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.

BACKGROUND:Nanocell vesicles possess functions such as re-epithelialization,antioxidation,anti-inflammation,and regulation of extracellular matrix remodeling.Meanwhile,apoptotic bodies have the immunomodulatory effects.Therefore,the combination of the two to form nanofusion vesicles can synergistically promote the healing of diabetic skin wounds.OBJECTIVE:To elucidate the impact of nanofusion vesicles on skin wound healing in a diabetic murine model.METHODS:(1)Material preparation and characterization:The primary bone marrow mesenchymal stem cells of C57BL/6J neonatal mice and the neutrophil apoptotic bodies of C57BL/6J mice were isolated and extracted.The nanofusion vesicles were prepared by micro-extrusion mechanism.(2)In vitro experiment:MTT assay was used to detect the proliferative effect of different concentrations of nanofusion vesicles on NIH-3T3 cells and human umbilical vein endothelial cells.Reactive oxygen species fluorescence probe was used to detect the antioxidant effect of nano-fusion vesicles on NIH-3T3 cells treated with hydrogen peroxide(H2O2).The inhibitory effect of nanofusion vesicles on RAW 264.7 macrophage inflammation induced by lipopolyside was detected by real-time quantitative RT-qPCR.(3)In vivo experiment:36 male C57BL/6J mice were employed to develop a murine model of diabetes mellitus.Following the successful induction of diabetes,two circular full-thickness wounds,each with a diameter of 6 mm,were created on either side of the diabetic mice's spine using a skin punch.The mice were divided into three groups by random number table method.The control group was injected with 0.1 mL of phosphate buffer solution.The nanovesicle group was injected with 0.1 mL nanovesicles(25 μg/mL).The nanofusion vesicle group was injected with 0.1 mL nanofusion(25 μg/mL)vesicles.After treatment for three consecutive days,the wound healing and histomorphological changes were observed.RESULTS AND CONCLUSION:(1)In vitro experiment:nanofusion vesicles,when administered at concentrations ranging from 0 to 100 μg/mL,exhibited no toxic effects and promoted the proliferation of NIH-3T3 and HUVEC cell lines.Notably,a concentration of 25 μg/mL nanofusion vesicle significantly enhanced the proliferation of NIH-3T3 cells.Furthermore,the survival rate of human umbilical vein endothelial cells was observed to increase in correlation with escalating concentrations of nanofusion vesicles.Nanofusion vesicles had a good antioxidant effect.In comparison to the H2O2 group,the fluorescence signal indicative of reactive oxygen species was progressively diminished in both the nanovesicle group and the nanofusion vesicle group.Furthermore,nanofusion vesicles possessed anti-inflammatory capabilities,effectively mitigating the inflammatory response in macrophages triggered by lipopolysaccharide stimulation.(2)In vivo experiment:Hematoxylin-eosin and Masson's trichrome staining revealed that in comparison to the control group,both the nanovesicle group and the nanofusion vesicle group exhibited a significant increase in granulation tissue formation and collagen fiber deposition within the wounds by day 6.Notably,the nanofusion vesicle group displayed the most pronounced effects.On day 12,the wound of nanofusion vesicle group was significantly reduced,and the healing rate was significantly faster than that of other groups(P＜0.01),and the effect of promoting wound healing was the most significant.Our findings demonstrated that nanofusion vesicles exhibited superior pro-cell proliferative,antioxidant,and anti-inflammatory properties,thereby exerting a beneficial effect on the promotion of skin wound healing in diabetic mouse models.

BACKGROUND:Nanocell vesicles possess functions such as re-epithelialization,antioxidation,anti-inflammation,and regulation of extracellular matrix remodeling.Meanwhile,apoptotic bodies have the immunomodulatory effects.Therefore,the combination of the two to form nanofusion vesicles can synergistically promote the healing of diabetic skin wounds.OBJECTIVE:To elucidate the impact of nanofusion vesicles on skin wound healing in a diabetic murine model.METHODS:(1)Material preparation and characterization:The primary bone marrow mesenchymal stem cells of C57BL/6J neonatal mice and the neutrophil apoptotic bodies of C57BL/6J mice were isolated and extracted.The nanofusion vesicles were prepared by micro-extrusion mechanism.(2)In vitro experiment:MTT assay was used to detect the proliferative effect of different concentrations of nanofusion vesicles on NIH-3T3 cells and human umbilical vein endothelial cells.Reactive oxygen species fluorescence probe was used to detect the antioxidant effect of nano-fusion vesicles on NIH-3T3 cells treated with hydrogen peroxide(H2O2).The inhibitory effect of nanofusion vesicles on RAW 264.7 macrophage inflammation induced by lipopolyside was detected by real-time quantitative RT-qPCR.(3)In vivo experiment:36 male C57BL/6J mice were employed to develop a murine model of diabetes mellitus.Following the successful induction of diabetes,two circular full-thickness wounds,each with a diameter of 6 mm,were created on either side of the diabetic mice's spine using a skin punch.The mice were divided into three groups by random number table method.The control group was injected with 0.1 mL of phosphate buffer solution.The nanovesicle group was injected with 0.1 mL nanovesicles(25 μg/mL).The nanofusion vesicle group was injected with 0.1 mL nanofusion(25 μg/mL)vesicles.After treatment for three consecutive days,the wound healing and histomorphological changes were observed.RESULTS AND CONCLUSION:(1)In vitro experiment:nanofusion vesicles,when administered at concentrations ranging from 0 to 100 μg/mL,exhibited no toxic effects and promoted the proliferation of NIH-3T3 and HUVEC cell lines.Notably,a concentration of 25 μg/mL nanofusion vesicle significantly enhanced the proliferation of NIH-3T3 cells.Furthermore,the survival rate of human umbilical vein endothelial cells was observed to increase in correlation with escalating concentrations of nanofusion vesicles.Nanofusion vesicles had a good antioxidant effect.In comparison to the H2O2 group,the fluorescence signal indicative of reactive oxygen species was progressively diminished in both the nanovesicle group and the nanofusion vesicle group.Furthermore,nanofusion vesicles possessed anti-inflammatory capabilities,effectively mitigating the inflammatory response in macrophages triggered by lipopolysaccharide stimulation.(2)In vivo experiment:Hematoxylin-eosin and Masson's trichrome staining revealed that in comparison to the control group,both the nanovesicle group and the nanofusion vesicle group exhibited a significant increase in granulation tissue formation and collagen fiber deposition within the wounds by day 6.Notably,the nanofusion vesicle group displayed the most pronounced effects.On day 12,the wound of nanofusion vesicle group was significantly reduced,and the healing rate was significantly faster than that of other groups(P＜0.01),and the effect of promoting wound healing was the most significant.Our findings demonstrated that nanofusion vesicles exhibited superior pro-cell proliferative,antioxidant,and anti-inflammatory properties,thereby exerting a beneficial effect on the promotion of skin wound healing in diabetic mouse models.

