Objective:To investigate the prognostic differences between endobronchial and invasive bronchial characteristics in patients with non-small cell lung cancer (NSCLC) undergoing sleeve lobectomy.Methods:This is a retrospective cohort study. A retrospective analysis was conducted on clinical data of 200 NSCLC patients who underwent sleeve lobectomy at the Department of Thoracic Surgery, Shanghai Pulmonary Hospital between January 2014 and December 2016. There were 181 males and 19 females, aged (61.3±8.1) years (range: 30 to 81 years). Based on imaging data, they were divided into the endobronchial group ( n=71) and the invasive bronchial group ( n=129). Clinical data and prognosis were collected and analyzed. Sex, age, hypertension, diabetes, smoking history, pathology type, tumor size, staging, surgical method, surgical site, and sleeve technique were included as covariates. Propensity score matching was performed with a 1∶1 ratio between the endobronchial and invasive bronchial groups using the nearest-neighbor matching method. The Kaplan-Meier method was used to plot survival curves, and the Log-rank test was applied to compare differences between groups. Independent sample t tests, Mann-Whitney U tests, χ2 tests, or Fisher′s exact tests was used for group comparisons. Results:After propensity score matching, 71 cases from each group (endobronchial and invasive bronchial) were included, with no significant differences in baseline characteristics between the two groups (all P>0.05). Endobronchial group showed significantly better overall survival (OS) and disease-free survival (DFS) compared to invasive bronchial group(Log-rank test: P=0.014,0.027). Further subgroup analysis revealed that in the minimally invasive surgery subgroup, the DFS of the endobronchial group was significantly better than that of the invasive bronchial group (Log-rank test: P=0.002), while in the open thoracotomy subgroup, there was no significant difference in DFS between the two groups (Log-rank test: P=0.290). In the right upper lobe sleeve resection subgroup, the endobronchial group had significantly better DFS than the invasive bronchial group (Log-rank test: P=0.039). For patients in the stage Ⅱ to Ⅲ subgroup, the endobronchial group had significantly better DFS than the invasive bronchial group (Log-rank test: P=0.005). Conclusion:In sleeve lobectomy, patients with endobronchial NSCLC have better OS and DFS compared to those with invasive bronchial type, particularly in patients undergoing minimally invasive surgery, right upper lobe sleeve lobectomy, and stage Ⅱ to Ⅲ patients.

Objective:To investigate the prognostic differences between endobronchial and invasive bronchial characteristics in patients with non-small cell lung cancer (NSCLC) undergoing sleeve lobectomy.Methods:This is a retrospective cohort study. A retrospective analysis was conducted on clinical data of 200 NSCLC patients who underwent sleeve lobectomy at the Department of Thoracic Surgery, Shanghai Pulmonary Hospital between January 2014 and December 2016. There were 181 males and 19 females, aged (61.3±8.1) years (range: 30 to 81 years). Based on imaging data, they were divided into the endobronchial group ( n=71) and the invasive bronchial group ( n=129). Clinical data and prognosis were collected and analyzed. Sex, age, hypertension, diabetes, smoking history, pathology type, tumor size, staging, surgical method, surgical site, and sleeve technique were included as covariates. Propensity score matching was performed with a 1∶1 ratio between the endobronchial and invasive bronchial groups using the nearest-neighbor matching method. The Kaplan-Meier method was used to plot survival curves, and the Log-rank test was applied to compare differences between groups. Independent sample t tests, Mann-Whitney U tests, χ2 tests, or Fisher′s exact tests was used for group comparisons. Results:After propensity score matching, 71 cases from each group (endobronchial and invasive bronchial) were included, with no significant differences in baseline characteristics between the two groups (all P>0.05). Endobronchial group showed significantly better overall survival (OS) and disease-free survival (DFS) compared to invasive bronchial group(Log-rank test: P=0.014,0.027). Further subgroup analysis revealed that in the minimally invasive surgery subgroup, the DFS of the endobronchial group was significantly better than that of the invasive bronchial group (Log-rank test: P=0.002), while in the open thoracotomy subgroup, there was no significant difference in DFS between the two groups (Log-rank test: P=0.290). In the right upper lobe sleeve resection subgroup, the endobronchial group had significantly better DFS than the invasive bronchial group (Log-rank test: P=0.039). For patients in the stage Ⅱ to Ⅲ subgroup, the endobronchial group had significantly better DFS than the invasive bronchial group (Log-rank test: P=0.005). Conclusion:In sleeve lobectomy, patients with endobronchial NSCLC have better OS and DFS compared to those with invasive bronchial type, particularly in patients undergoing minimally invasive surgery, right upper lobe sleeve lobectomy, and stage Ⅱ to Ⅲ patients.

