Objective: To understand prevalence and trend of drinking behavior among middle school students in Quzhou during 2012 to 2022, and to provide a basis for formulating scientific and effective intervention measures for adolescent drinking. Methods: By using stratified cluster sampling method, a questionnaire survey using Zhejiang adolescent health related behavior questionnaire was conducted anonymously in selected classes in May 2012, 2017 and 2022, respectively. Changes of drinking behavior of middle school students in different years were analyzed. Results: The prevalence of ever drinking, current drinking and drunkenness among middle school students in Quzhou decreased from 58.05%, 22.70% and 21.25% in 2012 to 41.83%, 15.35% and 11.54% in 2022, respectively ( χ 2 trend =82.69, 30.00，58.24, P <0.01). In the past 30 days, 66.67% of students reported drinking 1-2 days, the proportion of drinking for 3-5 days increased from 16.36% in 2012 to 26.19% in 2022, the proportion of drinking for 6-19 days decreased from 13.03% in 2012 to 3.40% in 2022. The proportion of buying alcohol increased from 22.12% in 2012 to 35.03% in 2022. The results of the three surveys showed that, now drinking rates, drinking rates, Male students (27.88%，23.96%，18.75%；24.69%，17.44%，13.75%) was higher than the girls (17.60%，17.25%，11.31%；17.87%，10.61%，8.91%)， non ordinary high schools (33.96%，34.69%，22.77%；33.65%，23.91%，19.49%) were higher than ordinary high schools (25.82%，18.80%， 12.62 %；25.82%，17.35%，9.94%) and junior middle school (16.53%，15.83%，12.22%；13.93%，8.47%，7.35%). Conclusion Progress in adolescent drinking control is being made in Quzhou, with the prevalence of ever drinking, current drinking and drunkenness significantly decreased. It is necessary to strengthen the control of drinking behavior among middle school students from the aspects of school, family and society, especially for boys and students in non ordinary high school students.

Objective: To investigate the trends in incidence and mortality of lung cancer in Kaihua County, Zhejiang Province from 2011 to 2022, so as to provide insights into improving lung cancer prevention and control strategy. Methods: The incidence and mortality of lung cancer in Kaihua County from 2011 to 2022 were collected through Zhejiang Provincial Chronic Disease Surveillance Information Management System. The crude incidence, standardized incidence, crude mortality and standardized mortality of lung cancer were analyzed, and the trends in incidence and mortality of lung cancer were evaluated using average annual percent change (AAPC). Results: The crude and standardized incidence of lung cancer appeared a tendency towards an increase (AAPC=5.409% and 2.957%, both P<0.05) from 2011 to 2022, with an average annual crude incidence of 75.17/105 and average annual standardized incidence of 44.37/105. Average annual crude incidence (100.16/105 vs. 48.55/105) and standardized incidence (58.03/105 vs. 30.61/105) of lung cancer was higher in males than in females (both P<0.05). The crude incidence of lung cancer in males appeared a tendency towards an increase (AAPC=2.878%, P<0.05), with no significant changing patterns seen in standardized incidence (P>0.05). The crude and standardized incidence of lung cancer in females showed a tendency towards an increase (AAPC=11.596% and 10.464%, both P<0.05). The crude incidence of lung cancer increased rapidly among residents at ages of 45 years and older, and peaked among residents at ages of 80 to 84 years (32.11/105). The crude and standardized mortality of lung cancer appeared a tendency towards a rise and decline (AAPC=1.554% and -2.491%, both P<0.05) from 2011 to 2022, with an average annual crude and standardized mortality of 52.83/105 and 29.09/105. Average annual crude mortality (77.92/105 vs. 26.10/105) and standardized mortality (43.66/105 vs. 14.33/105) of lung cancer was higher in males than in females (both P<0.05). The crude mortality of lung cancer in males appeared a tendency towards a rise, while the standardized mortality appeared a tendency towards a decline (AAPC=1.436% and -2.553%, both P<0.05). No significant changing patterns were seen in crude and standardized mortality of lung cancer in females (both P>0.05). The crude mortality of lung cancer increased rapidly among residents at ages of 50 years and older, and peaked among residents at ages of 80 to 84 years (37.26/105). Conclusions The incidence and mortality of lung cancer appeared a tendency towards an increase in Kaihua County from 2011 to 2022, and a rapid increase was seen in the incidence of lung cancer in females.

