Objective: To investigate the trend in incidence and change in age at onset of malignant tumor in cancer registration areas of Jiangsu Province from 2009 to 2021, so as to provide the evidence for formulating cancer prevention and control strategies and optimizing the allocation of healthcare resources. Methods: Incidence data of malignant tumor cases from 2009 to 2021 were collected from the aggregated database of 16 qualified cancer registries of Jiangsu Province. The crude incidence, age-specific incidence, average age at onset, proportion of age-specific incidence, and proportion of incidence in cases aged ≥60 years were calculated by genders and urban/rural areas, and age-standardized using the Segi's world standard population. The trend in incidence of malignant tumor from 2009 to 2021 was evaluated using average annual percent change (AAPC). The trend in average age at onset of malignant tumor from 2009 to 2021 was evaluated using the linear regression model. Results: From 2009 to 2021, a total of 703 185 cases of malignant tumor were reported in Jiangsu Province, comprising 400 970 males and 302 215 females. The crude incidence of malignant tumor increased from 268.26/100 000 in 2009 to 380.97/100 000 in 2021 (AAPC=2.880%, P<0.05). From 2009 to 2021, the world population-standardized incidence of malignant tumor showed upward trends in the total population, females, and urban and rural areas (AAPC=0.635%, 2.332%, 0.795%, and 0.385%, all P<0.05), while a downward trend was observed in males (AAPC=-0.608%, P<0.05). From 2009 to 2021, the crude incidence of malignant tumor in the groups aged 0-<30 years, 30-<40 years, 40-<50 years, 60-<70 years, and ≥80 years showed upward trends (AAPC=3.160%, 4.462%, 1.295%, 0.569%, and 1.496%, all P<0.05), a downward trend was found in the group aged 50-<60 years (AAPC=-0.860%, P<0.05), while no statistically significant trend was observed in the group aged 70-<80 years (P>0.05). The world population-standardized average age at onset showed downward trends in the total population, females, and urban areas, with average annual decreases of 0.085, 0.223, and 0.136 years, respectively (all P<0.05). Conversely, an upward trend was observed in males, with an average annual increase of 0.081 years (P<0.05). No statistically significant trend was found in rural areas (P>0.05). Compared with 2009, the proportion of malignant tumor incidence cases increased in all age groups between 20-<50 years in 2021. Additionally, the proportion of malignant tumor cases aged over 60 years showed a downward trend from 2009 to 2021 (AAPC=-0.322%, P<0.05). Conclusions From 2009 to 2021, the overall incidence of malignant tumor in registration areas of Jiangsu Province showed an upward trend, with the age at onset tending to become younger. There were differences in the incidence trends across genders and urban/rural areas.

BACKGROUND: Prolonged occupational noise exposure poses potential health risks, but its impact on mitochondrial DNA (mtDNA) damage and methylation patterns remains unclear. METHOD: We recruited 306 factory workers, using average binaural high-frequency hearing thresholds from pure-tone audiometry to assess noise exposure. MtDNA damage was evaluated through mitochondrial DNA copy number (mtDNAcn) and lesion rate, and mtDNA methylation changes were identified via pyrophosphate sequencing. RESULTS: There was a reduction in MT-RNR1 methylation of 4.52% (95% CI: -7.43% to -1.62%) among workers with abnormal hearing, whereas changes in the D-loop region were not statistically significant (β = -2.06%, 95% CI: -4.44% to 0.31%). MtDNAcn showed a negative association with MT-RNR1 methylation (β = -0.95, 95% CI: -1.23 to -0.66), while no significant link was found with D-loop methylation (β = -0.05, 95% CI: -0.58 to 0.48). Mediation analysis indicated a significant increase in mtDNAcn by 10.75 units (95% CI: 3.00 to 21.26) in those with abnormal hearing, with MT-RNR1 methylation mediating 35.9% of this effect. CONCLUSIONS These findings suggest that occupational noise exposure may influence compensatory increases in mtDNA content through altered MT-RNR1 methylation.
Humans ; DNA, Mitochondrial ; DNA Methylation ; Male ; Adult ; Noise, Occupational/adverse effects* ; Middle Aged ; Occupational Exposure/adverse effects* ; Biomarkers/blood* ; Female

