2.Recent advances in mechanisms of KRASG12C inhibitors anti-tumor resistance and relevant overcoming strategies
Ke-xin LIU ; Rui-lin WU ; Tao YUAN ; Kai-yue PU ; Qiao-jun HE ; Hong ZHU ; Bo YANG
Acta Pharmaceutica Sinica 2022;57(2):271-276
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 KRASG12C 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 KRASG12C 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 KRASG12C inhibitors, and discuss the mechanisms underlying KRASG12C inhibitor resistance, so as to provide the clues for the combat of drug resistance.
3.Study on chronic disease related behavior and lifestyle in adults in Beijing, 2005.
Pu-Hong ZHANG ; Shu-Fang JIAO ; Ying ZHOU ; Hong-Bo WANG ; Fan WU ; Yong JIANG ; Ze-Jun LIU
Chinese Journal of Epidemiology 2007;28(12):1162-1166
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
4.Isolation and characterization of an algicidal bacterium indigenous to lake Taihu with a red pigment able to lyse microcystis aeruginosa.
Fei YANG ; Hai Yan WEI ; Xiao Qin LI ; Yun Hui LI ; Xiao Bo LI ; Li Hong YIN ; Yue Pu PU
Biomedical and Environmental Sciences 2013;26(2):148-154
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
5.Estimation on the number of drug users in Hongjiang, Hunan: a capture-recapture study.
Xi CHEN ; Fan LV ; Jun ZHENG ; Hong-bo PU ; Xun-qiang YIN ; Yan-hui ZHANG ; Bi-yun QIN ; Hu PAN
Chinese Journal of Epidemiology 2005;26(6):417-420
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
6.A meta-analysis of nasal intermittent positive pressure ventilation in treatment of respiratory distress syndrome in premature infants.
Yun-Pu CUI ; Xiao-Mei TONG ; Hong-Mao YE ; Bo WANG ; Ya-Nan TANG
Chinese Journal of Pediatrics 2009;47(7):532-536
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
7.Multivariate analysis on the relationship between polymorphisms on chromosome 17 and essential hypertension
Ling-Yu FU ; Yan-Yan ZHAO ; Jing-Pu SHI ; Chun-Yi LI ; Hong LIU ; Bo ZHOU
Chinese Journal of Epidemiology 2008;29(6):522-525
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.
8.Effect of serum containing Jinmaitong Capsule on rats' Schwann cell apoptosis induced by high glucose concentration.
Pu-Yan WANG ; Xiao-Chun LIANG ; Hong ZHANG ; Li ZHAO ; Qing SUN ; Wen-Zhi HUANG ; Bo-Wu LI
Chinese journal of integrative medicine 2013;19(7):517-523
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
9.Study on DNA fingerprinting of Mycobacterium tuberculosis strains isolated in Southern Chinese army by IS6110-restriction fragment length polymorphism.
Nian-hua ZENG ; Zhi-bin WANG ; Hong XIAO ; Shan-shan WANG ; Jia-liang HUANG ; Jian-xin SU ; Pu-lin JIANG ; Bo-heng TANG
Chinese Journal of Epidemiology 2003;24(7):591-594
OBJECTIVETo study the correlation between DNA fingerprinting of Mycobacterium tuberculosis (MTB) stains isolated from the Chinese army in the south and from local residents, and to investigate the molecular epidemiological characteristics of tuberculosis (TB) in the army, for the sake of TB prevention in the army.
METHODSMTB DNA was digested with restriction endonuclease PvuII and electrophoresed in agarose gel, after Southern Blotting, the membrane was hybridized with a 245 bp fragment of IS6110 which labeled [alpha(32)P]-dCTP as probe. Finally, a restriction fragment length polymorphism (RFLP) patterns was shown, and analyzed logestic with epidemiological data from the patients.
RESULTSA total number of 185 TB strains were detected and the IS6110 copy numbers ranged from 1 - 22. No significant difference was found in the IS6110 copy numbers between patients from army and local patients. IS6110 copy numbers of TB strains in army patients were centered in 6 - 20, however, with 7 - 20 copies in local TB patients. The TB strains were dispersed into 8 groups and the majority of TB strains in both army and local patients was centered in groups I, II, III. The distribution of DNA fingerprint for drug resistance TB strains was significantly different from those for sensitive strains. No different distribution of among groups was found regarding BCG history.
CONCLUSIONSThe genetics of TB stains were roughly the same between the army patients and local ones, but there was a strong correlation in the gene levels. Data suggested that a close connection should be considered on TB prevention and treatment for TB patients in the army and local residents.
China ; epidemiology ; DNA Fingerprinting ; DNA, Bacterial ; analysis ; genetics ; Humans ; Military Personnel ; Molecular Epidemiology ; Mycobacterium tuberculosis ; genetics ; isolation & purification ; Polymorphism, Restriction Fragment Length ; Tuberculosis ; epidemiology ; genetics ; microbiology
10.Study on molecular epidemiology of Mycobacterium tuberculosis in Chinese army with PCR amplified fingerprinting methods.
Nian-hua ZENG ; Zhi-bin WANG ; Bo-heng TANG ; Hong XIAO ; Shan-shan WANG ; Xing-guo LI ; Jia-liang HUANG ; Pu-lin JIANG ; Chun-gang WU
Chinese Journal of Epidemiology 2003;24(5):377-380
OBJECTIVETyping of Mycobacterium tuberculosis strains and epidemiological studies in the army of southern China to provide scientific basis for prevention of pulmonary tuberculosis.
METHODSA rapid fingerprinting of M. tuberculosis strains method by polymerase chain reaction (PCR) with outward-directed primers that designed to the ends of the insertion sequence IS6110 was developed, and to analyze the relationship between the polymorphism of DNA fingerprinting and epidemiology of M. tuberculosis.
RESULTSOne hundred and fifty-four M. tuberculosis detected were classified into eight types according to their characters of PCR amplified fingerprints. The main types were type I (36.4%), type II (31.8%), and type III (21.4%), while other types were less than 4 percentage. In those main type groups, patients aged 20 to 29 and 30 to 39 took up 31.8% and 27.9% respectively. For those main types, the distribution of those types in the first treated patients showed significant difference compared with that in the retreated patients, and the rate of drug-resistance was also statistically different. However, the distribution was not statistically significant to history of BCG vaccination and patients living in urban or rural area. The main drug-resistant strains were only Isoniazid-resistant or Rifampin-resistant strains, while the drug-resistant strains were 44.4%, 29.6% and 14.8% respectively in type I, type II and type III.
CONCLUSIONPCR fingerprinting was a rapid, precise, sensitive, specific method to type M. tuberculosis, and could be used to study the epidemiology of tuberculosis; The prevalence of tuberculosis was primarily due to the transmission of type I, type II and type III in the army being studied from Southern China, to suggest that surveillance needs to be strengthened.
Adult ; China ; epidemiology ; DNA Fingerprinting ; methods ; DNA, Bacterial ; genetics ; Female ; Humans ; Male ; Military Personnel ; Molecular Epidemiology ; Mycobacterium tuberculosis ; classification ; genetics ; isolation & purification ; Polymerase Chain Reaction ; methods ; Polymorphism, Genetic ; Sensitivity and Specificity ; Tuberculosis ; epidemiology ; Tuberculosis, Multidrug-Resistant ; epidemiology ; microbiology