Objective:To investigate the significance and mechanism of ten-eleven translocation (Tet1) against Mycobacterium marinum ( Mm) infection in mice. Methods:SPF wild-type C57BL/6 and Tet1-knockout (Tet1KO) mice were injected intravenously with Mm. All mice were monitored and the abscesses formed in tail were observed and quantified. Pathological changes in mouse tail tissues were observed using hematoxylin and eosin (HE) staining and transmission electron microscopy and the differences between the two groups were analyzed. Immunohistochemistry staining was used to detect the expression and distribution of TNF-α and TGF-β in mouse tail tissues. Moreover, mouse tail tissues were cultured on 7H10 plates for bacterial counting. The expression of NF-κBp65 and TGF-β was detected by Western blot. Results:Obvious lesions including abscesses and ulcers were formed in the Mm-infected C57BL/6, but only scattered small abscesses were observed in Mm-infected Tet1KO mice. During Mm infection, the bacterial load was gradually increased in C57BL/6 mice, but decreased in Tet1KO mice. Histopathological examination showed that obvious inflammatory cell infiltration and typical granulomatous lesions were found in Mm-infected C57BL/6 mice, while no significant inflammatory cell infiltration was detected in Mm-infected Tet1KO mice. Immunohistochemistry staining demonstrated that the expression of TNF-α and TGF-β was lower in Mm-infected Tet1KO mice than in Mm-infected C57BL/6 mice. Moreover, the expression of phosphorylated NF-κBp65 and TGF-β was significantly reduced in Mm-infected Tet1KO mice as compared with that in Mm-infected C57BL/6 mice. Conclusions:Deletion of Tet1 could alleviate the inflammatory damage mediated by Mm and enhance the host immune response to bacteria.

This article reviews the training model of orthopedic residents in the world's top orthopedic hospitals, such as Hospital for Special Surgery Affiliated to Cornell University and The Affiliated Hospital of Harvard University Medical School, and it is found that there are differences between China and the US in the training of orthopedic residents in the aspects of the admittance system of physicians, the setting of training contents , and the training model of orthopedic residents . The training of orthopedic residents in the US adheres to the concept of elite education and pays attention to the construction of tutors and learning atmosphere. The enlightenment to the training of orthopedic residents in China includes further clarification of the training objectives of orthopedic residents , improvement of the stage-based training system , integration of excellent medical teaching resources , and improvement of teaching methods and assessment systems.

Objective: To explore outcomes in adult with de novo acute myeloid leukemia (AML) received IA10 (10 mg/m² d1-3 idarubicin plus cytarabine 100 mg/m² d1-7) regimen as induction chemotherapy. Methods: From January 2008 to February 2016, data of consecutive newly-diagnosed AML (non-M₃) adults treated with IA10 who achieved morphologic leukemia-free state (MLFS) but not accepted allogeneic hematopoietic stem cell transplantation (allo-HSCT) were assessed retrospectively. Results: A total of 198 patients were included in this study with 96 (48.5%) male and a median age of 42 years old (range, 18-62 years old). Using the SWOG cytogenetic classification, 45 (22.7%), 104 (52.5%), 24 (12.1%) and 25 (12.6%) patients belonged to favorable, intermediate, unfavorable and unknown categories, respectively. 6 (3.0%) patients had monosomal karyotype, and 28 (14.1%) positive FLT3-ITD mutation. A complete remission (CR, defined as MLFS with ANC ≥ 1×10⁹/L and PLT ≥ 100×10⁹/L) achieved in 168 (84.8%) patients, a CRp (defined as MLFS with incomplete PLT recovery) in 16 (8.1%) and a CRi (defined as MLFS with incomplete ANC and PLT recovery) in 14 (7.1%). With a median follow-up period of 15 months (range, 1 to 70 months) in survivors, the probabilities of cumulative incident of relapse (CIR), disease free survival (DFS) and overall survival (OS) rates at 2-year were 45.2%, 46.9% and 62.9%, respectively; the median durations of relapse, DFS and OS were 34, 20 and 37 months respectively. At the time of achieving first MLFS, multivariate analyses showed that positive FLT3-ITD mutation and CRi were common adverse factors affecting CIR, DFS and OS; unfavorable-risk of SWOG criteria was an adverse factor affecting CIR and DFS; monosomal karyotype was associated with shorter OS. After first consolidation therapy, FLT3-ITD mutation positive and unfavorable-risk of SWOG criteria had negatively impact on CIR, DFS and OS; peripheral blasts ≥ 0.50 and positive MRD (defined as RQ-PCR WT1 mRNA ≥ 0.6% or any level of abnormal blast population detected by flow cytometry) after first consolidation therapy were common adverse factors affecting CIR and DFS; CRi was an adverse factor affecting DFS and OS. Conclusions In adult with de novo AML received IA10 regimen as induction regimen, unfavorable molecular markers or cytogenetics at diagnosis and CRi independently predicted poor outcome. In addition, a higher percentage of peripheral blasts, monosomal karyotype and positive MRD after first consolidation therapy had negatively impact on outcomes.