Objective: To investigate the daily learning time status of elementary school students and understand the implementation of Health Requirements of Daily Learning Time for Secondary and Elementary School Students (GB/T 17223-2012) in schools, so as to provide a reference for strengthening and improving school health and health education in the new era. Methods: A stratified cluster random sampling method was used to select 7 776 primary school students in Shandong Province, and a survey questionnaire was designed based on the Health Requirements for Dayily Learning Time for Secondary and Elementary School Students(GB/T 17223-2012) standard to investigate their daily learning arrangements, sleep and physical activities, and breaks between classes. Comparison of intergroup differences were used by Chi square test and Kruskal-Wallis H test. Results: About 55.88 % of primary school students for daily learning time met the standard. There was a statistically significant difference in the daily learning time achievement rate among primary school students in three grades for first and second grade, third and fourth grade and fifth and sixth grade ( Z=1 629.47, P <0.01), and the fifth and sixth grade had the highest proportion of achieving the standard (85.92%). Specifically, the proportions of students whose class hours, class numbers and morning reading time meeting the standards were 30.07%, 10.20% and 42.19%, respectively. The sleep deficiency rate of primary school studnets was 58.69%, and the physical activity deficiency rate was 65.78%; and there was a statistically significant difference in the rate of insufficient sleep time and physical activity time among primary school students of different grades ( χ 2=56.39, 95.95, P <0.01), with sixth grade students showing the highest rates for both sleep and physical activity deficiencies (64.35%, 73.37%). Additionally, 49.78% of students had recess time below the standard requirements. Conclusion The health status of daily learning time among primary school students in Shandong Province is poor, with insufficient implementation of school standards, and the implementation of standards needs to be further strengthened.

OBJECTIVE: To retrospectively analyze the clinical phenotypes and genetic variants in two Chinese pedigrees affected with Hereditary hypofibrinemia (IFD) and explore their molecular pathogenesis. METHODS: Two probands and their pedigree members were admitted to the First Affiliated Hospital of Wenzhou Medical University on March 30, 2021 and May 27, 2021, respectively. Clinical phenotypes of the probands were collected, and blood clotting indexes of the probands and their pedigree members were determined. Variants of the FGA, FGB and FGG genes were analyzed by Sanger sequencing, and candidate variants were verified by sequence comparison. Bioinformatic software was used to analyze the conservation of the amino acids and pathogenicity of the proteins. Alteration in protein structure and intermolecular force before and after the variant was analyzed by simulating the protein model. RESULTS: Proband 1, a 18-year-old male, had significantly low plasma fibrinogen activity (Fg:C) and plasma fibrinogen antigen (Fg:Ag), respectively at 0.80 g/L and 1.00 g/L. Proband 2, a 43-year-old male, had slightly low Fg:C and Fg:Ag at 1.35 g/L and 1.30 g/L, respectively. The Fg:C and Fg:Ag of proband 1's father, proband 2's father and son were also below the normal level. Genetic testing showed that proband 1 had harbored a heterozygous missense variant of c.688T>G (p.Phe230Val) in exon 7 of the FGG gene, which was inherited from his father. Proband 2, his father and son all had harbored a heterozygous variant of c.2516A>C (p.Asn839Thr) in exon 6 of the FGA gene. Homology analysis showed that the Phe230 and Asn839 residues were highly conserved among homologous species. Bioinformatic analysis predicted that both p.Phe230Val and p.Asn839Thr were pathogenic variants. CONCLUSION Analysis of protein simulation model showed that the p.Asn839Thr variant has changed the hydrogen bo`nd between the amino acids, thus affecting the stability of the protein structure. The heterozygous missense variants of p.Phe230Val and p.Asn839Thr probably underlay the IFD in the two pedigrees.
Humans ; Male ; Amino Acids ; East Asian People ; Exons ; Pedigree ; Retrospective Studies ; Afibrinogenemia/genetics* ; Mutation, Missense ; Fibrinogen/genetics*

