With the rapid development of epidermal growth factor receptor (EGFR) gene testing of lung adenocarcinoma patients has been routinely carried out, EGFR mutations are also possible for some small samples of non-smoking female lung squamous cell carcinoma patients. This increases the opportunity for targeted therapy for this group of patients. However, drug resistance in patients with lung squamous cell carcinoma during targeted therapy is an important factor affecting subsequent treatment. There are multiple mechanisms of acquired drug resistance in targeted therapy, and the alteration of mesenchymal-epithelial transition factor (MET) signaling pathway is one of the common mechanisms of drug resistance. At present, some selective tyrosine kinase inhibitors (TKIs) of MET has been approved for non-small cell lung cancer with MET gene 14 exon skipping mutation, such as Glumetinib, Savolitinib, Tepotinib, Capmatinib, etc. Drugs that target secondary MET amplification are still in clinical trials. This paper retrospectively analyzed the clinical data of a female patient with EGFR-TKIs resistant secondary MET amplified squamous cell lung cancer, and reviewed relevant literature to explore how to optimize the treatment of lung squamous cell carcinoma patients with EGFR mutation, so as to provide clinical reference for the diagnosis and treatment of such patients.
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Female ; Humans ; Carcinoma, Squamous Cell/drug therapy* ; Drug Resistance, Neoplasm/genetics* ; ErbB Receptors/antagonists & inhibitors* ; Gene Amplification ; Lung Neoplasms/drug therapy* ; Protein Kinase Inhibitors/pharmacology* ; Proto-Oncogene Proteins c-met/genetics*

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

In this study, in order to overcome the shortcomings of the current methods used to identify Bifidobacterium animalis, such as long time, complicated operation and low adaptability of experimental environment, specific primer probes were designed based on ERIC-PCR technology to identify and detect B.animalis.Based on the genomic DNA of B.animalis HP-B1124, the ERIC-PCR reaction conditions of B.animalis HP-B1124 were optimized, and the ERIC-PCR fragments were obtained one by one and sequenced.Two pairs of specific primer probes were designed.The accuracy, specificity, limitation and universality of the two pairs of primer probes were evaluated, and the two pairs of specific primer probes were used for testing the products containing B.animalis in the commercially published formula.The two pairs of specific primer probes designed in this study could be used for identified strains of B.animalis more simply, quickly and targeted.This method has optimized the current relatively traditional methods of pure culture and plate counting identification of B.animalis, and has solved the high requirements of SNP genotyping technology and real-time fluorescence quantitative PCR method for experimental equipment and reagents in the identification of B.animalis to a certain extent.It has the characteristics of low cost, high specificity and earn a broad market development prospect.

BACKGROUND: The hemoglobin glycation index (HGI) was developed to quantify glucose metabolism and individual differences and proved to be a robust measure of individual glycosylated hemoglobin (HbA1c) bias. Here, we aimed to explore the relationship between different HGIs and the risk of 5-year major adverse cardiovascular events (MACEs) by performing a large multicenter cohort study in China. METHODS: A total of 9791 subjects from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a Longitudinal Study (the REACTION study) were divided into five subgroups (Q1-Q5) with the HGI quantiles (≤5th, >5th and ≤33.3th, >33.3th and ≤66.7th, >66.7th and ≤95th, and >95th percentile). A multivariate logistic regression model constructed by the restricted cubic spline method was used to evaluate the relationship between the HGI and the 5-year MACE risk. Subgroup analysis between the HGI and covariates were explored to detect differences among the five subgroups. RESULTS: The total 5-year MACE rate in the nationwide cohort was 6.87% (673/9791). Restricted cubic spline analysis suggested a U-shaped correlation between the HGI values and MACE risk after adjustment for cardiovascular risk factors ( χ2 = 29.5, P <0.001). After adjustment for potential confounders, subjects with HGIs ≤-0.75 or >0.82 showed odds ratios (ORs) for MACE of 1.471 (95% confidence interval [CI], 1.027-2.069) and 2.222 (95% CI, 1.641-3.026) compared to subjects with HGIs of >-0.75 and ≤-0.20. In the subgroup with non-coronary heart disease, the risk of MACE was significantly higher in subjects with HGIs ≤-0.75 (OR, 1.540 [1.039-2.234]; P = 0.027) and >0.82 (OR, 2.022 [1.392-2.890]; P <0.001) compared to those with HGIs of ≤-0.75 or >0.82 after adjustment for potential confounders. CONCLUSIONS We found a U-shaped correlation between the HGI values and the risk of 5-year MACE. Both low and high HGIs were associated with an increased risk of MACE. Therefore, the HGI may predict the 5-year MACE risk.
Humans ; Cohort Studies ; Longitudinal Studies ; Diabetes Mellitus, Type 2/diagnosis* ; Maillard Reaction ; Glycated Hemoglobin ; Cardiovascular Diseases