Objective: To explore age-related clinical characteristics, early responses and outcomes in non-senile adults with de novo acute myeloid leukemia (AML). Methods: Data of consecutive cases of 18-65 years adults with de novo AML (non-acute promyelocytic leukemia) were reviewed retrospectively. Clinical characteristics at diagnosis, early responses and outcomes across different age groups of patients were analyzed. Results: 1 097 patients were enrolled. 591 (53.9%) were male. Median age was 42 years. Increasing age was significantly associated with decreasing WBC count (P=0.003), increasing PLT count (P=0.034), lower blast proportions in bone marrow (P=0.021). The incidence of NPM1⁺/FLT3-ITD^- increased with age (P<0.001). Multivariate analyses showed that increasing age was associated with low probabilities of achieving morphologic leukemia free state (MLFS) (P=0.053) and complete remission (CR) (P=0.004) and poor overall survival (OS) (P=0.070) in the whole patients population. However, increasing age was not associated with low MLFS rate and poor OS, except low CR rate (P=0.075) in those receiving standard induction regimen instead of low-intensity regimen. Conclusions There were significant differences on clinical characteristics, cytogenetics and molecular genetics across different age groups in non-senile adults with de novo AML. In the patients receiving standard induction regimen, age was not associated with MLFS rate and OS.

Objective: To explore prognostic significance of early assessment of minimal residual leukemia (MRD) in adult patients with de novo acute myeloid leukemia (AML) with mutated NPM1. Methods: The response, NPM1 mutated transcript level after induction chemotherapy and the first 2 cycles of consolidation chemotherapy, disease-free survival (DFS) and overall survival (OS) in 137 patients with AML with NPM1 mutations of A, B and D were retrospectively analyzed. Results: Data of 137 patients were collected, 67 were male, the median age was 49 years (16-67 years) , 107 (78.1%) had normal karyotype, 57 (41.6%) had positive FLT3-ITD mutation, the median NPM1 mutated transcript level at diagnosis was 84.1%. Among the 134 evaluable patients, 115 (85.8%) achieved a complete remission (CR) . Multivariate analyses revealed that WBC<100×10⁹/L (OR=0.3, 95% CI 0.1-0.9, P=0.027) and first induction therapy with "IA10" protocol (OR=0.3, 95% CI 0.1-0.8, P=0.015) were factors associated with achieving a CR. With a median follow-up period of 24 months (range, 2 to 91 months) in 77 survived CR patients, the probabilities of DFS and OS at 3 years were 48.0% and 63.9%, respectively. Multivariate analyses showed that positive FLT3-ITD (HR=3.2, 95% CI 1.6-6.7, P=0.002) , high MRD level after 2 cycles of consolidation chemotherapy (NPM1 mutation transcript level <3-log reduction from the individual baseline, HR=23.2, 95% CI 7.0-76.6, P<0.001) and chemotherapy or autologous hematopoietic stem cell transplantation (auto-HSCT) rather than allogeneic HSCT (allo-HSCT) (HR=2.6, 95% CI 1.0-6.6, P=0.045) were the unfavorable factors affecting DFS, high MRD level at the time of achieving the first CR (NPM1 mutation transcript level <2-log reduction from the individual baseline, OR=2.5, 95% CI 1.0-6.1, P=0.040) and after 2 cycles of consolidation chemotherapy (HR=4.5, 95% CI 2.0-10.3, P<0.001) were the unfavorable factors affecting OS. Furthermore, DFS and OS rates at 3 years in those receiving chemotherapy or auto-HSCT were 39.7% and 59.1%, respectively; positive FLT3-ITD and high MRD level after 2 cycles of consolidation chemotherapy were independent factors associated with both shorter DFS (HR=3.5, 95% CI 1.6-7.6, P=0.002 and HR=8.9, 95% CI 3.8-20.7, P<0.001) and OS (HR=2.7, 95% CI 1.1-6.9, P=0.036 and HR=3.1, 95% CI 1.2-8.0, P=0.021) ; meanwhile, high MRD level at the time of achieving the first CR associated with shorter OS (HR=3.1, 95% CI 1.2-8.0, P=0.022) . Conclusion Positive FLT3-ITD mutation and high MRD level after induction or consolidation chemotherapy associated with poor outcomes in AML patients with mutated NPM1.

