Shift work, as a form of non-conventional work schedule, significantly increases the risk of vascular aging and related diseases due to circadian rhythm disruption, sleep disturbances, and unhealthy lifestyle behaviors. This review systematically summarized the mechanisms and epidemiological evidence linking shift work to vascular aging. Available studies indicated that shift work disrupts the rhythmic expression of core circadian clock genes (e.g., BMAL1, CLOCK, PER, CRY), leading to dysregulated glucose and lipid metabolism, enhanced oxidative stress, chronic inflammation, and altered diurnal blood pressure patterns, thereby directly impairing endothelial function and accelerating arterial stiffness. Sleep deprivation and fragmentation further reduce nitric oxide bioavailability and promote endothelin-1 secretion, exacerbating vascular constriction and inflammatory responses. Existing epidemiological data show that shift workers exhibit higher prevalence of hypertension, metabolic syndrome, and atherosclerosis compared with non-shift workers, accompanied by abnormal vascular function indicators such as pulse wave velocity and carotid intima-media thickness. Additionally, unhealthy dietary habits, psychological stress, and sedentary behavior in shift workers synergistically contribute to vascular aging. This review aims to provide a theoretical basis for the pathological link between shift work and vascular aging and to inform public health policy formulation and occupational health management.

To characterize the genomes of different emm-type group A Streptococcus (GAS), their virulence genes and drug resistance profiles in Tianjin City from 2011 to 2024. After PCR, a total of 42 strains with different years and emm types were selected for whole genome sequencing and multi-locus sequence typing (MLST), and the core genomes were used to generate a phylogenetic tree, after which the virulence genes and resistance genes were identified and analyzed, followed by the drug susceptibility test. In this study, the GAS strains were dominated by emm1 (50.0%) and emm12 (40.4%), and the MLST phenotypes were categorized into six types: ST36 (40.4%), ST1274 (26.1%), ST28 (23.8%), ST921 (4.7%), ST46 (2.3%), and ST403 (2.3%). There was a high consistency between their emm-types and ST types. A total of 68 virulence genes were detected in the genomes of 42 GAS strains, involving functional genes encoding exotoxin, bacterial adhesion, extracellular enzymes, etc. The virulence genes they carried were significantly different between emm1-type and emm12-type strains, such as speA. At the same time, the carrying rates of some virulence genes in the same emm-type strains changed with time, such as hyl. The resistance genes were basically the same among different emm-type strains except for the vanSE gene detected in all emm12 strains. The results of drug sensitivity showed that the GAS strains isolated in Tianjin City from 2011 to 2024 were sensitive to penicillin, cefazolin, chloramphenicol, vancomycin, and levofloxacin, while the resistance rates to erythromycin, azithromycin, clarithromycin, and clindamycin ranged from 88.5% to 100.0%, and there was a certain degree of consistency between the resistance phenotypes and the detected resistance genes. Overall, the main emm types and evolutionary features of GAS in Tianjin City from 2011 to 2024 were consistent with the dominant types in China, and the carrying rate of virulence genes and drug resistance genes differed significantly among different emm-type strains, and there were continuous evolution and variation in the prevalence of virulence genes in GAS.

Objective:To describe the distribution characteristics and trends of mortality and spatial aggregation of esophageal cancer in Shandong Province from 1970 to 2021.Methods:The mortality data of esophageal cancer were obtained from the death registration system of Shandong Province and three national all-cause mortality retrospective surveys. The crude mortality rate (CMR) and age-standardized mortality rate (ASMR, the Segi′s world standard population) were used to describe the mortality of esophageal cancer. Mortality differential decomposition was applied to quantify the contributions of demographic and non-demographic factors. The death levels of esophageal cancer in different counties (cities and districts) in Shandong Province from 1970 to 1974 and 2020 to 2021 were visualized by the ArcGIS 10.8 software, and global and local autocorrelation analyses were conducted by using the GeoDa 1.12 software.Results:The CMR of esophageal cancer in Shandong Province increased first and then decreased from 1970 to 2021. The CMR of esophageal cancer decreased from 17.59/100 000 in the period of 1970—1974 to 14.32/100 000 in the period of 2020—2021. The ASMR of esophageal cancer decreased from 20.04/100 000 in the period of 1970—1974 to 6.53/100 000 in the period of 2020—2021. Compared with the period of 1970—1974, both demographic and non-demographic factors contributed to the increase in esophageal cancer mortality rate from 1990 to 1992. However, demographic factors continued to contribute to the increase in esophageal cancer mortality rate from 2004 to 2005, 2011 to 2013, and 2020 to 2021, while non-demographic factors contributed to the continuous decrease in esophageal cancer mortality rate. The global autocorrelation analysis results showed that the Moran′s I index of ASMR of esophageal cancer in each county (city, district) of Shandong Province from 1970 to 1974 and from 2020 to 2021 were 0.67 and 0.57, respectively. Local autocorrelation analysis showed that there were 19 and 13 areas of high-high clustering of esophageal cancer in the periods of 1970—1974 and 2020—2021, respectively, with 12 overlapping counties (cities, districts). Conclusion:From 1970 to 2021, the CMR of esophageal cancer increases first and then decreases, while the ASMR of esophageal cancer gradually decreases in Shandong Province. The distribution of esophageal cancer mortality has significant spatial aggregation and changes over time.

