Background: Influenza A virus (IAV) is a negative-sense RNA virus of the Orthomyxoviridae family and is the etiological agent of a highly contagious acute respiratory disease that can lead to acute lung injury. Objective: To elucidate the molecular mechanisms of IAV infection, an integrative research approach combining gene expression profiling, multinetwork analysis, and in vivo experimental validations was employed. Methods: First, a series of network-based analyses were performed, including protein-protein interaction network construction, weighted gene co-expression network analysis, and subsequent gene set enrichment analysis, to identify the major underlying mechanisms of IAV infection. Following gene expression analysis, core targets, both direct and indirect regulators, were screened. An IAV (H1N1) strain A/PR/8/34-induced acute lung injury mouse model was constructed for in vivo validations. Batch one included two groups to evaluate findings from the multi-network analysis: Mock (n = 10; 5 males and 5 females) and IAV (n = 10; 5 males and 5 females). Batch two included three groups to assess the role of toll-like receptor 3 (TLR3) in IAV infection: Mock (n = 6; 3 males and 3 females), IAV (n = 6; 3 males and 3 females), and TLR3 inhibitor (n = 6; 3 males and 3 females). Body weight was measured on days 0, 3, and 5 after infection. On day 5, lung tissues were collected to assess viral load and histopathological changes. Key targets were examined using enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining, both in sera and lung tissues. Results: IAV infection was significantly associated with dysregulation of the immune-inflammation system, such as the LTR, nucle-otide-binding oligomerization domain-(NOD) like receptor, retinoic acid-inducible gene I-like receptor, and nuclear factor kappa-B signaling pathways. Gene set enrichment analysis further indicated that the TLR and necroptosis signaling pathways played crucial roles in the progression of IAV infection (TLR signaling pathway normalized enrichment score = 2.3941, P = 1.00 × 10 ⁻¹⁰; necroptosis normalized enrichment score = 1.9421, P = 6.21 × 10 ⁻⁷). Among the core targets, TLR3 and mixed lineage kinase domain-like protein (MLKL) may regulate gene expression at the transcriptional level (all P < 0.05). In vivo validation using an IAV (PR8) infected acute lung injury mouse model demonstrated increased viral load and lung index, alveolar structural damage, and inflammatory cell infiltration. Immunofluorescence staining exhibited large gaps in Lamin B1 staining and breaches in Emerin signals following IAV-PR8 infection. Expression levels of TLR3, p-receptor-interacting serine/threonine-protein kinase 3 (RIPK3)/RIPK3, and p-mixed lineage kinase domain-like protein (MLKL)/MLKL proteins in lung tissues, as well as proinflammatory factors and mediators in sera, were significantly elevated after IAV infection. Moreover, enhanced neutrophil infiltration (myeloperoxidase) and citrullinated histone H3 (a neutrophil extracellular trap-specific marker), both established indicators of neutrophil extracellular trap formation, were observed. Notably, treatment with a TLR3 inhibitor significantly ameliorated IAV-induced acute lung injury by regulating necroptosis-related targets. Conclusion: Our study provides network-based in vivo evidence that TLR3-receptor-interacting serine/threonine-protein kinase 3-MLKL-mediated necroptosis may underlie IAV-induced acute lung injury and could serve as a potential therapeutic target in severe influenza cases.

To investigate the clinical features and peripheral blood immune cell subsets ofelderly (≥60 years old) onset rheumatoid arthritis (EORA) patients.

Objective By organizing and implementing a laboratory proficiency validation plan for air change rate testing, this study aims to explore proficiency testing approaches in laboratory animal facilities, assess the current status of relevant laboratories regarding standard application and test capabilities, standardize air change rate testing methods, and ensure the accuracy and reliability of test results. Methods From September to November 2023, the National Institutes for Food and Drug Control (NIFDC) organized a laboratory proficiency validation plan for air change rate testing in laboratory animal facilities (Plan Number: NIFDC-PT-417). The proficiency testing was conducted on-site and consisted of two parts: a written test and practical operation. The written test was open-book. True/false questions focused on participants' understanding of specific clauses in relevant standards, while application-based questions assessed their ability to handle data processing in simulated testing scenarios. The practical operation was conducted according to the relevant criteria of the China National Accreditation Service for Conformity Assessment (CNAS). Two laboratory animal rooms were prepared as proficiency testing samples using a sample splitting approach. These rooms underwent uniformity and stability testing according to CNAS requirements and were approved. Participating laboratories were required to conduct three tests on each of the two laboratory animal rooms, complete the testing and calculation of air change rate within the specified timeframe, and submit their test result reports and original records. Results A total of 27 laboratories registered and participated in the proficiency testing. All participating laboratories submitted their results within the designated timeframe, and the outcomes of all tested laboratories were rated as satisfactory. Conclusion This proficiency validation program objectively and scientifically evaluates the air change rate testing capabilities of selected domestic laboratories, effectively promoting the overall improvement of testing capabilities in the industry. It provides technical support for regulatory authorities to standardize testing institutions and offers reliable references for the purchase of testing services. Through this activity, it was identified that some laboratories need to further enhance their calibration of instruments and the utilization of calibration results. Future efforts should focus on refining related standards to improve the accuracy and reliability of testing.

