Background Microparticles (MPs) are one of the main medium of inflammatory reaction with an important role in atherosclerotic progression. Studies on association of air pollution exposure and levels of peripheral blood MPs are limited among human. Objective To evaluate the effects of short-term exposure to air pollution on levels of peripheral blood MPs. Method A panel of 73 healthy adults was followed with 4 repeated follow-ups in Beijing, China, from November 2014 to January 2016. During each visit, we collected questionnaire information, fasting venous blood, urine, and exposures to fine particulate matter (PM_2.5), black carbon, nitric oxide, nitrogen dioxide, nitrogen oxide, sulfur dioxide, carbon monoxide, and ozone. We used linear mixed-effect models to analyze associations of air pollution exposure with levels of total MPs (TMPs) and MPs derived from various cells. Stratified analysis was conducted by levels of C-reactive protein (CRP) and malondialdehyde (MDA). Results The results showed significant associations between air pollution exposure and peripheral blood TMPs at 2 h-6 d prior to the follow-ups (P<0.05), while no statistical associations were found for MPs derived from different cell types. Significant increases in TMPs of 7.8% (95%CI: 0.7%, 15.3%) and 14.3% (95%CI: 2.8%, 27.2%) were observed with each interquartile range (IQR) increase in PM_2.5 (IQR=64.9 μg·m⁻³) at prior 18 h and NO (IQR=40.5 μg·m⁻³) at prior 48 h. Among participants with low levels of CRP and MDA, significantly positive associations were observed between air pollution exposure and levels of TMPs (P<0.05). Conclusion Short-term exposure to air pollution is significantly associated with increased levels of circulating MPs in healthy adults, and in people with lower systemic inflammation, peripheral blood MPs levels are more easily affected after exposure to air pollutants.

Food-derived bioactive peptides (FBPs), particularly those with ten or fewer amino acid residues and a molecular weight below 1300 Da, have gained increasing attention for their safe, diverse structures and specific biological activities. The development of FBP-based functional foods and potential medications depends on understanding their structure‒activity relationships (SARs), stability, and bioavailability properties. In this review, we provide an in-depth overview of the roles of FBPs in treating various diseases, including Alzheimer's disease, hypertension, type 2 diabetes mellitus, liver diseases, and inflammatory bowel diseases, based on the literature from July 2017 to Mar. 2023. Subsequently, attention is directed toward elucidating the associations between the bioactivities and structural characteristics (e.g., molecular weight and the presence of specific amino acids within sequences and compositions) of FBPs. We also discuss in silico approaches for FBP screening and their limitations. Finally, we summarize recent advancements in formulation techniques to improve the bioavailability of FBPs in the food industry, thereby contributing to healthcare applications.
Humans ; Peptides/therapeutic use* ; Structure-Activity Relationship ; Functional Food ; Diabetes Mellitus, Type 2/drug therapy* ; Biological Availability ; Alzheimer Disease/drug therapy* ; Inflammatory Bowel Diseases/drug therapy* ; Hypertension/drug therapy* ; Liver Diseases/drug therapy* ; Bioactive Peptides, Dietary

Objective:To evaluate the efficacy of cyclophosphamide in patients with T-cell large granular lymphocytic leukemia (T-LGLL) and the maintenance of treatment-free remission (TFR) following drug discontinuation.Methods:Clinical data were collected from 37 patients with T-LGLL who received oral cyclophosphamide at the Regenerative Medicine Clinic of the Institute of Hematology and Blood Diseases Hospital between June 2019 and March 2024. Patient clinical characteristics, treatment efficacy, and long-term TFR were analyzed.Results:The median age of the 37 patients was 60 years (range: 37-86), and 22 (59.5%) were male. Anemia was observed in 30 patients (81.1%), and 28 (75.7%) met the diagnostic criteria for secondary pure red cell aplasia. Neutropenia occurred in 15 patients (40.5%), lymphocytosis in 11 (29.7%), and thrombocytopenia in three (8.1%). Sixteen patients (43.2%) had not received prior immunosuppressive therapy (treatment-naive group), while 21 patients (56.8%) were refractory to or had relapsed after immunosuppressive treatment (refractory/relapsed group). All patients met the treatment criteria and received oral cyclophosphamide at doses of 50-100 mg/day. Among the 36 evaluable patients, hematologic remission was achieved in 25 (69.4%), with a median time of 2.0 months (range: 0.7-7.0). There was no statistically significant difference in remission rates between the treatment-naive and refractory/relapsed groups (68.5% vs. 66.7%, P=0.589). Among the 25 patients who achieved hematologic remission, 24 discontinued cyclophosphamide. With a median follow-up of 39.0 months (range: 8.0-56.0), the median TFR duration was not reached. The estimated TFR rates were (90.87± 6.16) % at 12 months and (75.72±11.04) % at 36 months. No significant difference in TFR was observed between the treatment-naive and refractory/relapsed groups ( P=0.451) . Conclusion:Oral cyclophosphamide is effective in the treatment of T-LGLL, and patients may maintain long-term TFR following drug discontinuation.

