Objective To investigate the global burden of visceral leishmaniasis (VL) from 1990 to 2021 and predict the trends in the burden of VL from 2022 to 2035, so as to provide insights into global VL prevention and control. Methods The global age-standardized incidence, prevalence, mortality and disability-adjusted life years (DALYs) rates of VL and their 95% uncertainty intervals (UI) were captured from the Global Burden of Disease Study 2021 (GBD 2021) data resources. The trends in the global burden of VL were evaluated with average annual percent change (AAPC) and 95% confidence interval (CI) from 1990 to 2021, and gender-, age-, country-, geographical area- and socio-demographic index (SDI)-stratified burdens of VL were analyzed. The trends in the global burden of VL were projected with a Bayesian age-period-cohort (BAPC) model from 2022 to 2035, and the associations of age-standardized incidence, prevalence, mortality, and DALYs rates of VL with SDI levels were examined with a smoothing spline model. Results The global age-standardized incidence [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)], prevalence [AAPC = -0.06%, 95% CI: (-0.06%, -0.06%)], mortality [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)] and DALYs rates of VL [AAPC = -2.38%, 95% CI: (-2.44%, -2.33%)] all appeared a tendency towards a decline from 1990 to 2021, and the highest age-standardized incidence [2.55/10⁵, 95% UI: (1.49/10⁵, 4.07/10⁵)], prevalence [0.64/10⁵, 95% UI: (0.37/10⁵, 1.02/10⁵)], mortality [0.51/10⁵, 95% UI: (0, 1.80/10⁵)] and DALYs rates of VL [33.81/10⁵, 95% UI: (0.06/10⁵, 124.09/10⁵)] were seen in tropical Latin America in 2021. The global age-standardized incidence and prevalence of VL were both higher among men [0.57/10⁵, 95% UI: (0.45/10⁵, 0.72/10⁵); 0.14/10⁵, 95% UI: (0.11/10⁵, 0.18/10⁵)] than among women [0.27/10⁵, 95% UI: (0.21/10⁵, 0.33/10⁵); 0.06/10⁵, 95% UI: (0.05/10⁵, 0.08/10⁵)], and the highest mortality of VL was found among children under 5 years of age [0.24/10⁵, 95% UI: (0.08/10⁵, 0.66/10⁵)]. The age-standardized incidence (r = -0.483, P < 0.001), prevalence (r = -0.483, P < 0.001), mortality (r = -0.511, P < 0.001) and DALYs rates of VL (r = -0.514, P < 0.001) correlated negatively with SDI levels from 1990 to 2021. In addition, the global burden of VL was projected with the BAPC model to appear a tendency towards a decline from 2022 to 2035, and the age-standardized incidence, prevalence, mortality and DALYs rates were projected to be reduced to 0.11/10⁵, 0.03/10⁵, 0.02/10⁵ and 1.44/10⁵ in 2035, respectively. Conclusions Although the global burden of VL appeared an overall tendency towards a decline from 1990 to 2021, the burden of VL showed a tendency towards a rise in Central Asia and western sub-Saharan African areas. The age-standardized incidence and prevalence rates of VL were relatively higher among men, and the age-standardized mortality of VL was relatively higher among children under 5 years of age. The global burden of VL was projected to continue to decline from 2022 to 2035.

