Objective To explore the effectiveness of the cumulative sum (CUSUM) and the exponentially weighted moving average (EWMA) for early warning of influenza epidemic using two datasets of reported influenza cases and influenza-like illness (ILI) cases. Methods Using the reported cases of influenza and ILI in Daxing District, Beijing, from week 23 of 2018 to week 22 of 2024 as data sets, the CUSUM and EWMA models were established, respectively. The positive rate of influenza etiology was used as the ^“gold standard^”, and the Youden index was used as the evaluation index to compare the early warning effect of the two models under different data sets and different parameters. Results In CUSUM, the optimal Youden indices of the reported influenza cases set and the ILI cases set were 0.751 and 0.635, respectively. In EWMA, the optimal Youden indices of the reported influenza cases set and the ILI cases set were 0.544 and 0.464, respectively. The optimal EWMA and CUSUM models could both issue early warning signals in advance of the ^“gold standard^”. Conclusion In the influenza epidemic early warning in Daxing District, Beijing, the CUSUM model established with the reported cases of influenza can achieve good early warning effects, but the model parameters need to be dynamically adjusted according to the local epidemic characteristics.

Objective To evaluate the effectiveness of active screening in improving the detection rate of carbape-nem-resistant Enterobacterales(CRE)in the intensive care units(ICUs).Methods From July 2023 to June 2024,active screening of rectal swab CRE was conducted on ICU patients in 10 hospitals.ICU patients who underwent ac-tive screening from July 2023 to June 2024 were selected as the study group,while those who did not undergo active screening from July 2022 to June 2023 were selected as the control group.Difference in CRE detection rates between the two groups of patients was compared.Results A total of 7 803 ICU patients were included in the study group,744 CRE strains were detected,with a detection rate of 9.53％,out of which 304 CRE strains were detected through routine detection(detection rate 3.90％),3 707 patients underwent active screen,440 CRE strains were detected(detection rate 11.87％).7 561 ICU patients were included in the control group,out of which 250 CRE strains were detected through routine detection,with a detection rate of 3.31％.There was a statistically significant difference in the overall detection rate of CRE between two groups of patients(x2=246.18,P＜0.001).In the study group,CRE detection rate of active screening(11.87％)was higher than that of routine detection(3.90％),with statistically significant difference(x2=264.26,P＜0.001).A total of 17 CRE strains were detected from the study group.The proportions of Klebsiella pneumoniae(80.92％vs 73.41％)and Serratia marcescens(2.30％vs0.23％)in the routine detection group were both higher than in the active screening group,while the proportion of Escherichia coli in the routine detection group was lower(8.22％vs 19.55％),all with statistically significant differences(all P＜0.05).Conclusion The prevalence of CRE in ICUs is relatively high,with a wide range of bac-terial species.Active screening can improve the detection rate of CRE.

Background Exposure to volatile organic compounds (VOCs) has been observed in both living and working environments. Volatile organic compounds metabolites (VOCMs) in urine can be used to assess the exposure to VOCs and potentially cause adverse effects on human body. Objective To quantitatively evaluate urinary VOCMs and their associations with renal function damage, and further trace the characteristics of potential environmental exposure to provide scientific evidence for effective prevention measures. Methods The study included a total of 6028 samples from four cross-sectional studies in the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2018, with exposure and health outcomes matched. Generalized linear models were employed to assess the associations of urinary VOCMs (urinary creatinine adjusted) with urinary protein levels and estimated glomerular filtration rate (eGFR), with coviriables including gender, age, body mass index, education, smoking, alcohol consumption, exercise frequency, diabetes, and hypertension. Weighted quantile sum (WQS) approach was utilized to analyze the effects of mixed exposure and to rank the contribution of individual VOCMs. The associations between VOCMs and associated living environments and occupational exposure characteristics were further investigated. Results Among the enrolled study participants (n=6028), a total of 11 urinary VOCMs were measured, with 10 metabolites having a positive rate of over 80% (84.59%-99.99%). There were 604 individuals (10.0%) having urinary protein abnormalities and 2831 individuals (47.0%) with eGFR reduced. Through a single and a multiple generalized linear model, 5 VOCMs exhibited statistically significant associations with urinary protein abnormalities and/or reduced eGFR levels (P<0.05): N-acetyl-S-(N-methylaminocarbonyl)-L-cysteine (AMC), N-acetyl-S-(2-carboxyethyl)-L-cysteine (CEM), N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHB), 2-hydroxy-2-phenylacetic acid (MAD), and N-acetyl-S-(4-hydroxy-2-butenyl)-L-cysteine (MB3). The WQS index indicated a significantly positive association between VOCMs and urinary protein abnormalities, and DHB contributed the most. The analysis on the potential sources of VOCs exposure showed that those who worked as a private entrepreneur or an employee (vs. government employees), rent houses (vs. owned real estate), had less number of rooms in the residence, fueled cars at self-service gas stations, and inhaled paint fumes in the past 48 h associated with higher VOCMs (P < 0.05) and DHB contributed the most. Conclusion Multiple VOCMs in urine are associated with significantly kidney function injuries. The mixture exposure to VOCMs is significantly associated with higher risks of urinary protein abnormalities. Occupational category, housing ownership, ways to fuel a car, and inhalation of paint odors are closely related with VOCMs levels.

