ObjectiveTo evaluate the validity of four screening questionnaires on chronic obstructive pulmonary disease (COPD) among community residents in Shanghai, and to provide a scientific basis for selecting suitable screening questionnaires and plans for the community use. MethodsA multi-stage random sampling method was used to select community residents aged ≥40 for COPD questionnaire screening and spirometry. The screening questionnaires included the COPD Population Screener Questionnaire (COPD-PS), the COPD Screening Questionnaire (COPD-SQ), the COPD Diagnosis Questionnaire (CDQ), and the Lung Function Questionnaire (LFQ). The diagnostic gold standard for COPD was defined as a ratio of post-bronchodilator forced expiratory volume in one second to forced vital capacity (FEV1/FVC) less than 0.7. The receiver operating characteristic (ROC) curve was used to assess the validity of each questionnaire, and DeLong’s test was used to compare the area under the curve (AUC) of different questionnaires. ResultsAmong the 1 122 residents screened, 99 (8.8%) were diagnosed with COPD based on the gold standard criteria. The AUC values for the four questionnaires ranged from 0.643 to 0.682, with no statistically significant differences in screening accuracy among them (P>0.05). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for each questionnaire at recommended cut-off points were as follows: COPD-PS (sensitivity: 33.3%, specificity: 84.9%, PPV: 17.6%, NPV: 92.9%), COPD-SQ (34.3%, 85.8%, 19.0%, 93.1%), CDQ (73.7%, 42.4%, 11.0%, 94.4%), and LFQ (48.5%, 74.8%, 15.7%, 93.8%). Optimal cut-off values for this population differed from the recommended values. When selecting the optimal cut-off value, the sensitivity of COPD-PS (58.6%), COPD-SQ (55.6%), and LFQ (64.7%) increased, while the specificity of CDQ (75.9%) increased. The AUC of sequential lung function testing for all four screening questionnaires increased to 0.7 or above. The optimal cut-off values for the four questionnaires in this population differed from the recommended values. When applying the optimal cut-off values, the sensitivity of three questionnaires increased: COPD-PS (58.6%), COPD-SQ (55.6%), and LFQ (64.7%), while the specificity of CDQ rose to 75.9%. The AUC of each questionnaire increased to above 0.7 when followed by sequential lung function testing. ConclusionThe COPD-PS, COPD-SQ, CDQ, and LFQ have limited value for COPD screening among Shanghai community residents, indicating that further refinement of these tools is needed.

Background Cadmium (Cd) is a ubiquitous and toxic heavy metal that can accumulate in human body. Previous studies have shown that Cd exposure can induce neurotoxicity, but the underlying mechanism remains unclear. Objective To investigate the metabolic impacts of multiple doses of Cd on mouse neural stem cells (NSCs), and to explore the potential mechanism and biomarkers of its neurotoxicity. Methods The NSCs were obtained from the subventricular zone (SVZ) of 1-day-old neonatal C57BL/6 mice. The passage 3 (P3) NSCs were exposed to CdCl₂ at designed doses (0, 0.5, 1.0, and 1.5 μmol·L⁻¹). The cells were treated with seven replicates, of which one plate was for cell counting. After 24 h of exposure, the intracellular and extracellular metabolites were extracted respectively and then detected by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS). The orthogonal partial least-squares discriminant analysis (OPLS-DA) was applied to visualize the alterations of metabolomic profiles and to identify the differential metabolites (DMs) based on their variable importance for the projection (VIP) value >1 and P<0.05. The metabolite set enrichment analysis (MSEA) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed to recognize the significantly altered metabolite sets and pathways. The dose-response relationships were established and the potential biomarkers of Cd exposure were identified by 10% up-regulated or 10% down-regulated effective concentration (EC) of target metabolites. Results A total of 1201 metabolites were identified in the intracellular metabolomic samples and 1207 for the extracellular metabolomic samples. The intracellular and extracellular metabolome of Cd-treated NSCs were distinct from that of the control group, and the difference grew more distant as the Cd dosage increased. At 0.5, 1.0, and 1.5 μmol·L⁻¹ dosage of Cd, 87, 83, and 185 intracellular DMs and 161, 176, and 166 extracellular DMs were identified, respectively. Within the significantly changed metabolites among the four groups, 176 intracellular DMs and 167 extracellular DMs were identified. Both intracellular and extracellular DMs were enriched in multiple lipid metabolite sets. Intracellular DMs were mainly enriched in taurine and hypotaurine metabolism, glycerophospholipid metabolism, and glycerolipid metabolism pathways. Extracellular DMs changed by Cd were mainly enriched in glycerophospholipid metabolism, steroid hormone biosynthesis, and cysteine and methionine metabolism pathways. Among intracellular DMs, 125 metabolites were fitted with dose-response relationships, of which 108 metabolites showed linear changes with the increase of Cd dosage. And 134 metabolites were fitted with dose-response relationships among extracellular DMs, of which 86 metabolites showed linear changes. The intracellular DMs with low EC values were hypotaurine, ethanolamine, phosphatidylethanolamine, and galactose, while the extracellular DMs with low EC values were acetylcholine and 1,5-anhydrosorbitol. Conclusion Cd treatment can significantly alter the intracellular and extracellular metabolome of mouse NSCs in a dose-dependent manner. The neurotoxicity of Cd may be related to glycerophospholipid metabolism. Acetylcholine, ethanolamine, and phosphatidylethanolamine involved in glycerophospholipid metabolism pathway might be potential biomarkers of Cd-induced neurotoxicity.

