Although current synthetic anti-gout drugs have significant therapeutic effects in reducing serum uric acid levels, they have serious side effects such as allergic reactions and liver and kidney damage. Natural products with a wide range of uric acid-lowering and high safety have played a critical role in anti-gout drug discovery and development. This paper reviews the natural products with uric acid-lowering or anti-gout pharmacological effects and the investigation on their mechanisms of action, to provide information for drug discovery and development.

Objective To study the relationship of MR delayed enhancement with cardiac troponin I in hypertrophic cardiomyopathy(HCM)and to evaluate their values on assessing HCM condition and prognosis.Methods Thirty-five HCM patients who were diagnosed by echocardiography were enrolled.All patients were performed MR scan and cTn Ⅰ test of blood.The relationships of MR delayed enhancement, myocardial hypertrophy and cTn Ⅰ were analyzed.Results(1)DE was found in 25 of total 35 HCM patients(71.4%).19 of 35 HCM patients(54.3%)had abnormal increased eTn Ⅰ value.The medians of cTn Ⅰ in patients with DE and without DE(110,5 ?g/ml,respectively)had statistics significance (P

Objective　To study the effect of portal vein blocking on the permeability of the intestinal mucosa in pigs. Methods　Healthy Rongchang pigs were divided into 3 groups: ① sham operation group(SO), ② portal vein clamping for 45 min group (PVC-45'), ③ portal vein clamping for 60 min group (PVC-60'). Urine lactulose/mannitol(L/M) ratio was measured after portal vein blocking. Results　The L/M ratio was increased significantly (P<0.05) in PVC-45' and 60' groups than in SO group, with that of PVC-60' higher than that of PVC-45' group, but not significantly. Conclusion　The increase of intestinal mucosal permeability after portal vein blocking is an early and important index for the damage of the intestinal mucosa barrier.

The urate transporter 1 (URAT1) which controls urate reabsorption is a membrane transporter in the apical membrane of human renal proximal tubule epithelial cells. It was found that about 90% of patients suffer from hyperuricemia due to insufficient uric acid excretion. Therefore, the development of URAT1 inhibitors that can reduce the level of serum uric acid in vivo by enhancing renal urate excretion has been a hot spot in seeking anti-gout drugs in recent years. In this article, the representative URAT1 inhibitors with uric acid-lowering or anti-gout effects are reviewed, and related medicinal chemical strategies are analyzed, hoping to provide valuable insights into the discovery of new URAT1 inhibitors.

From the process of human immunodeficiency virus-1 (HIV-1) invading cells, the combination of gp120 and CD4 is the first step for HIV-1 to invade cells. Interfering with this process can prevent HIV from recognizing target cells and inhibit virus replication. Therefore, HIV-1 gp120 is an important part of the HIV-1 life cycle. Fostesavir, a phosphatate prodrug derived from the gp120 inhibitor BMS-626529 modified by the prodrug strategy, was approved for the treatment of adult patients with multidrug resistant HIV-1 infection by the US FDA and the European Medicines Agency in 2020 and 2021, respectively. In this review, we focus on the research progress of small molecule inhibitors targeting the interaction of gp120-CD4 from the perspective of medicinal chemistry, in order to provide reference for the subsequent research of gp120 inhibitors.