Objective To observe the efficacy of modified endoscopic sinus surgery(ESS)in treatment of chronic rhinosinusitis with nasal polyps(CRSwNP)complicated by allergic rhinitis(AR).Methods Forty patients with CRSwNP and perennial AR who were scheduled for ESS were divided into study group and control group,with 20 cases in each group.The control group was treated with conventional ESS,while the study group underwent resection of a large part of the middle turbi-nate on the basis of ESS to enhance middle meatal drainage.The postoperative mucosal outcomes,complications,as well as the Visual Analog Scale(VAS),sino-nasal outcome test-20(SNOT-20),and nasal endoscopic Lund-Kennedy scores before surgery,at 3 months after surgery,and at 1 year af-ter surgery were compared between the two groups.Results In the control group,there were 3 cases of local adhesion between the displaced middle turbinate and the lateral nasal wall at 3 months after surgery,and 10 cases of middle turbinate edema at 1 year after surgery,including 4 cases with local polypoid changes in the middle turbinate and polypoid hyperplasia in the ethmoid sinus and frontal re-cess regions.No complications were observed in the study group,and the epithelialization of the surgical area was good.Moreover,the nasal congestion score,olfactory score,and Lund-Kennedy score at 1 year after surgery in the study group were lower than those in the control group,with statistically significant differences(P＜0.05).Conclusion Modified ESS can significantly improve nasal con-gestion and olfactory symptoms in patients with CRSwNP complicated by perennial AR and effective-ly enhance their quality of life.

OBJECTIVE: To investigate the predictive value of early lactate/albumin ratio (LAR) combined with quick sequential organ failure assessment (qSOFA) for the 28-day prognosis of patients with sepsis caused by emergency community-acquired pneumonia (CAP). METHODS: The clinical data of patients with sepsis caused by CAP admitted to the department of emergency of Beijing Haidian Hospital from June 2021 to August 2022 were retrospectively analyzed, including gender, age, comorbidities, lactic acid (Lac), serum albumin (Alb), LAR, procalcitonin (PCT) within 1 hour, and 28-day prognosis. Patients were divided into two groups based on 28-day prognosis, and risk factors affecting patients' prognosis were analyzed using univariate and multivariate Cox regression methods. Patients were divided into two groups according to the best cut-off value of LAR, and Kaplan-Meier survival curves were used to analyze the 28-day cumulative survival of patients in each group. Time-dependent receiver operator characteristic curve (ROC curve) were plotted to analyze the predictive value of sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II (APACHE II), and qSOFA+LAR score on the prognosis of patients with sepsis caused by CAP at 28 days. The area under the curve (AUC) was calculated and compared. RESULTS: A total of 116 patients with sepsis caused by CAP were included, of whom 80 survived at 28 days and 36 died, 28-day mortality of 31.0%. There were no statistically significant differences in age, gender, comorbidities, pH, platelet count, and fibrinogen between the survival and death groups, and there were significantly differences in blood urea nitrogen (BUN), white blood cell count (WBC), hemoglobin, Lac, Alb, PCT, D-dimer, LAR, as well as qSOFA score, SOFA score, and APACHE II score. Univariate Cox regression analyses showed that BUN, WBC, pH, Lac, Alb, PCT, LAR, qSOFA score, SOFA score, and APACHE II score were associated with mortality outcome. Multifactorial Cox regression analysis of the above variables showed that BUN, WBC, PCT, and APACHE II score were independent risk factors for 28-day death in the emergency department in patients with sepsis caused by CAP [hazard ratio (HR) were 1.081, 0.892, 1.034, and 1.135, respectively, all P < 0.05]. The best cut-off value of early LAR for predicting the 28-day prognosis of sepsis patients was 0.088, the Kaplan-Meier survival curve showed that the 28-day cumulative survival rate of sepsis patients in the LAR ≤ 0.088 group was significantly higher than that in the LAR > 0.088 group [82.9% (63/76) vs. 42.5% (17/40), Log-Rank test: χ² = 22.51, P < 0.001]. The qSOFA+LAR score was calculated based on the LAR cut-off value and qSOFA score, and ROC curve analysis showed that the AUCs of SOFA score, APACHE II score, and qSOFA+LAR score for predicting 28-day death of patients with sepsis caued by CAP were 0.741, 0.774, and 0.709, respectively, with the AUC of qSOFA+LAR score slightly lower than those of SOFA score and APACHE II score, but there were no significantly differences. When the best cut-off value of qSOFA+LAR score was 1, the sensitivity was 63.9% and the specificity was 80.0%. CONCLUSION The qSOFA+LAR score has predictive value for the 28-day prognosis of patients with sepsis caused by CAP in the emergency department, its predictive value is comparable to the SOFA score and the APACHE II score, and it is more convenient for early use in the emergency department.
Emergency Service, Hospital/statistics & numerical data* ; Sepsis/etiology* ; Prognosis ; Community-Acquired Pneumonia/mortality* ; Organ Dysfunction Scores ; Predictive Value of Tests ; Lactic Acid/blood* ; Serum Albumin, Human/analysis* ; Biomarkers/blood* ; Retrospective Studies ; Hospital Mortality ; Kaplan-Meier Estimate ; APACHE ; Procalcitonin/blood* ; ROC Curve ; Area Under Curve ; Humans

