Objective:To detect the prevalence of mosaic loss of chromosome Y in adult men in ten study areas in China, describe the epidemiological distribution of mosaic loss of chromosome Y (mLOY) carriers and assess its prospective association with lung cancer.Methods:Based on the data from baseline survey, genetic analysis and follow-up (as of December 31, 2018) from China Kadoorie Biobank, we used Mosaic Chromosomal Alterations pipeline to detect mLOY carriers in 10 areas in China and described the epidemiological characteristics of mLOY carriers in adult men, including age, area distribution, lifestyle and disease history. We used multivariate logistic regression model to identify the potential relevant factor of mLOY. Cox proportional hazard regression model was fitted to assess the prospective association of mLOY with lung cancer. Stratification analysis were conducted to evaluate the potential modification effects of smoking and age. We also conducted mediation analysis to assess the mediating effect of mLOY in the association between smoking and lung cancer.Results:A total of 42 859 adult men were included in our analysis, in whom 2 458 mLOY carriers were detected (5.7%). The detection rate increased with age ( P<0.05). The detection rate was higher in urban area (7.3%±0.2%) than that in rural area (4.7%±0.1%). The results of logistic regression analysis indicated that smoking might be a risk factor for the detection of mLOY ( OR=1.49, 95% CI:1.36-1.64). After follow-up for average 11.1 years, 1 041 lung cancer cases were observed. The prospective analysis showed that mLOY carriers had an increased risk for lung cancer by 24% compared with non-mLOY carriers ( HR=1.24, 95% CI:1.01-1.52) and expanded mLOY carriers (mLOY cell proportion ≥10%) had an increased risk for lung cancer by 50% ( HR=1.50, 95% CI:1.13-2.00). Stratification analysis showed no modification effects of smoking and age in the association between mLOY and lung cancer (interaction P>0.05). Mediation analysis showed that mLOY could be a mediating factor in the association between smoking and lung cancer, the estimated effect was 0.09 (0.01-0.17). Conclusions:There were significant differences in the detection rate of mLOY in adult men with different social-economic characteristics and lifestyles in ten areas in China. Besides, mLOY carriers, especially expanded mLOY carriers, had increased risk for lung cancer and mLOY might be a mediating factor in the association between smoking and lung cancer.

Quantum dots are an emerging semiconductor nanocrystalline material with optical and electronic properties. Quantum dots in the environment are transmitted into human body mainly via digestive system. Quantum dots in the workplace are transmitted into human body via various pathways such as the respiratory tract and mucocutaneous surface. They cross the blood brain barrier to affect the nervous system, eventually leading to irreversible damage. Quantum dots have more complex biological toxicity than ordinary nanomaterials and metal ions, due to their core-shell structure and surface modifiers. The physicochemical properties of quantum dots, such as particle size, surface modification, and charge, greatly influence their neurotoxic effects. Quantum dots can induce oxidative stress and inflammatory responses, causing neuronal damage and functional impairment, thereby affecting learning, memory, and synaptic plasticity. Its mechanisms may be the modulation of signaling pathways such as the mitogen-activated protein kinase/extracellular signal regulated kinase pathway. In the future, the neurotoxicity of different types of quantum dots should be systematically analyzed, and multi-omics methods should be used to elucidate the mechanism of quantum dots on neuronal damage to improve the safety of workers exposed to quantum dots.

Background::Cerebrovascular disease (CVD) ranks among the foremost factors responsible for mortality on a global scale. The mortality patterns of CVDs and temporal trends in China need to be well-illustrated and updated.Methods::We collected mortality data on patients with CVD from Chinese Center for Disease Control and Prevention’s Disease Surveillance Points (CDC-DSP) system. The mortality of CVD in 2020 was described by age, sex, residence, and region. The temporal trend from 2013 to 2019 was evaluated using joinpoint regression, and estimated rates of decline were extrapolated until 2030 using time series models.Results::In 2019, the age-standardized mortality in China (ASMRC) per 100,000 individuals was 113.2. The ASMRC for males (137.7/10 5) and rural areas (123.0/10 5) were both higher when stratified by gender and urban/rural residence. The central region had the highest mortality (126.5/10 5), the western region had a slightly lower mortality (123.5/10 5), and the eastern region had the lowest mortality (97.3/10 5). The age-specific mortality showed an accelerated upward trend from aged 55-59 years, with maximum mortality observed in individuals over 85 years of age. The age-standardized mortality of CVD decreased by 2.43% (95% confidence interval, 1.02-3.81%) annually from 2013 to 2019. Notably, the age-specific mortality of CVD increased from 2013 to 2019 for the age group of over 85 years. In 2020, both the absolute number of CVD cases and the crude mortality of CVD have increased compared to their values in 2019. The estimated total deaths due to CVD were estimated to reach 2.3 million in 2025 and 2.4 million in 2030. Conclusion::The heightened focus on the burden of CVD among males, rural areas, the central and western of China, and individuals aged 75 years and above has emerged as a pivotal determinant in further decreasing mortalities, consequently presenting novel challenges to strategies for disease prevention and control.