OBJECTIVE To assess the cost-effectiveness of durvalumab combined with chemotherapy as a first-line treatment for advanced biliary tract cancer from the perspective of the Chinese healthcare system. METHODS Using data from the TOPAZ-1 clinical trial， a three-state Markov model comprising progression-free survival （PFS）， progressive disease （PD） and death was developed， with a cycle length of 21 days and a 10-year time horizon. Patients in the observation group received durvalumab in combination with gemcitabine and cisplatin， whereas those in the control group received placebo plus the same chemotherapy regimen. The evaluation indexes were quality-adjusted life year （QALY） and the incremental cost-effectiveness ratio （ICER）. The willingness-to-pay （WTP） threshold was set at three times the 2024 Chinese per capita gross domestic product （GDP） （287 247 yuan/QALY）. The sensitivity analyses， along with scenario analyses， were performed. RESULTS In the base-case analysis， the ICER of observation group compared to control group was 1 166 344.46 yuan/QALY， far exceeding the WTP threshold， indicating that the regimen was not cost-effective. One-way sensitivity analysis identified the PD state utility， discount rate， cost of durvalumab， and PFS state utility as the main drivers of ICER variation. Probabilistic sensitivity analysis showed that， at the above WTP threshold， the probability of the acceeptance of this regimen was 0， further supporting the robustness of the base-case findings. In the scenario analysis， inclusion of a patient assistance program reduced the ICER to 235 885.16 yuan/ QALY， below the above WTP threshold， suggesting cost-effectiveness under this assistance program. However， when applying a regional WTP threshold set at three times the per capita GDP （158 475 yuan/QALY） of Gansu Province （the province with the lowest GDP in China in 2024）， the ICER remained above the threshold， indicating that the regimen was not cost-effective at the regional level. CONCLUSIONS At current pricing， durvalumab plus chemotherapy as a first-line treatment for advanced biliary tract cancer is not cost-effective in China. Although the introduction of a patient assistance program can substantially reduce the ICER and achieve cost-effectiveness at a WTP threshold set at three times the 2024 per capita GDP of China， due to limited affordability in low-income areas， the program remains not cost-effective.

This study aimed to investigate the effects of acupuncture on dynamic changes in Ca²⁺, Na⁺, and H₂O₂ flux following eccentric exercise-induced muscle injury. The total of 324 healthy male Wistar rats were randomly divided into 6 groups: control group (C), eccentric exercise group (E), eccentric exercise with acupuncture group (EA), EA with TRP channel blocker group (EAT), EA with NOX2 blocker group (EAN) and EA with placebo group (EAP). Gastrocnemius muscles were subject to lengthening contractions with percutaneous electrical stimulation, followed by immediate pretreatment with blocking agents. After 30 min, acupuncture needling was administered to the gastrocnemius muscle, and real-time dynamic changes of Ca²⁺, Na⁺ and H₂O₂ flux were measured with non-invasive micro-test technique during the needle retention period, immediately, 3 h, 6 h, and 24 h post-extraction respectively. Results showed that compared with the E group, acupuncture significantly increased net Ca²⁺ efflux (P < 0.05), extended the period of net Na⁺ influx, and significantly decreased net H₂O₂ efflux (P < 0.05). However, these effects were significantly attenuated in the EAT and EAN groups, where excessive net H₂O₂ efflux was observed (P < 0.001). These findings indicate that acupuncture regulates the dynamic changes of Ca²⁺, Na⁺ and H₂O₂ flux by activating the TRP channels and interacting with NOX2 activity following eccentric exercise-induced skeletal muscle injury.
Animals ; Muscle, Skeletal/metabolism* ; Rats, Wistar ; Rats ; Male ; Calcium/metabolism* ; Hydrogen Peroxide/metabolism* ; Physical Conditioning, Animal ; Sodium/metabolism* ; Acupuncture Therapy ; NADPH Oxidase 2

Objective To establish a sandwich enzyme-linked immunosorbent assay (ELISA) method for the quantitative detection of Chromogranin A (CHGA) in saliva, and to explore its preliminary application in the testing of saliva samples. Methods Recombinant human CHGA protein was used to immunize BALB/c mice, and monoclonal antibodies (mAbs) were prepared and screened using conventional hybridoma technology. A double-antibody sandwich ELISA detection method was constructed, and the matrix effect of saliva samples was optimized. This method was then applied to detect the concentration of CHGA in the saliva of stressed individuals. Results Twenty-one stable hybridoma cell lines secreting high affinity anti-human CHGA antibodies were obtained. A pair of detection antibodies with the best effect was selected, and the optimal coating concentration was determined to be 10 μg/mL, with the optimal dilution of detection antibodies being 1:32 000. The accuracy and reproducibility of this method were verified, with both intra-batch and inter-batch variation coefficients less than 15×, and the recovery rate between 80× and 120×. The matrix effect was further optimized to make it suitable for saliva sample detection. Saliva samples from individuals in different stress states were collected, and the CHGA levels were detected using the method established in this study, indicating its potential to reflect the intensity of stress. Conclusion A reliable saliva CHGA ELISA detection method has been successfully established, and its potential as a biomarker in stress-related research has been preliminarily explored.
Saliva/metabolism* ; Enzyme-Linked Immunosorbent Assay/methods* ; Humans ; Animals ; Mice, Inbred BALB C ; Mice ; Chromogranin A/immunology* ; Antibodies, Monoclonal/immunology* ; Female ; Male ; Reproducibility of Results ; Adult