Objective:To evaluate the efficacy of cyclophosphamide in patients with T-cell large granular lymphocytic leukemia (T-LGLL) and the maintenance of treatment-free remission (TFR) following drug discontinuation.Methods:Clinical data were collected from 37 patients with T-LGLL who received oral cyclophosphamide at the Regenerative Medicine Clinic of the Institute of Hematology and Blood Diseases Hospital between June 2019 and March 2024. Patient clinical characteristics, treatment efficacy, and long-term TFR were analyzed.Results:The median age of the 37 patients was 60 years (range: 37-86), and 22 (59.5%) were male. Anemia was observed in 30 patients (81.1%), and 28 (75.7%) met the diagnostic criteria for secondary pure red cell aplasia. Neutropenia occurred in 15 patients (40.5%), lymphocytosis in 11 (29.7%), and thrombocytopenia in three (8.1%). Sixteen patients (43.2%) had not received prior immunosuppressive therapy (treatment-naive group), while 21 patients (56.8%) were refractory to or had relapsed after immunosuppressive treatment (refractory/relapsed group). All patients met the treatment criteria and received oral cyclophosphamide at doses of 50-100 mg/day. Among the 36 evaluable patients, hematologic remission was achieved in 25 (69.4%), with a median time of 2.0 months (range: 0.7-7.0). There was no statistically significant difference in remission rates between the treatment-naive and refractory/relapsed groups (68.5% vs. 66.7%, P=0.589). Among the 25 patients who achieved hematologic remission, 24 discontinued cyclophosphamide. With a median follow-up of 39.0 months (range: 8.0-56.0), the median TFR duration was not reached. The estimated TFR rates were (90.87± 6.16) % at 12 months and (75.72±11.04) % at 36 months. No significant difference in TFR was observed between the treatment-naive and refractory/relapsed groups ( P=0.451) . Conclusion:Oral cyclophosphamide is effective in the treatment of T-LGLL, and patients may maintain long-term TFR following drug discontinuation.

Objective:To investigate the regulatory role of RNA m 6A methyltransferase (METTL14) in ultraviolet B (UVB) radiation-induced skin injury, and to preliminarily explore the potential of targeted inhibition of METTL14 for treating UVB-induced skin injury. Methods:A UVB radiation-induced skin injury model was established by exposing C57BL/6J mice to 150 mJ/cm 2 UVB, and was assessed and scored with HE staining and Masson staining. UVB radiation-induced cell injury models were established by exposing human immortalized keratinocytes (HaCaT) and human skin fibroblasts (WS1) to 10 and 30 mJ/cm 2 UVB, respectively. The m 6A levels in the mouse skin and cell models after UVB exposure were quantified by colorimetric assay, and m 6A-related enzymes in cells were measured by Western blot. HaCaT and WS1 cell lines overexpressing METTL14 were constructed using recombinant adenoviral vectors, and the overexpression effects were tested by Western blot. The METTL14 overexpression cells were examined for their m 6A levels, proliferative abilities after UVB exposure (by clone formation assay), and changes in apoptosis (by flow cytometry). The model mice with UVB-induced skin injury in the treatment groups received subcutaneous injection of the METTL14 inhibitor S-adenosylhomocysteine (SAH) solution (1 mg/kg, 5 mg/kg) twice consecutively before and after irradiation; and the mice were assessed and scored for skin injury with HE staining and Masson staining. Results:On the 4th day after 150 mJ/cm 2 UVB irradiation, the mice showed remarkable skin injury, pathologically featuring inflammatory infiltration, tissue structure disorganization, and collagen fiber degradation, reaching the maximum score; and the m 6A level in the skin was significantly downregulated ( t = 3.07, P < 0.05). At 24 h after 10 and 30 mJ/cm 2 irradiation, HaCaT and WS1 cells showed significantly reduced survival rates ( t = 7.64, 7.15, P < 0.05), significantly downregulated m 6A levels ( t = 4.78, 4.36, P <0.05), and significantly time-dependent downregulation of METTL14 