Objective To explore the impact of number of positive regional lymph nodes (nPRLN) in N1 stage on the prognosis of non-small cell lung cancer (NSCLC) patients. Methods Patients with TxN1M0 stage NSCLC who underwent lobectomy and mediastinal lymph node dissection from 2010 to 2015 were screened from SEER database (17 Regs, 2022nov sub). The optimal cutoff value of nPRLN was determined using X-tile software, and patients were divided into 2 groups according to the cutoff value: a nPRLN≤optimal cutoff group and a nPRLN>optimal cutoff group. The influence of confounding factors was minimized by propensity score matching (PSM) at a ratio of 1 : 1. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate overall survival (OS) and lung cancer-specific survival (LCSS) of patients. Results A total of 1316 patients with TxN1M0 stage NSCLC were included, including 662 males and 654 females, with a median age of 67 (60, 73) years. The optimal cutoff value of nPRLN was 3, with 1165 patients in the nPRLN≤3 group and 151 patients in the nPRLN>3 group. After PSM, there were 138 patients in each group. Regardless of before or after PSM, OS and LCSS of patients in the nPRLN≤3 group were superior to those in the nPRLN>3 group (P<0.001). N1 stage nPRLN>3 was an independent prognostic risk factor for OS [HR=1.52, 95%CI (1.22, 1.89), P<0.001] and LCSS [HR=1.72, 95%CI (1.36, 2.18), P<0.001]. Conclusion N1 stage nPRLN>3 is an independent prognostic risk factor for NSCLC patients in TxN1M0 stage, which may provide new evidence for future revision of TNM staging N1 stage subclassification.

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.

Objective To explore the change trend and related mechanism of resting metabolic rate induced by corticosterone in mice,and observe the intervention effects of Zhibai Dihuang Pill and Jinkui Shenqi pill.Methods Sixty-four mice were randomly divided into short-term and long-term groups,and each group was randomly divided into four groups.Mice in CORT group,ZBDH group and JKSQ group were given sterile drinking water containing corticosterone,and mice in Ctrl group were given sterile drinking water containing 1%anhydrous ethanol.Mice in ZBDH group and JKSQ group were given Chinese medicine by gavage.RMR of mice in each group was dynamically monitored during modeling and Chinese medicine intervention.The morphology of mitochondria in liver and muscle were observed by transmission electron microscope.The TR expression level in liver and muscle tissues of each group was observed by immunofluorescence,and MDA and ATP levels were detected in liver and muscle tissues of each group.levels of ACTH,TSH,INS,T3,T4,FT3,FT4,8-OHdG,FGF-21,GDF-15,L-lactic acid and pyruvic acid in serum were also detected.Results Compared with Ctrl group,the mitochondrial morphology of liver and muscle tissues in CORT group was damaged,and the expression of TR was decreased.In short-term(Day 8),RMR,ATP in liver,serum T4,ACTH and INS levels were significantly increased in the CORT group,while serum FGF-21,TSH levels and MDA in liver were significantly decreased.In long term(Day 56),RMR,serum 8-OhdG,INS,and ATP in liver and muscle were significantly decreased in the CORT group,serum FGF-21,GDF-15,T3,T4,FT3,FT4,MDA in liver and muscle were significantly increased.Compared with CORT group,in short term,RMR,serum L(+)-lactate in ZBDH group were significantly decreased,while serum 8-OHdG and the expression of TRα in muscle were significantly increased.In JKSQ group,the mitochondrial morphology of muscle tissue was improved,the expression of TRα and serum FGF-21 were significantly increased,while serum L(+)-lactic acid,FT4 and ATP in liver were significantly decreased.In long term,serum FGF-21 was significantly lower in ZBDH group,and in JKSQ group,RMR,ATP in liver tissue and TRα expression in muscle were significantly increased,while the levels of FGF-21,GDF-15,T3,FT4 in serum and MDA in muscle tissue were significantly decreased.Conclusion CORT induced RMR to increase first and then decrease with the intervention time.In the short term,Zhibai Dihuang Pill significantly decreased RMR in mice,while in the long term,Jinkui Shenqi Pill significantly increased RMR.The mechanism may be related to mitochondrial injury,thyroxine secretion and thyroxine receptor expression.