Progressive pulmonary fibrosis (PPF) is a progressive and lethal condition with few effective treatment options. Improvements in quality of life for patients with PPF remain limited even while receiving treatment with approved antifibrotic drugs. Traditional Chinese medicine (TCM) has the potential to improve cough, dyspnea and fatigue symptoms of patients with PPF. TCM treatments are typically diverse and individualized, requiring urgent development of efficient and precise design strategies to identify effective treatment options. We designed an innovative Bayesian adaptive two-stage trial, hoping to provide new ideas for the rapid evaluation of the effectiveness of TCM in PPF. An open-label, two-stage, adaptive Bayesian randomized controlled trial will be conducted in China. Based on Bayesian methods, the trial will employ response-adaptive randomization to allocate patients to study groups based on data collected over the course of the trial. The adaptive Bayesian trial design will employ a Bayesian hierarchical model with "stopping" and "continuation" criteria once a predetermined posterior probability of superiority or futility and a decision threshold are reached. The trial can be implemented more efficiently by sharing the master protocol and organizational management mechanisms of the sub-trial we have implemented. The primary patient-reported outcome is a change in the Leicester Cough Questionnaire score, reflecting an improvement in cough-specific quality of life. The adaptive Bayesian trial design may be a promising method to facilitate the rapid clinical evaluation of TCM effectiveness for PPF, and will provide an example for how to evaluate TCM effectiveness in rare and refractory diseases. However, due to the complexity of the trial implementation, sufficient simulation analysis by professional statistical analysts is required to construct a Bayesian response-adaptive randomization procedure for timely response. Moreover, detailed standard operating procedures need to be developed to ensure the feasibility of the trial implementation. Please cite this article as: Zhang C, Nie YS, Zhang CT, Yang HJ, Zhang HR, Xiao W, Cui GF, Li J, Li SJ, Huang QS, Yan SY. An adaptive Bayesian randomized controlled trial of traditional Chinese medicine in progressive pulmonary fibrosis: Rationale and study design. J Integr Med. 2025; 23(2): 138-145.
Female ; Humans ; Male ; Bayes Theorem ; Disease Progression ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional/methods* ; Pulmonary Fibrosis/therapy* ; Quality of Life ; Randomized Controlled Trials as Topic ; Research Design ; Adaptive Clinical Trials as Topic

Objective:To investigate the prospective association of sleep duration with the development of chronic obstructive pulmonary disease (COPD) in adults in Suzhou.Methods:The study used the data of 53 269 participants aged 30-79 years recruited in the baseline survey from 2004 to 2008 and the follow-up until December 31, 2017 of China Kadoorie Biobank (CKB) conducted in Wuzhong District, Suzhou. After excluding participants with airflow limitation, self-reported chronic bronchitis/emphysema/coronary heart disease history at the baseline survey and abnormal or incomplete data, a total of 45 336 participants were included in the final analysis. The association between daily sleep duration and the risk for developing COPD was analyzed by using a Cox proportional hazard regression model, and the hazard ratio ( HR) values and their 95% CI were calculated. The analysis was stratified by age, gender and lifestyle factors, and cross-analysis was conducted according to smoking status and daily sleep duration. Results:The median follow-up time was 11.12 years, with a total of 515 COPD diagnoses in the follow-up. After adjusting for potential confounders, multifactorial Cox proportional hazard regression analysis showed that daily sleep duration ≥10 hours was associated with higher risk for developing COPD ( HR=1.42, 95% CI: 1.03-1.97). The cross analysis showed that excessive daily sleep duration increased the risk for COPD in smokers ( HR=2.49, 95% CI: 1.35-4.59, interaction P<0.001). Conclusion:Longer daily sleep duration (≥10 hours) might increase the risk for COPD in adults in Suzhou, especially in smokers.