Objective To evaluate the predictive value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) 3.0T enhanced magnetic resonance imaging (MRI) for microvascular invasion (MVI) in young and middle-aged patients with small hepatocellular carcinoma (SHCC). Methods Seventy young and middle-aged patients with SHCC were divided into MVI (n=21) and non-MVI (n=49) groups. All patients underwent preoperative univariate analysis of qualitative and quantitative parameters of Gd-EOB-DTPA MRI enhancement, and multivariate logistic regression was performed using the parameters that differed between groups as independent variables. Receiver operating characteristic and Kaplan–Meier survival curves were drawn to determine the predictive parameters and predict postoperative recurrence and metastasis. Results Significant differences in the qualitative parameters of tumor shape, tumor margin, pseudocapsule completeness, peritumoral hypointensity in the hepatobiliary phase, and peritumoral enhancement in the artery phase were found between the MVI and non-MVI groups (P<0.05); with regard to the quantitative parameters, the apparent diffusion coefficient (ADC) values of tumors between two groups were statistically significant (P<0.05). Multivariate logistic regression analysis showed that small ADC, peritumoral hypointensity in the hepatobiliary phase, and peritumoral enhancement were independent risk factors of MVI in young and middle-aged patients with SHCC (P<0.05). Survival analysis revealed that the recurrence rate of the MVI group was higher than that of the non-MVI group in the first two years. Conclusion Gd-EOB-DTPA-enhanced MRI is valuable in predicting the presence of MVI and postoperative recurrence and metastasis in young and middle-aged patients with SHCC.

OBJECTIVE: To investigate the clinical value of MRI modified water-lipid separation technique (mDIXON-Quant) in terms of T2* values and fat fraction (FF) values for evaluating the degree of cervical intervertebral disc degeneration. METHODS: A total of 118 patients who underwent routine MRI of the cervical vertebra and the mDIXON-Quant examination in Fuyang People's Hospital from March 2019 to January 2024 were collected. The T2* values of C2/3 to C6/7 intervertebral discs and FF values of the upper and lower vertebral bodies were measured. Cervical intervertebral disc degeneration was graded according to the Pfirrmann criteria. The T2* values and FF values of different patients were compared with the Pfirrmann grades, and the correlation between T2* values, FF values, and Pfirrmann grades was analyzed by Spearman correlation. RESULTS: The T2* values of cervical intervertebral discs in grades I, II, III, IV, and V all showed a decreasing trend ( P＜0.05). The decreasing order of FF values in the upper cervical vertebra was IV, V, III, II, and I ( F=93.28, P＜0.05), and the decreasing order of FF values in the lower cervical vertebra was IV, III, V, II, and I ( F=112.037, P＜0.05). Spearman correlation analysis showed that the T2* values of cervical intervertebral discs were negatively correlated with the Pfirrmann grades ( P＜0.05), and the FF values of the upper and lower vertebrae were positively correlated with the Pfirrmann grades ( P＜0.05). CONCLUSION The mDIXON-Quant technique can be used to quantify the T2* values and FF values of cervical intervertebral disc degeneration and plays an important role in accurate clinical diagnosis and evaluation of treatment effects.
Humans ; Intervertebral Disc Degeneration/diagnostic imaging* ; Cervical Vertebrae/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Adult ; Intervertebral Disc/diagnostic imaging* ; Lipids

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.

The paper introduces Professor ZHUANG Lixing's academic thought on Daoqi Tongjing (directing qi to preserve essence) needling technique and the clinical experience. Based on Huangdi Neijing (the Yellow Emperor's Inner Classic), Dongyuan needling technique and Professor JIN Rui 's Daoqi Tongjing needling method, and by inheriting the valuable experience from the ancient masters and associating with his own clinical practices, Professor ZHUANG Lixing fully displayes the characteristics of principles, methods, formulas, acupoints and techniques of acupuncture in diagnosis and treatment of diseases. He integrates the thought of regulating the mind with Daoqi Tongjing needling. This needling method focuses on directing qi through mind regulation and needle manipulation, in which, the operation steps are refined. Besides, this needling method involves both the reinforcing and reducing techniques. The satisfactory effect of this needling has been obtained in clinical treatment for many disorders such as qi reversion and disharmony of yin and yang.
Acupuncture Therapy/instrumentation* ; Humans ; Acupuncture Points ; China ; Qi ; History, Ancient ; Medicine in Literature