigate the attenuating effect of curcumin, an anti-inflammatory compound derived from dietary spice turmeric (Curcuma longa) on the pro-inflammatory insulin-resistant state in 3T3-L1 adipocytes.

METHODSGlucose uptake rate was determined with the [3H] 2-deoxyglucose uptake method. Expressions of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured by quantitative RT-PCR analysis and ELISA. Nuclear transcription factor kappaB p65 (NF-kappa p65) and mitogen-activated protein kinase (MAPKs) were detected by Western blot assay.

RESULTSThe basal glucose uptake was not altered, and curcumin increased the insulin-stimulated glucose uptake in 3T3-L1 cells. Curcumin suppressed the transcription and secretion of TNF-alpha and IL-6 induced by palmitate in a concentration-dependent manner. Palmitate induced nuclear translocation of NF-kappaB. The activities of Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase1/2 (ERK1/2) and p38MAPK decreased in the presence of curcumin. Moreover, pretreatment with SP600125 (inhibitor of JNK) instead of PD98059 or SB203580 (inhibitor of ERK1/2 or p38MAPK, respectively) decreased the up-regulation of TNF-alpha induced by palmitate.

CONCLUSIONCurcumin reverses palmitate-induced insulin resistance state in 3T3-L1 adipocytes through the NF-kappaB and JNK pathway.

3T3-L1 Cells ; Animals ; Anthracenes ; pharmacology ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Curcumin ; pharmacology ; Glucose ; metabolism ; Insulin ; pharmacology ; Insulin Resistance ; Interleukin-6 ; genetics ; metabolism ; JNK Mitogen-Activated Protein Kinases ; metabolism ; MAP Kinase Signaling System ; Mice ; NF-kappa B ; metabolism ; Palmitates ; pharmacology ; Protein Kinase Inhibitors ; pharmacology ; Tumor Necrosis Factor-alpha ; genetics ; metabolism ; Up-Regulation

BACKGROUND:Studies confirm that electromagnetic field (EMF) can promote the synthesis and secretion of many bone growth factors,and some growth factors can induce the osteoblastic directional differentiation of bone marrow mesenchymal stem cells (MSCs).OBJECTIVE: To investigate the effect of power-frequency EMF on mRNA expressions of bone morphogenetic protein-2 (BMP-2) and transforming growth factor-beta 1 (TGF-β1) in mouse bone marrow MSCs cultured in vitro.DESTGN: Single sample, block design, observation and controlled animal trial.SETTING: Department of Traumatic Surgery, Tongji Hospital Affiliated to Tongji Medical .College, Huazhong University of Science and Technology.MATERIALS: This trial was carried out in the laboratory of Department of Traumatic Surgery, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology during February to December 2005. ①Twenty Kunming mice of clean grade were selected for harvest of bone marrow MSCs. ②Magnetic field generator,which could generate EMF with 0 to 100 mT field strength and successive adjustable 50 Hz sinusoidal wave, was developed by Wuhan Naval University of Engineering. ③ Primer was all synthesized by Saibaisheng Bioengineering Co.,Ltd., Beijing.NETHODS: ① The involved mice were sacrificed by cervical dislocation. Bilateral femora and tibia were harvested. Bone marrow MSCs were isolated and cultured in vitro, and the second generation of cells were used for the trial. ②Different intensities of EMF stimulation tests: Negative control group, positive control group, EMF 0.4, 0.8 and 1.6 mT stimulation groups were set. Five bottles of cells of the second generation were chosen from each group for test. The cells in the negative control group and positive control group were not exposed to EMF. But medium containing osteogenic inductor(10-8 mol/L dexamethasone, 10 mmol/L β-sodium glycerophosphate and 50 mg/L Vitamin C included) was added in the positive control group at passage. After adhering to the wall, the cells in the EMF 0.4,0.8 and 1.6 mT stimulation groups were exposed to EMF of 0.4,0.8 and 1.6 mT field strength, respectively, one hour per day, five days later, they were detected.③ EMF stimulation tests in the same field strength and different time: Negative control group, EMF 1.6 mT stimulation 15,30 and 60 minutes groups were set.Five bottles of cells of the second generation were chosen from each group for test. The cells in the negative control group were exposed to EMF. The cells in the EMF 1.6 mT stimulation 15,30 and 60 minutes groups were respectively given 15,30 and 60 minutes of EMF stimulation at 1.6 mT successively.Five days later, they were detected.④ The mRNA expressions of BMP-2 and TGF-β1 were detected in each group by reverse-transcriptase polymerase chain reaction (RT-PCR) technique.MAIN OUTCOME MEASURES: ① The effect of different field strength of exposure of 50 Hz EMF on mRNA expressions of BMP-2 and TGF-β1. ② The effect of the same field strength and different time of exposure of 50 Hz EMF on mRNA expressions of BMP-2 and TGF-β1.RESULTS: ①Five days after EMF stimulation, the mRNA expressions of BMP-2 and TGF-β1 in the positive control group and EMF 0.4,0.8 and 1.6 mT stimulation groups were significantly enhanced as compared with negative control group (all P ＜ 0.01), and the mRNA expression of BMP-2 in the EMF 1.6 mT stimulation group reached the peak [(57.74±0.23)％]and mRNA expression of TGF-β1 in the EMF 0.4 mT stimulation group also reached the peak [(126.20±0.21 )％].② Five days after EMF stimulation, the mRNA expressions of BMP-2 and TGF-β1 in the EMF 1.6 mT stimulation 15,30 and 60minutes groups were significantly enhanced (all P ＜ 0.01) as compared with negative control group, and the mRNA expressions of two factors in the EMF 1.6 mT stimulation 60 minutes group reached peak separately [(28.06±0.11 )％ and (75.20±0.16)％].CONCLUSION:Proper intensity and action time of exposure of power-frequency EMF can obviously promote the mRNA expressions of BMP-2 and TGF-β1 in mouse bone marrow MSCs cultured in vitro.