PURPOSE: Intertrochanteric fracture (ITF) classification is crucial for surgical decision-making. However, orthopedic trauma surgeons have shown lower accuracy in ITF classification than expected. The objective of this study was to utilize an artificial intelligence (AI) method to improve the accuracy of ITF classification. METHODS: We trained a network called YOLOX-SwinT, which is based on the You Only Look Once X (YOLOX) object detection network with Swin Transformer (SwinT) as the backbone architecture, using 762 radiographic ITF examinations as the training set. Subsequently, we recruited 5 senior orthopedic trauma surgeons (SOTS) and 5 junior orthopedic trauma surgeons (JOTS) to classify the 85 original images in the test set, as well as the images with the prediction results of the network model in sequence. Statistical analysis was performed using the SPSS 20.0 (IBM Corp., Armonk, NY, USA) to compare the differences among the SOTS, JOTS, SOTS + AI, JOTS + AI, SOTS + JOTS, and SOTS + JOTS + AI groups. All images were classified according to the AO/OTA 2018 classification system by 2 experienced trauma surgeons and verified by another expert in this field. Based on the actual clinical needs, after discussion, we integrated 8 subgroups into 5 new subgroups, and the dataset was divided into training, validation, and test sets by the ratio of 8:1:1. RESULTS: The mean average precision at the intersection over union (IoU) of 0.5 (mAP50) for subgroup detection reached 90.29%. The classification accuracy values of SOTS, JOTS, SOTS + AI, and JOTS + AI groups were 56.24% ± 4.02%, 35.29% ± 18.07%, 79.53% ± 7.14%, and 71.53% ± 5.22%, respectively. The paired t-test results showed that the difference between the SOTS and SOTS + AI groups was statistically significant, as well as the difference between the JOTS and JOTS + AI groups, and the SOTS + JOTS and SOTS + JOTS + AI groups. Moreover, the difference between the SOTS + JOTS and SOTS + JOTS + AI groups in each subgroup was statistically significant, with all p < 0.05. The independent samples t-test results showed that the difference between the SOTS and JOTS groups was statistically significant, while the difference between the SOTS + AI and JOTS + AI groups was not statistically significant. With the assistance of AI, the subgroup classification accuracy of both SOTS and JOTS was significantly improved, and JOTS achieved the same level as SOTS. CONCLUSION In conclusion, the YOLOX-SwinT network algorithm enhances the accuracy of AO/OTA subgroups classification of ITF by orthopedic trauma surgeons.
Humans ; Hip Fractures/diagnostic imaging* ; Orthopedic Surgeons ; Algorithms ; Artificial Intelligence

Objective To investigate the serum levels of homocysteine(HCY)and cystatin C(Cys-C)in patients with antineutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV)associated renal injury,and to explore the diagnostic value of combined detection of HCY and Cys-C in ANCA-associated renal injury.Methods We selected 70 ANCA-positive patients with renal injury admitted to the Department of Nephrology in our hospital from January 2016 to January 2019.Another 48 patients with ANCA-positive but not complicated with renal injury were in simple ANCA positive group while 50 patients with physical examination who came to the hospital during the same period were in control group.Healthy patients served as the control group.By comparing the differences in the test results of different groups,the area under the curve(AUC)of each test index for ANCA-positive renal injury was determined,and the correlation and diagnostic value of combined detection of HCY and Cys-C for ANCA-related renal injury were calculated.Results The levels of HCY and Cys-C in the ANCA positive combined with renal injury group,the pure ANCA positive group,and the control group differed significantly(P＜0.05).The positive rates of HCY and Cys-C in the two groups were significantly different(P＜0.05).The sensitivity and specificity of HCY and Cys-C in combination for the diagnosis of ANCA-positive related renal injury were significantly higher than those of the above indicators alone(P＜0.05).ROC curve results showed that HCY combined with Cys-C had a better diagnosis for patients with positive ANCA and associated renal injury and a higher correlation.Conclusion HCY combined with Cys-C is closely correlated to ANCA-related renal injury,and the combined detection has a positive effect on the diagnosis of patients with ANCA-positive related renal injury,and has guiding value for the treatment of patients.

