This study aimed to investigate the molecular mechanism by which astrocyte elevated gene 1 protein (AEG-1) upregulates the transcriptional expression of eukaryotic translation initiation factor 4E (eIF4E) and its role in the sensitivity of gastric cancer cells to cisplatin (CDDP). Transcriptomic and correlation analyses based on The Cancer Genome Atlas (TCGA) database were performed to screen potential transcriptional regulatory mechanisms of AEG-1. In gastric cancer cell lines, plasmid overexpression, siRNA interference, and pharmacological inhibition were applied, combined with luciferase reporter assay, qRT-PCR, and Western blot to detect the transcriptional and expression changes of eIF4E. Co-immunoprecipitation (Co-IP) was used to verify the interaction between AEG-1 and E1A binding protein p300 (p300), as well as their binding changes upon CXC chemokine ligand 12 (CXCL12) stimulation. Sulforhodamine B colorimetric assay and flow cytometry were employed to evaluate CDDP sensitivity and apoptosis levels, respectively. The transcriptomic and database analyses suggested that AEG-1 may regulate eIF4E expression through acetylation-related mechanisms, and that EP300 was positively correlated with both MTDH and EIF4E in gastric cancer tissues. Functional experiments confirmed that AEG-1 upregulated the transcriptional expression of eIF4E in a p300-dependent manner, and that phosphorylation of AEG-1 at the site of serine 426 (S426) inhibited this effect. CXCL12 stimulation enhanced the protein-protein interaction between AEG-1 and p300. In addition, AEG-1 reduced the sensitivity of gastric cancer cells to CDDP, whereas phosphorylated AEG-1 enhanced cellular sensitivity to CDDP. In conclusion, AEG-1 enhances eIF4E transcriptional expression in a p300-dependent manner, and the phosphorylation status of AEG-1 at the S426 site serves as a key regulatory switch. The AEG-1/p300/eIF4E axis modulates CDDP chemotherapy sensitivity in gastric cancer, providing a new theoretical basis and potential intervention target for precision therapy of gastric cancer.

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Objective:To investigate the expression levels and clinical significance of miR-627 and miR-448 in colorectal cancer tissues.Methods:Ninety-eight patients with colorectal cancer admitted to Xi’an Jiaotong University Affiliated Red Cross Hospital from Apr. 2019 to Apr. 2021 were gathered. Colorectal cancer tissue and adjacent tissues were collected during surgery, and the expression levels of miR-627 and miR-448 were detected by qRT-PCR. According to postoperative follow-up, patients were separated into a good prognosis group and a poor prognosis group. Kaplan-Meier survival curve was applied to analyze the relationship between miR-627, miR-448 and the prognosis of colorectal cancer patients. ROC curve was plotted to analyze the predictive value of miR-627 and miR-448 for poor prognosis in colorectal cancer. The prognostic factors of colorectal cancer patients were analyzed using COX regression.Results:There was a difference in the expression levels of miR-627 and miR-448 between colorectal cancer tissue and adjacent tissues ( P<0.05). The expression of miR-627 and miR-448 in colorectal cancer tissue was related to clinical features (TNM stage, differentiation degree, lymph node metastasis, and depth of infiltration) ( P<0.05). The survival rate of patients with high expression of miR-627 was higher than that of patients with low expression ( χ2=10.050, P<0.05); the survival rate of patients with high expression of miR-448 was higher than that of patients with low expression ( χ2=9.033, P<0.05). The expression levels of miR-627 and miR-448 in the poor prognosis group were greatly lower than those in the good prognosis group ( P<0.05). According to the ROC curve, the AUC of miR-627 in predicting poor prognosis of colorectal cancer was 0.811, the AUC of miR-448 in predicting poor prognosis of colorectal cancer was 0.772, and the AUC of combination of the two in predicting poor prognosis of colorectal cancer was 0.859. The combination of the two was better than their individual predictions (Z combination vs. miR-627=2.538, Z combination vs. miR-448=2.572, P<0.05). Multivariate COX regression found that miR-627, miR-448, and clinical features (TNM stage, degree of differentiation, lymph node metastasis, and depth of infiltration) were risk factors affecting the prognosis of colorectal cancer patients ( P<0.05) . Conclusion:The expression levels of miR-627 and miR-448 in colorectal cancer tissues were greatly reduced. The combination of the two is related to the clinical characteristics and prognosis of patients, and can greatly improve the predictive value for prognosis of colorectal cancer patients.

