Fine particulate matter (PM_2.5) is a critical environmental factor that currently affects human health. It primarily enters the body through inhalation and can induce adverse health effects in multiple systems, including respiratory, cardiovascular, nervous, and digestive systems. The homeostasis of gut microbiota is crucial for human health, and gut microbiota may exert multiple effects through the regulation of immune function, metabolic balance, and neural signal transmission. Recently, more and more studies have indicated that exposure to PM_2.5 may alter the composition and richness of gut microbiota and play a crucial role in the development and progression of various diseases through multiple pathways. Given the close interaction between PM_2.5 exposure and gut microbiota, we comprehensively reviewed the effects of ambient PM_2.5 exposure on gut microbiota and the potential underlying mechanisms based on existing epidemiological and toxicological studies. Additionally, the role of gut microbiota in the adverse health effects induced by PM_2.5 exposure, particularly in the context of gut-lung, gut-brain and gut-liver axis were also explored here.

Objective To investigate the feasibility of developing a grading diagnostic model for schistosomiasis-induced liver fibrosis based on B-mode ultrasonographic images and clinical laboratory indicators. Methods Ultrasound images and clinical laboratory testing data were captured from schistosomiasis patients admitted to the Second People’s Hospital of Duchang County, Jiangxi Province from 2018 to 2022. Patients with grade I schistosomiasis-induced liver fibrosis were enrolled in Group 1, and patients with grade II and III schistosomiasis-induced liver fibrosis were enrolled in Group 2. The machine learning binary classification tasks were created based on patients’radiomics and clinical laboratory data from 2018 to 2021 as the training set, and patients’radiomics and clinical laboratory data in 2022 as the validation set. The features of ultrasonographic images were labeled with the ITK-SNAP software, and the features of ultrasonographic images were extracted using the Python 3.7 package and PyRadiomics toolkit. The difference in the features of ultrasonographic images was compared between groups with t test or Mann-Whitney U test, and the key imaging features were selected with the least absolute shrinkage and selection operator (LASSO) regression algorithm. Four machine learning models were created using the Scikit-learn repository, including the support vector machine (SVM), random forest (RF), linear regression (LR) and extreme gradient boosting (XGBoost). The optimal machine learning model was screened with the receiver operating characteristic curve (ROC), and features with the greatest contributions to the differentiation features of ultrasound images in machine learning models with the SHapley Additive exPlanations (SHAP) method. Results The ultrasonographic imaging data and clinical laboratory testing data from 491 schistosomiasis patients from 2019 to 2022 were included in the study, and a total of 851 radiomics features and 54 clinical laboratory indicators were captured. Following statistical tests (t = −5.98 to 4.80, U = 6 550 to 20 994, all P values < 0.05) and screening of key features with LASSO regression, 44 features or indicators were included for the subsequent modeling. The areas under ROC curve (AUCs) were 0.763 and 0.611 for the training and validation sets of the SVM model based on clinical laboratory indicators, 0.951 and 0.892 for the training and validation sets of the SVM model based on radiomics, and 0.960 and 0.913 for the training and validation sets of the multimodal SVM model. The 10 greatest contributing features or indicators in machine learning models included 2 clinical laboratory indicators and 8 radiomics features. Conclusions The multimodal machine learning models created based on ultrasound-based radiomics and clinical laboratory indicators are feasible for intelligent identification of schistosomiasis-induced liver fibrosis, and are effective to improve the classification effect of one-class data models.

ObjectiveTo observe the effect of natural moxibustion at "Feishu （BL 13）" on immune balance of T helper cell 17 （Th17） / regulatory T cell （Treg） in healthy rats. MethodsForty-eight rats were randomly divided into 10 rats in the sham moxibustion group and 38 rats in natural moxibustion group. The rats in the sham moxibustion group applied blank acupoint stickers to bilateral "Feishu （BL 13）"， and the rats in natural moxibustion group applied acupoint stickers filled with Compound Banmao Ointment （复方斑蝥膏） to bilateral "Feishu （BL 13）" for a period of 8 h. Thirty rats in natural moxibustion group were successfully blistered after 8 h， and then were randomly divided into 1-day， 3-day and 7-day groups with 10 rats in each group. The general condition of rats was recorded during the experiment； different time groups of natural moxibustion were sampled at the corresponding time， and HE staining was used to observe the pathological changes of the skin in the area of application； flow cytometry was used to detect the subpopulations of Th17 and Treg in peripheral blood， and the value of Th17/Treg was calculated； and ELISA was used to detect the serum interleukin 17A （IL-17A） and interleukin 6 （IL-6）， interleukin 10 （IL-10） levels. ResultsCompared with sham moxibustion group， blisters can be seen in the application area of rats in 1-day natural moxibustion group， and the rats often scratched the skin of the moxibustion area， which showed loose stratum corneum， thickening of the stratum spinosum and stratum granulosum， absence of cells in the basal layer， inflammatory cell infiltration， and elevation of Treg in peripheral blood， and serum IL-17A， IL-6； in 3-day natural moxibustion group， the moxibustion area of the rats was scabbed and partially detached， with the most obvious dermatopathological changes， and elevated peripheral blood Th17 and Treg， and serum IL-17A， IL-6， IL-10； in 7-day natural moxibustion group， skin damage and pathological changes in the area of moxibustion were basically restored； Th17/Treg values were reduced in 1-， 3- and 7-day moxibustion groups after blistering （P＜0.05 or P＜0.01）. Compared with the 1-day moxibustion group， peripheral blood Th17， Treg， and serum IL-17A elevated in the 3-day moxibustion group； peripheral blood Treg， serum IL-17A， and IL-6 decreased， and Th17/Treg values elevated in the 7-day moxibustion group （P＜0.05 or P＜0.01）. Compared with the 3-day moxibustion group， the 7-day moxibustion group had lower peripheral blood Th17 and Treg， serum IL-17A， IL-6， and IL-10， and higher Th17/Treg values （P＜0.05 or P＜0.01）. ConclusionNatural moxibustion at "Feishu （BL 13）" can shift the Th17/Treg balance towards Treg of healthy rats， which will gradually lead to immune homeostasis， and regulate the relevant inflammatory factors in the serum to prevent inflammation from occurring and developing.