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

Acute respiratory distress syndrome (ARDS) is the leading cause of respiratory failure with high morbidity and mortality. Pulmonary surfactant (PS)-based complementary therapies have exhibited potential for ARDS healing and applied as an adjunctive therapy strategy. Coacervate (Coac) has the characteristics of softness, deformability and excellent molecular enrichment properties, and has attracted extensive attention in the biomedical field. Here PS and coacervate were combined for the potential ARDS treatment. The Coac, fabricated from polyallylamine hydrochloride (PAH) and adenosine triphosphate (ATP) by simple mixing, exhibited soft droplet property and high enrichment for dexamethasone sodium phosphate (DSP). To avoid the fusion effect of membraneless coacervate and endow it with biological functions of PS, liposomes with PS-biomimetic lipid components (PS-lipo) were further introduced to construct PS-biomimetic membranized coacervate (DSP@PS-Coac). The DSP@PS-Coac demonstrated high lung targeting effect and significant penetration efficiency after intravenous injection. Furthermore, PS-lipo replenished the endogenous PS pool and facilitated the distribution of DSP in inflammatory cells in the lung. In the ARDS mouse model, PS-Coac and DSP exerted synergetic anti-inflammatory functions, via reducing the recruitment of inflammatory neutrophils and modulating macrophages into anti-inflammatory phenotype. The overall results confirmed that DSP@PS-Coac may provide a promising delivery option for the treatment of ARDS.

Objective To evaluate the effectiveness of active screening in improving the detection rate of carbape-nem-resistant Enterobacterales(CRE)in the intensive care units(ICUs).Methods From July 2023 to June 2024,active screening of rectal swab CRE was conducted on ICU patients in 10 hospitals.ICU patients who underwent ac-tive screening from July 2023 to June 2024 were selected as the study group,while those who did not undergo active screening from July 2022 to June 2023 were selected as the control group.Difference in CRE detection rates between the two groups of patients was compared.Results A total of 7 803 ICU patients were included in the study group,744 CRE strains were detected,with a detection rate of 9.53％,out of which 304 CRE strains were detected through routine detection(detection rate 3.90％),3 707 patients underwent active screen,440 CRE strains were detected(detection rate 11.87％).7 561 ICU patients were included in the control group,out of which 250 CRE strains were detected through routine detection,with a detection rate of 3.31％.There was a statistically significant difference in the overall detection rate of CRE between two groups of patients(x2=246.18,P＜0.001).In the study group,CRE detection rate of active screening(11.87％)was higher than that of routine detection(3.90％),with statistically significant difference(x2=264.26,P＜0.001).A total of 17 CRE strains were detected from the study group.The proportions of Klebsiella pneumoniae(80.92％vs 73.41％)and Serratia marcescens(2.30％vs0.23％)in the routine detection group were both higher than in the active screening group,while the proportion of Escherichia coli in the routine detection group was lower(8.22％vs 19.55％),all with statistically significant differences(all P＜0.05).Conclusion The prevalence of CRE in ICUs is relatively high,with a wide range of bac-terial species.Active screening can improve the detection rate of CRE.

