ObjectiveIdentification and analysis, animal regression test, and drug susceptibility study were conducted on a pathogenic strain causing diarrhea in cynomolgus monkeys, aiming to provide a practical basis for the clinical treatment of Citrobacter freundii. MethodsFresh fecal samples were collected from nine diarrheal cynomolgus monkeys and streaked on Salmonella-Shigella (SS) medium, LB medium, and Columbia blood agar medium, and incubated at 37 ℃ for 24 h. Subsequently, the isolated strain was identified by colony morphology observation, Gram staining, biochemical tests and 16S rRNA gene sequencing, and PCR was used to detect its major virulence genes. After propagation, the isolate was intragastrically administered to healthy cynomolgus monkeys and C57BL/6 mice for animal regression tests to evaluate its pathogenicity. Finally, the disk-diffusion method was used to detect the antimicrobial susceptibility of the isolate. ResultsA single bacterial strain, designated MF071743, was isolated from 9 fecal samples collected from diarrheal cynomolgus monkeys. The isolate formed pink, smooth, round colonies on SS medium; translucent, smooth, moist, shiny colonies with neat edges on LB medium; and smooth, moist, off-white colonies on Columbia blood agar medium. Gram staining revealed that the isolate was a Gram-negative, spore-free short bacillus. Biochemical tests showed that the isolate was positive for motility test, mannitol test, hydrogen sulfide test, methyl red test, citrate utilization test, gas production from glucose test, raffinose test, sorbitol test, and D-xylose test, but negative for phenylalanine test, gluconate test, indole test, Voges Proskauer (VP) test, urease test, lysine test, ornithine test, and adonitol test. The results of 16S rRNA gene sequencing showed that the gene sequence similarity between strain MF071743 and Citrobacter freundii was 99.0%. PCR results showed that this strain carries genes encoding the urease accessory proteins UreD, UreE, and UreF. Animal intragastric administration assays demonstrated that the strain caused loose stools in cynomolgus monkeys, and all C57BL/6 mice died within 72 h. Drug susceptibility test results indicated that the isolate was sensitive to 16 antibiotics, including ceftriaxone, amikacin, gentamicin, ceftazidime, and levofloxacin, while it exhibited resistance to 5 antibiotics, including ampicillin, cefazolin, vancomycin, erythromycin, and cephalexin. ConclusionA strain of Citrobacter freundii with certain drug resistance was isolated from the feces of diarrheal cynomolgus monkeys. The results of this study provide a reference for the diagnosis and treatment of gastrointestinal diseases in captive laboratory monkeys.

[Purpose]To analyze the incidence and mortality of thyroid cancer in Zhejiang cancer registration areas in 2021 and trends from 2000 to 2021.[Methods]Based on cancer data from 22 registries across Zhejiang Province between 2000 and 2021,the crude incidence/mortality rates,age-standardized incidence/mortality rates of thyroid cancer by Chinese and world standard population(ASIRC/ASMRC,ASIRW/ASMRW),cumulative rate(0～74 years old)and truncated rate(35～64 years old)were analyzed.Joinpoint regression model was employed to calculate the annual percentage change(APC)and average annual percentage change(AAPC)with 95％confidence in-terval(CI)for analyzing trends of thyroid cancer incidence and mortality rates from 2000 to 2021.[Results]The crude incidence rate of thyroid cancer increased from 3.62/105 in 2000 to 79.66/105 in 2021,and ASIRC rose from 3.11/105 to 69.49/105(AAPC=15.55％,95％CI:14.65％～16.61％).The AAPC for ASIRC was slightly higher in female(15.54％,95％CI:14.71％～16.49％)than that in male(15.02％,95％CI:13.53％～16.82％).The increase was significantly more pronounced in rural areas(AAPC=23.34％,95％CI:21.48％～25.33％)compared to urban areas(AAPC=14.12％,95％CI:13.15％～15.43％).Among age groups,the age group of 15～44 years old showed the fastest increase in crude incidence rate(AAPC=20.37％,95％CI:18.46％～22.31％),followed by the age group of 45～64 years old(AAPC=18.41％,95％CI:16.65％～20.19％).Between 2000 and 2021,the crude mortality rate of thyroid cancer rose from 0.34/105 to 0.56/105(AAPC=5.52％,95％CI:3.45％～7.70％),the trend of ASMRC was relatively stable.[Conclusion]From 2000 to 2021,the incidence of thyroid cancer in Zhejiang Province increased markedly,especially among females and younger to middle-aged adults,while the age-standardized mortality rate remained stable.

[Purpose]To analyze the incidence and mortality of thyroid cancer in Zhejiang cancer registration areas in 2021 and trends from 2000 to 2021.[Methods]Based on cancer data from 22 registries across Zhejiang Province between 2000 and 2021,the crude incidence/mortality rates,age-standardized incidence/mortality rates of thyroid cancer by Chinese and world standard population(ASIRC/ASMRC,ASIRW/ASMRW),cumulative rate(0～74 years old)and truncated rate(35～64 years old)were analyzed.Joinpoint regression model was employed to calculate the annual percentage change(APC)and average annual percentage change(AAPC)with 95％confidence in-terval(CI)for analyzing trends of thyroid cancer incidence and mortality rates from 2000 to 2021.[Results]The crude incidence rate of thyroid cancer increased from 3.62/105 in 2000 to 79.66/105 in 2021,and ASIRC rose from 3.11/105 to 69.49/105(AAPC=15.55％,95％CI:14.65％～16.61％).The AAPC for ASIRC was slightly higher in female(15.54％,95％CI:14.71％～16.49％)than that in male(15.02％,95％CI:13.53％～16.82％).The increase was significantly more pronounced in rural areas(AAPC=23.34％,95％CI:21.48％～25.33％)compared to urban areas(AAPC=14.12％,95％CI:13.15％～15.43％).Among age groups,the age group of 15～44 years old showed the fastest increase in crude incidence rate(AAPC=20.37％,95％CI:18.46％～22.31％),followed by the age group of 45～64 years old(AAPC=18.41％,95％CI:16.65％～20.19％).Between 2000 and 2021,the crude mortality rate of thyroid cancer rose from 0.34/105 to 0.56/105(AAPC=5.52％,95％CI:3.45％～7.70％),the trend of ASMRC was relatively stable.[Conclusion]From 2000 to 2021,the incidence of thyroid cancer in Zhejiang Province increased markedly,especially among females and younger to middle-aged adults,while the age-standardized mortality rate remained stable.

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.