Objectives:To explore the risk factors for death from ruptured acute aortic dissection during emergency treatment,construct and validate a risk prediction model for death from ruptured acute aortic dissection during emergency treatment. Methods:A total of 301 cases of acute aortic dissection patients who were admitted to Chinese Academy of Medical Sciences Fuwai Hospital from January 2018 to August 2021 were included in this study.Patients were divided into survival subgroup(n=239)and death subgroup(n=62)according to whether dissection rupture occurred in the acute stage of the disease.Univariate and multivariate analyses were performed.Logistic regression analysis was used to establish the risk prediction model.The Hosmer-Lemeshow test was conducted to assess the model's goodness of fit,and the receiver operating characteristic curve(ROC curve)was used to evaluate the model's predictive performance.A prospective validation was performed on 129 cases of acute aortic dissection patients admitted to our hospital's emergency department from September 2021 to September 2022. Results:Among the 301 cases of acute aortic dissection patients,there were 62 cases of rupture and death,with an incidence rate of 20.6%.The results of multivariate analysis showed that age(OR=1.066,95%CI:1.034-1.099),type A dissection(OR=0.045,95%CI:0.006-0.364),history of hypertension(OR=0.377,95%CI:0.167-0.850),and concomitant hypotension(OR=4.424,95%CI:1.467-13.340)were determinants of deaths.The model formula was Z=-5.624+0.064×age-0.976×history of hypertension(yes=1,no=0)-3.104×type(Type A=0,Type B=1)+1.487×concomitant hypotension(yes=1,no=0).The Hosmer-Lemeshow test result showed χ2=9.328,df=8,P=0.315,the area under the ROC curve was 0.874,sensitivity was 79.0%,specificity was 81.6%,and the maximum Youden index was 0.606.The model validation result showed that the area under the ROC curve was 0.722,sensitivity was 73.7%,specificity was 69.1%,and accuracy was 89.9%. Conclusions:Age,history of hypertension,dissection type,and combined hypotension are predictors of the risk prediction model for death from dissection rupture in patients with acute aortic dissection during emergency treatment.The model constructed in this study has good predictive performance,which can provide reference for medical staffto quickly identify high-risk patients for death from ruptured acute aortic dissection and timely predictive measures could be highlighted in indicated cases.

Objective To explore the cell subsets and characteristics related to the prognosis of osteosarcoma by analyzing the cellular composition of tumor tissue samples from different osteosarcoma patients.Methods The single-cell sequencing data and bulk sequencing data of different osteosarcoma patients were downloaded.We extracted the information of cell samples for dimensionality reduction,annotation,and cell function analysis,so as to identify the cell subsets and clarify the cell characteristics related to the prognosis of osteosarcoma.The development trajectory of macrophages with prognostic significance was analyzed,and the prognostic model of osteosarcoma was established based on the differentially expressed genes of macrophage differentiation.Results The cellular composition presented heterogeneity in the patients with osteosarcoma.The infiltration of mononuclear phagocytes in osteosarcoma had prognostic significance(P=0.003).Four macrophage subsets were associated with prognosis,and their signature transcription factors included RUNX3(+),ETS1(+),HOXD11(+),ZNF281(+),and PRRX1(+).Prog_Macro2 and Prog_Macro4 were located at the end of the developmental trajectory,and the prognostic ability of macrophage subsets increased with the progression of osteosarcoma.The prognostic model established based on the differentially expressed genes involved in macrophage differentiation can distinguish the survival rate of osteosarcoma patients with different risks(P<0.001).Conclusion Macrophage subsets are closely related to the prognosis of osteosarcoma and can be used as the key target cells for the immunotherapy of osteosarcoma.
Humans ; Prognosis ; Osteosarcoma/genetics* ; Immunotherapy ; Macrophages ; Transcription Factors ; Bone Neoplasms/genetics* ; Homeodomain Proteins ; Repressor Proteins