Coptis chinensis Franch. and Panax ginseng C. A. Mey. are traditional herbal medicines with millennia of documented use and broad therapeutic applications, including anti-diabetic properties. However, the synergistic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus (T2DM) and its underlying mechanism remain unclear. The research demonstrated that the optimal ratio of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng was 4∶1, exhibiting maximal efficacy in improving insulin resistance and gluconeogenesis in primary mouse hepatocytes. This combination demonstrated significant synergistic effects in improving glucose tolerance, reducing fasting blood glucose (FBG), the weight ratio of epididymal white adipose tissue (eWAT), and the homeostasis model assessment of insulin resistance (HOMA-IR) in leptin receptor-deficient (db/db) mice. Subsequently, a T2DM liver-specific network was constructed based on RNA sequencing (RNA-seq) experiments and public databases by integrating transcriptional properties of disease-associated proteins and protein-protein interactions (PPIs). The network recovery index (NRI) score of the combined treatment group with a 4∶1 ratio exceeded that of groups treated with individual components. The research identified that activated adenosine 5'-monophosphate-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling in the liver played a crucial role in the synergistic treatment of T2DM, as verified by western blot experiment in db/db mice. These findings demonstrate that the 4∶1 combination of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng significantly improves insulin resistance and glucose and lipid metabolism disorders in db/db mice, surpassing the efficacy of individual treatments. The synergistic mechanism correlates with enhanced AMPK/ACC signaling pathway activity.
Animals ; Panax/chemistry* ; Ginsenosides/administration & dosage* ; Diabetes Mellitus, Type 2/metabolism* ; Mice ; Male ; Alkaloids/pharmacology* ; Coptis/chemistry* ; Drug Synergism ; Insulin Resistance ; Mice, Inbred C57BL ; Humans ; Transcriptome/drug effects* ; Blood Glucose/metabolism* ; Hypoglycemic Agents/administration & dosage* ; Drugs, Chinese Herbal/administration & dosage* ; Hepatocytes/metabolism*

To analyze the clinical data of patients with recurrent Clostridioides difficile infection(rCDI)in the southwestern region,and help clinicians identify high-risk populations early and adopt appropriate treatment strate-gies.Methods Clinical data of rCDI cases from a tertiary first-class hospital in southwest China from July 2019 to June 2024 were collected,and their host-related risk factors,exogenous risk factors,treatment schemes,and end-point outcomes were analyzed.Results In the past five years,a total of 26 cases of rCDI were detected from a ter-tiary first-class hospital in southwest China,accounting for 4.04％of the total positive cases(n=643)detected during the same period.19.23％of the recurrent patients experienced a second recurrence.The median age of rCDI patients was 66.5 years old,with males accounting for 73.08％.The major comorbidity included diabetes mellitus(34.62％),malignant tumors(30.77％),and chronic renal diseases(23.08％).In the 8 weeks before the first on-set of rCDI in patients,the top three drugs used were β-lactam and enzyme inhibitor compound(69.23％),proton pump inhibitors(65.38％),and carbapenems(46.15％).In the initial treatment of recurrent patients,3.85％(1/26)of the cases were treated with metronidazole,19.23％(5/26)of the cases received non-standard vancomy-cin/norvancomycin treatment in usage or dosage,46.15％(12/26)of the cases received treatment with course less than 10 days.In the treatment of the first recurrence,34.78％(8/26)of the cases received treatment with course less than 10 days.Conclusion For elderly patients and patients with diabetes mellitus,malignant tumors,and chronic renal diseases,who have used β-lactam and enzyme inhibitor compound,proton pump inhibitors,carbapene-ms within 8 weeks before disease onset,standard dose and treatment course of vancomycin or norvancomycin are recommended under permitted conditions,so as to reduce the risk of recurrence.