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

Objective:To develop an automatic diagnostic model for temporomandibular joint osteoarthritis(TMJOA)imaging based on deep learning technology,and to assist clinical diagnosis and improve the efficiency and accuracy of TMJOA diagnosis.Methods:CBCT data of 220 patients were collected,and 2 052 sagittal images were exported.Regions of interest were delineated according to the imaging analysis criteria for temporomandibular joint disorders,and the images were classified into TMJOA-free,TMJOA-uncer-tain and TMJOA.The data were randomly divided into a training set and a validation set according to 8∶2 ratio,and the training set data were used to train a TMJOA detection model based on three lightweight YOLOV5 deep learning frameworks,and the models' performance was evaluated on the validation set.Results:The Yolov5N model demonstrated the best performance,achieving a de-tection accuracy,recall,and precision of 92.5％,90.1％and 85.7％on the validation set,respectively.Conclusion:The auto-matic detection model for TMJOA imaging developed in this study can effectively identify arthritic lesions.Artificial intelligence tools are expected to become a powerful auxiliary tool for the clinical diagnosis of TMJOA.

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

Objective:To develop an automatic diagnostic model for temporomandibular joint osteoarthritis(TMJOA)imaging based on deep learning technology,and to assist clinical diagnosis and improve the efficiency and accuracy of TMJOA diagnosis.Methods:CBCT data of 220 patients were collected,and 2 052 sagittal images were exported.Regions of interest were delineated according to the imaging analysis criteria for temporomandibular joint disorders,and the images were classified into TMJOA-free,TMJOA-uncer-tain and TMJOA.The data were randomly divided into a training set and a validation set according to 8∶2 ratio,and the training set data were used to train a TMJOA detection model based on three lightweight YOLOV5 deep learning frameworks,and the models' performance was evaluated on the validation set.Results:The Yolov5N model demonstrated the best performance,achieving a de-tection accuracy,recall,and precision of 92.5％,90.1％and 85.7％on the validation set,respectively.Conclusion:The auto-matic detection model for TMJOA imaging developed in this study can effectively identify arthritic lesions.Artificial intelligence tools are expected to become a powerful auxiliary tool for the clinical diagnosis of TMJOA.

Objective To explore the change trend and related mechanism of resting metabolic rate induced by corticosterone in mice,and observe the intervention effects of Zhibai Dihuang Pill and Jinkui Shenqi pill.Methods Sixty-four mice were randomly divided into short-term and long-term groups,and each group was randomly divided into four groups.Mice in CORT group,ZBDH group and JKSQ group were given sterile drinking water containing corticosterone,and mice in Ctrl group were given sterile drinking water containing 1%anhydrous ethanol.Mice in ZBDH group and JKSQ group were given Chinese medicine by gavage.RMR of mice in each group was dynamically monitored during modeling and Chinese medicine intervention.The morphology of mitochondria in liver and muscle were observed by transmission electron microscope.The TR expression level in liver and muscle tissues of each group was observed by immunofluorescence,and MDA and ATP levels were detected in liver and muscle tissues of each group.levels of ACTH,TSH,INS,T3,T4,FT3,FT4,8-OHdG,FGF-21,GDF-15,L-lactic acid and pyruvic acid in serum were also detected.Results Compared with Ctrl group,the mitochondrial morphology of liver and muscle tissues in CORT group was damaged,and the expression of TR was decreased.In short-term(Day 8),RMR,ATP in liver,serum T4,ACTH and INS levels were significantly increased in the CORT group,while serum FGF-21,TSH levels and MDA in liver were significantly decreased.In long term(Day 56),RMR,serum 8-OhdG,INS,and ATP in liver and muscle were significantly decreased in the CORT group,serum FGF-21,GDF-15,T3,T4,FT3,FT4,MDA in liver and muscle were significantly increased.Compared with CORT group,in short term,RMR,serum L(+)-lactate in ZBDH group were significantly decreased,while serum 8-OHdG and the expression of TRα in muscle were significantly increased.In JKSQ group,the mitochondrial morphology of muscle tissue was improved,the expression of TRα and serum FGF-21 were significantly increased,while serum L(+)-lactic acid,FT4 and ATP in liver were significantly decreased.In long term,serum FGF-21 was significantly lower in ZBDH group,and in JKSQ group,RMR,ATP in liver tissue and TRα expression in muscle were significantly increased,while the levels of FGF-21,GDF-15,T3,FT4 in serum and MDA in muscle tissue were significantly decreased.Conclusion CORT induced RMR to increase first and then decrease with the intervention time.In the short term,Zhibai Dihuang Pill significantly decreased RMR in mice,while in the long term,Jinkui Shenqi Pill significantly increased RMR.The mechanism may be related to mitochondrial injury,thyroxine secretion and thyroxine receptor expression.