Malignant pleural mesothelioma(MPM) is a kind of rare and aggressive malignant neoplasm. Surgery plays one of the most important roles in the treatment of MPM. However, due to the high morbidity and mortality reported, the survival benefit and indication of surgery are still controversial. This article will review the surgical indications, discuss and compare the roles of extrapleural pneumonectomy(EPP) and pleurectomy / decortication(P/D) which aim to achieve macroscopic complete resection(MCR) in the treatment of MPM. Finally, we summarized the progress of other treatment methods including targeted therapy and immunotherapy.

Objective:To investigate the molecular pathogenesis of a newly discovered gene mutation in a family with hereditary coagulation factor Ⅺ(FⅪ) deficiency.Methods:The proband was admitted to the First Affiliated Hospital of Wenzhou Medical University in September 2021 due to "calculus of intrahepatic duct". The patient had no symptoms of spontaneous bleeding.The clinical data and blood samples of the proband and her family members (10 persons in 3 generations) were collected.The activated partial thromboplastin time (APTT) and FⅪ activity (FⅪ:C) were performed by the one-stage clotting assay. FⅪ antigen (FⅪ:Ag) were detected by enzyme linked immunosorbent assay (ELISA). Genomic DNA extracted from peripheral blood cells of subjects was used as template to analyze F11 gene mutation by DNA direct sequencing. Bioinformatics software was used to analyze the effects of mutations on protein structure and function. Wild-type and mutant FⅪ protein expression vectors were constructed and transient transfected into HEK293T cells. The total RNA was extracted from positive transfected cells and then reversely transcribed into cDNA. The mRNA expression level of F11 gene in transfected cells was detected by real-time fluorescence quantitative PCR (qRT-PCR). The content of FⅪ:Ag and the expression of FⅪ protein in transfected cell lysates and culture supernatant were detected by ELISA and western blot.Results:The APTT of the proband was significantly prolonged to 107.9s (reference range 29.0-43.0s), while FⅪ:C and FⅪ:Ag were significantly decreased to 2% (reference range 84%-122%) and 5% (reference range 76%-127%), respectively. Gene sequencing analysis indicated that the proband had c.536C>T (p.Thr161Met) heterozygous missense mutation and c.1556G>A (p.Trp501Ter) heterozygous nonsense mutation in exon 6 and 13 of the F11 gene, respectively. Bioinformatics analysis showed that the amino acids at site 161 of FⅪ protein were threonine (Thr) in the matrix composed of five different species, indicating that Thr161 site was highly conserved among homologous genes in different species. p.Thr161Met heterozygous mutation affected the stability of local intermolecular structure of FⅪ protein. In vitro expression experiments of p.Thr161Met mutation showed that FⅪ protein had a normal synthesis in the cells but secretion dysfunction.Conclusions:c.536C>T (p.Thr161Met) heterozygous missense mutation and c.1556G>A (p.Trp501Ter) heterozygous nonsense mutation were mainly responsible for the decrease of FⅪ in this family. p.Thr161Met mutation was first reported in the world and did not affect the normal synthesis of FⅪ protein, but caused secretion dysfunction.