Tissue engineering bone technology, grounded in seed cells, cytokines, and scaffold supports, provides an effective solution for addressing extensive bone defects, demonstrating significant potentials in the field of bone repair. However, this technology still faces numerous challenges. Focusing on vascularization in engineered bones, this article reviews various methods to enhance vascularization within tissue-engineered bones, including multicellular co-culture, application of angiogenic factors, advanced 3D printing, and aid of surgical interventions. This article also analyses the latest research developments and the limitations of the methods, and speculates future research directions for tissue engineered bone.

Objective:To explore the clinical and genetic characteristics of patients with Ehlers-Danlos syndrome (EDS) and gastrointestinal involvement.Methods:We retrospectively collected the clinical data of patients with EDS and gastrointestinal involvement from the electronic medical records at Peking Union Medical College Hospital (PUMCH) from January 2003 to September 2023. Additionally, we conducted a systematic review by searching cases with EDS and gastrointestinal involvement in PubMed, Embase, Web of Science, and the Cochrane Library databases from January 2000 to September 2023.Results:Ninety-four patients with EDS and gastrointestinal involvement were retrieved, including five patients from PUMCH and 89 patients from 80 published articles. The average age of patients was (29±14) years. The most common manifestation of gastrointestinal involvement was gastrointestinal perforation ( n=46, 48.9%), followed by functional gastrointestinal symptoms ( n=33, 35.1%), and digestive arterial disorders ( n=10, 10.6%). The most common clinical subtype was vascular-EDS (vEDS) ( n=50, 53.2%) followed by hypermobile-EDS (hEDS) ( n=20, 21.3%). The most frequent genetic mutation occurred in the COL3A1 gene ( n=30, 31.9%). Among patients with vEDS, gastrointestinal manifestations included gastrointestinal perforation ( n=33, 66.0%), arterial lesions ( n=9, 18.0%), and functional gastrointestinal symptoms ( n=7, 14.0%). Among patients with hEDS, gastrointestinal manifestations included functional gastrointestinal symptoms ( n=18, 90.0%), visceral prolapse ( n=3, 15.0%) and intestinal volvulus ( n=1, 5.0%). Conclusions:The most common subtypes of gastrointestinal involvement in EDS were vEDS and hEDS. Patients with hEDS mainly presented with functional gastrointestinal symptoms, whereas those with vEDS primarily showed gastrointestinal perforation and digestive arterial disorders.

Objective:To investigate the application value of standardized outcomes in nephrology hemodialysis (SONG-HD) scale in evaluating the fatigue level of patients undergoing maintenance hemodialysis (MHD) patients and the factors that affect fatigue.Methods:A total of 201 patients undergoing regular MHD who received treatment in the Department of Nephrology, The First Affiliated Hospital of Xiamen University in April 2021 were included in April, 2021. The SONG-HD scale was used to evaluate patient's fatigue level. Fatigue was assessed using face-to-face interview questionnaire. Clinical and laboratory indicators were analyzed. Univariate logistic regression analysis and multivariate logistic regression analysis were performed to analyze the factors that affect fatigue of patients undergoing MHD.Results:Among the 201 MHD patients, 73.1% (147/201) had fatigue. The high-sensitivity C-reactive protein and parathyroid hormone levels in patients with fatigue were 0.91 (0.30, 3.63) mg/L and 216.00 (141.00, 347.00) ng/L, respectively, which were significantly higher than 0.40 (0.30, 2.01) mg/L and 153.00 (96.73, 308.50) ng/L in patients who had no fatigue ( Z = 2.12, 2.17, both P < 0.05). The pre-dialysis carbon dioxide binding capacity and blood albumin levels in patients who had fatigue were (21.03 ± 2.65) mmol/L and (36.76 ± 3.20) g/L, respectively, which were significantly lower than (22.68 ± 3.01) mmol/L and (38.61 ± 2.85) g/L in patients who had no fatigue ( t = 3.77, 3.73, both P < 0.05). Univariate logistic regression analysis showed that high-sensitivity C-reactive protein, pre-dialysis carbon dioxide binding capacity, serum albumin level, and parathyroid hormone level were related to the occurrence of fatigue in patients undergoing MHD ( Wald = 4.32, 12.39, 12.23, 4.66, all P < 0.05). Additionally, in a multivariate model adjusted for confounding factors, the independent risk factors for fatigue in patients undergoing MHD were relatively low pre-dialysis carbon dioxide binding capacity and serum albumin level ( Wald = 12.41, 11.67, both P < 0.05). Conclusion:The incidence of fatigue is high in patients undergoing MHD. The SONG-HD scale is convenient to use in assessing the fatigue level of patients undergoing MHD. After adjusting for confounding factors, fatigue in patients undergoing MHD is associated with reduced levels of pre-dialysis carbon dioxide binding capacity and serum albumin.