Objective:To investigate the risk factors of pancreatic fistula after radical resection of gastric cancer, and to establish a risk prediction scoring model for pancreatic fistula.Methods:The clinico-pathological data of 312 patients with gastric cancer admitted to the Fourth Hospital of Hebei Medical University from January 2019 to January 2020 were retrospectively analyzed. Multiple factor logistic regression model was used to analyze the risk factors of pancreatic fistula after radical resection of gastric cancer, and a risk prediction scoring model based on the risk factors was established. Hosmer-Lemeshow test was used to detect the goodness of fit of regression equation, and receiver operating characteristics (ROC) curve was used to evaluate the distinction degree of regression equation.Results:Among 312 patients with gastric cancer, 27 cases (8.65%) had pancreatic fistula after radical resection of gastric cancer. Multiple factor logistic regression analysis showed that male patients ( OR = 5.312, 95% CI 1.532-18.420, P = 0.008), age ≥ 60 years old ( OR = 4.928, 95% CI 1.493-16.250, P = 0.009), preoperative diabetes mellitus ( OR = 3.062, 95% CI 1.091-8.589, P = 0.034), lesion location in the gastric body-gastric antrum ( OR = 3.121, 95% CI 1.052-9.251, P = 0.040), intraoperative omental bursa resection ( OR = 6.209, 95% CI 2.084-18.478, P = 0.001), intraoperative lymph node dissection at D2+ station ( OR = 3.114, 95% CI 1.044-9.281, P = 0.042), intraoperative combined organ resection ( OR = 5.063, 95% CI 1.473-17.400, P = 0.010), preoperative TNM stage Ⅲ ( OR = 4.973, 95% CI 1.189-20.792, P = 0.028) were independent risk factors for pancreatic fistula after radical resection of gastric cancer. A risk prediction equation of pancreatic fistula after radical resection of patients with gastric cancer was established: P = -8.619+1.670X 1+1.595X 2+1.119X 3+1.138X 4+1.826X 5+1.136X 6+1.622X 7+1.604X 8; factor X was set as a binomial assignment (0 or 1); X1-X8 were listed as follows respectively: gender (the male was 1), age (≥60 years old was 1), preoperative diabetes history (yes was 1), lesion location (gastric body-gastric antrum was 1), intraoperative resection of omental bursa or not (yes was 1), intraoperative lymph node dissection at D2+ station or not (yes was 1), intraoperative combined organ resection or not (yes was 1), preoperative TNM stage (stage Ⅲ was 1). The goodness of fit of regression equation was high ( P = 0.395). The area under the curve of ROC by using risk prediction scoring model to judge pancreatic fistula was 0.916 (95% CI 0.872-0.960, P<0.01). The probability of pancreatic fistula in patients with score ≥ 5 was 40.90%, and the probability of pancreatic fistula in patients with score < 5 was 3.35%. Conclusions:The occurrence of pancreatic fistula after radical resection of gastric cancer is closely related to a variety of risk factors. By establishing a risk prediction scoring model for pancreatic fistula after radical resection of gastric cancer, it is helpful to effectively identify patients with high risk of pancreatic fistula after radical surgery during the perioperative period.

OBJECTIVETo assess the regulating effects of interleukin-1 (IL-1) on gene expression of cartilage specificity gene Sox9 and type II collagen mRNA in the human intervertebral discs.

METHODSRT-PCR were used to investigate the effects of IL-1 on gene expression of Sox9 and type II collagen mRNA in intervertebral discs cells cultures of embryo.

RESULTSThe Sox9 and type II collagen mRNA in intervertebral discs were decreased progressively along with the addition concentrations of IL-1 than the controls. And the mRNA of Sox9 and type II collagen also markedly decreased with the time of culture.

CONCLUSIONSIL-1 could cause dose-dependent and time-dependent inhibition effects on Sox9 and type II collagen gene expression in human intervertebral discs.

Cells, Cultured ; Collagen Type II ; genetics ; Dose-Response Relationship, Drug ; Gene Expression ; drug effects ; High Mobility Group Proteins ; genetics ; Humans ; Interleukin-1 ; pharmacology ; Intervertebral Disc ; cytology ; drug effects ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; SOX9 Transcription Factor ; Time Factors ; Transcription Factors ; genetics

OBJECTIVETo investigate the effect of omega-3 polyunsaturated fatty acids(omega-3PUFAs) on the apoptosis of human gastric cancer cell line SGC-7901 and to explore the potential mechanisms.

METHODSCells were treated with eicosapentaenoic acid (20:5 omega-3,EPA) or docosahexaenoic acid (22:6 omega-3, DHA) at concentrations of 10, 20 and 40 microg/ml. Cell growth and apoptosis were analyzed with MTT assay, cell morphology, DNA electrophoresis and flow cytometry. Mitochondrial membrane potential ( triangle right psi mt) was measured by fluorescent probe rhodamine 123. The distribution of cytochrome C in mitochondria and cytosol was determined by enzyme-linked immunoadsorbent assay. The composition of mitochondrial membrane phospholipid(MMP)was examined by gas chromatography.