Objective:To explore the effect of early education intervention combined with touching therapy intervention on infants' intelligence and motor function.Methods:Convenient sampling was used to 300 infants admitted from January 2018 to May 2019 in Zhumadian Central Hospital of Henan Province, According to the intervention method, infants were divided into observation group and control group, each with 150 cases. Control group carried out routine care, while observation group was treated with early education intervention combined with touching therapy. The Mental Development Index (MDI) , Psychomotor Development Index (PDI) , and Gesell Developmental Schedules were compared between the two groups at 3 and 6 months after intervention.Results:The MDI score, PDI score, social competence score, language score, fine motor score, large motor score, and adaptability score of observation group 3 and 6 months after intervention were all higher than those of control group, and the differences were statistically significant ( P<0.05) . Conclusions:Early education intervention combined with touching therapy for infants has a significant effect, which can promote growth and intellectual development.

Polycystic ovary syndrome (PCOS) is a common clinical reproductive endocrine disease, and its incidence is increasing year by year. The occurrence and development of PCOS are related to many factors, among which genetic factors may play a key role. Circular RNA (circRNA) is a new type of universal and diverse endogenous non-coding RNA. The 3' and 5' ends of circRNA can be covalently linked together, causing it to form a circular structure. In addition, circRNA can resist degradation and maintain a high degree of stability under the mediation of RNA exonuclease. CircRNA also has cell specificity, tissue specificity and timing specificity. Compared with microRNA, circRNA is a more ideal disease biomarker, providing a new target for subsequent treatment of various diseases. An increasing number of studies have shown that circRNA is related to the pathophysiology of PCOS, and plays a role in endocrine hormone secretion, follicle development, granulosa cell proliferation and apoptosis, and genetic tendency, and participates in each link of the occurrence and development of PCOS. This article reviews the research reports on the relationship between circRNA and PCOS in recent years, hoping to provide new ideas for the diagnosis and treatment of PCOS.

Polycystic ovary syndrome (PCOS) is a common clinical reproductive endocrine disease, and its incidence is increasing year by year. The occurrence and development of PCOS are related to many factors, among which genetic factors may play a key role. Circular RNA (circRNA) is a new type of universal and diverse endogenous non-coding RNA. The 3' and 5' ends of circRNA can be covalently linked together, causing it to form a circular structure. In addition, circRNA can resist degradation and maintain a high degree of stability under the mediation of RNA exonuclease. CircRNA also has cell specificity, tissue specificity and timing specificity. Compared with microRNA, circRNA is a more ideal disease biomarker, providing a new target for subsequent treatment of various diseases. An increasing number of studies have shown that circRNA is related to the pathophysiology of PCOS, and plays a role in endocrine hormone secretion, follicle development, granulosa cell proliferation and apoptosis, and genetic tendency, and participates in each link of the occurrence and development of PCOS. This article reviews the research reports on the relationship between circRNA and PCOS in recent years, hoping to provide new ideas for the diagnosis and treatment of PCOS.

