Adult ; Eosinophilic Granuloma ; Humans ; Male

KRAS is one of the most frequently mutated human oncogenes. In spite of mounting efforts on the development of direct or indirect inhibition targeting KRAS, little has been achieved because of insurmountable difficulties, titling KRAS "undruggable". Recently, subtype-specific inhibitors have shown great hope. Some KRAS^G12C inhibitors have entered clinical trials, including adagrasib and sotorasib, and have shown preliminary clinical effectiveness. Experiences from the inhibitors targeting the downstream factors of RAS pathways show that the anticancer activity of these drugs will be limited due to the development of drug resistance. Preclinical studies of KRAS^G12C inhibitors have revealed that the application of these agents might be hampered by the drug resistance issue. The current review aims to describe the current status of KRAS^G12C inhibitors, and discuss the mechanisms underlying KRAS^G12C inhibitor resistance, so as to provide the clues for the combat of drug resistance.

OBJECTIVETo understand the distribution of chronic disease related behavior and lifestyle in adults from Beijing.

METHODS16,658 adult residents from Beijing city were randomly selected with stratified multi-stage cluster sampling method in 2005. Each participant was invited to receive a set of standardized questionnaire, physical examinations and laboratory tests.

RESULTSIn the adults living in Beijing, 33.2% were overweight and 16.4% were obesive. The current smoking rate was 26.2% and the regular smoking rate was 21.4%. 57.7% of the male and 4.6% of the female adults were current smokers. In male adults, 64.3% drank alcoholic beverage at least once per month while 16.1% drank almost everyday, 16.5% drank more alcohol than moderate, and 18.5% were binge drinkers. 46.0% of Beijing adults were in lack of active physical exercise. Unhealthy dietary habits such as:excess consumption of sodium or oil, lower intake of vegetable, milk and soybean productions, skipping breakfast, fond of salted vegetable and fried food intake, as well as eating snacks etc. were quite commonly seen in the adults from Beijing. In addition, most of the risk factors had a higher prevalence in the suburban areas and population at working-age.

CONCLUSIONThe prevalence rate of chronic risk factors was still high in adults of Beijing. Effective interventions should be carried out to prevent further worsening of the situation, especially in the suburban areas and people at working-age.

Adolescent ; Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Alcohol Drinking ; epidemiology ; China ; epidemiology ; Chronic Disease ; epidemiology ; Feeding Behavior ; Female ; Health Behavior ; Humans ; Life Style ; Male ; Middle Aged ; Obesity ; epidemiology ; Overweight ; epidemiology ; Smoking ; epidemiology ; Surveys and Questionnaires ; Young Adult

OBJECTIVETo isolate and characterize indigenous algicidal bacteria and their algae-lysing compounds active against Microcystis aeruginosa, strains TH1, TH2, and FACHB 905.

METHODSThe bacteria were identified using the Biolog automated microbial identification system and 16S rDNA sequence analysis. The algae-lysing compounds were isolated and purified by silica gel column chromatography and reverse-phase high performance liquid chromatography. Their structures were confirmed by Nuclear Magnetic Resonance (NMR) and Fourier Transform Infrared (FT-IR) spectroscopy. Algae-lysing activity was observed using microscopy.

RESULTSThe algae-lysing bacterium LTH-2 isolated from Lake Taihu was identified as Serratia marcescens. Strain LTH-2 secreted a red pigment identified as prodigiosin (C20H25N3O), which showed strong lytic activity with algal strains M. aeruginosa TH1, TH2, and FACHB 905 in a concentration-dependent manner. The 50% inhibitory concentration (IC50) of prodigiosin with the algal strains was 4.8 (± 0.4)× 10⁻² μg/mL, 8.9 (± 1.1)× 10⁻² μg/mL, and 1.7 (± 0.1)× 10⁻¹ μg/mL in 24 h, respectively.

CONCLUSIONThe bacterium LTH-2 and its pigment had strong Microcystis-lysing activity probably related to damage of cell membranes. The bacterium LTH-2 and its red pigment are potentially useful for regulating blooms of harmful M. aeruginosa.

Anti-Bacterial Agents ; pharmacology ; Bacteria ; classification ; genetics ; metabolism ; Lakes ; Microcystis ; growth & development ; Phylogeny

OBJECTIVETo assess the efficacy of nasal intermittent positive pressure ventilation (NIPPV) in treatment of respiratory distress syndrome (RDS) in premature infants.