The study aims to investigate the mechanism of Fengshining fecal microbiota transplants in the intervention of rheumatoid arthritis by ultra-performance liquid chromatography-quadrupole/electrostatic field obitrap high-resolution mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS). All animal welfare and experimental procedures followed the regulations of the Medical Ethics Committee of Shanxi University of Chinese medicine. The rats were randomly divided into normal group, model group, fecal microbiota transplantation group and Tripterygium wilfordii polyglycoside group, and the collagen induced arthritis (CIA) was established. The changes of body weight and metatarpodal lesions of rats were evaluated. The serum of rats in each group was analyzed by liquid chromatography-mass spectrometry and metagenomic technology for differential metabolites and microflora. The protein expression levels of Toll-like receptors (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor of kappa B (NF-κB p65) were detected by Western blot. A total of 13 different metabolites, including arachidonic acid, docosahexaenoic acid, 13S-hydroxyoctadecanodienoic acid and L-phenylalanine were screened from serum. Three metabolic pathways, including phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism and arachidonic acid metabolism were identified through pathway enrichment. Metagenomic analysis showed that the abundance of g_Bacteroides, g_Prevotella and p_Actinobacteria in CIA group was higher. The abundance of c_Clostridia, g_Akkermansia and s_Akkermansia_muciniphila in fecal microbiota transplantation group is higher. The hierarchical cluster heat map showed that Akkermansia was negatively correlated with L-phenylalanine; while positively correlated with docosahexaenoic acid. Prevotella was positively correlated with L-phenylalanine. Fecal microbiota transplantation group could significantly inhibit the expression of TLR4, MyD88 and p65 proteins in the synovium of rats (P < 0.01). The anti-rheumatoid arthritis effects of fecal microbiota transplantation group is closely related to the intervention of the metabolism of phenylalanine and arachidonic acid, through Akkermansia, Prevotella and other microorganisms, inhibition the TLR4/MyD88/NF-κB pathway.

Objective: To investigate the surgical indications and perioperative clinical outcomes of pelvic exenteration (PE) for locally advanced, recurrent pelvic malignancies and complex pelvic fistulas. Methods: This was a descriptive study.The indications for performing PE were: (1) locally advanced, recurrent pelvic malignancy or complex pelvic fistula diagnosed preoperatively by imaging and pathological examination of a biopsy; (2)preoperative agreement by a multi-disciplinary team that non-surgical and conventional surgical treatment had failed and PE was required; and (3) findings on intraoperative exploration confirming this conclusion.Contraindications to this surgical procedure comprised cardiac and respiratory dysfunction, poor nutritional status,and mental state too poor to tolerate the procedure.Clinical data of 141 patients who met the above criteria, had undergone PE in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to September 2022, had complete perioperative clinical data, and had given written informed consent to the procedure were collected,and the operation,relevant perioperative variables, postoperative pathological findings (curative resection), and early postoperative complications were analyzed. Results: Of the 141 included patients, 43 (30.5%) had primary malignancies, 61 (43.3%) recurrent malignancies, 28 (19.9%) complex fistulas after radical resection of malignancies,and nine (6.4%)complex fistulas caused by benign disease. There were 79 cases (56.0%) of gastrointestinal tumors, 30 cases (21.3%) of reproductive tumors, 16 cases (11.3%) of urinary tumors, and 7 cases (5.0%) of other tumors such mesenchymal tissue tumors. Among the 104 patients with primary and recurrent malignancies, 15 patients with severe complications of pelvic perineum of advanced tumors were planned to undergo palliative PE surgery for symptom relief after preoperative assessment of multidisciplinary team; the other 89 patients were evaluated for radical PE surgery. All surgeries were successfully completed. Total PE was performed on 73 patients (51.8%),anterior PE on 22 (15.6%),and posterior PE in 46 (32.6%). The median operative time was 576 (453,679) minutes, median intraoperative blood loss 500 (200, 1 200) ml, and median hospital stay 17 (13.0,30.5)days.There were no intraoperative deaths. Of the 89 patients evaluated for radical PE surgery, the radical R0 resection was achieved in 64 (71.9%) of them, R1 resection in 23 (25.8%), and R2 resection in two (2.2%). One or more postoperative complications occurred in 85 cases (60.3%), 32 (22.7%)of which were Clavien-Dindo grade III and above.One patient (0.7%)died during the perioperative period. Conclusion: PE is a valid option for treating locally advanced or recurrent pelvic malignancies and complex pelvic fistulas.
Humans ; Pelvic Exenteration/methods* ; Pelvic Neoplasms/surgery* ; Retrospective Studies ; Neoplasm Recurrence, Local/surgery* ; Postoperative Complications

