Background Lung cancer, one of the most common malignant tumors worldwide, has long ranked first in cancer incidence and mortality, posing a severe challenge to public health systems. Objective To analyze the trends in incidence, mortality, and disability-adjusted life years (DALYs) of lung cancer among residents in Jing'an District, Shanghai, from 2002 to 2021, explore the impacts of population aging, population growth, and age-specific prevalence on disease burden, and provide a scientific basis for optimizing regional lung cancer prevention and control strategies. Methods Based on the cancer registration and cause-of-death surveillance data of registered residents in Jing'an District, Shanghai, from 2002 to 2021, Joinpoint regression models were used to analyze the annual change trends (APC) and average annual change trends (AAPC) of lung cancer incidence, mortality, DALY rate, and their age-standardized rates. Decomposition analysis was applied to quantify the contribution of population aging, population growth, and age-specific prevalence to changes in the number of new cases, deaths, and DALYs. Results From 2002 to 2021, the crude incidence rate of lung cancer in Jing'an District increased from 68.00 per 100000 to 144.36 per 100000 (AAPC=4.86%, P<0.001), and the age-standardized incidence rate rose from 43.09 per 100000 to 61.46 per 100000 (AAPC=2.89%, P<0.001). The growth rate of incidence was significantly higher in females (AAPC=6.73%) than in males (AAPC=3.62%). The crude mortality rate increased from 58.08 per 100000 to 66.11 per 100000 (AAPC=1.10%, P<0.001), while the age-standardized mortality rate decreased (AAPC=−1.54%, P<0.001). The crude DALY rate showed an upward trend (AAPC=0.94%, P=0.002), whereas the age-standardized DALY rate declined (AAPC=−1.63%, P<0.001). Significant differences were observed across genders and age groups: the mortality and DALY rates increased in males aged 60-64 years, while the fastest incidence growth occurred in females aged 45-64 years. The results of decomposition analysis indicated that the increase in new cases was primarily attributed to age-specific incidence (38.15%) and aging (37.31%); the growth in deaths and DALYs was driven by aging, while age-specific mortality and population growth showed offsetting effects. From 2002 to 2021, the probability of premature death from lung cancer among males (2.04%-2.52%) in Jing'an District showed no statistically significant trend (AAPC=−0.28%, P=0.440), while it presented a decreasing trend in the total population (1.37%-1.89%) and females (0.72%-1.26%) (AAPC=−0.80% and −2.23%, respectively; P=0.029 and <0.001, respectively). Conclusion From 2002 to 2021, the risk of lung cancer incidence in Jing’an District, Shanghai, continue to increase, with a disease burden exhibiting significant heterogeneity by gender and age: key features include a rapid increase in new cases and a trend toward younger onset among females, alongside rising mortality risk among males aged 60–64 years. Population aging and increasing age-specific incidence rates are primary drivers of the growing number of cases, while declining age-specific mortality rates mitigate the rise in mortality burden.

