Objective To establish an individualized nomogram model and evaluate its efficacy to provide a possible evaluation basis for the prognosis of lower third and abdominal part of oesophageal adenocarcinoma (EAC). Methods Lower third and abdominal part of EAC patients from 2010 to 2015 were chosen from the SEER Research Plus Database (17 Regs, 2022nov sub). The patients were randomly allocated to the training cohort and the internal validation cohort with a ratio of 7∶3 using bootstrap resampling. The Cox proportional hazards regression analysis was used to determine significant contributors to overall survival (OS) in EAC patients, which would be elected to construct the nomogram prediction model. C-index, calibration curve and receiver operating characteristic (ROC) curve were performed to evaluate its efficacy. Finally, the efficacy to evaluate the OS of EAC patients was compared between the nomogram prediction model and TNM staging system. Results In total, 3945 patients with lower third and abdominal part of EAC were enrolled, including 3475 males and 470 females with a median age of 65 (57-72) years. The 2761 patients were allocated to the training cohort and the remaining 1184 patients to the internal validation cohort. In the training and the internal validation cohorts, the C-index of the nomogram model was 0.705 and 0.713, respectively. Meanwhile, the calibration curve also suggested that the nomogram model had a strong capability of predicting 1-, 3-, and 5-year OS rates of EAC patients. The nomogram also had a higher efficacy than the TNM staging system in predicting 1-, 3-, and 5-year OS rates of EAC patients. Conclusion This nomogram prediction model has a high efficiency for predicting OS in the patients with lower third and abdominal part of EAC, which is higher than that of the current TNM staging system.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Iron overload is strongly associated with heart disease. Ferroptosis is a new form of regulated cell death indicated in cardiac ischemia-reperfusion (I/R) injury. However, the specific molecular mechanism of myocardial injury caused by iron overload in the heart is still unclear, and the involvement of ferroptosis in iron overload-induced myocardial injury is not fully understood. In this study, we observed that ferroptosis participated in developing of iron overload and I/R-induced cardiomyopathy. Mechanistically, we discovered that Parkin inhibited iron overload-induced ferroptosis in cardiomyocytes by promoting the ubiquitination of long-chain acyl-CoA synthetase 4 (ACSL4), a crucial protein involved in ferroptosis-related lipid metabolism pathways. Additionally, we identified p53 as a transcription factor that transcriptionally suppressed Parkin expression in iron-overloaded cardiomyocytes, thereby regulating iron overload-induced ferroptosis. In animal studies, cardiac-specific Parkin knockout mice (Myh6-CreER ^T2 /Parkin ^fl/fl ) fed a high-iron diet presented more severe myocardial damage, and the high iron levels exacerbated myocardial I/R injury. However, the ferroptosis inhibitor Fer-1 significantly suppressed iron overload-induced ferroptosis and myocardial I/R injury. Moreover, Parkin effectively protected against impaired mitochondrial function and prevented iron overload-induced mitochondrial lipid peroxidation. These findings unveil a novel regulatory pathway involving p53-Parkin-ACSL4 in heart disease by inhibiting of ferroptosis.

Primary health care institutions should be the main force of China's medical and health service system and the cornerstone of the national health care system. During the COVID-19 pandemic, China's primary health care institutions played a critical role, but many deficiencies and weaknesses were also highlighted. Through systematic literature search and analysis, this article finds that China's primary health care institutions have some problems such as low demand for patient care, weak integration of the health system, weak service foundation, and insufficient emergency response capacity for public health emergencies. Accordingly, we put forward a strategy for the construction of primary health care institutions based on the "Three Forces Theory", which aims to improve the primary medical and health care service system, upgrade the capacity of primary medical and health care services, and better fulfill the strategic goal of "Healthy China 2030".

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer, although it is limited by the low tumor delivery efficacy of anticancer drugs. Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect; however, excessively generated immunogenicity will cause serious inflammatory response syndrome. Here, we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts (LP@BG@CCM) by layer-by-layer encapsulation for the treatment of metastatic lung cancer. The preparation processes were simple, only involving film formation, electroporation, and pore extrusion. LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells. In the 4T1 breast cancer metastatic lung cancer mouse models, the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance, the reduced lung weight, the clear lung tissue structure, and the enhanced cancer cell apoptosis compared to its precursors. Moreover, several major immune factors were improved after administration of LP@BG@CCM, including the CD4⁺/CD8a⁺ T cells in the spleen and the TNF-α, IFN-γ, and IL-4 in the lung. LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy, which is a promising medication for the treatment of metastatic lung cancer.

