BACKGROUND:Autophagy,as a key regulatory mechanism of cell development,plays an important role in different stages of embryonic development.The mechanism of how autophagy regulates embryonic development through histone modifications is currently unclear.OBJECTIVE:To investigate the effect of autophagy on trimethylation of lysine 4 on histone H3(H3K4me3)modification in embryos and its effect on embryonic development.METHODS:Mouse fertilized eggs were divided into control and autophagy inhibitor-treated groups(chloroquine phosphate-treated group and 3-methyladenine-treated group),and cultured in vitro to different periods of time,and were then classified as early 2-cell embryos,middle 2-cell embryos,late 2-cell embryos,4-cell embryos,8-cell embryos,morula stage,and blastocyst stage.Levels of reactive oxygen species,autophagy marker proteins LC3B and P62,DNA loss marker γH2AX,and H3K4me3 were analyzed by immunofluorescence assay in late 2-cell embryos of each group.Changes in H3K4me3 modification in late 2-cell embryos of each group were detected by CUT&Tag.RESULTS AND CONCLUSION:(1)Autophagy inhibition caused embryo development arrest.(2)There was no significant difference in reactive oxygen species and γH2AX between the autophagy inhibitor-treated groups and control group.(3)H3K4me3 levels were significantly elevated in the autophagy inhibitor-treated group compared with the control group.(4)CUT&Tag results showed a significantly increased H3K4me3 peaks on the proximal promoter region of the genes after autophagy inhibition and an increase of H3K4me3-specific modification genes.These findings suggest that autophagy may affect embryonic development by regulating the level of H3K4me3 modification.

Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

ObjectiveTo construct a risk prediction model for frequent acute exacerbations of chronic obstructive pulmonary disease （COPD） under disease-syndrome combination， thus providing decision support for precise clinical intervention. MethodsA total of 2 029 patients with acute exacerbations of COPD admitted to the First Affiliated Hospital of Anhui University of Chinese Medicine from January 2020 to August 2024 were retrospectively included. These patients were classified into groups of frequent acute exacerbations （≥2 times/year） and infrequent acute exacerbations （<2 times/year） according to the hospitalization times per year. Risk factors were screened by LASSO regression combined with logistic regression， and a nomogram model was constructed. The model performance was assessed based on the area under the curve （AUC）， calibration curves， and decision curve analysis （DCA）. ResultsThe differences in baseline characteristics between the frequent acute exacerbations group （1 196 cases） and infrequent acute exacerbations group （833 cases） were not statistically significant. LASSO regression combined with multivariate logistic regression screened the following independent risk factors： body mass index （BMI）， hospitalization days， number of smoking years， place of residence， use of noninvasive ventilators， oxygen-demanding therapy， liver cirrhosis， use of systemic glucocorticosteroids， and traditional Chinese medicine syndrome （phlegm and stasis obstructing the lung）. The nomogram model showed good discrimination and calibration in both the training set （AUC=0.748） and validation set （AUC=0.774）. ConclusionThe risk prediction model for frequent acute exacerbations of COPD， integrating traditional Chinese medicine syndrome， constructed in this study has high accuracy. It can provide a scientific basis for early clinical identification of high-risk patients and individualized intervention.

Objective To introduce the causes of accidents and the diagnosis and treatment of two patients with radiation-induced skin injury admitted to our hospital in 2023, and to provide a reference for the clinical treatment of subsequent radiation-induced skin injury. Methods The clinical treatment process of two patients with acute skin injury caused by external radiation exposure were summarized and analyzed. Results The exposure history of the two patients was reconstructed, the flaw detection scenario was simulated, the biological dose and hand skin exposure dose were estimated, and the infrared thermal imaging device was used for dynamic monitoring. A comprehensive analysis was conducted based on clinical manifestations and other data. The diagnosis of “Xie” was excessive exposure combined with acute radiation-induced skin injury on both hands (Grade IV for the right hand palm, index finger, and middle finger and Grade II for the left hand little finger). The diagnosis of “Hao” was acute radiation-induced skin injury on both hands (Grade I). The two patients received different clinical treatment measures: “Xie” was treated with both local and systemic therapies, while “Hao” was mainly treated with systemic therapy. Conclusion After systematic and effective treatment, the radiation-induced skin injuries healed in both patients.