Objective:To analyze the epidemic characteristics and trends of newly reported HIV-infected people among Chinese and Burmese in Dehong Dai and Jingpo Autonomous Prefecture (Dehong Prefecture) of Yunnan Province, China, from 2000 to 2023, and provide evidence for formμlating AIDS prevention and control measures for the Burmese living in Dehong.Methods:The data were obtained from the Chinese Disease Control and Prevention Information System. The distribution of HIV-infected people with different population characteristics was analyzed, and the Joinpoint regression model was used to analyze the temporal trend of crude detection rate in different genders, ethnicities, and ages.Results:From 2000 to 2023, 24 989 newly HIV infections were reported in Dehong Prefecture, of which 14 594 (58.4%) were Chinese and 10 395 (41.6%) were Burmese. Compared with Chinese, Burmese women (32.9%, 3 416/10 395), those aged 20-29 (40.9%, 4 248/10 395), and Jingpo people (26.7%, 2 773/10 395) accounted for a higher proportion. The new diagnosis rate of Chinese nationals increased from 1.0/10 000 in 2000 to 15.4/10 000 in 2004, and then showed a downward trend, falling to 1.2/10 000 in 2023. Among them, compared with other age groups, Dai and other ethnic groups and women, the new diagnosis rate among 20-49 age group, Jingpo and men were relatively higher, at 1.7/10 000, 2.3/10 000 and 1.3/10 000 respectively. Regarding the method of detection, the Chinese HIV-infected people were mainly detected by key population testing (35.7%), while the Burmese HIV-infected people by key population testing (28.9%) and physical examination for entry-exit personnel (25.3%). The transmission routes of both nationalities were mainly heterosexual transmission, but compared with Chinese HIV-infected persons, the proportion of Burmese infected persons through non-marital non-commercial transmission was relatively higher (66.4% vs. 60.6%). The proportion of Chinese nationals with a first CD4 +T lymphocyte (CD4) counts of <200 cells/μl (28.9%) was higher than that of Burmese nationals (19.8%). Conclusions:The rising trend of HIV infection among Chinese and Burmese people in Dehong Prefecture from 2000 to 2023 slowed down. The new diagnosis rate was higher in the 20-49 age group, Jingpo and men. Compared with Burmese HIV-infected people, the proportion of Chinese HIV-infected people with first CD4 counts <200 cells/μl was relatively higher. Comprehensive interventions should be further carried out for Myanmar nationals, and efforts should be made to expand testing for Chinese nationals.

Objective:To analyze the genetic stability of two recombinant rotaviruses (rLLR/NSP3 NLuc) and (rLLR/NSP3 CoV2/RBD) that are inserted and express exogenous genes for continuous passage and proliferation on MA104 cells.Methods:After measuring the titers of two recombinant rotavirus strains, they were transferred to the P2 generation according to MOI0.01. Subsequently, the previous generation of virus lysate was diluted and activated at 1∶100, and MA104 cells were continuously infected for 18 generations (P20). The virus titers of the P1, P5, P10, P15, and P20 generation of cell lysate were measured using indirect immunofluorescence, and RT-PCR identification and dsRNA PAGE silver staining were performed. The luciferase activity of rLLR/NSP3-NLUc was also detected.Results:No inserted fragment loss was found in the recombinant rotavirus rLLR/NSP3 NLuc within 20 generations, with recombinant virus titers ranging from 3.85~5.16 × 10 6 FFU/ml, with strong luciferase signals in each generation. The recombinant rotavirus rLLR/NSP3 CoV2/RBD showed loss of inserted fragments in the 6th generation, with infectivity titers ranging from 2.6 to 3.36 in the first 5 generations of the recombinant virus × 10 6 FFU/ml. Conclusions:The recombinant rotavirus with 582 bp NLuc inserted at the end of the NSP3 gene has good genetic stability, while the recombinant rotavirus with 885 bp RBD inserted at the end of the NSP3 gene was only stable in the first 5 generations, indicating that foreign genes can be inserted at the end of the NSP3 gene of the recombinant rotavirus, and the insert can express, but its stability requires more in-depth research.