Objective: To understand the incidence of chronic obstructive pulmonary disease (COPD) in the Suzhou cohort, and explore the risk factors for the development of COPD in Suzhou, and provide a scientific basis for COPD prevention. Methods: This study was based on the China Kadoorie Biobank project in Wuzhong District, Suzhou. After excluding individuals with airflow obstruction and self-reported chronic bronchitis, emphysema, or pulmonary heart disease at baseline, 45 484 individuals were finally included in the analysis. Cox proportional risk models were used to analyze risk factors of COPD and calculate hazard ratios and 95% confidence interval (CI) in the Suzhou cohort. The effect modifications of smoking on the association between other risk factors and COPD were evaluated. Results: Complete follow-up was available through December 31, 2017. Participants were followed up for a median of 11.12 years, and 524 individuals were diagnosed with COPD during the follow-up period; the incidence was 105.54 per 100 000 person-years. Multivariate Cox proportional risk regression models showed that age (HR=3.78, 95%CI:3.32-4.30), former smoking (HR=2.00, 95%CI:1.24-3.22), current smoking (<10 cigarettes/day, HR=2.14, 95%CI:1.36-3.35;≥10 cigarettes/day, HR=2.69, 95%CI:1.60-4.54), history of respiratory disease (HR=2.08, 95%CI:1.33-3.26), daily sleep duration ≥10 hours (HR=1.41, 95%CI:1.02-1.95) were associated with increased risk of COPD. However, education level of primary school and above (primary or junior high school, HR=0.65, 95%CI:0.52-0.81; high school and above, HR=0.54, 95%CI:0.33-0.87), consuming fresh fruit daily (HR=0.59, 95%CI:0.42-0.83) and consuming spicy food weekly (HR=0.71, 95%CI:0.53-0.94) were associated with reduced risk of COPD. Conclusions: The incidence of COPD is low in Suzhou. Older age, smoking, history of respiratory disease, and long sleep duration were risk factors for the development of COPD in the Suzhou cohort.
Humans ; Incidence ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Risk Factors ; Smoking/epidemiology* ; Tobacco Smoking

The COVID-19 pandemic is still spreading around the world,posing a severe challenge to public health security and economic development in China and beyond. The pivotal process of SARS-COV-2 invasion is that the receptor binding domain (RBD) of Coronavirus spike protein binds with the angioten-sin converting enzyme 2 (ACE2) receptor on host cells. Therefore, RBD is closely related to our major anti-epidemic strategies such as rapid pathogen detection and development of vaccines and antiviral drugs. In this study, we aim to compare the anti-RBD IgG by immunizing mice with the recombinant RBDs of novel Coronavirus spike protein, and evaluate the antibody titers and duration elicited by RBD produced from different host cells and used in different doses, which can be used for vaccine evaluation, drug development, and pathogen detection. SDS-PAGE and mass spectrometry analysis showed that the molecular weight of bRBD (produced by insect cells) and hRBD (produced by mammalian cells) were slightly different, which are mainly caused by different glycosylation modification. Flow cytometry revealed that the binding rates of bRBD and hRBD to HEK293-ACE2-overexpressing cells were 88. 5% and 92. 7%, respectively, indicating that both antigens have favorable bioactivity. Balb/ c mice are immunized intramuscularly with 10 μg and 20 μg per mouse of RBD proteins, which were mixed with Quick Antibody adjuvant previously, and blood samples collected from the tail at 2, 4, 6, 8, 12 and 24 weeks after the primary immunization. Enzyme-linked immunosorbent assay (ELISA) showed that both RBD immunization with 10 μg or 20 μg could induce a rapid immune response to produce IgG antibodies. The antibody titers reached the peak at 4-6 weeks post first immunization, and persisted over a long time up to 6 months. No significant difference was observed in the induced antibody titers by bRBD and hRBD as well as their different doses. Virus Neutralization Assays showed that specific antibodies induced by RBD-immunized mice could inhibit the infection of ACE2-positive cells by SARS-CoV-2 pseudovirus. These results suggest that both RBD proteins through commendable adjuvant inoculation can rapidly induce an effective humoral immune response and generate specific neutralizing antibodies. It is expected to be helpful for rapid preparation of antibodies against the future various RBD mutants during the pandemic.