Objective To provide the basis for the differentiation with similar species of intestinal flukes through observing the figure of Haplorchis pumilio. Methods Adults of H. pumilio were collected from the intestine of the cat which was infected with the encysted cercariae of H.pumilio for 45 days. The worms were observed after staining. Eggs and metacercariae of H.pumilio were collected and examined for their shape, size and morphological characteristics. Pseudorasbora parva, the fish host, was examined for the parasitized sites of metacercariae. Results The principal characteristics of the adults is the acetabulum degradation. There are only the genital sucker with 44-48 hamuli. The average measurement of eggs is 31.2?16.7 ?m with a smooth shell. Its aceromion is not evident. The average diameter of metacercariae is 168.5 ?m. There are squamous spines on metacercaria. The metacercariae only parasitize in the muscle between the basis of the fin and the fish body. The average measurement of metacercaria cyst is 445?95?m, with squamous spines on the body surface. Hamuli are found on the genital sucker of metacercaria cyst. Conclusion The morphological figures and parasitic sites of metacercaria, the genital sucker of the adult, and the number and form of the hamulus on the genital sucker provide basis for distinguishing H. pumilio from other intestinal flukes.

Objective To explore the effects and relationship of tert-butyl hydroperoxide (t-BHP) and hypoxia in transient ischemia-like attack (TIA-like) in Kunming mice.Methods Fifty-six mice were randomly divided into normal saline group (group A), t-BHP group (group B), t-BHP plus hypoxia group (group C) and model group (group D). Fourteen mice in group D were injected t-BHP (0.11 mol/L, 10 ml/kg) through tail vein with an interval of 24 hrs to induce TIA-like attack. The average time of TIA-like was ( 3.7? 1.1) days, and this time was used as experimental evidence to collect blood sample in other groups. Hemorheological indexes before TIA-like attack were observed in different experimental conditions.Results Compared with group A, the whole blood viscosity at shear rate 100S-1, 1S-1 and Fibrinogen were significantly increased in group B and group C (all P

Objective To make etiological and epidemiological investigation on the infection of Angiostrongylus canto-nensis in 8 pupils in Changle City. Methods (1) CSF of patients was examined with the conventional method to detect pathogens and eosinophiles. (2) The fecal samples of wild rodents were collected from the spot and examined microscopically to discover the first stage larvae of A. cantonensis. (3) Snails (Pila gigas) were collected in the spot. The smashed head tissue was examined for the third stage larvae of A. cantonensis. (4) The patient's clinical symptoms and physical signs were recorded with an emphasis on central nervous system. Results (1) Two larvae of the third stage of A. cantonensis were found in CSF of one patient. Eosinophiles occupied 68% of the cell number in average (ranged from 47% to 83%) in CSF of the 8 patients. (2) The infection rate of the first stage larvae of A. cantonensis was 39.3% (44/112) in feces of the rodents. (3) The infection rate of the third stage larvae of A. cantonensis was 40. 0% (82/205) in the snails. (4) Major clinical manifestations in the 8 patients included: severe headache(8/8), dizziness(8/8), nausea(8/8), vomiting(8/8), lethargy(7/8), lower limb hypody-namia(7/8). Conclusion The confirmation of severe infection of A. cantonensis in 8 child patients demonstrated that a natural nidus of angiostrongyliasis is present in Chengle City.