Objective: To explore prognostic significance of blood count at the time of achieving first morphologic leukemia-free state[complete remission (CR, ANC ≥1×10⁹/L and PLT ≥100×10⁹/L) , CR with incomplete PLT recovery (CRp) and CR with incomplete ANC and PLT recovery (CRi) ]in adult patients with de novo acute myeloid leukemia (AML) . Methods: From January 2008 to February 2016, data of consecutive newly-diagnosed AML (non-APL) adults who received continuous chemotherapy in our hospital were analyzed retrospectively. Results: 352 patients were included in the study. 179 (50.9%) were male. Median age was 44 (17-65) years. Using the SWOG cytogenetic classification, 87 (24.7%) , 171 (48.6%) , 46 (13.1%) and 48 (13.6%) patients belonged to favorable, intermediate, unfavorable and unknown categories, respectively. 16 (4.5%) had monosomal karyotype and 41 (11.6%) had FLT3-ITD mutation positive. Best response achieved at the time of achieving first morphologic leukemia-free state was CR in 299 (84.9%) patients, CRp in 26 (7.4%) and CRi in 27 (8.1%) . With a median follow-up period of 16 (2-94) months in survivors, the probabilities of cumulative incident of relapse (CIR) rate, disease free survival (DFS) and overall survival (OS) at 30 months were 47.5%, 46.0% and 58.6%, respectively. Multivariate analyses showed that non-CR (CRp or CRi) , was associated with high relapse rate, shorter DFS and OS. In addition, intermediate or high risk of SWOG cytogenetic classification and FLT3-ITD positive were common unfavorable factors affecting CIR, DFS and OS. Peripheral blast ≥60% at diagnosis was adverse factors affecting DFS. Age ≥48 years and bone marrow blasts ≥67% were associated with shorter OS. Conclusion Blood count at the time of achieving morphologic leukemia-free state was one of the key markers associated with treatment outcomes in adults with AML.

Objective: To explore impact of minimal residual leukemia (MRD) on outcomes in the non-favorable risk adults with de novo acute myeloid leukemia (AML) . Methods: From January 2008 to February 2016, data of consecutive newly-diagnosed non-favorable risk adults with AML (non-APL) according to SWOG criteria who achieved morphologic leukemia-free state (MLFS) and received continuous chemotherapy were assessed retrospectively. Results: 292 AML patients were enrolled, 150 (51.4%) were male. Median age was 46 years (range, 18-65 years) . Using the SWOG cytogenetic classification, 186 (63.7%) , 49 (16.8%) and 57 (19.5%) patients belonged to intermediate, unfavorable and unknown categories, respectively. With a median follow-up period of 15 months (range, 1 to 94 months) in survivors, the probabilities of cumulative rates of relapse (CIR) , disease free survival (DFS) and overall survival (OS) at 2-years were 51.6%, 42.6% and 60.0%, respectively. Multivariate analyses showed that MRD positive (defined as Q-PCR WT1 mRNA ≥0.6% or any level of abnormal blast population detected by flow cytometry) after achieving MLFS and PLT<100×10⁹/L were common adverse factors affecting CIR and DFS. In addition, positive FLT3-ITD mutation and CRp/CRi had negatively impact on CIR, DFS and OS. Monosomal karyotype was adverse factors affecting CIR and OS. Age ≥44 years and unfavorable-risk of SWOG criteria were associated with shorter DFS. Conclusions MRD level after achieving MLFS had prognostic significance on outcomes in non-favorable adults with AML who received continuous chemotherapy after achieving MLFS.