Objective Using the concept of allostatic load(AL)to evaluate aging of male SD rats and the effectiveness of Zuogui Pill in naturally aging rats.Methods Naturally aging male SD rats were tested at the ages of 2,5,8,14,18,and 21 months.They were divided into an elderly control group,low-dose Zuogui Pill group,and high-dose Zuogui Pill group.Intervention with Zuogui Pill was trialed for 3 months.Blood samples were taken from the tails of rats each month,and the number of T lymphocytes and rate of apoptosis were measured by flow cytometry.Low-density lipoprotein cholesterol(LDL-c),high-density lipoprotein cholesterol(HDL-c),triglycerides(TG),total cholesterol(TC),free fatty acids(FFA),25 hydroxyvitamin D(25-OH-D),corticosterone(CORT),C-reactive protein(CRP),and interleukin-6(IL-6)were detected in rat sera.By identifying the collinearity between indicators and professional considerations,LDL-c,TC,HDL-c,FFA,TG,CORT,IL-6,CRP,25-OH-D,CD3+T cell count,and CD3+T cell apoptosis rate were included in the AL scoring.The threshold for each indicator was established with data from 5-month-old rats,and the score was 1 point below or/and above the threshold.Results The serum levels of LDL-c,TG,TC,25-OH-D,CRP,and IL-6 of rats showed significant changes with age,although the patterns of change differed.The CD3+T lymphocyte count significantly decreased with age(P＜0.01),while the apoptosis rates of CD3+,CD4+,and CD8+T lymphocytes significantly increased with age(P＜0.01).Zuogui Pill significantly increased serum CORT levels in elderly rats(P＜0.01)and reduced the apoptosis rate of CD8+T lymphocytes(P＜0.05).The AL score began to increase in rats at 5 months of age and reached its peak in those of 18 months of age.Conclusions AL can better characterize the aging process compared to a single indicator.Zuogui Pill can improve the stress response ability of aging rats and alleviate immunosenescence.

Objective:To evaluate the effectiveness,safety and economics of absorbable drug-eluting coronary stent systems using rapid health technology assessment tools,and to provide evidence-based basis for rational use for clinicians use and expert evaluation.Methods:A computer search was performed on PubMed,CNKI,Wanfang,VIP and other databases from 1 January 2014 to 1 January 2023 for relevant literature on patients with coronary artery disease who were treated with coronary artery stent interventional surgery.The 210 collected literatures were screened and extracted according to the inclusion and exclusion criteria,and the literature quality evaluation was carried out.The extracted data related to the intravascular thrombosis rate,myocardial infarction rate,cardiac mortality rate,all-cause mortality rate,target lesion revascularization rate and intravascular adverse event incidence of absorbable drug-eluting coronary stents and drug-eluting coronary stents were meta-analyzed by Revman5.4 software.Results:7 studies were ultimately included in the comparative study of absorbable drug-eluting coronary stents and drug-eluting coronary stents.The thrombosis rate,all-cause mortality rate and intravascular adverse event rate of absorbable drug-eluting coronary stents were lower than those of drug-eluting coronary stents,and the difference was statistically significant(Z=2.16,1.89,2.22,P＜0.05).There were no statistically significant difference in the myocardial infarction rate,cardiac mortality rate and target lesion revascularization rate between absorbable drug-eluting coronary stents and drug-eluting coronary stents(P＞0.05).Conclusion:There was no significant difference in safety and efficacy between absorbable drug-eluting coronary stents and drug-eluting coronary stents.In terms of economy,the cost of absorbable drug-eluting coronary stents is significantly higher than that of drug-eluting coronary stents,and patients can choose stents according to their own economic conditions and other actual conditions.

