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.

ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

Objective To investigate the spatial distribution of Aedes albopictus in China at different time periods from 2000 to 2019, so as to provide insights into precise management of Ae. albopictus in China. Methods Data pertaining to the distribution of Ae. albopictus in China from 2000 to 2019 were collected through literature retrieval with terms of “Aedes albopictus”, “monitoring”, “survey”, “density”, “distribution”, and “outbreak” in national and international databases. The title and time of the publication, sampling sites, sampling time, mosquito capture methods, and mosquito species and density were extracted, and the longitude and latitude of sampling sites were obtained through Baidu Map. Meteorological element data at meteorological observation stations within China were obtained from the National Climatic Data Center of the United States, and the annual maximum temperature, annual minimum temperature, average temperature in January, average temperature in July, annual temperature range, daily temperature range and relative humidity were calculated and subjected to Kriging interpolation. Monthly cumulative precipitation grid data and monthly average temperature grid data with a resolution of 1 km for China from 2000 to 2019 were obtained from the National Tibetan Plateau Scientific Data Center, and the annual precipitation and annual average temperature were calculated cumulatively. Population density data in China from 2000 to 2019 were obtained from the WorldPop Hub, and the gross domestic product (GDP) in China was obtained from the Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences. The above data were divided into 5-year intervals to calculate data during the periods from 2000 to 2004, from 2005 to 2009, from 2010 to 2014, and from 2015 to 2019. Ae. albopictus distribution data were modeled in China from 2000 to 2019 and during each period with the classification random forest (RF) model, to predict the distribution of Ae. albopictus across the country and analyze the distribution of Ae. albopictus based on the seven major climate zones in China. The performance of RF models was evaluated by accuracy, precision, recall, and area under the receiver operating characteristic curve (AUC), and the importance of each feature in the RF model was evaluated with mean decrease accuracy (MDA). Results A total of 1 191 Chinese publictions and 391 English publications were retrieved, among which 580 articles provided detailed data on the sampling sites of Ae. albopictus and specific sampling years, meeting the inclusion criteria. A total of 2 234 Ae. albopictus sampling sites were included in China from 2000 to 2019, and RF modeling results showed that the overall Ae. Albopictus distribution area was mainly found in southeastern and southwestern provinces of China from 2000 to 2019, with scattered distribution in coastal areas of northeastern provinces, such as Liaoning Province. The accuracy, precision, recall and AUC of the RF model were 0.915 to 0.947, 0.933 to 0.975, 0.898 to 0.978, and 0.902 to 0.932 for the distribution of Ae. albopictus at different time periods from 2000 to 2019. Among all features in the RF models, population density was the most contributing factor to the distribution of Ae. albopictus in China, followed by GDP, and all meteorological variables contributed relatively less to the predictive power of the RF model. In China’s seven major climate zones, Ae. albopictus was almost entirely distributed in the marginal tropical humid region, the north subtropical humid region, and the warm temperate semi-humid region. The combined distribution area of these three zones accounted for 100.0% of the national distribution area from 2000 to 2004, from 2005 to 2009, and from 2010 to 2014, and 99.9% from 2015 to 2019, and the proportion of Ae. albopictus distribution area in the warm temperate semihumid region increased gradually from 20.2% to 30.2%. Conclusions Ae. albopictus is mainly distributed in the southeastern and southwestern provinces of China and is greatly influenced by population and economic factors. The warm temperate semi-humid region in China is gradually becoming a hot spot for the distribution of Ae. albopictus.

In cases where a tracheal injury exceeds half the length of the adult trachea or one-third of the length of the child trachea, it becomes difficult to perform end-to-end anastomosis after tracheal resection due to excessive tension at the anastomosis site. In such cases, tracheal replacement therapy is required. Advances in tissue engineering technology have led to the development of tissue engineering tracheal substitutes, which have promising applications. Hydrogels, which are highly hydrated and possess a good three-dimensional network structure, biocompatibility, low immunogenicity, biodegradability, and modifiability, have had wide applications in the field of tissue engineering. This article provides a review of the characteristics, advantages, disadvantages, and effects of various hydrogels commonly used in tissue engineering trachea in recent years. Additionally, the article discusses and offers prospects for the future application of hydrogels in the field of tissue engineering trachea.