METHODSAccording to the requirements of Cochrane systematic review, a thorough literature search was performed among PubMed (1977-2008), Embase (1989-2008), OVID, Cochrane (2008), Chinese Digital Hospital Library (www.chkd.cnki.net) and Chinese Biomedical Literature Disk Database (CBMdisc). Quality assessments of clinical trials were carried out. Randomized controlled trials (RCTs) with NIPPV and RDS were enrolled, and Revman 4.2 software was used for meta-analysis. The trials were analyzed using relative risk (RR) for dichotomous data, weighted mean difference (WMD) were used for continuous data, both kind of data were expressed by 95% confidence intervals (95% CI). For homogenous data (P> or =0.10), fixed effects model was calculated, for heterogeneity data (P<0.10), random effects model was calculated.

RESULTSFive RCTs involving 284 premature infants diagnosed as respiratory distress syndrome (RDS) were included. Three studies comparing NIPPV with nasal continuous positive airway pressure (NCPAP) in the postextubation period, the extubation failure rate was 8.34% vs 40.79% in NIPPV group and NCPAP group, the NIPPV group had significantly lower extubation failure rates [RR 0.21 (95% CI: 0.10-0.45; P<0.001)]. Two of the above-mentioned three studies analyzed bronchopulmonary dysplasia (BPD) rates, the incidence of BPD was 39.34% vs 54.39% in NIPPV group and NCPAP group, the NIPPV group had a trend towards lower BPD rates, but this did not reach statistical significance [RR 0.73 (95% CI: 0.49-1.07; P=0.11)]. NIPPV was used as primary mode in two studies, one compared with conventional ventilation (CV), which detected that the NIPPV group had significantly lower BPD rates (10% vs. 33.33%, P=0.04); the other compared with NCPAP, which also showed that NIPPV group had significantly lower BPD rates (2.33% vs. 17.07%, P=0.03).

CONCLUSIONThe primary mode NIPPV was found to be feasible as a method of ventilation in preterm infants with RDS, and was associated with a decreased incidence of BPD. In the postextubation period, NIPPV is more effective in preventing failure of extubation than NCPAP.

Humans ; Infant, Newborn ; Infant, Premature ; Intermittent Positive-Pressure Ventilation ; Respiratory Distress Syndrome, Newborn ; therapy

OBJECTIVETo estimate the number of drug users in Hongjiang, Hunan and to develop strategy for drug reduction in the future.

METHODSTwo capture-recapture methods were used to estimate the numbers of drug addicts. Random stratified sampling survey was used to verify the optimum allocation. The first capture-recapture method (CR1) referred to the number from optimum allocation random stratified sampling survey conducted in the communities and the number from local Public Security Bureau list being the second capture. The second capture-recapture method (CR2) referred to the collection of records in the detoxification unit with an interval of 4 months. The estimated number was calculated under Seber's adjustment formula. Face to face interview was carried out during the optimum allocation random stratified sampling survey process.

RESULTSOf 1388 interviewed in the communities, 24 (1.73%) were identified as drug addicts under the optimum allocation random stratified sampling survey. When the figure 1.73% was applied to the total population (72,709) in Hongjiang, the result yielded an estimation of 1258 drug addicts. The estimated numbers of CR1 and CR2 were 904 and 1069 respectively. However, the number was 1.3 to 1.6 fold higher than the reported number (687) by local Public Security Bureau.

CONCLUSIONThe capture-recapture method seemed a better method in estimating the number of drug addicts.

China ; epidemiology ; Female ; Humans ; Incidence ; Male ; Needle Sharing ; Population Surveillance ; methods ; Substance Abuse, Intravenous ; epidemiology

Objective To explore the relationship of polymorphisms of D17S1878, D17S932 sites and essential hypertension.Methods Sixty-seven pedigrees were collected at the region with high prevalence of hypertension. The polymorphisms of D17S1878 and D17S932 sites were genotyped using Genetic Analyzer and GeneScan Software. Case-control study in sibs with different phenotype was carried out and logistic analysis was used for multivariate analysis. Results There were significant differences on the distributions of age, male, drinking, average systolic pressure, average diastolic pressure, the characteristics of rash, body mass index (BMI), total cholesterol amount, triglyceride, low density lipoprotein(LDL) between the hypertensive-affected sibs and the normotensive sibs (P＜0.05). There was significant difference between the affected hypertensive and normotensive sibs in the D17S1878 site (P＜0.05), while there was no significant difference in D17S932 (P＞0.05 ). After non-conditional logistic analysis, data showed that both sites were not included in the model, while age( OR = 1.044,95%CI:1. 019-1. 069), drinking ( OR = 2. 644,95% CI : 1. 778-3. 932), the characteristics of rash ( OR = 3. 078,95%CI:1.721-5.504), triglyceride (OR= 1.305,95%CI: 1.016-1.676), LDL-C (OR= 1.787,95% CI:1. 296-2. 646), as risk factors, were included in the model. Conclusion The polymorphisms of D17S1878 and D17S932 possibly were not associated with essential hypertension.