Objective:To investigate the correlation between serum albumin, urea nitrogen and Fazekas scores and cognitive function scores in patients with mild and medium ischemic stroke.Methods:Clinical data of 160 patients with acute ischemic stroke with the National Institutes of Health Stroke Scale (NIHSS)≤7 scores admitted to the Department of Neurology of the First Affiliated Hospital of Hainan Medical College from June 2021 to April 2023 were selected for a cross-sectional study. According to the Montreal Cognitive Assessment (MoCA) score, they were divided into normal cognitive group (28 cases) (MoCA≥26 scores), mild to moderate cognitive impairment group (74 cases) (MoCA 15-<26 scores), and severe cognitive impairment group (58 cases) (MoCA<15 scores). Demographic characteristics, serological indicators and imaging data of patients were collected, and the correlation between serum albumin, urea nitrogen and Fazekas scores and the total score of MoCA and the scores of each cognitive domain was analyzed. One-way ANOVA was used for comparison between the normal distribution and homogeneous variance data sets, LSD analysis was used for pairwise comparison, Kruskal-Wallis H test was used between the skew distribution or heterogeneous variance data sets. Bonferroni correction analysis was used for pairwise comparison. Chi-square test or Fisher exact probability method was used after the comparison between the count data sets. Spearman Spearman correlation analysis was performed on serum albumin, urea nitrogen and Fazekas scores with MoCA scores and cognitive domain scores. Multivariate ordered Logistic regression was used to analyze the independent risk factors of cognitive function in acute stage of mild and medium ischemic stroke patients. Results:The incidence of cognitive impairment in patients with acute mild and medium ischemic stroke was 82.50% (132/160). Comparison of age ((56.71±7.35), (60.32±10.20), (66.40±11.88) years old), sex (male/female: (23/5, 58/16, 33/25)), the proportion of education level above high school (25.0%(7/28), 16.2%(12/74), 6.9%(4/58)), hemoglobin ((149.26±14.91), (144.85±16.85), (137.63±17.22) g/L), albumin (39.5 (37.0, 41.2), 38.6(35.6, 40.8), 37.4 (34.5, 39.8) g/L), urea nitrogen (5.30 (4.00, 6.60), 4.81 (4.00, 6.32), 5.86 (4.55, 6.97) mmol/L), Hamilton Anxiety Scale (HAMA) score (5.0 (2.0, 10.0), 7.5 (5.0, 11.0), 10.0 (6.0, 14.3) scores),Hamilton Depression Scale (HAMA) score (5.5 (3.0, 12.5), 7.0 (4.0, 11.0), 9.5 (5.0, 14.0) scores), and Fazekas score (2.00 (1.25, 3.00), 2.00 (1.00, 4.00), 3.00 (2.00, 5.00) scores) among cognitive normal group, mild to moderate cognitive impairment group, and severe cognitive impairment group of patients, the difference were statistically significant (the statistical values were F=9.68, χ 2=9.29, χ 2=30.77, F=5.31, H=7.06, H=6.71, H=12.37, H=8.91, and H=10.96, respectively;the P values were <0.001, 0.010, <0.001, 0.006, 0.029, 0.035, 0.002, 0.012, and 0.004, respectively ). The total score of MoCA was negatively correlated with Fazekas score and serum urea nitrogen, but positively correlated with serum albumin ( r s values were -0.250, -0.168, and 0.212, respectively; P values were 0.001, 0.036, and 0.009, respectively). Serum albumin was positively correlated with scores in visual space and execution, naming, attention and orientation, serum urea nitrogen was negatively correlated with scores in language and orientation, and Fazekas score was negatively correlated with scores in visual space and execution, orientation, attention and language ( r s values were 0.291, 0.196, 0.191, 0.209, -0.205, -0.180, -0.248, -0.193, -0.188, and -0.183, respectively; P values were <0.001, 0.017, 0.020, 0.011, 0.012, 0.027, 0.002, 0.016, 0.020, and 0.023, respectively). Multiple Logistic regression analysis showed that low albumin ( OR=0.884, 95% CI: 0.813-0.963, P=0.005) and high urea nitrogen ( OR=1.195, 95% CI: 1.003-1.425, P=0.047) and high Fazekas scores ( OR=1.401, 95% CI: 1.132-1.733, P=0.002) were independent risk factors for cognitive function, while high education level was a protective factor ( OR=0.062, 95% CI: 0.019-0.202, P<0.001). Conclusion:The incidence of acute cognitive impairment is high in patients with mild and medium ischemic stroke. Higher education level is a protective factor for cognitive function. Low albumin, high urea nitrogen and high Fazekas score are independent risk factors for cognitive function.