Objective:To investigate the delay in medical care-seeking and diagnosis of human brucellosis cases in Daxing District, Beijing City, and analyze the relevant influencing factors.Methods:Retrospective analysis method was used to collect the information on brucellosis cases reported by the Infectious Disease Reporting Information Management System of the China Disease Prevention and Control Information System in Daxing District, Beijing City from January 1, 2013 to December 31, 2022. And the case information was reviewed, including demographic information, clinical manifestations, medical care-seeking, diagnosis, etc. Binary logistic regression was used to analyze the influencing factors of delayed diagnosis.Results:A total of 120 cases of brucellosis were included, including 91 males and 29 females, with a male-to-female ratio of 3.14 ∶ 1.00. The majority were aged 40 - 79 years, accounting for 81.7% (98/120). Farmers and unemployed household workers were the main occupations, accounting for 67.5% (81/120). The main clinical manifestations were fever (85.8%, 103/120), hyperhidrosis (65.8%, 79/120), fatigue (61.7%, 74/120), and muscle soreness (60.0%, 72/120). The delay rate of medical care-seeking was 33.3% (40/120), with a median medical care-seeking time of 6 days (interquartile range: 2 - 22 days, range: 0 - 727 days). The diagnosis delay rate was 50.8% (61/120), with a median diagnosis time of 10 days (interquartile range: 3 - 22 days, range: 0 - 1 530 days). The results of binary logistic regression analysis showed that the reasons for initial diagnosis were severe or recurrent symptoms ( OR = 6.76, 95% CI: 2.40 - 19.01), serological monitoring or other diseases ( OR = 36.00, 95% CI: 3.57 - 362.72), and delayed medical care-seeking ( OR = 4.30, 95% CI: 1.68 - 11.01) were risk factors for delayed diagnosis of brucellosis cases. The location of the diagnostic hospitals outside the city ( OR = 0.27, 95% CI: 0.08 - 0.92) was a protective factor for delayed diagnosis of brucellosis cases. Conclusions:The medical care-seeking and diagnosis of brucellosis cases in Daxing District, Beijing City have been delayed to varying degrees. The reasons of initial diagnosis are severe or recurrent symptoms, serological monitoring or other diseases, and medical care-seeking delay are the risk factors for the delayed diagnosis of brucellosis cases. The location of the diagnostic hospitals outside the city is a protective factor for delayed diagnosis of brucellosis cases.

Objective:To investigate the delay in medical care-seeking and diagnosis of human brucellosis cases in Daxing District, Beijing City, and analyze the relevant influencing factors.Methods:Retrospective analysis method was used to collect the information on brucellosis cases reported by the Infectious Disease Reporting Information Management System of the China Disease Prevention and Control Information System in Daxing District, Beijing City from January 1, 2013 to December 31, 2022. And the case information was reviewed, including demographic information, clinical manifestations, medical care-seeking, diagnosis, etc. Binary logistic regression was used to analyze the influencing factors of delayed diagnosis.Results:A total of 120 cases of brucellosis were included, including 91 males and 29 females, with a male-to-female ratio of 3.14 ∶ 1.00. The majority were aged 40 - 79 years, accounting for 81.7% (98/120). Farmers and unemployed household workers were the main occupations, accounting for 67.5% (81/120). The main clinical manifestations were fever (85.8%, 103/120), hyperhidrosis (65.8%, 79/120), fatigue (61.7%, 74/120), and muscle soreness (60.0%, 72/120). The delay rate of medical care-seeking was 33.3% (40/120), with a median medical care-seeking time of 6 days (interquartile range: 2 - 22 days, range: 0 - 727 days). The diagnosis delay rate was 50.8% (61/120), with a median diagnosis time of 10 days (interquartile range: 3 - 22 days, range: 0 - 1 530 days). The results of binary logistic regression analysis showed that the reasons for initial diagnosis were severe or recurrent symptoms ( OR = 6.76, 95% CI: 2.40 - 19.01), serological monitoring or other diseases ( OR = 36.00, 95% CI: 3.57 - 362.72), and delayed medical care-seeking ( OR = 4.30, 95% CI: 1.68 - 11.01) were risk factors for delayed diagnosis of brucellosis cases. The location of the diagnostic hospitals outside the city ( OR = 0.27, 95% CI: 0.08 - 0.92) was a protective factor for delayed diagnosis of brucellosis cases. Conclusions:The medical care-seeking and diagnosis of brucellosis cases in Daxing District, Beijing City have been delayed to varying degrees. The reasons of initial diagnosis are severe or recurrent symptoms, serological monitoring or other diseases, and medical care-seeking delay are the risk factors for the delayed diagnosis of brucellosis cases. The location of the diagnostic hospitals outside the city is a protective factor for delayed diagnosis of brucellosis cases.