protein expression ( t = 6.39, 4.76, P < 0.05). In HaCaT and WS1 cells, METTL14 overexpression significantly up-regulated m 6A levels ( t = 7.66, 3.67, P < 0.05), significantly inhibited the clone-forming ability of cells after UVB irradiation ( t = 6.29, 3.84, P < 0.05), and significantly increased the rate of cell apoptosis ( t = 3.48, 9.54, P < 0.05). Compared with those in the normal saline group, the model mice with UVB-induced skin injury in the SAH treatment group (5 mg/kg) showed significantly decreased pathological scores of skin injury ( t = 3.21, 4.27, 5.81, P < 0.05), with milder inflammatory infiltration, more orderly tissue structure, and less collagen fiber degradation. Conclusions:METTL14 can increase the sensitivity of skin cells to UVB radiation, and targeted inhibition of METTL14 can effectively alleviate UVB radiation-induced skin injury, which may be a potential new target for the treatment of UVB radiation-induced skin injury.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective:To investigate the differences in the clinical and imaging characteristics between intraductal tubularpapillary neoplasm of the pancreas (ITPN) and intraductal papillary mucinous neoplasm of pancreas (IPMN).Methods:From January 26, 2015 to October 31, 2023, at the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital), the clinical, pathological and imaging datas of 28 patients with ITPN and 68 patients with IPMN pathologically diagnosed after surgical resection were retrospectively analyzed. The clinical characteristics included age, gender, body mass index, presence or absense of jaundice, history of pancreatitis and surgical methods. Imaging features included the type of pancreatic duct involved by the tumor, location of the tumor, diameter of the main pancreatic duct (MPD) and common bile duct, location of solid components of the tumor, 2-tone duct sign of the MPD, morphology of the MPD upstream of the tumor, pancreatic atrophy, presence or absense of cystic lesions, calcification, and duodenum invasion. Multivariate logistic regression was performed to analyze independent predictive factors of ITPN and establish a diagnostic model. The receiver operating characteristic curve was drawn and the area under the curve (AUC) was calculated. Independent sample t-test, rank-sum test and chi-square test were used for statistical analysis. Results:All the patients with ITPN and IPMN had invasive cancer which was composed of ductal adenocarcinoma. The age of the patients with ITPN was younger than that of the patients with IPMN ((57.2±8.1) years old vs. (63.6±7.9) years old); the diameter of MPD of patients with ITPN was larger than that of the patients with IPMN (12.00 (8.00, 14.50) mm vs. 9.00 (6.00, 11.00) mm); the proportions of the solid tumor component confined within intraductal of pancreas (82.1%, 23/28 vs. 27.9%, 19/68), 2-tone duct sign of the MPD (67.9%, 19/28 vs. 8.8%, 6/68), and pancreatic atrophy (71.4%, 20/28 vs. 47.1%, 32/68) were all higher than those of patients with IPMN; and the proportions of abrupt change in caliber of upstream MPD and cystic lesions were both lower than those of patients with IPMN (25.0%, 7/28 vs. 60.3%, 41/68; 10.7%, 3/28 vs. 41.2%, 28/68); the differences were all statistically significant ( t=-3.53, Z=-2.34, χ2=23.68, 35.89, 4.74, 9.88 and 7.08; all P < 0.05). The results of multivariate logistic regression analysis showed that age, 2-tone duct sign of the MPD, and absence of cystic lesions were independent predictive factors of ITPN ( HR=1.11, 5.54, 10.13, 95% confidence interval (95% CI) 1.02 to 1.21, 1.22 to 25.17, 1.52 to 62.78, respectively; all P < 0.05). The AUC of the model distinguishing ITPN and IPMN established with the combination of the above 3 independent predictive factors was 0.87 (95% CI 0.79 to 0.95) with a sensitivity of 88.2% and with a specificity of 78.6%. Conclusion:Age, 2-tone duct sign of the MPD, and absence of cystic lesions are independent predictive factors of ITPN and IPMN, and the differential diagnosis model shows good diagnostic efficacy.