OBJECTIVES: To investigate the antioxidative mechanism of snake venom-derived protein C activator (PCA) in mitigating vascular endothelial cell injury. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured in DMEM containing 1.0 g/L D-glucose and exposed to hypoxia (1% O₂) for 6 h followed by reoxygenation for 2 h to establish a cell model of oxygen-glucose deprivation/reoxygenation (OGD/R). The cell model was treated with 2 μg/mL PCA alone or in combination with 2-ME2 (a HIF-1α inhibitor) or DMOG (a HIF-1α stabilizer), and intracellular production of reactive oxygen species (ROS) and protein expression levels of HIF-1α, BNIP3, and Beclin-1 were detected using DCFH-DA fluorescence probe, flow cytometry, and Western blotting. The OGD/R cell model was transfected with a BNIP3-specific siRNA or a scrambled control sequence prior to PCA treatment, and the changes in protein expressions of HIF-1α, BNIP3 and Beclin-1 and intracellular ROS production were examined. RESULTS: In the OGD/R cell model, PCA treatment significantly upregulated HIF-1α, BNIP3 and Beclin-1 expressions and reduced ROS production. The effects of PCA were obviously attenuated by co-treatment with 2-ME2 but augmented by treatment with DMOG (a HIF-1α stabilizer). In the cell model with BNIP3 knockdown, PCA treatment increased BNIP3 expression and decreased ROS production without causing significant changes in HIF-1α expression. Compared with HUVECs with PCA treatment only, the cells with BNIP3 knockdown prior to PCA treatment showed significantly lower Beclin-1 expression and higher ROS levels. CONCLUSIONS Snake venom PCA alleviates OGD/R-induced endothelial cell injury by upregulating HIF-1α/BNIP3 signaling to suppress ROS generation, suggesting its potential as a therapeutic agent against oxidative stress in vascular pathologies.
Humans ; Reactive Oxygen Species/metabolism* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Human Umbilical Vein Endothelial Cells/drug effects* ; Membrane Proteins/metabolism* ; Proto-Oncogene Proteins/metabolism* ; Up-Regulation ; Cell Hypoxia ; Cells, Cultured ; Snake Venoms/chemistry* ; Beclin-1

Objective To investigate the clinical efficacy of the Lower Limb Detumescence Formula(derived from Taohong Siwu Decoction)in treating lower limb swelling in patients with qi stagnation and blood stasis syndrome after total knee arthroplasty(TKA),and to analyze the changes in traditional Chinese medicine(TCM)syndrome types before and after surgery.Methods A total of 60 patients diagnosed with knee osteoarthritis and lower limb swelling with qi stagnation and blood stasis syndrome after TKA,hospitalized in the Department of Artificial Joints and Knee Surgery,The First Affiliated Hospital of Guangzhou University of Chinese Medicine between November 2024 and January 2025,were selected.Based on patients' preferences and postoperative medication,the patients were divided into three groups:the Chinese medicine Group(25 cases),the Lishang Group(15 cases),and the Aescuven Forte Group(20 cases).Changes in limb circumference on the affected side were used to describe knee volume changes,and were measured preoperatively and on postoperative days 1,3,and 30.Results(1)Regarding lower limb swelling,the calf and thigh circumferences of the affected side in all three groups showed a trend of early exacerbation(on postoperative days 1 and 3)followed by later relief(on postoperative day 30).Peak swelling occurred on postoperative day 3,with statistically significant differences compared to preoperative measurements(P＜0.05).Subsequently,swelling gradually alleviated,and the calf and thigh circumferences of the affected side progressively decreased,the circum ferences on postoperative day 30 differed from those on postoperative days 1 and 3(P＜0.05).However,there were no statistically significant differences in improving calf and thigh circumferences among the three groups(P＞0.05).(2)In terms of adverse reactions,the Lishang Group and the Aescuven Forte Group each reported two adverse events,including postoperative wound bleeding,subcutaneous ecchymosis,pulmonary infection,and constipation.The Chinese medicine group reported no gastrointestinal adverse events,and patient treatment compliance was better than that in the Lishang Group and the Aescuven Forte Group.(3)Regarding TCM syndrome differentiation,each patient received four assessments at different time points(preoperatively and on postoperative days 1,3,and 30),resulting in 240 valid data entries.Among these,qi stagnation and blood stasis syndrome was the most common(170 cases,70.83％),followed by liver and kidney deficiency syndrome(64 cases,26.67％),and qi and blood deficiency syndrome was the least common(6 cases,2.50％).(4)Comparison of the relationship between different groups and syndrome types revealed no significant association between group distribution and syndrome type(P＞0.05).Further generalized estimating equation analysis showed that grouping had no significant effect on TCM syndrome differentiation(P＞0.05).(5)Comparison of the relationship between different time points and syndrome types revealed that preoperative syndromes predominantly consisted of liver and kidney deficiency(96.67％),while on postoperative days 1 and 3,all cases were classified as qi stagnation and blood stasis syndrome(100.00％).On postoperative day 30,qi stagnation and blood stasis syndrome remained the most common(80.00％).There was a significant association between time points and syndrome distribution(P＜0.05).Further generalized estimating equation analysis indicated that time points significantly influenced TCM syndrome differentiation(P＜0.001).Conclusion The Lower Limb Detumescence Formula demonstrates efficacy comparable to Lishang Xiaozhong Oral Liquid and Aescuven Forte Tablets in improving lower limb swelling in patients with qi stagnation and blood stasis syndrome after TKA.By promoting blood circulation,resolving stasis,strengthening the spleen,and eliminating accumulation,this formula reduces the incidence of adverse reactions such as postoperative wound bleeding,subcutaneous ecchymosis,and constipation.It provides a new pharmacological option for treating lower limb swelling after TKA,and is particularly suitable for patients with qi stagnation and blood stasis syndrome accompanied by spleen deficiency.