ObjectiveTo construct an animal model of respiratory syncytial virus（RSV）-infected pneumonia suitable for preclinical studies. MethodsThe virulence of RSV to the four cell lines was observed by cytopathic effect （CPE）， and 50% tissue culture infective dose（TCID₅₀） was calculated. Twenty BALB/c mice were randomly divided into a normal group and a model group. Six BALB/c-hIGF1R mice served as the humanized IGF1R model group. Except for the normal group， the other groups received intranasal RSV infection on days 1 and 3 to establish a viral pneumonia model. The efficacy of establishing an RSV-induced pneumonia animal model based on humanized insulin-like growth factor 1 receptor （IGF1R） mice was evaluated by measuring organ indices， peripheral blood lymphocyte percentages， pulmonary pathology and imaging， and pulmonary viral load. Additionally， ten BALB/c mice served as normal group， and thirty-two BALB/c-hIGF1R mice were randomly assigned to humanized IGF1R model group， ribavirin group （82.5 mg·kg^-¹·d^-¹）， and high and low dose groups of Lianhua Qingwen （3.3 mg·kg^-¹·d^-¹ ， 1.65 mg·kg^-¹·d^-¹）， with 8 mice per group. The viral load in lung tissue was measured after ribavirin and Lianhua Qingwen intervention， and the model was applied to the evaluation of anti-RSV drugs. ResultsIn the lungs of the humanized IGF1R model group， large solid and diffuse ground-glass shadows were seen， and the lung volume was significantly increased （P<0.01）. The lung index was significantly increased （P<0.01）， and both the spleen index and thymus index were significantly decreased （P<0.01）. The percentages of CD3⁺ and CD4⁺T cells were significantly decreased （P<0.05）， and there was a large amount of inflammation and stasis in the perivascular area of the lung tissue， which was predominantly characterized by lymphocytes. The endothelium of blood vessels was partially detached， with a small number of eosinophils. After infecting BALB/c-hIGF1R mice with RSV， the expression of viral nucleic acids in the lung tissue of the mice was significantly increased， with significant differences compared with the normal group （P<0.01）. The expression of viral nucleic acids in the ribavirin group and the high and low dose groups of Lianhua Qingwen was significantly reduced， with significant differences compared with the normal group （P<0.01）. ConclusionHumanized IGF1R mice are more susceptible to respiratory SVC， and the animal model of RSV-infected pneumonia based on humanized IGF1R mice was successfully constructed， which is suitable for the evaluation of anti-RSV drugs.

ObjectiveTo construct an animal model of respiratory syncytial virus（RSV）-infected pneumonia suitable for preclinical studies. MethodsThe virulence of RSV to the four cell lines was observed by cytopathic effect （CPE）， and 50% tissue culture infective dose（TCID₅₀） was calculated. Twenty BALB/c mice were randomly divided into a normal group and a model group. Six BALB/c-hIGF1R mice served as the humanized IGF1R model group. Except for the normal group， the other groups received intranasal RSV infection on days 1 and 3 to establish a viral pneumonia model. The efficacy of establishing an RSV-induced pneumonia animal model based on humanized insulin-like growth factor 1 receptor （IGF1R） mice was evaluated by measuring organ indices， peripheral blood lymphocyte percentages， pulmonary pathology and imaging， and pulmonary viral load. Additionally， ten BALB/c mice served as normal group， and thirty-two BALB/c-hIGF1R mice were randomly assigned to humanized IGF1R model group， ribavirin group （82.5 mg·kg^-¹·d^-¹）， and high and low dose groups of Lianhua Qingwen （3.3 mg·kg^-¹·d^-¹ ， 1.65 mg·kg^-¹·d^-¹）， with 8 mice per group. The viral load in lung tissue was measured after ribavirin and Lianhua Qingwen intervention， and the model was applied to the evaluation of anti-RSV drugs. ResultsIn the lungs of the humanized IGF1R model group， large solid and diffuse ground-glass shadows were seen， and the lung volume was significantly increased （P<0.01）. The lung index was significantly increased （P<0.01）， and both the spleen index and thymus index were significantly decreased （P<0.01）. The percentages of CD3⁺ and CD4⁺T cells were significantly decreased （P<0.05）， and there was a large amount of inflammation and stasis in the perivascular area of the lung tissue， which was predominantly characterized by lymphocytes. The endothelium of blood vessels was partially detached， with a small number of eosinophils. After infecting BALB/c-hIGF1R mice with RSV， the expression of viral nucleic acids in the lung tissue of the mice was significantly increased， with significant differences compared with the normal group （P<0.01）. The expression of viral nucleic acids in the ribavirin group and the high and low dose groups of Lianhua Qingwen was significantly reduced， with significant differences compared with the normal group （P<0.01）. ConclusionHumanized IGF1R mice are more susceptible to respiratory SVC， and the animal model of RSV-infected pneumonia based on humanized IGF1R mice was successfully constructed， which is suitable for the evaluation of anti-RSV drugs.