Objective To evaluate the efficacy of Schroth PSSE combined with 3D printing braces in the treatment of adolescent idiopathic scoliosis.Method Forty patients were included and divided into a support group(3D printing support group)and a support+exercise therapy group(3D printing support+Schroth PSSE group).Excluding outliers and lost follow-up data,32 patients were ultimately included,with 16 patients in each group.Wearing time≥18 h for both groups of 3D printing supports.The intervention period of Schroth PSSE is 12 weeks,and exercise is maintained after 12 weeks until the end of follow-up.The longest follow-up time for the brace group was 25 months,with an average follow-up time of(15.00±1.29)months.The longest follow-up time for the brace+exercise therapy group was 24 months,with an average follow-up time of(16.59±1.01)months.Relevant indicators were evaluated after follow-up.Results The support and exercise therapy group showed better improvement in Cobb angle and trunk rotation angle(ATR)than the support group,with statistically significant differences(P<0.05);The distance between the midpoint of the C7 vertebral body and the midline of the sacrum(C7-CSVL)in the support and exercise therapy group showed a statistically significant difference before and after treatment(P<0.05),while there was a significant difference before and after Apical Vertebral Translation(AVT)treatment(P<0.01).There was no statistically significant difference compared to the support group(P<0.05);In terms of SRS-22 score,the brace+exercise therapy group can comprehensively improve the SRS-22 score.Conclusion The combination of Schroth PSSE and 3D printing braces has a better effect on improving Cobb angle and torso rotation angle,improving coronary imbalance,increasing patient satisfaction,and improving quality of life compared to using 3D printing braces alone.

Objective:The epidemiological and host animal pathogen data of leptospirosis in the population of Zhejiang Province in 2023 were analyzed, providing scientific basis for formulating prevention and control strategies of leptospirosis.Methods:The data of human leptospirosis in the population were collected from the China Information System for Disease Control and Prevention, and analyzed using descriptive epidemiological methods. The data on isolation, culture, and nucleic acid testing of Leptospira pathogens from mouse kidneys, frog kidneys, pig kidneys, and duck kidneys as well as duck serum antibody data were collected from Zhejiang Provincial Center for Disease Control and Prevention "Leptospirosis Surveillance Project of Zhejiang Province". The carrying and changing status of Leptospira epidemic microbiota in populations and host animals were analyzed. Results:In 2023, a total of 83 cases of leptospirosis were reported in Zhejiang Province, with a incidence rate of 0.126 2/ 100 000, aged (62.66 ± 11.31) years, including 68 males and 15 females. Leptospirosis cases were reported in 11 cities, mainly concentrated in the southern cities of Wenzhou City, Lishui City and Taizhou City(a total of 68 cases), accounting for 81.93% of the total number of cases. August to October were high incidence months for leptospirosis (a total of 70 cases), accounting for 84.34% of the total number cases. The male to female ratio of patients was 4.53 ∶ 1.00, and all were adults ≥20 years old, the middle and old people aged 45 - 79 years were the high-risk population (a total of 77 cases), accounting for 92.77% of the total number of cases. The patient's occupation was mainly farmers, with a total of 54 cases, accounting for 65.06% of the total number cases. The shortest time from onset to initial diagnosis for patients with leptospirosis was 0 day, and the longest was 13 days. The shortest time from initial diagnosis to confirmed diagnosis was 0 day, and the longest was 16 days. The 72.29% of the leptospirosis cases (60 cases) had a history of field labor or suspected contact with contaminated water within one month before the onset of the disease, and 18.07% of the leptospirosis cases (15 cases) had a history of contact with animals such as mice, frogs, pigs, cows, dogs, fish or ducks, or their excreta within one month before the onset of the disease. The average nucleic acid positive rate of host animals with leptospirosis was 5.92% (31/524) in mouse kidney, 6.74% (36/534) in frog kidney, and 0.66% (1/151) in pig kidney. The isolation and culture of leptospirosis from duck kidney, nucleic acid detection, and antibody detection in duck blood were all negative. The leptospirosis bacteria detected in human population were serogroup Icterohaemorrhagiae (3 samples) and Hebdomadis (4 samples), and the bacteria group detected in host animals was serogroup Icterohaemorrhagiae (3 samples). Conclusions:The outbreak of leptospirosis in Zhejiang Province mainly occurs in the summer and autumn, with the affected areas mainly concentrated in the southern region of Zhejiang Province. The affected population is mainly middle-aged and elderly males, and the population carrying Leptospira is still mainly composed of the serogroup Icterohaemorrhagiae and the Hebdomadis, with the host animal being the serogroup Icterohaemorrhagiae.