Objective:To correlate peripheral blood neutrophil-to-lymphocyte ratio with the occurrence of restless legs syndrome (RLS) in patients undergoing maintenance hemodialysis (MHD).Methods:This is a cross-sectional study. A total of 203 patients who underwent long-term MHD at the Blood Purification Center, Department of Nephrology, The First Affiliated Hospital of Xiamen University from May to June 2021 were included in this study. The counts of peripheral blood neutrophils and lymphocytes were determined and the neutrophil-to-lymphocyte ratio was calculated. These patients were divided into a RLS group and a non-RLS group according to whether they developed RLS. RLS-related factors were evaluated using face-to-face interview questionnaires. Various clinical and laboratory parameters were analyzed. The influential factors of RLS in patients undergoing MHD were analyzed through univariate regression analysis and multivariate logistic regression analysis.Results:A total of 203 patients undergoing MHD were enrolled, 30 individuals were determined as current RLS cases (14.78%). The levels of NLR and PTH in the RLS group were 4.86 (3.39, 5.82) L/L and 244.50 (143.25, 406.50) ng/L, respectively, which were significantly higher than those in the normal group [3.51 (2.60, 5.24) L/L, 147.00 (94.80, 263.50) ng/L, Z = -3.38, -2.64, both P < 0.05]. Univariate logistic regression analysis showed that NLR, PTH, uric acid, and neutrophil count were correlated with RLS (Wald χ2 = 7.96, 4.99, 4.76, 8.33, all P < 0.05). NLR was the independent risk factor of RLS (Wald χ2 = 6.14, P < 0.05) in multivariate models adjusting for confounding factor. Conclusion:The prevalence of RLS is high in patients undergoing MHD. RLS is assicuated with NLR among patients undergoing MHD after adjusting for confounding factor. RLS is likely associated with systemic inflammatory diseases.

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

Aim To investigate the protective effect of compound total flavonoids on atherosclerosis in ApoE -/- knockout mice.Methods Seven-week old C57BL/6 mice considered of the normal group (n =1 5 );seven-week old ApoE -/- mice were fed with high-fat diet and were assigned randomly into 5 groups:model group,simvastatin group,the low com-pound flavonoids group,the middle compound fla-vonoids group and the high compound flavonoids group.After 1 6 weeks,mice serum and aortas were harvested.The formation of atherosclerotic plaque was analyzed by HE staining,The serum level of lipids pro-files and superoxide dismutase (SOD )were deter-rnined.The levels of IL-1 βand NF-κB in serum were detected by ELISA assay.Results Area of atheroscle-rotic lesion was significantly less in the compound fla-vones group than in model.The level of TC,TG,LDL-C,IL-1 β,NF-κB in serum of the compound flavonoids group were decreased significantly,while SOD and HDL-C increased significantly compared with the mod-el group,and the difference was significant (P <0.05).Conclusion The compound flavonoids have a good protective effect on early atherosclerosis in mice, which may be due to its alleviating effects on hyperlipi-demia and inflammation and oxidation.

Objective To investigate the establishment,operation and performance of external quality assessment(EQA) system for microbial morphology and detection of special drug-resistance in clinical laboratory,and explore the value of the developed system in clinical application.Methods The pictures of known bacteria and fungi colony,gram staining and acid-fast staining from clinical microbiology were distributed to the participating laboratories in Gansu province twice a year at regular intervals.The pictures of standard knowledge points from CLSI,such as special drug resistance were distributed simultaneously.All the participating laboratories were required to complete the interpretation for the pictures and report their resuhs in a scheduled time.Then the resuhs were summarized and analyzed as 3 modes:complete consistency,general consistency and non-consistency.Results During the 2 years when the EQA system for microbial morphology and detection of special drug-resistance were performed for 24 times,the rate of annual complete consistency increased year by year and reached to 91.3％ in 2015.Conclusion The EQA system based on the examinations of microbial morphology and CLSI standard knowledge points for clinical laboratory may supervise the staff of clinical microbiology laboratories in the hospitals at second grade or above to master the skills of morphological identification and learn CLSI knowledge points,so their professional skills of clinical microbiology could be comprehensively improved.