Objective:To explore the clinical characteristics, diagnosis, and treatment of chylous pleural effusion caused by liver cirrhosis.Methods:The clinical data of 19 cases of liver cirrhosis complicated with chylous pleural effusion admitted at Department of Lymphatic Surgery, Beijing Shijitan Hospital from Jun 2013 to Oct 2022 was retrospectively analyzed.Results:There were 12 males (63.2%) and 7 females (36.8%).Ten cases (52.6%) had right chylothorax, and 9 cases (47.4%) had bilateral chylothorax; Seventeen cases (89.5%) had concurrent ascites. Chest fluid examination: 3 cases were milky white (16%), 10 cases were yellow white (53%), 4 cases were orange yellow (21%), and 2 cases were pink (10%).There were 2 cases of exudate and 17 cases of transudate. By radionuclide lymphatic imaging, 9 cases showed increased radiation in the right chest cavity; One case showed increased radiation in the left chest cavity; Five cases showed bilateral chest radiation elevation. By lymphangiography,11 cases showed complete visualization of the thoracic duct, of which 10 cases showed obstruction at the outlet of the thoracic duct. The 10 patients underwent surgical treatment for the release of adhesions at the end of the thoracic duct, and the postoperative result was good. Six patients died during follow-up.Conclusions:Cirrhosis combined with chylous pleural effusion is rare in clinical practice and prognosis is poor. The laboratory examination of pleural effusion is an important basis for determining chylous pleural effusion. The lysis of adhesions at the end of the thoracic duct has a certain therapeutic effect on patients with lymphangiography indicating thoracic duct outlet obstruction.

Objective:To investigate the correlation between plasma Dickkopf-1 (DKK1) and post-stroke cognitive impairment (PSCI) in patients with acute ischemic stroke.Methods:Consecutive patients with first-ever acute ischemic stroke admitted to the Department of Neurology, Nanjing Jiangbei Hospital from March 2023 to February 2024 were included prospectively. Enzyme-linked immunosorbent assay was used to detect plasma DKK1 within 24 hours of onset. The Montreal Cognitive Assessment Scale was used to evaluate cognitive function at 3 months after onset. A score ≤22 was defined as PSCI. Multivariate logistic regression analysis was used to determine the correlation between DKK1 and PSCI. The relationship between DKK1 and PSCI risks was evaluated through restrictive cubic spline analysis. Results:A total of 205 patients with acute ischemic stroke were enrolled, including 106 males (51.7%), aged 67.0±9.4 years; 61 patients (29.8%) experienced PSCI. Multivariate logistic regression analysis showed that after adjusting for age, gender, education level, and other confounding factors, there was a significant independent correlation between higher plasma DKK1 and PSCI (odds ratio 1.778, 95% confidence interval 1.313-2.408; P=0.001). Subgroup analysis showed that age, gender, etiological classification of stroke, and education level had no significant effect on the above correlation. Restrictive cubic spline analysis showed plasma DKK1 had a linear relationship with the risk of PSCI ( P=0.003). Conclusion:Higher plasma DKK1 level is significantly correlated with PSCI in patients with acute ischemic stroke at 90 days after onset.

Pulmonary anthrax is an acute zoonotic infectious disease caused by Bacillus anthracis infecting the human body. Humans can be infected by coming into contact with diseased animals and their products or by consuming diseased animals. According to the different infection routes, it can be classified into cutaneous anthrax, pulmonary anthrax and intestinal anthrax, etc. Among them, cutaneous anthrax is the most common, while case reports of pulmonary anthrax are rare. This article analyzes the clinical data of a case of occupational pulmonary anthrax diagnosed by metagenomic next-generation sequencing (mNGS) and successfully treated, so as to provide a reference for the clinical treatment of pulmonary anthrax.