Objective:To investigate the application value of 0.9% sodium chloride injection for a balloon catheter in bedside Doppler ultrasound-guided percutaneous dilatational tracheostomy in critically ill patients.Methods:A randomized controlled study was conducted involving 54 critically ill patients who were scheduled for tracheostomy at the Intensive Care Medicine, Jilin Province People's Hospital, from September 2022 to April 2024. These patients were randomly divided into a conventional group ( n = 27) and an ultrasound group ( n = 27) using the random number table method. The conventional group underwent empirical extubation, while the ultrasound group received extubation guided by a balloon catheter filled with 0.9% sodium chloride injection under ultrasound guidance. The following parameters were observed in both groups: duration of operation, incidence of blood oxygen saturation < 90%, incidence of puncturing the endotracheal tube or balloon catheter, distance from extubation site to the incisors, dosage of propofol, length of incision, and amount of bleeding. Results:Both groups of patients successfully completed the procedure on the first attempt, with no significant complications such as extensive bleeding, vascular injury, thyroid damage, or pneumothorax. In the ultrasound group, the incidence of puncturing the endotracheal tube or balloon catheter, duration of operation, and dosage of propofol were 3.7% (1/27), (6.2 ± 1.4) minutes, and 40 (40, 40) mg, respectively, all of which were superior to those in the conventional group [48.1% (13/27), (9.8 ± 2.7) minutes, 80 (70, 80) mg, χ2 = 23.19, t = 6.11, Z = -6.29, all P < 0.05]. The incidence of hypoxemia in the ultrasound group was 0, which was significantly lower than that in the conventional group [29.6% (8/27), P < 0.05]. The distance from extubation site to the incisors in the ultrasound group was 18 (17, 18) cm, which was significantly different from 18 cm of the conventional group ( Z = -2.62, P < 0.05). There were no statistically significant differences in length of incision and amount of bleeding between the two groups ( P = 0.652, 0.878). Conclusion:Performing PDT under bedside Doppler ultrasound guidance with a 0.9% sodium chloride injection-filled balloon catheter in patients requiring mechanical ventilation can reduce procedure duration, lower the incidence of hypoxemia and puncturing of the endotracheal tube or balloon catheter, decrease the use of sedative medications, and enhance the accuracy and safety of the procedure.

