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.

The underlying cause of low response rates to existing immunotherapies is that tumor cells dominate tumor immune escape through surface antigen deficiency and inducing tumor immunosuppressive microenvironment (TIME). Here, we proposed an in situ tumor cell engineering strategy to disrupt tumor immune escape at the root by restoring tumor cell MHC-I/tumor-specific antigen complex (MHC-I/TSA) expression to promote T-cell recognition and by silencing tumor cell CD55 to increase the ICOSL⁺ B-cell proportion and reverse the TIME. A doxorubicin (DOX) and dual-gene plasmid (MAC pDNA, encoding both MHC-I/ASMTNMELM and CD55-shRNA) coloaded drug delivery system (LCPN@ACD) with tumor targeting and charge/size dual-conversion properties was prepared. LCPN@ACD-induced ICD promoted DC maturation and enhanced T-cell activation and infiltration. LCPN@ACD enabled effective expression of MHC-I/TSA on tumor cells, increasing the ability of tumor cell recognition and killing. LCPN@ACD downregulated tumor cell CD55 expression, increased the proportion of ICOSL⁺ B cells and CTLs, and reversed the TIME, thus greatly improving the efficacy of αPD-1 and CAR-T therapies. The application of this in situ tumor cell engineering strategy eliminated the source of tumor immune escape, providing new ideas for solving the challenges of clinical immunotherapy.

Objective:To analyze the effects of fluorine exposure on calcium ion metabolism and the expression of related calcium-regulating proteins in the kidneys of rats.Methods:Forty-five 5-week-old specific pathogen-free male Wistar rats (weighed 90 - 120 g) were selected and divided into three groups according to the randomized numeric table: 0 (control), 50, and 100 mg/L fluorine exposure groups, with 15 rats in each group. The control group was given deionized water, while the 50 and 100 mg/L fluorine exposure groups were given sodium fluoride solutions containing 50 and 100 mg/L fluorine ions, respectively. After 12 weeks, urine samples were collected, and kidneys and blood were harvested. Urinary fluorine levels were measured using a fluoride ion-selective electrode method. Calcium ion levels in the urine, kidneys, and serum were determinated using the methylthymol blue microplate method. The protein expression levels of transient receptor potential vanilloid receptor 5 (TRPV5), calbindin-D28K (CB-D28K), sodium-calcium exchanger-1 (NCX1), Klotho and plasma membrane calcium ATPase 1b (PMCA1b) in the kidneys were detected by Western blotting and immunohistochemistry.Results:The urinary fluorine levels in the control group and the 50 and 100 mg/L fluorine exposure groups were (0.48 ± 0.09), (20.01 ± 1.68), (37.45 ± 2.45) mg/L, respectively, with statistically significant differences between the groups ( F = 929.58, P < 0.001). Significant differences in calcium ion levels in urine, kidneys, and serum were observed among the three groups ( F = 14.66, 11.09, 10.31, P < 0.05). Compared with the control group, the 100 mg/L fluorine exposure group exhibited higher levels of calcium ion in the urine and kidneys, and lower serum calcium ion levels ( P < 0.05). The results of Western blotting analysis revealed that the protein expression levels of TRPV5 and CB-D28K in the kidneys increased with the increase of fluorine exposure level ( Z = 2.11, 2.11, P = 0.035). The protein expression level of NCX1 in the kidneys showed a decreasing trend with increasing fluorine exposure level ( Z = - 2.11, P = 0.035). Significant differences were also observed in the protein expression levels of Klotho and PMCA1b among the three groups ( F = 8.93, 7.08, P < 0.05). Compared with the control group, the 100 mg/L fluorine exposure group showed higher level of Klotho protein expression and lower level of PMCA1b protein expression in the kidneys ( P < 0.05). Immunohistochemical results indicated significant differences in the protein expression levels of TRPV5, CB-D28K, NCX1, and Klotho in the kidneys of the three groups ( F = 27.56, 24.94, 16.05, 32.72, P < 0.05). Compared with the control group, the protein expression levels of TRPV5, CB-D28K, and Klotho in kidneys of 50 and 100 mg/L fluorine exposure groups were higher, while the protein expression levels of NCX1 were lower ( P < 0.05). Conclusion:Fluorine exposure may cause calcium ion metabolism disorders by regulating the expression levels of Klotho and other calcium-regulating proteins in the kidneys.