Objective:To analyze the correlation between respiratory event duration and nocturnal oxygen saturation (SpO 2) in adults with obstructive sleep apnea (OSA), and to explore its significance in assessing nocturnal hypoxemia and OSA severity. Methods:A prospective study was conducted on adult OSA patients diagnosed via overnight standard polysomnography (PSG) at the Department of Otolaryngology, First Affiliated Hospital of Sun Yat-sen University from June 2019 to December 2023. Data collected included demographic information, PSG reports, scale scores, and comorbidities. Patients were first stratified by apnea-hypopnea index (AHI) severity. Relationships between respiratory event duration parameters,including total apnea-hypopnea time (TAHT), percentage of total sleep time with apnea-hypopnea (AHT%), total apnea time (TAT), total hypopnea time (THT), and mean apnea-hypopnea time (MAHT), and nocturnal SpO? parameters, including average SpO? (aSpO?), minimal SpO? (mSpO?), mean oxygen desaturation (MOD), and percentage of total sleep time with SpO?<90% (CT90), were analyzed. Patients were then divided into two groups based on the median MAHT (27.6 s) for SpO? comparison. Finally, severe OSA patients were further subclassified using an AHI inflection point (50 events/h) identified via scatter plot analysis to compare nocturnal SpO?. Statistical analysis was performed using SPSS 27.0.Results:Among the 250 study subjects, there were 201 males and 49 females, with ages ranging from 18 to 76 years (mean age: 41.6 ± 11.9 years).TAHT, AHT%, and TAT in OSA patients demonstrated significant negative correlations with aSpO?( r=-0.698, -0.718, -0.646)and mSpO?( r=-0.746, -0.746, -0.748), while showing positive correlations with MOD ( r=0.783, 0.791, 0.823)and CT90 ( r=0.868, 0.866, 0.852), P<0.05. When stratified by MAHT median ( M=27.6 s), the "long-event" subgroup ( n=125) displayed significantly lower mSpO 2 and higher MOD and CT90 compared to the "short-event" subgroup ( n=125), Z=-3.319, 3.288, 2.242; P<0.05. No significant difference in aSpO 2 was observed ( P>0.05). Subgrouping severe OSA patients at AHI=50 events/hour revealed significant differences in aSpO 2, mSpO 2, MOD, and CT90 between groups ( Z=-5.011, -4.787, 5.142, 6.117, P<0.05). Conclusions:TAHT, AHT%, and TAT significantly correlate with nocturnal SpO? parameters in OSA patients and can supplement AHI in assessing OSA severity. MAHT independently reflects nocturnal oxygenation status beyond AHI.

Objective:To analyze the trend of infertility disease burden from 1990 to 2019 and predict the age-standardized prevalence rate (ASPR) and age-standardized disability-adjusted life-year (DALY) rate of male and female infertility for 2020—2029, providing a certain reference for the prevention and treatment of infertility diseases.Methods:Based on the Global Burden of Disease 2019, prevalence, ASPR, DALY rate, and age-standardized DALY rate were used to evaluate the global burden of infertility comprehensively. The estimated annual percentage change was used to describe trends in the disease burden of infertility in 21 regions worldwide. The Bayesian age period cohort model was used to predict the ASPR and age-standardized DALY rate for male and female infertility in 204 countries and regions from 2020 to 2029. Sensitivity analysis was performed using the autoregressive integrated moving average model.Results:The prevalence, DALY rate, ASPR and age-standardized DALY rate of global male infertility increased from 319.52 per 100 000,1.82 per 100 000, 2 856.53 per 100 000, and 16.19 per 100 000 in 1990 to 565.30 per 100 000, 3.22 per 100 000, 3 398.53 per 100 000, and 19.36 per 100 000 in 2019, respectively. The prevalence, DALY rate, ASPR, and age-standardized DALY rate of global female infertility increased from 656.67 per 100 000, 3.53 per 100 000, 6 036.36 per 100 000, and 32.27 per 100 000 in 1990 to 1 223.78 per 100 000, 6.59 per 10 000, 7 483.12 per 100 000, and 40.33 per 100 000 in 2019, respectively. The burden of infertility disease was the highest in men and women aged 30-34 years, and the ASPR and age-standardized DALY rates were 4 407.47 per 100 000, 25.08 per 100 000, 10 270.55 per 100 000 and 55.65 per 100 000, respectively. Only in 45-49 years of age, the prevalence of infertility (11.31 per 100 000) and DALY rate (0.06 per 100 000) in women were lower than those in men (15.68 per 100 000 and 0.08 per 100 000). In addition, the burden of infertility was the lowest in high socio-demographic index regions. Cameroon had the highest ASPR (7 652.40 per 100 000) and age-standardized DALY rate (43.94 per 100 000) for male infertility. Chinese women had the highest ASPR (20 402.30 per 100 000) and age-standardized DALY rate (106.16 per 100 000) of infertility. The forecast results show that the burden of male and female infertility diseases will increase in 204 countries and regions from 2020 to 2029.Conclusion:The burden of infertility diseases in men and women increased in 204 countries and regions from 1990 to 2019, and it is predicted that the global burden of infertility diseases will continue to rise in 2020—2029. Preliminary screening of infertility should be carried out as soon as possible, health education should be strengthened and effective prevention and treatment strategies should be formulated.

Pulmonary anthrax is an acute zoonotic infectious disease caused by Bacillus anthracis infecting the human body. Humans can be infected by coming into contact with diseased animals and their products or by consuming diseased animals. According to the different infection routes, it can be classified into cutaneous anthrax, pulmonary anthrax and intestinal anthrax, etc. Among them, cutaneous anthrax is the most common, while case reports of pulmonary anthrax are rare. This article analyzes the clinical data of a case of occupational pulmonary anthrax diagnosed by metagenomic next-generation sequencing (mNGS) and successfully treated, so as to provide a reference for the clinical treatment of pulmonary anthrax.