Objective:To investigate the perioperative efficacy of robot surgical system assisted anatomic and non-anatomic hepatectomy.Methods:The propensity score matching and retrospective cohort study was conducted. The clinical data of 103 patients who underwent robot surgical system assisted hepatectomy in Sir Run Run Shaw Hospital, Affiliated with the Zhejiang University School of Medicine from March 2016 to December 2021 were collected. There were 54 males and 49 females, aged 56(range, 44?64)years. Of the 103 patients, 55 cases undergoing robot surgical system assisted anatomic hepatectomy were divided into the anatomic group, and 48 cases undergoing robot surgical system assisted non-anatomic hepatectomy were divided into the non-anatomic group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) intraoperative conditions; (3) perioperative complications. Propensity score matching was done by the 1:1 nearest neighbor matching method. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were expressed as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the rank sum test. Results:(1) Propensity score matching and compari-son of general data of patients between the two groups after matching. Of the 103 patients, 94 cases were successfully matched, including 47 cases in the anatomic group and 47 cases in the non-anatomic group. The elimination of preoperative body mass index, preoperative platelet and preoperative albumin confounding bias ensured comparability between the two groups after propensity score matching. (2) Intraoperative conditions. After propensity score matching, the operation time and volume of intraoperative blood loss were 175(range, 120?240)minutes and 50(range, 50?100)mL in patients of the anatomic group, versus 155(range, 105?190)minutes and 100(range, 50?200)mL in patients of the non-anatomic group, showing significant differences in the above indicators between the two groups ( Z=1.97, 2.49, P<0.05). (3) Perioperative complications. After propensity score matching, cases with pleural fluid and/or ascites, case with biliary fistula, case with thrombosis, case with peritoneal infection, case with incision infection were 11, 1, 2, 4, 1 in patients of the anatomic group, versus 12, 0, 4, 1, 0 in patients of the non-anatomic group, showing no significant difference in the above indicators between the two groups ( P>0.05). Cases with complications classified as grade Ⅰ, grade Ⅱ, grade Ⅲ, grade Ⅳ of the Clavien-Dindo classification were 33, 14, 0, 0 in patients of the anatomic group, versus 28, 14, 3, 2 in patients of the non-anatomic group, showing no significant difference in the above indicators between the two groups ( Z=?1.38, P>0.05). Conclusions:Robotic surgical system assisted anatomic and non-anatomic hepatectomy are safe and feasible for clinical application. Compared with robot surgical system assisted non-anatomic hepatectomy, patients under-going robot surgical system assisted anatomic hepatectomy have long operation time and less volume of intraoperative blood loss.

Objective:To explore the clinical value of 18F-fluoromisonidazole (FMISO) PET/CT hypoxia imaging in early response to heavy ion radiotherapy in patients with non-small cell lung cancer(NSCLC). Methods:From April 2018 to January 2021, the 18F-FMISO PET/CT images of 23 NSCLC patients (19 males, 4 females; age (64.9±10.3) years) who received heavy ion radiotherapy in Shanghai Proton and Heavy Ion Center were retrospectively analyzed. The evaluation parameters included tumor volume (TV), tumor to background ratio (TBR) before and after radiotherapy. Patients were divided into hypoxia group and non-hypoxia group with the baseline TBR value≥1.4 as hypoxia threshold. Wilcoxon signed rank test was used to compare the differences of TV and TBR before and after radiotherapy in 2 groups. Results:Of 23 NSCLC patients, 17 were hypoxia and 6 were non-hypoxia. Compared with the baseline, TV after the radiotherapy (59.44(22.86, 99.43) and 33.78(8.68, 54.44) cm 3; z=-3.05, P=0.002) and TBR after the radiotherapy (2.25(2.09, 2.82) and 1.42(1.24, 1.67); z=-3.39, P=0.001) of the hypoxia group were significantly lower, while TV (16.19(6.74, 36.52) and 8.59(4.38, 25.47) cm 3; z=-1.57, P=0.120) and TBR (1.19(1.05, 1.27) and 1.10 (0.97, 1.14); z=-1.89, P=0.060) of the non-hypoxia group decreased with no significant differences. Conclusions:Hypoxic NSCLC tumors are sensitive to heavy ion radiation. Compared with non-hypoxic tumors, hypoxic tumors respond more quickly, and a significant reduction in TV can be observed early after radiotherapy. Heavy ion radiation can significantly improve tumor hypoxia.

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1H-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound 55 exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound 55 exhibited potent in vivo antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition (EMT).

Somatic mosaicism is defined as the occurrence and accumulation of somatic mutations in humans, and mosaic chromosomal alterations (mCA) are recognized as one of the aging phenotypes due to their impact on genome integrity. With the coming acceleration of global population aging, understanding the prevalence and influencing factors of mCA will help to explore the "genomic instability" of human aging and its biological mechanisms and provide the scientific basis for the primary prevention of age-related diseases. This review aims to summarize the epidemiological distribution and influencing factors of autosomal mCA in peripheral blood based on previous large-scale population-based studies.