Objective:To explore the establishment and application of ovarian cancer organoids.Methods:Fresh ovarian tumor tissues, obtaining from patients underwent surgery in the First Affiliated Hospital of Nanjing Medical University between October 2021 and March 2022, were collected, enzymatic degraded, digested, and embedded into matrigel to establish organoids. A total of 32 ovarian cancer samples were collected. Hematoxylin eosin (HE) staining and immunofluorescence (IF) procedure were used to verify the morphological structure of organoids and their expression of molecular markers. 3D cyto-live or dead assay was used to detecte the live or dead cells in organoids. Carboplatin with a concentration ranging from 5 to 80 μmol/L (5, 10, 20, 40, 80 μmol/L) was added to organoids to calculate the 50% inhibitory concentration (IC 50) in different organoids. Results:(1) Organoids from a total of 32 patients were established, of which 18 cases could be passaged stably in the long term in vitro, while 14 could be passaged in the short time. The average amplification time of long-term passage in vitro was over 3 months, and the longest reached 9 months. (2) In HE staining, significant nuclei atypia and local micropapillary structures were observed in organoids. IF staining revealed that ovarian cancer organoids expressed molecular markers similar to primary tumor tissues, such as Pan cytokeratin (Pan-CK), p53, paired box gene 8 (PAX8), and Wilms tumor gene 1 (WT1). (3) In 3D cyto-live or dead assay, a large number of apoptotic cells were observed inside and around the organoids after added carboplatin. The sensitivity to carboplatin varied in 18 organoids could amplify in the long term, with an average IC 50 of (29.5±15.8) μmol/L. Moreover, IC 50 values of 4 organoids derived from patients received neoadjuvant chemotherapy were much higher than the 14 organoids which did not received neoadjuvant chemotherapy [(48.7±11.3) μmol/L vs (24.0±12.1) μmol/L; t=3.429, P=0.022]. Conclusions:Organoids recapitulate ovarian cancers in vitro and could be stably passaged. Organoids derived from patients received neoadjuvant chemotherapy have higher resistance to carboplatin.