BACKGROUND:Autophagy,as a key regulatory mechanism of cell development,plays an important role in different stages of embryonic development.The mechanism of how autophagy regulates embryonic development through histone modifications is currently unclear.OBJECTIVE:To investigate the effect of autophagy on trimethylation of lysine 4 on histone H3(H3K4me3)modification in embryos and its effect on embryonic development.METHODS:Mouse fertilized eggs were divided into control and autophagy inhibitor-treated groups(chloroquine phosphate-treated group and 3-methyladenine-treated group),and cultured in vitro to different periods of time,and were then classified as early 2-cell embryos,middle 2-cell embryos,late 2-cell embryos,4-cell embryos,8-cell embryos,morula stage,and blastocyst stage.Levels of reactive oxygen species,autophagy marker proteins LC3B and P62,DNA loss marker γH2AX,and H3K4me3 were analyzed by immunofluorescence assay in late 2-cell embryos of each group.Changes in H3K4me3 modification in late 2-cell embryos of each group were detected by CUT&Tag.RESULTS AND CONCLUSION:(1)Autophagy inhibition caused embryo development arrest.(2)There was no significant difference in reactive oxygen species and γH2AX between the autophagy inhibitor-treated groups and control group.(3)H3K4me3 levels were significantly elevated in the autophagy inhibitor-treated group compared with the control group.(4)CUT&Tag results showed a significantly increased H3K4me3 peaks on the proximal promoter region of the genes after autophagy inhibition and an increase of H3K4me3-specific modification genes.These findings suggest that autophagy may affect embryonic development by regulating the level of H3K4me3 modification.

BACKGROUND:The guinea pig is considered to be the most useful spontaneous model for evaluating primary osteoarthritis in humans because of its similar knee joint structure and close histopathologic features to those of humans. OBJECTIVE:To investigate the pathological process of spontaneous knee osteoarthritis in guinea pigs by analyzing the histopathology of the total knee joint of guinea pigs aged 1 to 18 months. METHODS:Eight healthy female Hartley guinea pigs in each age group of 1,6,10,14,16,and 18 months old were selected.The quadriceps femoris was taken for hematoxylin-eosin staining,and the total knee joint was stained with hematoxylin-eosin and toluidine blue.The histopathology of the cartilage,subchondral bone,synovium,meniscus,and muscles were observed under light microscope.Mankin's score and synovitis score were compared,and the correlation analysis was conducted. RESULTS AND CONCLUSION:As the guinea pig age increased,the Mankin's score increased(P<0.05),and the pathological score of synovitis also gradually increased(P<0.05),and there was a significant positive correlation between the two(r=0.641,P<0.001).The incidence rate of subchondral bone marrow lesion in 18-month-old guinea pigs was 50%,and the incidence of meniscus injury was 37.5%.In addition,osteophyte and narrowing of the joint space were observed,and only a few guinea pigs had inflammation in the quadriceps femoris.To conclude,guinea pigs develop significant cartilage defects,synovial inflammation,subchondral bone lesions,meniscus injury,osteophyte formation,and joint space narrowing as they age,all of which are similar to the pathological processes of primary knee osteoarthritis in humans,making it an ideal model of spontaneous knee osteoarthritis.

OBJECTIVE To explore the effect of tracking methodology on investigation of contamination incidents of bronchoalveolar lavage fluid(BALF)specimens from the children.METHODS The onsite tracking was carried out for the contamination incidents of BALF specimens of the children through the tracking methodology,the quality control processes of cleaning and disinfection of bronchofiberscopes and the tracking routes were determined.The quality control process of cleaning and disinfection of bronchofiberscopes were evaluated,the existing risks were found out,and the specific improvement measures were formulated.RESULTS The onsite tracking was carried out for the incident of carbapenem-resistant Klebsiella pneumoniae(CRKP)that was caused by the contamination of 12 BALF specimens from pediatrics department wards before and after Nov.1,2021.No.2180014C bronchofiber-scope without biological surveillance was determined as the high-risk point of contamination of BALF specimens,the monitoring procedure of cleaning and disinfection of the bronchofiberscopes was revised.The BALF specimens that were submitted from Dec.1,2021 to Dec.31,2021 were tracked,and no CRKP was detected among the 23 submitted specimens.Totally 12 bronchofiberscope specimens were collected for biological surveillance,and the qualified rate was 100.00％.The treatment rooms of pediatrics department,hand disinfection effect of health care workers of cleaning and disinfection rooms and disinfection effect of object surfaces were monitored,and the quali-fied rate was increased from 98.39％to 100.00％.CONCLUSIONS The tracking methodology is an effective tool for quality management and can be used for evaluation of quality process of cleaning and disinfection of bronchofi-berscopes,which may find out the causes for adverse events in a timely manner and raise the medical safety.