Objective:To understand spatial aggregation of lung cancer mortality and its changing trends over the past fifty years in different counties and districts of Shandong Province from 1970 to 2021.Methods:The mortality data of lung cancer were obtained from the death registration system of Shandong province and three retrospective surveys of death cause. The mortality rate and age-standardized mortality rate were used to describe the changing trend of lung cancer in different years, and the contribution value of population factors and non-population factors in lung cancer mortality change was calculated by the mortality differential decomposition method. GeoDa 1.20 and ArcGIS 10.8 software were used for spatial autocorrelation analysis and visualization map display.Results:The crude mortality rate of lung cancer in Shandong Province showed a significant upward trend from 1970 to 2021, rising from 7.22 per 100 000 in 1970-1974 to 62.73 per 100 000 in 2020-2021, with an increase of 7.69 times. Meanwhile, the standardized mortality rate of lung cancer exhibited a trend of increasing first and then decreasing. The differential analysis of lung cancer mortality in different years revealed that changes in crude mortality rates were the result of the combined effects of demographic and non-demographic factors. The proportion of population factors (aging population) leading to an increase in lung cancer mortality rate rose from 2.12% in 1990-1992 to 40.20% in 2020-2021. From a spatial distribution perspective, there were significant regional differences in lung cancer mortality rates among counties (cities, districts) in Shandong Province across different eras. Compared to the period of 1970-1974, the lung cancer mortality rates in all counties and districts in 2020-2021 showed a considerable increase, and there were noticeable changes in the areas of high-high and low-low clustering of lung cancer mortality rates across different eras.Conclusion:There have been significant temporal and spatial changes in the mortality rate of lung cancer in Shandong Province from 1970 to 2021. The crude mortality rate has shown an upward trend, while the standardized mortality rate increases first and then decreases. The concentration of lung cancer mortality rates in counties and districts has also undergone significant changes.

To characterize the genomes of different emm-type group A Streptococcus (GAS), their virulence genes and drug resistance profiles in Tianjin City from 2011 to 2024. After PCR, a total of 42 strains with different years and emm types were selected for whole genome sequencing and multi-locus sequence typing (MLST), and the core genomes were used to generate a phylogenetic tree, after which the virulence genes and resistance genes were identified and analyzed, followed by the drug susceptibility test. In this study, the GAS strains were dominated by emm1 (50.0%) and emm12 (40.4%), and the MLST phenotypes were categorized into six types: ST36 (40.4%), ST1274 (26.1%), ST28 (23.8%), ST921 (4.7%), ST46 (2.3%), and ST403 (2.3%). There was a high consistency between their emm-types and ST types. A total of 68 virulence genes were detected in the genomes of 42 GAS strains, involving functional genes encoding exotoxin, bacterial adhesion, extracellular enzymes, etc. The virulence genes they carried were significantly different between emm1-type and emm12-type strains, such as speA. At the same time, the carrying rates of some virulence genes in the same emm-type strains changed with time, such as hyl. The resistance genes were basically the same among different emm-type strains except for the vanSE gene detected in all emm12 strains. The results of drug sensitivity showed that the GAS strains isolated in Tianjin City from 2011 to 2024 were sensitive to penicillin, cefazolin, chloramphenicol, vancomycin, and levofloxacin, while the resistance rates to erythromycin, azithromycin, clarithromycin, and clindamycin ranged from 88.5% to 100.0%, and there was a certain degree of consistency between the resistance phenotypes and the detected resistance genes. Overall, the main emm types and evolutionary features of GAS in Tianjin City from 2011 to 2024 were consistent with the dominant types in China, and the carrying rate of virulence genes and drug resistance genes differed significantly among different emm-type strains, and there were continuous evolution and variation in the prevalence of virulence genes in GAS.

Objective:To describe the distribution characteristics and trends of mortality and spatial aggregation of esophageal cancer in Shandong Province from 1970 to 2021.Methods:The mortality data of esophageal cancer were obtained from the death registration system of Shandong Province and three national all-cause mortality retrospective surveys. The crude mortality rate (CMR) and age-standardized mortality rate (ASMR, the Segi′s world standard population) were used to describe the mortality of esophageal cancer. Mortality differential decomposition was applied to quantify the contributions of demographic and non-demographic factors. The death levels of esophageal cancer in different counties (cities and districts) in Shandong Province from 1970 to 1974 and 2020 to 2021 were visualized by the ArcGIS 10.8 software, and global and local autocorrelation analyses were conducted by using the GeoDa 1.12 software.Results:The CMR of esophageal cancer in Shandong Province increased first and then decreased from 1970 to 2021. The CMR of esophageal cancer decreased from 17.59/100 000 in the period of 1970—1974 to 14.32/100 000 in the period of 2020—2021. The ASMR of esophageal cancer decreased from 20.04/100 000 in the period of 1970—1974 to 6.53/100 000 in the period of 2020—2021. Compared with the period of 1970—1974, both demographic and non-demographic factors contributed to the increase in esophageal cancer mortality rate from 1990 to 1992. However, demographic factors continued to contribute to the increase in esophageal cancer mortality rate from 2004 to 2005, 2011 to 2013, and 2020 to 2021, while non-demographic factors contributed to the continuous decrease in esophageal cancer mortality rate. The global autocorrelation analysis results showed that the Moran′s I index of ASMR of esophageal cancer in each county (city, district) of Shandong Province from 1970 to 1974 and from 2020 to 2021 were 0.67 and 0.57, respectively. Local autocorrelation analysis showed that there were 19 and 13 areas of high-high clustering of esophageal cancer in the periods of 1970—1974 and 2020—2021, respectively, with 12 overlapping counties (cities, districts). Conclusion:From 1970 to 2021, the CMR of esophageal cancer increases first and then decreases, while the ASMR of esophageal cancer gradually decreases in Shandong Province. The distribution of esophageal cancer mortality has significant spatial aggregation and changes over time.