Objective:To investigate the effects of standardized treatment combined with medical nutrition intervention on blood glucose level, body mass management and glucose metabolism at 3 months postpartum in patients with gestational diabetes mellitus (GDM).Methods:A total of 114 patients with GDM who received treatment in Shunyi District Hospital of Beijing from June 2017 to October 2019 were included in this study. They were randomly divided into observation group ( n = 57) and control group ( n = 57). The control group was treated with standardized therapy, and the observation group was treated with standardized therapy combined with medical nutrition intervention. Blood glucose level, body mass management, glucose metabolism outcomes at 3 months postpartum, pregnancy outcome, and neonatal outcome were compared between the two groups. Results:After treatment, hemoglobin A1c (HbA1c), fasting blood glucose, 2-hour plasma glucose (2hPG) after breakfast, and 2hPG after dinner in the observation group were (5.20 ± 0.34)%, (4.69 ± 0.31) mmol/L, (7.32 ± 2.13) mmol/L, and (7.54 ± 2.36) mmol/L, respectively, which were significantly lower than those in the control group [(6.38 ± 0.42)%, (6.34 ± 0.45) mmol/L, (9.01 ± 2.27) mmol/L, (9.35 ± 2.47) mmol/L, t = 16.48, 22.79, 4.09, 4.00, all P < 0.001]. The increases in body mass and body mass index during pregnancy in the observation groups were (12.19 ± 2.35) kg and (4.52 ± 1.13) kg/m 2, respectively, which were significantly lower than those in the control group [(16.21 ± 2.64) kg, (6.11 ± 1.25) kg/m 2, t = 8.58, 7.12, both P < 0.001]. The abnormal rate of glucose metabolism at 3 months postpartum in the observation group was significantly lower than that in the control group [5.3% (3/57) vs. 8.8% (5/57), χ2 = 0.53, P = 0.462]. The incidences of premature rupture of membranes, polyhydramnios, and cesarean section in the observation group were 5.3% (3/57), 14.0% (8/57) and 15.8% (9/57), which were significantly lower than those in the control group [22.8% (13/57), 35.1% (20/57), 40.4% (23/57), χ2 = 7.27, 6.81, 8.51, all P < 0.05]. There were no significant differences in the incidences of pregnancy-induced hypertension and postpartum hemorrhage between the two groups (both P > 0.05). The incidences of premature births, macrosomia, respiratory distress, neonatal hypoglycemia and hyperbilirubinemia in the observation groups were 5.3% (3/57), 3.5% (2/57), 7.0% (4/57), 3.5% (2/57), 5.3% (3/57), respectively, which were significantly lower than those in the control group [22.8% (13/57), 17.5% (10/57), 21.1% (12/57), 15.8% (9/57), 19.3% (11/57), χ2 = 7.27, 5.96, 5.60, 4.93, 5.21, all P < 0.05). Conclusion:Standardized treatment combined with medical nutrition intervention can effectively reduce blood glucose level in patients with GMD, control body mass, and improve glucose metabolism at 3 months after delivery.

Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

Objective:To study the association between apparent temperature (AT) and the incidence of hand,foot, and mouth disease (HFMD) and its spatial heterogeneity in 46 cities in Guangdong, Anhui and Jilin provinces, and provide scientific evidence for the early warning of HFMD.Methods:The data of HFMD incidence and meteorological factors from 2009 to 2018 in Guangdong province, 2009 to 2015 in Anhui province, and 2013 to 2018 in Jilin province were collected. Distributed lag non-linear models were constructed to investigate the association between AT and the incidence of HFMD in 46 cities from three provinces in China. Meta-analysis was used to pool the city-specific estimates, and Meta-regression was applied to analyze the factors that may cause spatial heterogeneity.Results:The relationship between daily AT and the incidence of HFMD in 46 cities appeared nonlinear. The association in Guangdong was similar to that in Jilin, and the risk of HFMD increased with the increase of AT. While the risk of HFMD in Anhui first increased with the increase of AT, and peaked at 18.1 ℃ and then went down. AT on different levels showed different lag impacts and the higher AT showed greater and longer lag impact. The spatial heterogeneity of associations may have been caused by latitude, longitude, average temperature, and average sunshine hours.Conclusions:AT is a comprehensive index to evaluate the association between temperature, relative humidity and wind speed and the incidence of HFMD. Higher AT may increase the risk of HFMD. The AT and HFMD relationship across spatial heterogeneity varies depending on geographic location and meteorological conditions.