Objective: To analyze the impact of persistent obesity on their lung function, so as to offer insights for implementing intervention measures to increase lung function in obese school age children. Methods: A total of 335 children from the Sheyang Mini Birth Cohort established in 2009 in Yancheng City, Jiangsu Province, who participated in the follow up at the ages of 7 years (2016) and 10 years (2019), were selected as the study participants. Physical measurements including height, weight, and lung function were recorded. According to the World Health Organization standard, that is, gender and age specific to correct the body mass index to calculate the body mass index Z score, was used to evaluate the obesity status of children at the age of 7 and 10. Children were divided into four groups, including sustained non obesity group, restored obesity group, newly classified obesity group, and persistent obesity group. Meanwhile, the lung function prediction equations recommended by the Global Lung Function Initiative were used to standardize the lung function indexes of children. Pulmonary function differences among these groups were examined, and the relationship between childhood obesity and pulmonary function was longitudinally analyzed using generalized estimating equations. Results: The prevalence of obesity were 9.0% and 16.1% at the age of 7 and 10 years, respectively. The proportion of both newly classified and persistent obesity group were 8.1%, respectively. The forced expiratory volume in one second (FEV 1) and forced vital capacity (FVC) were (1 269.90±202.70) and (1 415.70±230.00) mL, respectively, at the age of 7 years. FEV 1 and FVC at the age of 10 years were (1 440.80±403.20) and (1 555.60±517.60) mL, respectively. Cross sectional analysis at age 7 showed that forced expiratory flow at 75% vital capacity (FEF 75 ) ( β=-0.52, 95%CI =-0.96--0.07) and maximal mid expiratary flow (MMEF) ( β=-0.45, 95%CI =-0.89--0.00) were significantly lower in obese children compared to their non obese peers ( P < 0.05). Longitudinal analysis indicated that obese children had lower levels of lung pulmonary function, with a statistically significant difference in FEV 1 ( β=-0.44, 95%CI=-0.85--0.02, P <0.05). There was no significant difference among the various obesity groups ( P >0.05), while gender stratified results revealed significant reductions in FEV 1/FVC in newly classified obese girls at age 10 years ( β=-1.76, 95%CI =-3.13--0.38) and in MMEF in persistently obese girls at age 10 years ( β=-1.44, 95%CI = -2.79- -0.09) ( P <0.05). Conclusion Obesity may contribute to reduced lung function levels in school aged children, with newly classified and persistent obesity having more pronounced effects on lung function in girls.

Objective:To explore the application value of optical surface monitoring system (OSMS) volume rendering technique (VRT) body surface imaging in intensity-modulated radiotherapy for thoracic tumors.Methods:A retrospective case series study was performed. The clinical data of 65 patients with thoracic tumors treated with intensity-modulated radiotherapy at Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from September 2021 to October 2022 were retrospectively analyzed. In the first treatment,after cone-beam computed tomography (CBCT) scan and correction, VRT body surface images were obtained by using OSMS. In subsequent treatment, the VRT image was used as the benchmark and the 6-dimensional bed was automatically positioned to record the 6-dimensional bed positioning value. The CBCT scan was performed to record the translation and rotation errors of left-right direction (X-axis), head-foot direction (Y-axis) and front-rear direction (Z-axis). After the calibration of the 6-dimensional automatic bed shifting, the new real-time deltas (RTD) value of digital imaging and communications in medicine (DICOM) body surface image was recorded, and the new VRT image was obtained. CBCT registration error value was defined as VRT image-guided setup error. The sum of CBCT registration error value and moving bed movement value was defined as the body surface marker line-guided setup error. The sum of CBCT registration error value and the recorded DICOM image RTD value was defined as the theoretical error of DICOM image-guided setup. The advantages and disadvantages of VRT image, body surface marker line and DICOM image-guided setup were compared and analyzed.Results:There were 42 males and 23 females in 65 patients with thoracic tumors, and the age [ M ( Q1, Q3)] was 58 years (51 years, 64 years). The linear errors [ M ( Q1, Q3)] of VRT image-guided setup in X, Y and Z axes were 0.6 mm (0.3 mm, 1.2 mm), 1.2 mm (0.5 mm, 2.4 mm) and 1.1 mm (0.5 mm, 1.9 mm); and the rotational errors were 0.4° (0.1°, 0.7°), 0.4° (0.1°, 0.6°) and 0.4° (0.2°, 0.6°). The linear errors of the marker line-guided setup were 1.6 mm (0.9 mm, 2.6 mm), 2.2 mm (1.1 mm, 3.8 mm) and 1.0 mm (0.4 mm, 1.8 mm); and the rotational errors were 0.7° (0.3°, 1.2°), 0.5° (0.2°, 0.8°) and 0.5° (0.2°, 0.8°). The linear errors of the DICOM image-guided positioning were 1.1 mm (0.6 mm, 1.9 mm), 2.1 mm (1.0 mm, 3.4 mm) and 1.3 mm (0.6 mm, 3.1 mm), and the rotational errors were 0.6° (0.2°, 1.1°), 0.7° (0.3°, 1.1°), 0.7° (0.2°, 1.1°). Compared with the marker line-guided setup, except for Z-axis linear error ( P = 0.218), the VRT-guided setup errors were low (all P < 0.001). Compared with the DICOM imaging-guided setup, the VRT image-guided setup linear error and rotational error in X-, Y- and Z-axis were low (all P < 0.01). Conclusions:VRT image-guided setup is superior to traditional body surface marker setup and DICOM imaging setup; OSMS VRT body surface imaging can effectively improve the setup accuracy and stability of intensity-modulated radiotherapy for thoracic tumors, and reduce the setup errors.