To explore the relationship between progesterone receptor (PGR) gene G1978T polymorphism and endometrial carcinoma. METHODS: After searching PubMed, EMBASE, Wan-fang and CNKI databases for literatures on PGR G1978T genotyping of endometrial cancer patients, the data were extracted and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using STATA15. The whole blood samples of endometrial carcinoma cases (EC group) and normal women (control group) were collected. Allelic-specific primers matching G1978T wild type G allele and mutant type T allele were designed with 3' terminal phosphorothioate modification, and the two-directional primer extension was performed using Exo + polymerase to genotype PGR gene G1978T polymorphism and Sanger sequencing was used to verify the genotype. RESULTS: PGR gene G1978T mutation was marginally associated with endometrial carcinoma risk (ORper allele =1.10, 95%CI=0.98-1.24, P= 0.072). At the same time, only 1 normal blood samples were found with PGR gene G1978T mutation, and the differences in genotypes and allele frequency between the case group and the control group were not statistically significantP>0.05. CONCLUSION: The G1978T polymorphism of the PGR gene maybe not be associated with the risk of endometrial carcinoma.

Objective: To search for specific metabolites in the lungs of pneumonia rats fed with a high-calorie diet, as well as explore the changes in the lung metabolites of young rats treated with Yinlai Decoction (YD) and its effects on inflammation-related metabolic pathways.Methods: Lipopolysaccharides (LPS) and a special high-calorie diet were used to induce Sprague Dawley (SD) rats to simulate the intestinal state of infant pneumonia. Liquid chromatography-mass spectrometry technology (LC-MS/MS) was used to detect metabolites in each group. Supervised orthogonal partial least squares discriminant analysis (OPLS-DA) model values were used for the detection results to find the differential metabolites. The metabolic pathways that are involved with the differential metabolites were clarified through enrichment analysis and topological analysis. Finally, the T cell receptor signaling pathway (TCR) signal conversion was analyzed by the network pharmacology method. Results: In the high-calorie diet combined with pneumonia group (M3), a total of 55 metabolites were determined to be different from the normal group (N). A total of 36 metabolites were determined to be different from those in the lung metabolites of the YD treatment group (T1). YD had a regulatory effect on glutathione metabolism, arginine and proline metabolism, ascorbic acid and aldehyde metabolism and phenylalanine metabolism. And the small molecule metabolites could act on the FYN and lymphocyte-specific protein tyrosine kinase (LCK) target proteins in the TCR signaling pathway, thereby affecting the immune function of the lungs. Conclusion: A high-calorie diet can cause abnormal sphingolipid metabolism in the lungs of young rats, thereby creating chronic lung inflammation in young rats. YD has a beneficial effect when used to treat young rats with LPS-induced pneumonia fed on high-calorie diets. Its mechanisms of action may affect the body's immune pathways by regulating the oxidative stress pathway affected by glutathione metabolism.