A total of 1 557 cases were included in the Febrile Respiratory Syndrome (FRS) surveillance conducted in Daxing District between 2018 and 2023. Twelve respiratory pathogens were investigated: human influenza virus (HIFV), human respiratory syncytial virus (HRSV), human parainfluenza virus (HPIV), human rhinovirus (HRV), human enterovirus (HEV), human adenovirus (HadV), human metapneumovirus (HMPV), human bocavirus (HBoV), Mycoplasma pneumoniae (MP), Chlamydia pneumoniae (CP), human coronavirus (HCoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results demonstrated an overall pathogen detection rate of 25.31% (394/1 557), with descending prevalence as follows: HIFV, SARS-CoV-2, HRV, HPIV, MP, HCoV, HRSV, HEV, HMPV, HadV, HBoV, and CP. Temporal analysis revealed detection rates of 26.98% (150/556) for 2018-2019, 15.81% (95/601) for 2020-2022, and 37.25% (149/400) for 2023, showing statistically significant interannual variation (χ2=59.703, P<0.001). Compared with 2018-2019, 2023 exhibited significantly elevated detection rates for HIFV and HMPV ( P<0.05), while HRV, MP, HEV, and HBoV demonstrated significantly reduced rates ( P<0.05). Age-stratified analysis identified HIFV, HRSV, and HadV as the predominant pathogens in individuals aged <15 years, whereas SARS-CoV-2, HIFV, and HRV predominated in those aged ≥60 years.

Objective:To evaluate the performance of three mainstream large language models (LLMs) in the review of drug reimbursement indications in hospitals, and to explore their potential in improving audit quality and efficiency, thereby safeguarding the medical insurance fund.Methods:A total of 3 247 outpatient prescription records were retrospectively collected from a specialized oncology hospital between January 2, 2022, and June 30, 2023. Manual assessment of the consistency between clinical diagnoses and drug reimbursement indications was used as the gold standard. Three LLMs, Baidu′s ERNIE Bot, Alibaba′s Tongyi Qianwen, and OpenAI′s ChatGPT-4o, were evaluated on the same task. Performance metrics included accuracy, precision, sensitivity, specificity, F1 score, and area under the curve (AUC).Results:The ERNIE Bot model returned 3 242 valid data, which took 314 min; The Tongyi Qianwen model returned a total of 3 162 valid data, taking 384 min; The ChatGPT-4o model returned a total of 3 218 valid data, taking 150 min. ChatGPT-4o demonstrated the best performance, with an accuracy of 88.41%, precision of 60.48%, sensitivity of 78.75%, specificity of 90.24%, F1 score of 0.68, and an AUC of 0.88.Conclusions:LLMs demonstrate stable performance in determining whether prescriptions align with reimbursement indications, with ChatGPT-4o approaching human-level accuracy and exhibiting more conservative specificity. These findings suggest that LLMs have practical value as auxiliary tools in drug indication reviews, contributing to improved audit efficiency and more refined management of medical insurance funds.

Purpose To investigate the expression of SNRPA in gastric cancer and its effect on the proliferation,migration and invasion of gastric cancer cells.Methods The expression of SNRPA in gastric cancer tissues was ana-lyzed using The Cancer Genome Atlas(TCGA)database.The level of SNRPA was detected by immunohistochemistry(EnVision method),and its relationship with clinicopathological parameters was analyzed.Western blot was used to detect the expression of SNRPA in 15 cases of fresh gastric cancer and paracancerous tissues.The expression of SNRPA in MGC-803 and GES-1 cells was detected by immunofluorescence staining.The effects of SNRPA expression on the proliferation,migration and invasion of gastric cancer cell lines were determined by RNA interference technology and cell function assays,and the expression levels of Cyclin D1 protein and EMT-related proteins(E-cadherin,N-cadher-in)were detected by Western blot.Results The expression level of SNRPA in gastric cancer tissues was significantly higher than that in normal gastric mucosal tissues(P＜0.05),with an area under the curve(AUC)of 0.902 for diag-nostic accuracy.The Kaplan-Meier survival curves showed that the survival time of the group with high expression of SNRPA was shorter.SNRPA expression correlated with tumor size,Ki67,infiltration depth,and p53 status(P＜0.05).Compared with the corresponding control group,SNRPA silencing inhibited the proliferation,migration and in-vasion ability of gastric cancer cells,accompanied by decreased Cyclin D1 and N-cadherin expression and increased E-cadherin expression(P＜0.05).Conclusion SNRPA expression is upregulated in gastric cancer tissues and cell lines,promoting the proliferation,migration,and invasion of gastric cancer cells,and may be a potential molecular marker for gastric cancer.