ObjectiveTo prepare oral nanoemulsions encapsulating essential oil from Alpinia zerumbet fructus（EOFAZ） and to investigate its pro-absorption effect in vitro and distribution in vivo. MethodThe proteoglycan conjugate polysaccharides of vinegar-processed Bupleuri Radix-bovine serum albumin（VBCP-BSA） was prepared by Maillard reaction of VBCP and BSA. Taking VBCP-BSA as emulsifier， vitamin B₁₂（VB₁₂） as absorption enhancer， and medium chain triglycerides mixed with EOFAZ as oil phase， the nanoemulsions loaded with EOFAZ was prepared by high energy emulsification method. The particle size， particle size distribution， surface Zeta potential， EOFAZ content and appearance and morphology of the nanoemulsions were characterized， and fluorescein tracer method was used to investigate the absorption effect of fluorescein-labeled EOFAZ nanoemulsions in vitro and their distribution in vivo. ResultVBCP-BSA was formed by Maillard reaction for 48 h with high grafting rate. Using VBCP-BSA as emulsifier， the homogeneous pink nanoemulsions was prepared and denoted as EOFAZ@VBCP-BSA/VB₁₂. The particle size of the nanoemulsions was less than 100 nm and the particle size distribution was uniform. The surface of the nanoemulsions was a weak negative charge， and the shape was spherical. The encapsulation rate of the nanoemulsions for EOFAZ was greater than 80%， which had a good absorption effect in vitro and could enhance liver accumulation after oral administration. ConclusionThe designed proteoglycan nanoemulsions can effectively load EOFAZ， promote oral absorption and enhance liver distribution， which can provide experimental basis for the development of oral EOFAZ liver protection preparations.

Objective To investigate the mechanism of metformin for regulating tumor-stromal cell cross-talk in breast cancer.Methods Tumor associated fibroblasts(CAFs)co-cultured with breast cancer cells were treated with metformin,and the changes in expressions of hypoxia-inducible factor-1α(HIF-1α),p-AMPK,stroma-derived factor-1(SDF-1)and interleukin-8(IL-8)in the CAFs were detected using ELISA,RT-qPCR or Western blotting;Transwell assay was used to evaluate the invasiveness of the tumor cells and its changes following treatment with exogenous SDF-1,IL-8 and TGF-β1.The effects of HIF-1α shRNA or overexpression plasmid,AMPK shRNA,and treatment with OG(a proline hydroxylase inhibitor)or 2-OXO(a proline hydroxylase activator)were examined on p-AMPK,HIF-1α,SDF-1 and IL-8 expressions and invasiveness of the CAFs.Results Metformin treatment significantly increased the expression levels of p-AMPK,SDF-1 and IL-8(P<0.05)and decreased HIF-1α expression(P<0.05)without affecting AMPK expression level(P>0.05)in the CAFs.The invasion ability of metformin-treated breast cancer cells was significantly decreased(P<0.05).Exogenous SDF-1 and IL-8,HIF-1α overexpression,and OG-induced upregulation of HIF-1α all significantly attenuated the inhibitory effects of metformin on breast cancer cell invasion(P<0.05)and HIF-1α,SDF-1 and IL-8 expressions in CAFs(P<0.05).Transfection with HIF-1α shRNA or treatment with 2-OXO significantly decreased the invasiveness of breast cancer cells(P<0.05).P-AMPK knockdown significantly suppressed the inhibitory effect of metformin on HIF-1α expression in CAFs and on invasion of breast cancer cells(P<0.05).Treatment with TGF-β1 partially decreased the inhibitory effect of metformin on HIF-1α expression in CAFs and invasiveness of the breast cancer cells(P<0.05).Conclusion Metformin suppresses HIF-1α expression in CAFs to block tumor-stromal cross talk in breast cancer.

