Objective To quantitatively assess the exposure-response association between exposure to heatwave and sudden death, estimate the attributable excess deaths, and identify potential vulnerable subgroups. Methods A time-stratified case-crossover study was conducted among residents who died from sudden death in Jiangsu Province, China between 2015 and 2021. Heatwave events in Jiangsu Province, defined using varying relative temperature thresholds and durations, were identified using temperature data from the China Meteorological Administration Land Data Assimilation System (CLDAS V2.0). Individual heatwave exposure was assessed based on each subject's residential address. The exposure-response association between heatwave and sudden death was evaluated using conditional logistic regression model combined with a Distributed Lag Nonlinear Model(DLNM). Heatwave-attributable excess deaths were estimated. Stratified analyses by sex and age were performed to assess potential effect modifications. Results Under all definitions, exposure to heatwave was significantly associated with an increased risk of sudden death, and the risk increased with the intensity of heatwave. Using the P95_3d definition (temperature exceeding the 95th percentile for ≥3 consecutive days), heatwave was significantlyassociated with a 56% increased risk of sudden death (95% CI: 31%, 86%). The population-attributable fraction of sudden death due to heatwave exposure was 1.45% (95% CI: 0.97%, 1.90%). Stratified analyses indicated no statistically significant differences in the association between heatwave exposure and sudden death across age or sex subgroups. Conclusion Heatwave exposure was associated with an increased risk of sudden death. Reducing heatwave exposure during summer may help lower the occurrence of sudden death.

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

Objective To analyze the expression and clinical significance of stimulator of interfer-on genes(STING),C-C motif chemokine ligand 5(CCL5),interferon regulatory factor 3(IRF3)and programmed death ligand-1(PDL1)in squamous cell lung cancer.Methods A total of 56 pa-tients with squamous cell lung cancer were enrolled.Resected tumor tissues and adjacent non-tumor tissues(located more than 5 cm from the tumor margin)were collected.Immunohistochemical staining was performed to detect the expression of STING,CCL5,IRF3 and PDL1.The correlations of STING,CCL5,IRF3 and PDL1 with clinical data were analyzed.The relationship between the expression of STING,CCL5,IRF3 and PDL1 in lung squamous cell carcinoma tissues and prognosis was also evalua-ted.The prognostic factors of patients with lung squamous cell carcinoma were analyzed.Results The positive rate of STING expression in lung squamous cell carcinoma tissues was significantly lower than that in adjacent non-tumor tissues,whereas the positive rates of CCL5,IRF3 and PDL1 were significantly higher(P＜0.05).The expression levels of STING,CCL5,IRF3 and PDL1 were associated with tumor diameter,TNM stage,lymph node metastasis and differentiation degree(P＜0.05).The 3-year survival rate of STING positive expression patients was significantly higher than that of STING negative expression patients(P＜0.05).The 3-year survival rate of CCL5 positive,IRF3 positive and PDL1 positive expression patients was significantly lower than that of CCL5 negative,IRF3 negative and PDL1 negative expression patients(P＜0.05).STING,CCL5,IRF3 and PDL1 were identified as prognostic factors for patients with squamous cell lung cancer(P＜0.05).Conclusion In squamous cell lung cancer tissues,STING is expressed at low levels,while CCL5,IRF3 and PDL1 are ex-pressed at high levels.These findings have significant clinical value in assessing the prognosis of pa-tients with squamous cell lung cancer.

As an independent first-level discipline,an appropriate classification of nursing science is significant.In China,each nursing degree-granting institution has developed its own secondary-level discipline directions based on its research characteristics and strengths,with varying names and research scopes.Furthermore,there is no unified global classification system.This paper,based on the characteristics of nursing as a discipline and combined with China's discipline classification principles,used literature analysis,comprehensive classification,philosophical reflection,logical reasoning,and expert consultation methods to explore the connotation of nursing,its unique research objects and scope,and to construct a secondary-level discipline classification system for nursing science that is suitable for China's national conditions.The paper also discussed the challenges faced by the nursing discipline and its future development directions,providing theoretical and practical guidance for the development of the nursing discipline.

Objective To analyze the research status and hotspots in the field of astragalus polysaccharides;To provide references for further research.Methods Research literature about astragalus polysaccharides was retrieved from CNKI,Wanfang Data,VIP,PubMed,and Web of Science databases from 1st,Jan.2013 to 1st,July 2023.NoteExpress 3.7 software was used to manage the literature and ultimately establish a database.Excel 2019,CiteSpace 6.2.2R and VOSviewer 1.6.18 were used to visually analyze the publication volume,authors,institutions,and keywords of the included literature.Results A total of 2 462 articles were included,with 1 284 Chinese articles and 1 178 English articles.The main research institutions were Gansu University of Chinese Medicine,Shandong University of Traditional Chinese Medicine,and Beijing University of Chinese Medicine.The core authors of Chinese literature were Liu Yongqi,Wang Hongxin,Lu Meili,etc.The core authors of English literature included Zhang Wei,Li Ke,Yang Xiaojun,etc.High-frequency keywords of Chinese literature included Astragali Radix,rats,polysaccharides,cell apoptosis,and oxidative stress,etc.High frequency keywords in English literature included expression,in vitro,oxidative stress,apoptosis,etc.Conclusion The research on astragalus polysaccharides focuses on their pharmacological effects and mechanisms.Intestinal flora,immune regulation,autophagy and apoptosis are the hot action mechanisms in this field.The focus of disease research involves tumor and diabetes,and antiviral,anti infection and other pharmacological effects are the research trend.