Objective To analyze the influencing factors of tumor-specific mortality in patients with advanced endometrial carcinoma and construct a risk prediction model.Methods A total of 150 patients with advanced endometrial carcinoma admitted to the Fourth Clinical College of Zhejiang Chinese Medical University,Hangzhou First People's Hospital from January 2020 to January 2023 were selected as subjects.Cox regression was employed to analyze factors influencing mortality in advanced endometrial carcinoma.A Logistic regression model was constructed,with receiver operating characteristic(ROC)curve used to evaluate model discrimination,calibration curve for precision assessment,and decision curve for net benefit evaluation.Results Overall 2-year survival rate of 150 patients was 58.67％.The univariate analysis demonstrated that histological grade,lymph node metastasis,tumor maximum diameter,and preoperative carcinoembryonic antigen 125(CA125)levels were all significant risk factors for mortality in advanced endometrial carcinoma(P＜0.05).Multivariate analysis confirmed these parameters as independent prognostic indicators(P＜0.05).A Logistic regression model established using multivariate Cox regression yielded a C index of 0.873(95％CI:0.792-0.951).ROC curve analysis revealed the model's area under the curve for predicting mortality risk factors in advanced endometrial carcinoma was 0.916(95％CI:0.872-0.960).Conclusion The linear chart prediction model constructed based on histological grading,lymph node metastasis,maximum tumor diameter and preoperative CA125 level in this study can effectively predict the death of advanced endometrial carcinoma.