Objective:To investigate the effect of genetic polymorphisms of TPMT*2 rs1800462, TPMT*3B rs1800460, TPMT*3C rs1142345, and NUDT15 rs116855232 on the tolerance of 6-mercaptopurine (6-MP) therapy in adult acute lymphoblastic leukemia (ALL) .Methods:A total of 216 adult patients who were diagnosed with ALL and treated with cyclophosphamide, cytarabine, and 6-MP [complementary and alternative medicine (CAM) regimen] from September 2015 to December 2019 were included. Polymorphisms were detected by TaqMan SNP Genotyping Assay. Combined with clinical data, the influence of genetic polymorphism on the tolerance of 6-MP in the treatment of ALL was analyzed.Results:Among the 216 patients, 185 (85.65%) patients had B-ALL and 31 (14.35%) patients had T-ALL. 216 (100%) patients had CC genotype for both TPMT*2 rs1800462 and TPMT*3B rs1800460. The number of TT and TC genotypes for TPMT*3C rs1142345 was 209 (96.76%) and 7 (3.24%) , respectively. The allele frequency was 1.62% for TPMT*3C rs1142345. The number of CC, CT, and TT genotypes for NUDT15 rs116855232 was 166 (76.85%) , 48 (22.22%) , and 2 (0.93%) , respectively. The allele frequency was 12.04% for NUDT15 rs116855232. The TPMT*3C rs1142345 mutant group (TC+CC genotype) had less transfusion volume of packed red blood cell than the wild group (CC genotype) ( P=0.036) , and the mutant group (TC+CC genotype) had a higher risk to develop hepatotoxicity (increased aspartate aminotransferase) than the wild group (CC genotype) ( OR=9.559, 95% CI 1.135-80.475, P=0.038) . The durations of white blood cells (WBC) <1×10 9/L and absolute neutrophil count (ANC) <0.5×10 9/L in the NUDT15 rs116855232 mutation group (CT+TT genotype) were longer than that in the wild group (CC genotype) ( P=0.005, P=0.007) , and the transfusion volume of apheresis-derived platelets in the mutant group (CT+TT type) was greater than that in the wild group (CC genotype) ( P=0.014) . Conclusion:Genetic polymorphism of TMPT and NUDT15 has an effect on the tolerance of 6-MP in the treatment of adult ALL. Detecting genotypes of patients with ALL before treatment helps to optimize the dosage of 6-MP, which may help shorten the bone marrow suppression duration and reduce blood transfusion volume.

Objective: To investigate the spectrum of gene mutations in adult patients with B-acute lymphoblastic leukemia (B-ALL), and to analyze the influences of different gene mutations on prognosis. Methods: DNA samples from 113 adult B-ALL patients who administered from June 2009 to September 2015 were collected. Target-specific next generation sequencing (NGS) approach was used to analyze the mutations of 112 genes (focused on the specific mutational hotspots) and all putative mutations were compared against multiple databases to calculate the frequency spectrum. The impact of gene mutation on the patients’ overall survival (OS) and recurrence free survival (RFS) was analyzed by the putative mutations through Kaplan-Meier, and Cox regression methods. Results: Of the 113 patients, 103 (92.0%) harbored at least one mutation and 29 (25.6%) harbored more than 3 genes mutation. The five most frequently mutated genes in B-ALL are SF1, FAT1, MPL, PTPN11 and NRAS. Gene mutations are different between Ph⁺ B-ALL and Ph^- B-ALL patients. Ph^- B-ALL patients with JAK-STAT signal pathway related gene mutation, such as JAK1/JAK2 mutation showed a poor prognosis compared to the patients without mutation (OS: P=0.011, 0.001; RFS: P=0.014,<0.001). Patients with PTPN11 mutation showed better survival than those without mutation, but the difference was not statistically significant (P value > 0.05). Besides, in Ph⁺ B-ALL patients whose epigenetic modifications related signaling pathway genes were affected, they had a worse prognosis (OS: P=0.038; RFS: P=0.047). Conclusion Gene mutations are common in adult ALL patients, a variety of signaling pathways are involved. The frequency and spectrum are varied in different types of B-ALL. JAK family gene mutation usually indicates poor prognosis. The co-occurrence of somatic mutations in adult B-ALL patients indicate the genetic complex and instability of adult B-ALL patients.