Objective:To explore the sex-based heterogeneity in demographic and pathological trends of lung cancer during the past 30 years.Methods:Patients with primary lung cancer who received surgical treatment in the Department of thoracic surgery, Shanghai Pulmonary Hospital Tongji University from 1989 to 2018 were retrospectively analyzed. The differences between male and female patients in age, smoking history, pathological stage and type were compared. Mann- Kendall trend test was performed for trend analysis. Results:A total of 58 433 patients were included in this study, encompassing 30 729(52.6%) men and 27 , 704(47.4%) women. Compared with male patients, female patients were younger(56.0 years old vs. 59.7 years old), and had a higher proportion of non-smokers(98.3% vs. 52.3%), stage Ⅰ lung cancers(60.6% vs. 49.3%), and adenocarcinoma(93.7% vs. 56.1%, all P-values <0.001). Trend analyses revealed that the proportion of female patients increased year by year, and surpassed males in 2015, with the current ratio of male to female being 1∶1.5. After 2013, the age of onset in females was getting younger, and the average age decreased from 58.7 years old to 54.7 years old( P=0.02). The decrease in the proportion of smoking patients was mainly reflected by male patients(from 68.5% to 31.1%, P<0.01). Stage Ⅰ lung cancers in male and females outnumbered advanced stage in 2012 and 2010, respectively, with a much higher proportion in female patients. Among male patients, adenocarcinoma has replaced squamous cell carcinoma as the most common pathological type since 2012, while in female patients adenocarcinoma remained the most common pathological type of lung cancer, and its proportion continued to increase reaching over 98%. Conclusion:A dramatic change in gender distribution was noticed during the past 30 years. Female patients became the primary population in surgically-treated lung cancers, with a trend of getting younger. The proportion of smokers and squamous cell carcinoma decreased significantly in male patients, and adenocarcinoma has become the most common pathological type of lung cancer. The proportion of stage Ⅰ lung cancers was on a dramatic rise, with the popularization of CT screening for lung cancer.

Objective:To analyze the phenotype and genotype of two propositi with inherited hypodysfibrinogenaemia caused by compound heterozygous mutations, and investigate the molecular mechanism.Metheds:Two propositi and their family members(7 person in 3 generations and 10 person in 3 generations,respectively) were investigated. The activity of plasma fibrinogen (Fg:C) and thrombin time (TT) were analyzed by coagulation method, the antigen of plasma fibrinogen (Fg:Ag) was detected by immunoturbidimetry. All of the exons and flanking sequences of FGA,FGB,FGG of two propositi were amplified by PCR, followed by direct sequencing. The ClustalX-2, 1-win software was used to analyze the conservatism of mutated gene locus. PROVEAN and Mutation Taster were applied to analyze the pathogenicity of mutated amino acid. The changes of the protein spatial structure and intermolecular interaction were analyzed by Pymol.Results:Fg:C and Fg:Ag of proposita A and B were both significantly decreased (0.74 and 0.78 g/L, 0.96 and 0.94 g/L, respectively). Gene analysis revealed that proposita A and B both carried a heterozygous mutation c.2185G>A(p.AαGlu710Lys) in exon 6 of FGA. Furthermore, proposita A also carried a heterozygous mutation c.701G>T(p.γTrp208Leu) in exon 7 of FGG, and proposita B carried a heterozygous mutation c.1015A>C(p.γSer313Arg) in exon 8 of FGG. Phylogenetic analysis suggested that p.AαGlu710,p.γTrp208 and p.γSer313 were highly conserved among homologous species. All variants were predicted to be deleterious by two online bioinformatic softwares. The protein model analysis indicated that protein spatial structure and intermolecular hydrogen bonds were changed by these variants, which destroyed the stability of Fg.Conclusion:The compound heterozygous mutations of p.AαGlu710Lys and p.γTrp208Leu,p.AαGlu710Lys and p.γSer313Arg might account for the hypodysfibrinogenemia in two propositi.