Objective:To explore the predictive value of ultrasonic shear wave elastography (SWE) parameters and pathological characteristics on the status of human epidermal growth factor receptor 2 (HER2), which is difficult to be determined by immunohistochemistry (IHC) in breast cancer, and to construct a nomogram model.Methods:A retrospective case-control study was conducted. One hundred and fifteen cases of breast cancer diagnosed and treated in Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from September 2018 to April 2022 were selected, and their HER2 was evaluated as IHC 2+; the HER2 expression status was determined by fluorescence in situ hybridization (FISH) detection, including 23 HER2 positive cases and 92 HER2 negative cases. The ultrasound SWE parameters [including maximum shear wave velocity (V max), mean shear wave velocity (V mean), median shear wave velocity (V median), minimum shear wave velocity (V min)] and clinicopathological characteristics between HER2 positive and negative groups were compared. The variables with statistically significant differences ( P < 0.05) between groups were included in a multivariate logistic regression model, the independent risk factors for HER2 positivity were screened, and a nomogram model was constructed based on these independent risk factors. With the FISH test results as the gold standard, the efficacy of nomogram in judging HER2 positivity in breast cancer which was difficult to be identified by IHC was evaluated with the receiver operating characteristic (ROC) curve; the accuracy and clinical net benefit of the nomogram model were evaluated using calibration curve and decision curve analysis (DCA), respectively. Results:The patients were all female, aged (56±13) years, ranging from 30 to 88 years old. V max [ M ( Q1, Q3)] [8.54 (7.38, 9.47) m/s vs. 6.46 (5.07, 8.42) m/s], V mean [(5.41±0.78) m/s vs. (4.53±1.22) m/s], V median [5.06 (4.48, 5.52) m/s vs. 4.35 (3.42, 4.96) m/s], V min [3.35 (2.68, 3.88) m/s vs. 2.59 (2.11, 3.34) m/s], the proportion of patients with axillary lymph node metastasis [56.5% (13/23) vs. 22.8% (21/92)], and the Ki-67 positivity index [35% (30%, 55%) vs. 25% (15%, 35%)] in the HER2 positive group were higher than those in the HER2 negative group, and the differences were statistically significant (all P < 0.05); There was no statistically significant difference in age, lesion location, pathological type, vascular invasion, nerve invasion and long diameter, short diameter, echo, regular shape, clear boundary, posterior echo, calcification, blood flow grading, Breast Imaging Report and Data System (BI-RADS) classification detected by ultrasound between the two groups (all P > 0.05). Multivariate logistic regression analysis showed that increased ultrasound V max ( OR = 1.786, 95% CI: 1.283-2.485, P = 0.001) and axillary lymph node metastasis ( OR = 4.185, 95% CI: 1.327-13.197, P = 0.015) and elevated Ki-67 positivity index ( OR = 1.042, 95% CI: 1.014-1.071, P = 0.003) were independent risk factors for HER2 positivity. ROC curve analysis showed that the area under the curve (AUC) of HER2 positive breast cancer which was difficult to be determined by IHC was 0.816 (95% CI: 0.732-0.883), that was higher than 0.712 (95% CI: 0.620-0.794) of V max, 0.601 (95% CI: 0.504-0.692) of axillary lymph node metastasis and 0.706 (95% CI: 0.613-0.788) of Ki-67 positivity index based on the nomogram constructed by the above independent risk factors, with statistically significant differences (all P < 0.05). The calibration curve showed that the predicted probability of the nomogram model was close to the actual probability, and DCA indicated that the clinical net benefit of the model was good. Conclusions:The nomogram constructed based on ultrasonic SWE parameter V max, axillary lymph node metastasis and Ki-67 positivity index has a good predictive effect on HER2 status of breast cancer which is difficult to be determined by IHC.

Objective:To compare the application effects of the solution-focused nursing model (SFNM) and conventional care in the perioperative care for patients with pelvic fractures.Methods:A retrospective cohort study was conducted to analyze the clinical data of 62 patients with pelvic fractures admitted to the Third Affiliated Hospital of Southern Medical University between February 2023 and July 2023, including 41 males and 21 females, aged 26-63 years [(44.1±15.7)years]. All the patients underwent open or closed reduction and internal fixation. According to different perioperative nursing intervention, 31 patients were treated with conventional care (conventional care group) and 31 with SFNM intervention based on conventional care (SFNM group). A comparative analysis was conducted between the two groups regarding general self-efficacy scale (GSES) score, Barthel index (BI) score, self-rating anxiety scale (SAS) score, and self-rating depression scale (SDS) score preoperatively, at discharge, and at 6 months postoperatively. The excellent-to-good rate of Majeed pelvic function score and nursing satisfaction at the final follow-up and perioperative complication incidence were compared between the two group.Results:All the patients were followed up for 12-15 months [(13.5±0.9)months]. No significant differences were observed between the two groups in GSES, BI, SAS or SDS scores ( P>0.05). At discharge, the GSES and BI scores in the SFNM group were (29.0±3.8)points and (37.4±8.7)points, significantly higher than (20.9±3.0)points and (31.5±12.1)points in the conventional care group ( P<0.05); the SAS and SDS scores were (41.9±5.1)points and (40.6±4.9)points in the SFNM group, significantly lower than (53.7±9.1)points and (42.9±7.5)points in the conventional care group ( P<0.01). At 6 months postoperatively, the SFNM group achieved GSES and BI scores of (34.0±4.0)points and (40.3±9.0)points, significantly higher than (25.2±3.7)points and (35.7±10.5)points in the conventional care group ( P<0.05); the SAS and SDS scores were (45.8±5.0)points and (38.2±3.0)points in the SFNM group, significantly lower than (50.0±8.5)points and (40.7±6.5)points in the conventional care group ( P<0.01). At the final follow-up, the excellent-to-good rate of Majeed pelvic function score was 90% (28/31) in the SFNM group and 87% (27/31) in the conventional care group ( P>0.05). At the final follow-up, nursing satisfaction rate was 100% (31/31) in the SFNM group, significantly higher than 77% (24/31) in the conventional care group ( P<0.05). The perioperative complication rate was 6% (2/31) in the SFNM group, significantly lower than 38% (12/31) in the conventional care group ( P<0.05). Conclusion:Compared with conventional care, perioperative intervention with SFNM for patients with pelvic fractures can enhance self-efficacy and daily living self-care ability, reduce negative emotions such as anxiety and depression, improve nursing satisfaction, and lower the incidence of complications, making it worthy of clinical promotion.