Objective:To investigate a case of antibodies against high-frequency erythrocyte antigens and elucidate the genetic mechanism underlying the blood group.Methods:A Lan-negative patient referred to the Zhejiang Blood Center by Quzhou Hospital of Traditional Chinese Medicine in August 2016 was selected as the study subject. A retrospective study was conducted to collect the proband′s clinical data. The proband′s erythrocyte antigens and unexpected serum antibodies were identified using tube saline and microcolumn agglutination anti-human globulin methods. Antibody specificity was determined by treating erythrocytes with 7 enzymes and 2 chemical reducing agents. Genomic DNA was extracted from the proband′s blood sample for whole genome sequencing (WGS) and erythrocyte blood group gene analysis, with validation by Sanger sequencing. Multiple bioinformatics tools were used to analyze the pathogenicity of the variant. The rare blood group and unexpected antibody specificity were comprehensively determined based on the results of serological and genetic testing. This study has been approved by the Zhejiang Provincial Blood Center Medical Ethics Committee(Ethics No.20190201).Results:The proband was a 91-year-old Han Chinese male with prostatitis, cystitis, and malnutrition in conjunct with emaciation. He had a history of multiple erythrocyte transfusions without observable adverse reactions. Prior to the most recent transfusion, major crossmatch agglutination was observed, which prompted antibody identification. Antibodies against high-frequency antigens were detected in the proband′s serum, with enzyme and reducing agent treatments ruling out antibody specificities associated with 17 blood group systems, e. g., MNS, LU, KEL. WGS analysis identified 4 525 SNPs and 1 046 INDEL variants among erythrocyte blood group genes. Further screening revealed that the proband had a rare blood group due to a homozygous rs755723161 variant. This variant in the ABCB6 gene (c.459delC) has led to a frameshifting mutation (p.Trp154GlyfsTer96), resulting in the Lan-negative rare blood group with a high-frequency antigen deficiency and the production of IgG anti-Lan antibodies in the serum. Conclusion:This study has identified anti-Lan alloantibodies in a Lan-negative patient and, for the first time, elucidated the ABCB6 gene variant underlying the Lan-negative rare blood group in the Chinese population.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Objective:To evaluate the clinical value of high-risk human papillomavirus (HPV) viral load for the cervical cancer screening and triage of high-risk HPV positive populations without additional tests.Methods:(1) This study conducted a retrospective analysis of 29 720 women aged 35-64 years who received cervical cancer screening in Quanzhou, China, in 2021. Fourteen high-risk HPV types (including HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) were detected for cervical cancer primary screening using hybrid capture-chemiluminescence method. High-risk HPV positive samples were further subjected to HPV 16/18 genotyping using hybrid capture-chemiluminescence method. Among them, HPV 16/18 positive women were directly referred to colposcopy, while the other 12 high-risk HPV positive samples were further subjected to liquid based cytology test. Those with abnormal or suspicious cytology were referred to colposcopy. Biopsies were taken for histopathological examination of suspicious or abnormal individuals under colposcopy. (2) Ten cases of colposcopy loss or refusal to undergo examination were excluded, and the data from the 29 710 cases were analyzed. The HPV viral loads of the other 12 high-risk HPV positive populations were focused and evaluated their HPV viral loads for further cervical intraepithelial neoplasia (CIN) Ⅱ and above lesions (CINⅡ +) triage in cervical cancer screening. Results:(1) Among 29 720 women, 2 487 women (8.37%, 2 487/29 720) were positive for high-risk HPV, including 807 women (2.72%, 807/29 720) were positive for HPV 16/18 and 1 680 patients (5.65%, 1 680/29 720) were positive for the other 12 high-risk HPV types. Among 1 680 women who tested positive for the other 12 high-risk HPV types, 573 patients were atypical squamous cell carcinoma of unclear significance or above, 346 patients were CIN Ⅰ, 122 patients were CIN Ⅱ-Ⅲ, 9 patients were squamous cell carcinoma patients, and 4 patients were adenocarcinoma in situ. The immediate risk of CIN Ⅱ + in HPV 16/18 positive women (11.13%) was approximately four times higher than that of other 12 high-risk HPV positive women (2.74%). (2) Through the viral load analysis of the other 12 high-risk HPV types, we found that the viral load of the other 12 high-risk HPV provide a good value for the pathological results, with a clinical cutoff (CO) value of 11.21 relative light unit/CO (RLU/CO) for the CINⅡ + detection. Except for HPV 16/18 positive patients, when the viral load values of the other 12 high-risk HPV types were greater than 10 RLU/CO, these patients had a higher risk of CINⅡ +, with a positive predictive value of 31.29%. CINⅡ + was not found in any of the other 12 high-risk HPV positive with viral load values less than or equal to 10 RLU/CO. Conclusions:Using hybrid capture-chemiluminescence HPV tests for HPV 16/18 genotyping, combined with the viral loads (>10 RLU/CO) of the other 12 high-risk HPV analysis, one could triage HPV positive population without additional tests. Such triage strategy could promote the coverage of cervical cancer screening, particularly where cytology pathologists or economic resources are limited.