Objective To explore the relationship between community health follow-up management and the mental health of the long-term care insurance residents,and to provide a basis for the construction of an integrated community home care service mode for disabled elders.Methods The residents were selected through cluster sampling who participated in LTCI home care from Jan 1 to Dec 31,2021.After a year of participation,the subjects'mental health was assessed face-to-face by trained community doctors using the Self-Rating Anxiety Scale and the Self-Rating Depression Scale.By referring to residents'electronic health records combined with on-site questionnaire survey,community doctors collected the demographic information and health follow-up management provided by primary medical and health institutions.The multivariate logistic regression were conducted to evaluate the association between follow-up care and mental health outcomes.Results The study consisted of 399 LTCI-enrolled individuals,57.64%(n=230)received follow-up care by family physicians.The prevalence of anxiety and depression among participants was 19.80%(n=79)and 67.67%(n=270),respectively.Univariate analysis found that community health follow-up management could underscore the potential impact of follow-up care in mitigating anxiety(χ2=38.926,P<0.001)and depression(χ2=14.598,P<0.001)among LTCI enrollees.Multivariate analysis revealed that follow-up care was an independent protective factor against anxiety(adjusted OR=0.351,95%CI:0.176-0.701,P=0.003).However,follow-up care did not significantly impact depression prevalence.Additionally,LTCI grade and education level were also identified factors influencing the mental health of participants(P<0.05).Conclusion Community health service centers provide health follow-up management that plays a positive role in alleviating the anxiety symptoms of disabled residents under long-term care insurance home care.It is an effective way to improve the quality of LTCI home care services.

Objective:To apply statistical process control (SPC) techniques to the quality assurance of non-normal radiotherapy plans through Johnson transformation, establishing patient-specific tolerance and action limits based on treatment sites and dose/distance assessment criteria, thereby enhancing the intensity-modulated radiation therapy (IMRT) verification accuracy and dose delivery precision.Methods:In this study, 951 gamma analysis data of patient-specific quality assurance (PSQA) executed on the Halcyon accelerator platform were selected and categorized into six groups based on treatment sites, including brain (102 cases), head and neck (100 cases), breast (229 cases), lung (154 cases), esophagus (223 cases), and pelvic (143 cases) groups. The six groups of data were statistically analyzed through Anderson-Darling normality tests ( α = 0.05) using Minitab 21 software. Non-normal data were transformed into normal data through Johnson transformation and then were used to establish treatment site-specific tolerance and action limits, which were compared with the Shewhart control charts based on normal distributions. Results:The PSQA result of the six groups all exhibited non-normal distributions ( P < 0.05). Through Johnson transformation, the tolerance and action limits for the head and neck, breast, lung, esophagus, and pelvic areas under the 3%/2 mm criterion ranged from 95.13% to 96.16% and 94.19% to 95.91%, respectively. In contrast, the tolerance and action limits ranged from 91.15% to 94.86% and 89.94% to 94.78% under the 2%/2 mm criterion. Directly applying Shewhart control charts without normality assumptions yielded higher tolerance limits compared to the application of Johnson transformation, increasing the false positive rate in the non-normal PSQA process. Conclusions:Applying the SPC techniques directly to a non-normal process can lead to an increased false alarm rate and wrong process interpretation. The SPC techniques combined with Johnson transformation enable more effective monitoring of a non-normal PSQA process, facilitating timely identification of potential factors that may lead to an out-of-control process based on the treatment site-specific limits.

Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.