A comprehensive understanding of the nutritional composition and active components of human milk are important for promoting infant health. However, in the design and implementation of scientific research on human milk, the lack of standardized research and implementation methods have led to the collection, storage, and testing processes of human milk samples being largely based on reference literature and practical experience. This has resulted in variability in the representativeness of human milk samples and differences in the comparability of research results between different studies. This article summarizes the principles and guidelines for the " Specification for collection and storage of human milk samples for research", published by the Chinese Nutrition Society on December 30, 2022, and discusses the feasibility and importance of standardized management in the process of scientific research on human milk.

Objective Coronary heart disease(CHD)is one of the major lethal diseases in the world at present.The detection of biomarkers is an important non-invasive method to evaluate the progression of CHD,which is of great significance for the diagnosis and secondary prevention of CHD.This study aims to screen diagnostic biomarkers in the pathogenesis of myocardial infarction,analyze cuprotosis-related genes in the development of this disease,and further predict the traditional Chinese medicine of regulating cuprotosis-related genes.Methods The GEO database was searched to obtain chip data of myocardial infarction,differentially expressed genes(DEGs)were analyzed.Then,DEGs enrichment analysis was performed,and key genes were screened based on least absolute shrinkage and selection operator(LASSO)and random forest(RF)methods.Diagnostic model was constructed and verified.After immune cell infiltration analysis was performed on differential genes,the results were further combined with weighted gene co-expression network analysis to obtain differentially expressed immune-related genes,which were intersected with cuproptosis genes to obtain cuproptosis immune-related Hub genes.The correlation between cuproptosis-related genes and diagnostic genes were analyzed.Gene set enrichment analysis(GSEA)was performed on cuproptosis-related genes to further predict the traditional Chinese medicines of regulating the genes related to cuproptosis.Results A total of 115 DEGs,which were mainly enriched in the biological processes and pathways related to lymphocyte-mediated immunity,mitochondrial respiratory chain complex Ⅳ,C-type lectin receptor signaling pathway,and chemokine signaling pathway,were obtained by differential analysis.Five diagnostic genes,SNORA20,SNORA19,H4C3,SNORD81,and COX7B,were screened out by machine learning methods.Immune infiltration analysis found dendritic cells,macrophages M2,monocytes,neutrophils,natural killer cells,CD4+T cells,CD8+T cells,and γδ T cells.It was indicated the above eight immune cells play a certain role in the pathogenesis of myocardial infarction in coronary heart disease.Weighted correlation network analysis(WGCNA)and immune infiltration analysis were used to obtain 358 key module genes,which were intersected with cuproptosis genes to obtain three cuproptosis and immune signature genes.The correlation analysis results of five diagnostic genes and Hub genes showed that there was a correlation between the expressions of SLC31A1 and SNORA20,LIAS and SNORA19,SNORD81,MTF1 and H4C3,SNORA20,SNORA19,SNORD81.GSEA analysis results indicated that LIAS and MTF1 had a significant effect on the NF-κB signaling pathway,NOD-like receptor signaling pathway and Toll-like receptor signaling pathway.The potential regulatory Chinese medicines are mainly blood-activating and stasis-eliminating,qi-promoting and analgesic drugs.Conclusion SNORA20,SNORA19,H4C3,SNORD81,COX7B have a certain diagnostic value for myocardial infarction in coronary heart disease.The prediction of genes related to cuproptosis and immune infiltration in the pathogenesis of myocardial infarction provides a certain reference for the study of the mechanism of traditional Chinese medicine intervention in myocardial infarction.