RESULTSBoth EPA and DHA markedly inhibited the SGC-7901 cell growth and induced apoptosis in a time- and dose-dependent manner. After incubation of the cells with 40 microg/ml EPA or DHA for 24 hours, the level of Deltapsimt siginificantly decreased (P<0.001), and cytochrome C largely released into cytosol from mitochondria. The proportions of EPA and DHA in MMP rapidly elevated while that of arachidonic acid sharply decreased.

CONCLUSIONSomega-3PUFAs inhibit the growth of gastric cancer cells through promoting apoptosis. Compositional and functional alterations in mitochondrial membrane may be an important initiator of apoptosis induced by omega-3PUFAs.

Apoptosis ; drug effects ; Cell Line, Tumor ; Cytochromes c ; metabolism ; Fatty Acids, Omega-3 ; pharmacology ; Humans ; Membrane Potential, Mitochondrial ; Mitochondria ; metabolism ; pathology ; Stomach Neoplasms ; metabolism

BACKGROUNDStreptococcus mutans (S. mutans) is the prime pathogen of dental caries. There are few reports that studied the relationship between S. mutans, bacteria and dental caries in permanent teeth when compared to those in primary teeth. This study aimed to detect S. mutans and bacteria of dental caries and non-caries groups in permanent teeth from a north China population by real-time polymerase chain reaction (PCR) and compare the relationship between the number of these bacteria and the prevalence of dental caries in permanent teeth.

METHODSHuman saliva samples were collected from 142 subjects with permanent teeth. According to their dental tooth (DT), 142 subjects were divided into a dental caries group (DT ≥ 1) and a non-caries group (DT = 0). With specific primers for S. mutans and 16S rRNA, the total number of S. mutans and total bacteria of 142 saliva samples were detected by real-time PCR and statistically analyzed.

RESULTSThere was no significant difference between the detection rates of S. mutans (P = 0.118) and medians of S. mutans (P = 0.115). The ratio of S. mutans to total bacteria in people with dental caries was significantly higher than in those without caries (P < 0.001), but the total number of bacteria in people with dental caries was significantly lower than in those without caries (P < 0.001).

CONCLUSIONSS. mutans had different effects on caries in the permanent teeth of several individuals from a north China population. The ratios of S. mutans to total bacteria in saliva detected by real-time PCR with Sm479F/R and 16S RNA primers were closely associated with the prevalence of dental caries in the same population. These assays may be useful for the assessment of an individual's risk of dental caries.

Adolescent ; Adult ; Aged ; Bacteria ; isolation & purification ; Dental Caries ; microbiology ; Female ; Humans ; Male ; Middle Aged ; Real-Time Polymerase Chain Reaction ; Saliva ; microbiology ; Sensitivity and Specificity ; Streptococcus mutans ; isolation & purification ; Tooth ; microbiology

BACKGROUNDControl of hypersecretion of certain hormones is one of the key targets in the treatment of pituitary adenomas. RNA interference has been shown to inhibit protein expression, and thus it may represent a promising method for the treatment of pituitary adenomas. In the present study, transfection efficiency of small interfering RNA (siRNA) was optimized in human prolactinoma cells.

METHODSFirst, a method was optimized to extract highly purified human prolactinoma cells in vitro. The extracted cells were verified to retain the physiological features of prolactin (PRL) secretion. Second, three conditions for siRNA transfection were tested by the evaluation of transfection efficiency and cell viability. The proper transfection condition was verified for human prolactinoma cells. Third, the siRNA for prolactin was transfected into the human prolactinoma cells, and the suppression of PRL mRNA was evaluated by quantitative real-time reverse transcription-PCR.

RESULTSThe siRNA of 100 pmol with Lipofectamine 2000 of 5 µl for 1 × 10(6) cells was proved preferable, with transfection efficiency being 53.3% and cell viability being 69.7%. In the preliminary experiment the siRNA against PRL decreased the mRNA of PRL by 34.0%.

CONCLUSIONIt is possible to inhibit hormone hypersecretion by RNA interference, that may eventually enable therapeutic siRNA drugs developed.

Adolescent ; Adult ; Cell Line, Tumor ; Cell Separation ; Female ; Humans ; Male ; Middle Aged ; Pituitary Neoplasms ; pathology ; therapy ; Prolactinoma ; pathology ; therapy ; RNA, Small Interfering ; genetics ; Transfection