Objective: To investigate the feasibility of multiplex real-time RT-PCR with fluorescent probes in early screening of Ph-like acute lymphoblastic leukemia (ALL) and analyze the clinical feature and prognos. Method: A total of 118 adult B-ALL patients diagnosed between October 2010 and March 2016 were enrolled in this study. Multiplex RT-PCR was used to detect the Ph-like ALL related fusion gene and CRLF2 expression in 58 BCR-ABL and MLL rearrangement negative patients. The clinical features, treatment response and prognosis were analyzed in Ph-like fusion gene positive and/or CRLF2 over-expression patients. Result: Among 58 patients, 9 patients (9/58, 15.5%) showed Ph-like ALL related fusion genes positive and 10 patients (10/58, 17.2%) showed CRLF2 over-expression. There were statistical differences in age, WBC count, immunophenotypes, cytogenetics and risk stratification among Ph-like fusion gene positive or CRLF2 over-expression patients, Ph⁺ patients, MLL⁺ patients and B-other patients. The 2-year overall survival rates were 65%, 47%, 64% and 74% respectively among these four groups (P=0.043) . The 2-year relapse free survival rates were 51%, 39%, 62% and 70% respectively among these four groups (P=0.010) . Conclusion Routine screening of Ph-like ALL by multiplex RTPCR is feasible.

Objective To examine the effect of positive and negative evaluative conditioning (EC) on neutral faces.Methods The experiment consisted of three phases:baseline phase,conditioning phase,and re-evaluative phase,in which 41 college students participated,watching sequences of neutral faces (CS) pairing to either a positive stimulus (USpos) or a negative stimulus (USneg).Their emotional experiences (valence and arousal) and physiological reactivity (eyeblink startle reflex and skin conductance) were recor ded.Results (1) In the re-evaluative phase,CSpos was rated significantly more positive than CSneg and CSneut,while CSneg was rated significantly more negative than CSneut (CSpos (5.05± 1.24),CSneg (3.73± 1.48),CSneut (4.46± 1.04),P＜0.05).(2)In the re-evaluative phase,the mean startle eyeblink response magnitude(T score) to CSpos was significantly smaller than the responses elicited by CSneg and CSneut (CSpos (45.04±5.56),CSneg (51.44±9.30),CSneut (54.52± 10.60),P＜0.01).Conclusion The findings suggest that neutral faces can acquire valences and approach motivation through EC.

BACKGROUND:In recent years, based on high-throughput molecular imaging, integration of genomics, proteomics and computer aided design and the application of correlative “technical chains” have achieved great achievements in the research of breast cancer, lung cancer, gastric cancer, colon cancer, ovarian cancer and melanin tumor. However, there are few researches on oral squamous cel carcinoma. OBJECTIVE:To detect the gene expression profile of the oral squamous cel carcinoma tissue and normal paracarcinoma tissue using DNA chip-based gene expression profile. METHODS:Two samples of oral squamous cel carcinoma tissue and normal paracarcinoma tissue of patients who received treatment at Stomatological Hospital of Guangdong Province of China in 2013 were included in this study. The gene expression profiles of oral squamous cel carcinoma and normal paracarcinoma tissue were determined by the Roche NimbleGen gene expression microarrays. RESULTS AND CONCLUSION: According to screening criteria of differential genes, 7 872 out of 32 448 detected genes were differentialy expressed genes of oral squamous cel carcinoma, which accounts for 24% of the total number of the screening genes. 3 800 genes were up-regulated, and 4 072 were down-regulated. The results confirm that through detection with the help of gene expression profile clip, 7 872 differentialy expressed genes were obtained through DNA chip-based gene expression profiles according to the screening criteria. Thus it can be concluded that the occurrence and development of the tumors are not a result of single or several genes. Previous experiments based on a single or several genes have great limitations. These findings also suggest that the occurrence of tumor is a result of mutual regulatory effects of many genes forming a network, moreover, the interactions of the network is quite complicated.