Objective:To determine the viral load of human herpesvirus 6 A (HHV-6A), HHV-6B and chromosomal integrated HHV-6 (ciHHV-6) simultaneously through a triple chip digital PCR (tcdPCR) method for detection of HHV-6A/6B and ribonuclease P-30 (RPP30).Methods:According to optimal reaction conditions of real-time fluorescence quantitative PCR (RT-qPCR) method, the tcdPCR mehod of HHV-6A, HHV-6B and RPP30 was established. The sensitivity of tcdPCR was determined by virus cultures and the specificity of tcdPCR was detected with other herpesviruses. Subsequently, the tcdPCR of HHV-6A, HHV-6B and RPP30 was verified through 127 whole blood samples.Results:The consistency between RT-qPCR and tcdPCR for HHV-6 detection was good (R 2>0.97). And there was no cross-reaction with other herpesviruses. The 14 positive samples could be detected effectively by the tcdPCR of HHV-6A, HHV-6B and RPP30. The lowest detectable viral load of HHV-6A and HHV-6B was 50 copies/ml and 105 copies/ml, respectively. And the ratio of HHV-6/(RPP30/2) in 14 positive samples was less than 1. Conclusions:The tcdPCR has good sensitivity and specificity. And HHV-6 tcdPCR method can quantitatively detect the viral load of HHV-6 infection and the copy number of RPP30, and ciHHV-6 can be judged by ratio of HHV-6/(RPP30/2) in clinical samples.

Objective To compare the epidemiological characteristics of COVID-19 in Guangzhou and Wenzhou, and evaluate the effectiveness of their prevention and control measures. Methods Data of COVID-19 cases reported in Guangzhou and Wenzhou as of 29 February, 2020 were collected. The incidence curves of COVID-19 in two cities were constructed. The real time reproduction number ( R t ) of COVID-19 in two cities was calculated respectively. Results A total of 346 and 465 confirmed COVID-19 cases were analysed in Guangzhou and Wenzhou, respectively. In two cities, most cases were aged 30-59 years (Guangzhou: 54.9%; Wenzhou: 70.3%). The incidence curve peaked on 27 January, 2020 in Guangzhou and on 26 January, 2020 in Wenzhou, then began to decline in both cities. The peaks of imported COVID-19 cases from Hubei occurred earlier than the peak of COVID-19 incidences in two cities, and the peak of imported cases from Hubei occurred earlier in Wenzhou than in Guangzhou. In early epidemic phase, imported cases were predominant in both cities, then the number of local cases increased and gradually took the dominance in Wenzhou. In Guangzhou, the imported cases was still predominant. Despite the different epidemic pattern, the R t and the number of COVID-19 cases declined after strict prevention and control measures were taken in Guangzhou and in Wenzhou. Conclusion The time and scale specific differences of imported COVID-19 resulted in different epidemic patterns in two cities, but the spread of the disease were effectively controlled after taking strict prevention and control measures.

Objective To assess the imported risk of COVID-19 in Guangdong province and its cities, and conduct early warning. Methods Data of reported COVID-19 cases and Baidu Migration Index of 21 cities in Guangdong province and other provinces of China as of February 25, 2020 were collected. The imported risk index of each city in Guangdong province were calculated, and then correlation analysis was performed between reported cases and the imported risk index to identify lag time. Finally, we classified the early warming levels of epidemic by imported risk index. Results A total of 1 347 confirmed cases were reported in Guangdong province, and 90.0% of the cases were clustered in the Pearl River Delta region. The average daily imported risk index of Guangdong was 44.03. Among the imported risk sources of each city, the highest risk of almost all cities came from Hubei province, except for Zhanjiang from Hainan province. In addition, the neighboring provinces of Guangdong province also had a greater impact. The correlation between the imported risk index with a lag of 4 days and the daily reported cases was the strongest (correlation coefficient: 0.73). The early warning base on cumulative 4-day risk of each city showed that Dongguan, Shenzhen, Zhongshan, Guangzhou, Foshan and Huizhou have high imported risks in the next 4 days, with imported risk indexes of 38.85, 21.59, 11.67, 11.25, 6.19 and 5.92, and the highest risk still comes from Hubei province. Conclusions Cities with a large number of migrants in Guangdong province have a higher risk of import. Hubei province and neighboring provinces in Guangdong province are the main source of the imported risk. Each city must strengthen the health management of migrants in high-risk provinces and reduce the imported risk of Guangdong province.