Objectives:To examine the influence of the proportion of pathological subtypes on the prognosis of stage ⅠA lung adenocarcinoma cases, and to explore the association between the presence/absence of solid or micropapillary (S/M) components and survival outcome.Methods:Totally 321 patients with stage ⅠA lung adenocarcinoma who received complete surgical resection at Department of Thoracic Surgery, Tongji University Affiliated Shanghai Pulmonary Hospital from January 2011 to December 2013 were retrospectively analyzed. There were 130 males and 191 females, aging 59(11) years ( M(IQR)) (range: 55 to 66 years). The diagnostic value of the proportion of each pathological growth subtype on relapse-free survival (RFS) and overall survival (OS) were analyzed by using receiver operator characteristic curve. Patients were firstly divided into two groups according to the presence or absence of S/M components. And patients without S/M components were farther divided into two groups according to predominant growth pattern. There were three groups in total: with S/M components (group S/M +), without S/M components and lepidic growth pattern predominant (group S/M -LPA), without S/M components and papillary or acinar growth pattern predominant (group S/M -P/A). Kaplan-Meier method were used to draw the survival curves of the three groups, and Log-rank test were used to compare RFS and OS among the three groups. Cox proportional risk model was used to verify whether the presence of S/M components was a prognostic factor on RFS. Results:The proportion of S/M components had no diagnostic value for recurrence (solid: area under curve (AUC)=0.588, P=0.095; micropapillary: AUC=0.566, P=0.106) and death (AUC=0.589, P=0.104; AUC=0.607, P=0.056). The 5-year RFS rate of group S/M -LPA, S/M -P/A and S/M + were 92.4%, 82.3% and 77.3%, respectively (all P<0.05), while the 5-year OS rate were 97.4%, 94.5% and 83.2%, respectively (all P<0.05). Multivariable analysis showed that the 3 groups were independent predictors of recurrence (S/M -P/A vs. S/M - LPA: HR=2.691, 95% CI: 1.249 to 5.799, P=0.011; S/M +vs. S/M -LPA, HR=6.763, 95% CI: 3.050 to 14.996, P<0.01). Conclusions:The proportion of S/M components in stage ⅠA lung adenocarcinoma with complete resection cases did not affect survival outcome. New grouping method based on the presence or absence of S/M components were significantly associated with patient survival outcomes: S/M + patients had the worst prognosis and S/M -LPA patients had the best prognosis.

Objectives:To examine the influence of the proportion of pathological subtypes on the prognosis of stage ⅠA lung adenocarcinoma cases, and to explore the association between the presence/absence of solid or micropapillary (S/M) components and survival outcome.Methods:Totally 321 patients with stage ⅠA lung adenocarcinoma who received complete surgical resection at Department of Thoracic Surgery, Tongji University Affiliated Shanghai Pulmonary Hospital from January 2011 to December 2013 were retrospectively analyzed. There were 130 males and 191 females, aging 59(11) years ( M(IQR)) (range: 55 to 66 years). The diagnostic value of the proportion of each pathological growth subtype on relapse-free survival (RFS) and overall survival (OS) were analyzed by using receiver operator characteristic curve. Patients were firstly divided into two groups according to the presence or absence of S/M components. And patients without S/M components were farther divided into two groups according to predominant growth pattern. There were three groups in total: with S/M components (group S/M +), without S/M components and lepidic growth pattern predominant (group S/M -LPA), without S/M components and papillary or acinar growth pattern predominant (group S/M -P/A). Kaplan-Meier method were used to draw the survival curves of the three groups, and Log-rank test were used to compare RFS and OS among the three groups. Cox proportional risk model was used to verify whether the presence of S/M components was a prognostic factor on RFS. Results:The proportion of S/M components had no diagnostic value for recurrence (solid: area under curve (AUC)=0.588, P=0.095; micropapillary: AUC=0.566, P=0.106) and death (AUC=0.589, P=0.104; AUC=0.607, P=0.056). The 5-year RFS rate of group S/M -LPA, S/M -P/A and S/M + were 92.4%, 82.3% and 77.3%, respectively (all P<0.05), while the 5-year OS rate were 97.4%, 94.5% and 83.2%, respectively (all P<0.05). Multivariable analysis showed that the 3 groups were independent predictors of recurrence (S/M -P/A vs. S/M - LPA: HR=2.691, 95% CI: 1.249 to 5.799, P=0.011; S/M +vs. S/M -LPA, HR=6.763, 95% CI: 3.050 to 14.996, P<0.01). Conclusions:The proportion of S/M components in stage ⅠA lung adenocarcinoma with complete resection cases did not affect survival outcome. New grouping method based on the presence or absence of S/M components were significantly associated with patient survival outcomes: S/M + patients had the worst prognosis and S/M -LPA patients had the best prognosis.