Acute-on-chronic liver failure is a clinical syndrome with acute exacerbation on the basis of chronic liver disease and can cause severe liver injury and dysfunctions of liver synthesis, detoxification, metabolism, and biotransformation. Intestinal dysbacteriosis is an important factor for the acceleration of liver failure. Therefore, it is important to prevent or delay the progression of liver failure by improving intestinal dysbacteriosis and liver function.

Fusidic acid is the only fusidane-type antibiotic that has been clinically used. However, biosynthesis of this important molecule in fungi is poorly understood. We have recently elucidated the biosynthesis of fusidane-type antibiotic helvolic acid, which provides us with clues to identify a possible gene cluster for fusidic acid ( cluster). This gene cluster consists of eight genes, among which six are conserved in the helvolic acid gene cluster except and . Introduction of the two genes into the NSAR1 expressing the conserved six genes led to the production of fusidic acid. A stepwise introduction of and revealed that the two genes worked independently without a strict reaction order. Notably, we identified two short-chain dehydrogenase/reductase genes and in the cluster, which showed converse stereoselectivity in 3-ketoreduction. This is the first report on the biosynthesis and heterologous expression of fusidic acid.

Objectives To evaluate the effectiveness and safety of peramivir trihydrate in patients with influenza.Methods This was a randomized,double-blind,double-dummy,placebo and positive control,multicenter clinical trial,comparing peramivir trihydrate with oseltamivir and placebo.The inclusive criteria were 15-70 years old,onset within 48 h,positive rapid influenza antigen test,and febrile(＞38℃) accompanied with at least two associated symptoms.The severe cases complicated with chronic pulmonary and cardiac diseases,malignancies,organ transplantation,hemodialysis,uncontrolled diabetes,immunocompromised status,pregnancy and coexistence of bacterium infections were excluded.All patients were randomized 2:2:1 to receive peramivir,oseltamivir and placebo respectively.The primary endpoint was the disease duration,the secondary endpoints included time to normal axillary temperature and normal living activities,viral response,and adverse effects.Results Following informed consent,133 patients were included in this study.Four patients were exclude due to missing medical records,not fitting inclusion or exclusion criteria and poor compliance.A total of 129 patients were finally analyzed,including 49 cases,54 cases and 26 cases in peramivir group,oseltamivir group and placebo group.The median disease duration were 96 (76,120)hours,105(90,124) hours,and 124 (104,172)hours in three groups respectively(P＞0.05).The time to normal axillary temperature,normal living activities and viral response were not significantly different in three groups(P＞0.05).Conclusion The value of antiviral therapy in patients with mild influenza needs to be further determined.

Objective To explore the impact of WeChat-assisted follow-up on self-administer medication capability of stroke survivors.Methods Seventy patients were recruited from a tertiary hospital and randomly divided into intervention group (n=35) and control group (n=35).Patients in intervention group were given WeChat-assisted follow-up including health education program and behavior guidance,and patients in control group received regular discharge care.The effects of WeChat-assisted follow-up and regular care on self-administer medication ability,cognitive and behavior level were assessed.Results After three months' follow-up,the scores of self-administer medication capability (38 (32,42)),experience (25 (20,28) and the integral level (87 (71,92)) in intervention group were significantly higher than those in control group (capability 25(16,38),experience 21 (8.75,27),total score 68 (38,87)) (Z=-2.511,-2.033,-2.209,P＜0.05).The self-administer medication experience,cognitive,capability and total scores increased significantly in intervention group after intervention(Z=-4.525,-4.610,-3.806,-4.718,all P＜ 0.01),while only the cognitive level increased slightly in control group (18 (10,24) vs 13 (11,18),Z =-1.794,P=0.073).Conclusions Follow-up intervention based on WeChat platform can improve the stroke patients' self-administration medication capability,however,the long-term effects on cognitive level and further reform need to be strengthened.