Objective:To analyze the diagnostic value of preoperative magnetic resonance imaging (MRI) in the diagnosis of pancreatic mucinous cystic neoplasm (MCN).Methods:The clinical, pathological and MRI imaging data of 128 patients with MCN diagnosed pathologically after surgical resection in the First Affiliated Hospital of Naval Medical University from March 2011 to February 2024 were retrospectively analyzed. According to the results of pre-opearative MRI diagnosis report, the patients were divided into correct diagnosis group and wrong diagnosis group, and the differences on the diagnostic doctors' subspecialty and MCN imaging features were compared between the two groups. According to the pathological grading criteria of MCN, the two groups were divided into benign group (low-grade dysplasia) and malignant group (high-grade dysplasia, invasive carcinoma), and the differences in imaging features between the two groups were compared. Imaging features included tumor location, tumor shape, monocyst or polycystic, unilocular or multilocular, tumor size, thickening of the wall or septa, hyperintensity on T 1WI, heterogeneity on T 2WI, enhanced mural nodule, main pancreatic duct dilation, and pancreatic parenchyma atrophy. Results:There were 53 cases (41.4%) in the correct diagnosis group and 75 cases (58.6%) in the wrong diagnosis group. There were 23 cases of fuzzy diagnosis (18.0%), 13 cases of serous cystadenoma (10.2%), 12 cases of pseudocyst (9.4%), 10 cases of intraductal papillary mucous neoplasm (7.8%), 9 cases of solid pseudopapillary neoplasm (7%), 3 cases of retention cyst (2.3%), 3 cases of pancreatic cancer (2.3%), and 2 cases of neuroendocrine neoplasm (1.6%). There was no significant difference between the two groups on the diagnostic doctors' subspecialty. The MCN being multilocular in the correct diagnosis group were more than that of the wrong diagnosis group and the difference was statistically significant ( P<0.05). There were 112 cases (87.5%) in the benign group and 16 cases (12.5%) in the malignant group. The MCN with being polycstic, thickening of the wall or septa, hyperintensity on T 1WI, enhanced mural nodule, main pancreatic duct dilation, and pancreatic parenchyma atrophy in the malignant group were more than that of the benign group, and the difference was statistically significant ( P<0.05). Conclusions:Preoperative MRI diagnosis of pancreatic MCN is difficult. The MCN being multilocular could significantly improve the accuracy of preoperative MRI diagnosis. Being polycystic, thickening of the wall or septa, hyperintensity on T 1WI, enhanced mural nodule, main pancreatic duct dilation, and pancreatic parenchyma atrophy are imaging features suggesting malignant MCN.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective:To analyze the diagnostic value of preoperative magnetic resonance imaging (MRI) in the diagnosis of pancreatic mucinous cystic neoplasm (MCN).Methods:The clinical, pathological and MRI imaging data of 128 patients with MCN diagnosed pathologically after surgical resection in the First Affiliated Hospital of Naval Medical University from March 2011 to February 2024 were retrospectively analyzed. According to the results of pre-opearative MRI diagnosis report, the patients were divided into correct diagnosis group and wrong diagnosis group, and the differences on the diagnostic doctors' subspecialty and MCN imaging features were compared between the two groups. According to the pathological grading criteria of MCN, the two groups were divided into benign group (low-grade dysplasia) and malignant group (high-grade dysplasia, invasive carcinoma), and the differences in imaging features between the two groups were compared. Imaging features included tumor location, tumor shape, monocyst or polycystic, unilocular or multilocular, tumor size, thickening of the wall or septa, hyperintensity on T 1WI, heterogeneity on T 2WI, enhanced mural nodule, main pancreatic duct dilation, and pancreatic parenchyma atrophy. Results:There were 53 cases (41.4%) in the correct diagnosis group and 75 cases (58.6%) in the wrong diagnosis group. There were 23 cases of fuzzy diagnosis (18.0%), 13 cases of serous cystadenoma (10.2%), 12 cases of pseudocyst (9.4%), 10 cases of intraductal papillary mucous neoplasm (7.8%), 9 cases of solid pseudopapillary neoplasm (7%), 3 cases of retention cyst (2.3%), 3 cases of pancreatic cancer (2.3%), and 2 cases of neuroendocrine neoplasm (1.6%). There was no significant difference between the two groups on the diagnostic doctors' subspecialty. The MCN being multilocular in the correct diagnosis group were more than that of the wrong diagnosis group and the difference was statistically significant ( P<0.05). There were 112 cases (87.5%) in the benign group and 16 cases (12.5%) in the malignant group. The MCN with being polycstic, thickening of the wall or septa, hyperintensity on T 1WI, enhanced mural nodule, main pancreatic duct dilation, and pancreatic parenchyma atrophy in the malignant group were more than that of the benign group, and the difference was statistically significant ( P<0.05). Conclusions:Preoperative MRI diagnosis of pancreatic MCN is difficult. The MCN being multilocular could significantly improve the accuracy of preoperative MRI diagnosis. Being polycystic, thickening of the wall or septa, hyperintensity on T 1WI, enhanced mural nodule, main pancreatic duct dilation, and pancreatic parenchyma atrophy are imaging features suggesting malignant MCN.