Objective:To evaluate the performance of three mainstream large language models (LLMs) in the review of drug reimbursement indications in hospitals, and to explore their potential in improving audit quality and efficiency, thereby safeguarding the medical insurance fund.Methods:A total of 3 247 outpatient prescription records were retrospectively collected from a specialized oncology hospital between January 2, 2022, and June 30, 2023. Manual assessment of the consistency between clinical diagnoses and drug reimbursement indications was used as the gold standard. Three LLMs, Baidu′s ERNIE Bot, Alibaba′s Tongyi Qianwen, and OpenAI′s ChatGPT-4o, were evaluated on the same task. Performance metrics included accuracy, precision, sensitivity, specificity, F1 score, and area under the curve (AUC).Results:The ERNIE Bot model returned 3 242 valid data, which took 314 min; The Tongyi Qianwen model returned a total of 3 162 valid data, taking 384 min; The ChatGPT-4o model returned a total of 3 218 valid data, taking 150 min. ChatGPT-4o demonstrated the best performance, with an accuracy of 88.41%, precision of 60.48%, sensitivity of 78.75%, specificity of 90.24%, F1 score of 0.68, and an AUC of 0.88.Conclusions:LLMs demonstrate stable performance in determining whether prescriptions align with reimbursement indications, with ChatGPT-4o approaching human-level accuracy and exhibiting more conservative specificity. These findings suggest that LLMs have practical value as auxiliary tools in drug indication reviews, contributing to improved audit efficiency and more refined management of medical insurance funds.

A total of 1 557 cases were included in the Febrile Respiratory Syndrome (FRS) surveillance conducted in Daxing District between 2018 and 2023. Twelve respiratory pathogens were investigated: human influenza virus (HIFV), human respiratory syncytial virus (HRSV), human parainfluenza virus (HPIV), human rhinovirus (HRV), human enterovirus (HEV), human adenovirus (HadV), human metapneumovirus (HMPV), human bocavirus (HBoV), Mycoplasma pneumoniae (MP), Chlamydia pneumoniae (CP), human coronavirus (HCoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results demonstrated an overall pathogen detection rate of 25.31% (394/1 557), with descending prevalence as follows: HIFV, SARS-CoV-2, HRV, HPIV, MP, HCoV, HRSV, HEV, HMPV, HadV, HBoV, and CP. Temporal analysis revealed detection rates of 26.98% (150/556) for 2018-2019, 15.81% (95/601) for 2020-2022, and 37.25% (149/400) for 2023, showing statistically significant interannual variation (χ2=59.703, P<0.001). Compared with 2018-2019, 2023 exhibited significantly elevated detection rates for HIFV and HMPV ( P<0.05), while HRV, MP, HEV, and HBoV demonstrated significantly reduced rates ( P<0.05). Age-stratified analysis identified HIFV, HRSV, and HadV as the predominant pathogens in individuals aged <15 years, whereas SARS-CoV-2, HIFV, and HRV predominated in those aged ≥60 years.