Objective:To establish a method for the determination of 2, 3-Butanedione (BUT) in the air of workplace, which including the process of collection by absorption in phosphoric acid aqueous solution and the process of analysis and detection by high performance liquid chromatography with derivatization.Methods:In October 2022, a porous glass plate absorption tube containing 10 ml of 0.01% phosphoric acid solution was used to collect BUT in the air of the workplace at a flow rate of 0.2 L/min. The absorption solution was derived by 2, 4-dinitrophenylhydrazine for 75 min and separated on a SB-C18 column (250 mm×4.6 mm, 5 μm) . At the column temperature of 30 ℃, the mixture of acetonitrile-water ( V∶ V, 1∶1) was eluted at the flow rate of 1.0 ml/min. It was detected by UV detector (λ=365 nm) , qualitatived by retention time and quantitatived by external standard. Results:It showed that BUT in phosphoric acid aqueous solution could be stored for at least 7 d at 4 ℃. There was a linear relationship within the determination range of 0.05-6.00 μg/ml, the linear regression equation was y=89.610 x+0.133, r=0.9999. The sampling absorption efficiencies were 98.33%-100.00%, the detection limit of the method was 0.005 μg/ml, the minimum detection concentration was 0.016 mg/m 3 (based on V0=3.0 L) . The recovery rates were 95.96%-102.44%, the intra batch precision were 4.36%-7.78%, and the inter batch precision were 4.96%-6.06%. Conclusion:The method has the advantages of simple operation, high sensitivity and good accuracy. It can prevent the loss and degradation of BUT. It can be used for the determination of BUT in the air of workplace.

Objective:To explore the risk factors of coal workers' pneumoconiosis, reveal the molecular mechanism of pyroptosis in peripheral blood of coal workers' pneumoconiosis patients, and provide new strategies and potential diagnostic biomarkers for the treatment of the disease.Methods:From January 1, 2020 to December 31, 2022, workers with suspected occupational diseases who were diagnosed with coal workers' pneumoconiosis in the Third People's Hospital of Xinjiang Uygur Autonomous Region were included in the study, including 77 patients with coal workers' pneumoconiosis stage Ⅰ, 10 patients with stage Ⅱ, 6 patients with stage Ⅲ, and 49 workers with dust-free lung disease as the control group. General information of the subjects was collected, blood samples were collected for routine blood and blood biochemical results, and plasma levels of interleukin (IL) -1β and IL-18 were measured. Combined with the results of clinical examination, multi-factor ordered logistic regression analysis was carried out to evaluate the influencing factors of coal workers' pneumoconiosis. At the same time, the expression of pyroptosis related proteins in blood cells was detected to reveal the molecular mechanism of coal workers' pneumoconiosis.Results:All 142 subjects were male, with an average age of (51.65±6.31) years old and an average working age of (15.94±9.38) years. There were significant differences in smoking age ( F=4.95, P=0.003) and lunch break distribution ( H=8.84, P=0.031) among all groups. The hemoglobin content of stage Ⅰ patients was higher than that of stage Ⅱ patients, and the neutrophil percentage of stage Ⅲ patients was higher than that of the other 3 groups ( P<0.05). The levels of total bilirubin and indirect bilirubin in stage Ⅰ patients were higher than those in control group, while the erythrocyte sedimentation rate in stage Ⅱ patients was higher than that in the other 3 groups ( P<0.05). The levels of IL-18 and IL-1β in stage Ⅲ of coal workers' pneumoconiosis were higher than those in the other 3 groups ( P<0.05). Multiple logistic regression analysis showed that smoking age ( OR=1.03, 95% CI: 1.00-1.06) and IL-1β level ( OR=4.61, 95% CI: 1.59-13.32) were independent risk factors for coal workers' pneumoconiosis ( P<0.05). Compared with the control group, the expression levels of nucleotide-binding of oligomeric domain-like receptor protein 3 (NLRP3), Caspase-1, GSDMD, Caspase-4 and other proteins in stage Ⅲ of coal workers' pneumoconiosis were significantly increased ( P<0.05) . Conclusion:Smoking age is a risk factor for coal workers' pneumoconiosis, IL-1β may be a potential biomarker for the diagnosis of coal workers' pneumoconiosis, and pyroptosis may play a role in the development of peripheral inflammation of coal workers' pneumoconiosis.