OBJECTIVETo evaluate the effect of serum containing Jinmaitong Capsule (JMT) on apoptosis of Schwann cells (SCs) that are cultured in high glucose at the cellular and molecular levels.

METHODSSCs were cultured in Dulbecco's modified Eagle's medium (control group), high glucose (50 mmol/L) medium supplemented with 20% rat serum (HG group), and 50 mmol/L glucose medium supplemented with serum containing JMT (JMT group). SC apoptosis was detected using a terminal deoxynucleotidyl transferase dUTP nick end labeling kit. The expression of Bcl-2 and the caspase-3 p20 subunit in SCs were detected by realtime fluorogenic quantitative polymerase chain reaction and confocal laser scanning microscopy, respectively.

RESULTSNo apoptosis was detected in SCs that were cultured in the control group. The percentage of apoptosis of SCs cultured in the HG group was much higher than that in the control group. The apoptosis of SCs in the JMT group was lower than that in the HG group. Fluorescence intensity of Bcl-2 and the expression of Bcl-2 mRNA in SCs that were cultured in the HG group were much lower than those in the control group and much higher than those in the JMT group (P<0.01). The fluorescence intensity of caspase-3 p20 and the expression of caspase-3 p20 mRNA in SCs that were cultured in the HG group were much higher than those in the control group (P<0.01), and they were remarkably lower in the JMT group (P<0.01).

CONCLUSIONSJMT effectively prevents SC apoptosis that is induced by high glucose. This effect may be because of increased expression of Bcl-2 mRNA and protein and decreased expression of caspase-3 p20 mRNA and protein.

Animals ; Apoptosis ; drug effects ; Capsules ; Caspase 3 ; genetics ; metabolism ; Cell Proliferation ; drug effects ; Cell Shape ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation ; drug effects ; Glucose ; pharmacology ; Male ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; S100 Proteins ; metabolism ; Schwann Cells ; cytology ; drug effects ; enzymology ; Serum ; metabolism

Objective] To investigate the relationship between hepatitis B virus( HBV) genotype and their mutations on the development of hepatocellular carcinoma ( HCC ) . [ Methods ] A cohort study on patients with chronic HBV infection was followed up.HBV genotypes were identified by nested multiplex PCR and multiplex PCR.And HBV mutations in the basic core promoter region were sequencing by PCR amplification. [ Results] The patients infected with genotype B were followed up for an average of 8.52 years (IQR:6.67-10.75), of whom the incidence of HCC was 6.55/1 000 person-years.After follow up with an average of 8.87 years (IQR:6.85-11.33), the incidence of HCC was 11.63/1 000 person-years for the patients infected with genotype C, which were significantly higher than those infected with genotype B (P=0.006).In genotype B HBV infected patients, age (≥60 years), cirrhosis can in-crease the risk of HCC, and in genotype C patients, male, age (≥40 years), cirrhosis, C1653T, T1753V, A1762T/G1764A mutation as well.Interferon therapy can reduce the risk of HCC.In genotype C group, interferon treatment reduced HCC risk in patients carrying A1762T/G1764A mutation (HR=0.21, P=0.008) and in those without T1753V ( HR=0.08, P=0.012) and C1653T mutation ( HR=0.17, P=0.013). [Conclusion] HBV genotypes and mutation are closely associated with HCC.Patients infected with genotype C, carrying 1762T/G1764A mutation should be given priority of receiving antiviral treatments in order to prevent HCC;those carrying C1653T or T1753V mutation should be monitored closely to detect early HCC and receive timely surgical resection.

BACKGROUNDMicroRNAs (miRNAs) control gene expression by destabilizing target transcripts and inhibiting their translation. Aberrant expression of miRNAs has been described in many human diseases, including schizophrenia. However, the effects on miRNA expression in response to antipsychotic treatment in peripheral circulation have not been thoroughly examined.

METHODSUsing quantitative real-time PCR (qRT-PCR), We quantified the expression of seven candidate miRNAs in plasma samples of 40 first-episode schizophrenics before and after antipsychotic treatment. The patients were all treated with risperidone and achieved remission in 1 year.

RESULTSCompared with the baseline, the expression levels of miR-365 and miR-520c-3p were significantly down-regulated after 1 year of risperidone treatment (P < 0.001). There were no significant correlations between the clinical symptoms and the expression levels of these two miRNAs (P > 0.05).

CONCLUSIONSThis study analyzed possible circulating miRNAs in response to antipsychotic monotherapy for schizophrenia, the further mechanism need to be confirmed.

Adult ; Antipsychotic Agents ; therapeutic use ; Female ; Humans ; Male ; MicroRNAs ; blood ; Risperidone ; therapeutic use ; Schizophrenia ; drug therapy ; genetics