Purpose To investigate the expression of SNRPA in gastric cancer and its effect on the proliferation,migration and invasion of gastric cancer cells.Methods The expression of SNRPA in gastric cancer tissues was ana-lyzed using The Cancer Genome Atlas(TCGA)database.The level of SNRPA was detected by immunohistochemistry(EnVision method),and its relationship with clinicopathological parameters was analyzed.Western blot was used to detect the expression of SNRPA in 15 cases of fresh gastric cancer and paracancerous tissues.The expression of SNRPA in MGC-803 and GES-1 cells was detected by immunofluorescence staining.The effects of SNRPA expression on the proliferation,migration and invasion of gastric cancer cell lines were determined by RNA interference technology and cell function assays,and the expression levels of Cyclin D1 protein and EMT-related proteins(E-cadherin,N-cadher-in)were detected by Western blot.Results The expression level of SNRPA in gastric cancer tissues was significantly higher than that in normal gastric mucosal tissues(P＜0.05),with an area under the curve(AUC)of 0.902 for diag-nostic accuracy.The Kaplan-Meier survival curves showed that the survival time of the group with high expression of SNRPA was shorter.SNRPA expression correlated with tumor size,Ki67,infiltration depth,and p53 status(P＜0.05).Compared with the corresponding control group,SNRPA silencing inhibited the proliferation,migration and in-vasion ability of gastric cancer cells,accompanied by decreased Cyclin D1 and N-cadherin expression and increased E-cadherin expression(P＜0.05).Conclusion SNRPA expression is upregulated in gastric cancer tissues and cell lines,promoting the proliferation,migration,and invasion of gastric cancer cells,and may be a potential molecular marker for gastric cancer.

Objective:To analyze the effects of fluorine exposure on calcium ion metabolism and the expression of related calcium-regulating proteins in the kidneys of rats.Methods:Forty-five 5-week-old specific pathogen-free male Wistar rats (weighed 90 - 120 g) were selected and divided into three groups according to the randomized numeric table: 0 (control), 50, and 100 mg/L fluorine exposure groups, with 15 rats in each group. The control group was given deionized water, while the 50 and 100 mg/L fluorine exposure groups were given sodium fluoride solutions containing 50 and 100 mg/L fluorine ions, respectively. After 12 weeks, urine samples were collected, and kidneys and blood were harvested. Urinary fluorine levels were measured using a fluoride ion-selective electrode method. Calcium ion levels in the urine, kidneys, and serum were determinated using the methylthymol blue microplate method. The protein expression levels of transient receptor potential vanilloid receptor 5 (TRPV5), calbindin-D28K (CB-D28K), sodium-calcium exchanger-1 (NCX1), Klotho and plasma membrane calcium ATPase 1b (PMCA1b) in the kidneys were detected by Western blotting and immunohistochemistry.Results:The urinary fluorine levels in the control group and the 50 and 100 mg/L fluorine exposure groups were (0.48 ± 0.09), (20.01 ± 1.68), (37.45 ± 2.45) mg/L, respectively, with statistically significant differences between the groups ( F = 929.58, P < 0.001). Significant differences in calcium ion levels in urine, kidneys, and serum were observed among the three groups ( F = 14.66, 11.09, 10.31, P < 0.05). Compared with the control group, the 100 mg/L fluorine exposure group exhibited higher levels of calcium ion in the urine and kidneys, and lower serum calcium ion levels ( P < 0.05). The results of Western blotting analysis revealed that the protein expression levels of TRPV5 and CB-D28K in the kidneys increased with the increase of fluorine exposure level ( Z = 2.11, 2.11, P = 0.035). The protein expression level of NCX1 in the kidneys showed a decreasing trend with increasing fluorine exposure level ( Z = - 2.11, P = 0.035). Significant differences were also observed in the protein expression levels of Klotho and PMCA1b among the three groups ( F = 8.93, 7.08, P < 0.05). Compared with the control group, the 100 mg/L fluorine exposure group showed higher level of Klotho protein expression and lower level of PMCA1b protein expression in the kidneys ( P < 0.05). Immunohistochemical results indicated significant differences in the protein expression levels of TRPV5, CB-D28K, NCX1, and Klotho in the kidneys of the three groups ( F = 27.56, 24.94, 16.05, 32.72, P < 0.05). Compared with the control group, the protein expression levels of TRPV5, CB-D28K, and Klotho in kidneys of 50 and 100 mg/L fluorine exposure groups were higher, while the protein expression levels of NCX1 were lower ( P < 0.05). Conclusion:Fluorine exposure may cause calcium ion metabolism disorders by regulating the expression levels of Klotho and other calcium-regulating proteins in the kidneys.