This study aimed to explore the relationship between comorbidity factors and in-hospital mortality related to factors in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) pneumonia. This study collected clinical data from 218 patients with CRKP pneumonia in Beijing hospital from November 2011 to December 2023, analyzed the number of comorbidities carried by CRKP pneumonia patients, comorbidity patterns, Charlson Comorbidity Index (CCI) scores, and comorbidity of underlying diseases, and explored the relationship between various indicators and comorbidity factors and in-hospital mortality in CRKP pneumonia patients. The Ward.D cluster analysis was performed on the comorbidities of patients and used to draw heatmaps. Using a multiple logistic regression model, a nomogram model was constructed to predict in-hospital mortality in patients with CRKP pneumonia. This study included 218 patients with CRKP pneumonia. The results showed that there were significant differences in the age ( P=0.003), comorbidities such as heart failure ( P<0.001), arrhythmia ( P=0.002), chronic liver disease ( P=0.003), chronic kidney disease ( P=0.002), CCI score ( P=0.007), total number of comorbidities ( P<0.001), and comorbidity patterns (respiratory/immune/psychiatric disease patterns and cardiovascular/tumor/metabolic disease patterns, P=0.003) between the survival and death groups of CRKP pneumonia patients. The multiple logistic regression showed that cardiovascular/tumor/metabolic disease patterns ( P=0.030), CCI score ( P=0.040), concomitant heart failure ( P=0.011), and concomitant arrhythmia ( P=0.025) were independent risk factors for in-hospital mortality in patients with CRKP pneumonia. The nomogram model for predicting the risk of in-hospital mortality in patients with CRKP pneumonia, constructed based on the identified risk factors, had an area under the ROC curve of 0.758. Both the ROC curve and validation curve indicated that the nomogram model had stable performance in predicting in-hospital mortality in patients with CRKP pneumonia. In summary, comorbidity factors are risk factors for predicting in-hospital mortality in patients with CRKP pneumonia, and the role of comorbidity factors in in-hospital mortality in patients with CRKP pneumonia should be taken seriously.

Objective To explore the potential mechanism of Benzo(K)fluoranthene(BkF)on male reproductive injury in mice by proteomics and metabolomics.Methods Twenty healthy and clean male Kunming mice(6 weeks old,18±2 g)were randomly divided into control group(corn oil group),low-,medium-and high-dose BkF groups(7.5,15.0 and 30.0 mg/kg),with 5 mice in each group.The corresponding agents were gavaged at a dose of 10 mL/kg,5 d per week,for 35 consecutive days.After modeling,the rats were fasted for 10 h,and then sperm samples and testicular tissues were harvested.Computer assisted sperm analysis(CASA)was used to detect and analyze semen parameters.HE staining was employed to observe the histopathological structure of the testicular tissue.Bioinformatics analysis was applied to analyze the differential protein pathways.Volcano plot were conducted to analyze the top 10 differentially expressed proteins(DEPs)in the control and high-dose BkF group.Liquid chromatography-tandem mass spectrometry(LC-MS/MS)untargeted metabolomics techniques were utilized to screen out differential metabolites.KEGG signaling pathway and KEGG annotation analyses and GO enrichment analysis were used to analyze the differential metabolites.Results Compared with the control group,the sperm number and motility of BkF-treated mice showed a decreased trend,with statistical differences(P＜0.05).Pathological observation showed that BkF treatment resulted in dilated seminal tubules and badly-arranged spermatogenic cells when compared with the control group.Proteomics analysis found that the protein levels of Spata46 and Rab5b were decreased,while those of Zscan21 and Aifm2 were increased(P＜0.01).Proteomic KEGG enrichment analysis showed that it was mainly involved in phagosome,protein export,ribosome and other pathways.GO enrichment analysis indicated that it was mainly involved in male meiosis I,histone acetylation,regulation of p53 signaling pathway,positive regulation of cell cycle,positive regulation of cell death and other signaling pathways.Metabonomics KEGG displayed that amino sugar and nucleotide sugar metabolism were most closely related to other metabolic pathways.Conclusion Proteomics and metabolomics analyses show that BkF exposure is associated with spermatogenesis,apoptosis and cell cycle,DNA damage,amino sugar and nucleotide sugar metabolism.