Objective:To explore the spatial clustering of the mortality rate of cervical cancer in different counties (cities, districts) in Shandong Province from 1970 to 2021 and its 50-year changing trend, so as to provide basis for the implementation and evaluation of prevention and control strategies and programs such as cervical cancer screening, early diagnosis and treatment, human papilloma virus (HPV) vaccination, etc.Methods:The mortality data of cervical cancer were obtained from the death registration system of Shandong Province and the data of three retrospective surveys of death causes. The mortality rate and age-standardized mortality rate (using the population composition of China in 1964) are used to describe the changing trend of cervical cancer in different years. The contribution values of population factors and non-population factors in cervical cancer mortality change are calculated by mortality differential decomposition method. ArcGIS 10.8 software is used for spatial distribution and spatial autocorrelation analysis.Results:From 1970 to 2021, the crude mortality rate and age standardized mortality rate of cervical cancer in Shandong Province showed a trend of first rapid decline and then slow increase. The crude mortality rate and standardized mortality rate of female cervical cancer in Shandong Province in 1970-1974 were the highest, reaching 17.22/10 5 and 13.17/10 5, respectively. In 2004-2005, it dropped to the lowest levels of 1.50/10 5 and 0.83/10 5. Subsequently, it slowly rose to 4.12/10 5 and 1.56/10 5 in 2020-2021. The differential analysis of cervical cancer mortality in different years found that the change of cervical cancer mortality was caused by the combined action of population factors and non-population factors. Among them, demographic factors (aging population) led to the increase of cervical cancer mortality, but non-demographic factors (early diagnosis and treatment, HPV infection level, medical technology level, etc) lead to the decrease of cervical cancer mortality. Compared with 1970-1974, with the passage of time, the absolute values of the contribution values of population factors and non-population factors showed an increasing trend, while the contribution of non-population factors was greater than that of population factors, which led to the decline of cervical cancer mortality. From the perspective of spatial distribution, there were great regional differences in the mortality rate of cervical cancer in different counties of Shandong Province. In 2020-2021, the mortality rate of cervical cancer in all counties decreased to a great extent compared with that in 1970-1974, and the high-high and low-low concentration areas of cervical cancer mortality in different years changed obviously. The high-aggregation areas of the cervical cancer mortality rate in Shandong Province from 2020 to 2021 were mainly distributed in some counties and districts of Linyi City, Zaozhuang City, and Heze City in the southwest. Conclusions:There are significant temporal and spatial changes in the mortality rate of cervical cancer in Shandong Province from 1970 to 2021. According to these trends and their geographical and spatial clustering, prevention and control strategies of cervical cancer in different regions should be further formulated and evaluated.

Objective:To evaluate the efficacy of eculizumab in treating hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) .Methods:This retrospective study included 11 patients who developed TA-TMA after allogeneic hematopoietic stem cell transplantation and subsequently received eculizumab treatment at Peking University People′s Hospital between June 2018 and May 2024. The incidence of TA-TMA, treatment details, and clinical outcomes were analyzed.Results:Among the 11 included patients [4 males, 7 females; median age: 29 years (range: 9-56) ], underlying diseases were severe aplastic anemia (SAA) in 5 patients, acute lymphoblastic leukemia (ALL) in 3 patients, and acute myeloid leukemia (AML) in 3 patients. The median time to TA-TMA diagnosis was 48 days post-transplantation (range: 4-213 days), and all patients met the diagnostic criteria for high-risk TA-TMA. The median interval from TA-TMA diagnosis to the initiation of eculizumab treatment was 12 days (range: 1-56 days). Patients received a median of 3 doses of eculizumab (range: 1-14). Ten of the 11 patients were assessed as having no response (NR) to eculizumab at the end of treatment or at death. One patient achieved a partial response (PR) but subsequently died after TA-TMA relapsed due to infection. At the last follow-up, all patients were either lost to follow-up or had died. The median follow-up duration was 88 days (range: 33-326 days), and the median time from TA-TMA diagnosis to the last follow-up was 31 days (range: 21-113 days) .Conclusion:Eculizumab demonstrated poor efficacy in this TA-TMA cohort. This might be attributable to the critical and complex condition of the patients, delayed initiation of eculizumab treatment, and insufficient dosage.