Objective:To investigate the correlation between insulin resistance surrogate indicators and early-stage kidney injury in type 2 diabetes mellitus(T2DM).Methods:A total of 918 T2DM patients hospitalized in the Endocrinology Department of Xinhua Hospital from January 2018 to December 2020 were selected, including 313 patients with early-stage kidney injury and 605 without. Differences in insulin resistance surrogate indicators, including triglyceride to high-density lipoprotein cholesterol ratio(TG/HDL-C), triglyceride glucose(TyG) index, and triglyceride glucose-body mass index(TyG-BMI), were compared between the two groups. Factors associated with early-stage kidney injury in T2DM were analyzed, and the impact of TG/HDL-C, TyG index, and TyG-BMI on early-stage kidney injury in T2DM were explored.Results:Compared with T2DM patients without early-stage kidney injury, those with early-stage kidney injury exhibited significantly elevated levels of TG/HDL-C, TyG index, and TyG-BMI( P< 0.001). TG/HDL-C, TyG index, TyG-BMI, age, duration of diabetes, systolic blood pressure, fasting insulin, and HbA 1C were identified as independent risk factors for early-stage kidney injury in T2DM. Compared to the Q1 quartile, the risk in the Q4 quartile was 3.168 times(95% CI 1.993-5.036) for TG/HDL-C, 2.714 times(95% CI 1.710-4.306) for TyG index, and 2.893 times(95% CI 1.820-5.598) for TyG-BMI. Conclusion:Insulin resistance surrogate indicators TG/HDL-C, TyG index, and TyG-BMI are significantly elevated in T2DM patients with early-stage kidney injury, serving as independent risk factors for early-stage renal impairment in T2DM.

Objective:To evaluate the epidemiological characteristics and influencing factors of out-of-hospital sudden cardiac death (SCD) in Hangzhou from 2016 to 2019.Methods:SCD events recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019 were reviewed. Demographic and mortality data were recorded, and the distribution patterns of SCD events in terms of date, time, and population with different characteristics were observed. Time series analysis method and a distributed lag nonlinear model based on quasi-Poisson distribution were used to explore the possible nonlinear association between ambient temperature and SCD incidence.Results:A total of 4 744 out-of-hospital sudden death events were recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019. After excluding non-SCD events and observed events with missing items, 3 743 SCD events were finally included in the study. The survey results showed that the incidence of out-of-hospital SCD in Hangzhou was 96.5 cases per 100 000 person-years. Most of the people who experienced SCD were aged ≥60 years. The incidence in males (2 462 cases, 66%) was significantly higher than that in females (1 281 cases, 34%), and the proportion of events occurring during the day (2 737 cases, 73%) was significantly higher than that at night (1 006 cases, 27%), mainly occurring between 7: 00 and 9: 00. High temperature was associated with an increased risk of SCD. When the average daily temperature was higher than 25.5 ℃, the risk of SCD increased with the further increase of average daily temperature.Conclusions:SCD events mainly occur in the elderly population aged ≥60 years, with a significantly higher incidence in males than in females, and more frequently during the day than at night, mainly between 7: 00 and 9: 00 in the morning. High temperature is closely related to the risk of SCD. It is particularly important to carry out targeted SCD screening and prevention for different populations and implement appropriate prevention strategies for high-risk groups of SCD in high-temperature weather.