Influenza poses a significant public health burden with distinct seasonality. In regions with pronounced climatic features like Gansu Province, China, traditional statistical models often fail to capture the nonlinear and lagged effects of meteorological drivers on influenza transmission. A deeper understanding of these complex relationships is essential for improving predictive accuracy. A Random Forest-based nonlinear Granger causality test was employed to systematically identify significant lagged predictive relationships between eight meteorological variables and monthly influenza incidence in Gansu Province (2004–2020). This approach accommodates complex, nonlinear dependencies that linear Granger causality cannot capture. Meteorological features exhibiting significant predictive improvement were selected via Random Forest and combined with influenza autocorrelation features as inputs to an LSTM-Transformer hybrid model. The model was trained using a rigorous time-series split (60%-20%-20%) and evaluated primarily using the Weighted Mean Absolute Percentage Error (WMAPE). Model explainability was assessed using SHapley Additive exPlanations (SHAP). The nonlinear Granger causality test identified significant statistical predictive relationships for all eight meteorological factors. Temperature-related variables exhibited a 6-month lag (improvement rates: 22.56%-23.99%). Precipitation showed a 1-month lag (improvement rate: 19.37%). Sunshine duration displayed a persistent predictive pattern across lags of 1 to 6 months (improvement rates: 15.8%-22.85%). The hybrid model achieved an R² of 0.786 and a WMAPE of 30.19% on the independent test set. SHAP-based explainability analysis ranked sunshine duration lagged by 2 months as the most influential predictor (mean absolute SHAP value = 0.0609), followed by the 6-month rolling mean of minimum temperature (0.0322). Meteorological factors offered important statistical predictive information for influenza incidence in Gansu Province, with sunshine duration exhibiting a persistent predictive pattern across multiple lags. The hybrid model demonstrated robust predictive performance on the independent test set.

Droughts, historically recognized as drivers of societal transformation, have been implicated in the emergence of infectious diseases. While existing research has concentrated on the impact of climate change on infectious diseases outbreaks in modern, industrialized, and urban settings, there is a dearth of epidemiological evidence regarding the historical interplay between drought and disease. Here, we analyze the 1585-1590 extreme drought in Ming Dynasty China to investigate the concurrent development of drought and infectious diseases, as well as the temporal and spatial effects of drought on disease outbreaks. The findings reveal a positive correlation between drought and infectious diseases in both temporal and spatial dimensions, with famine identified as a critical intermediate factor. Drought's influence on famine and disease is both immediate and delayed, with the most significant effects occurring within the same year. Additionally, a north-to-south pattern in the occurrence of drought and infectious diseases is observed, with northern droughts more likely to precipitate disease outbreaks. These insights offer valuable perspectives for future strategies.

Extreme drought events can impact human health, notably triggering epidemics that impose significant global health and economic burdens. Understanding these effects and developing response strategies is crucial. However, there is limited epidemiological evidence on how climate change influenced ancient epidemics before large-scale urbanization and frequent population movements. In this study, we utilized the Reconstructed East Asian Climate Historical Encoded Series (REACHES) climate database and the self-constructed ancient Chinese epidemics database to examine extreme drought events in ancient China from 1784–1787 CE. We analyzed factors like grain prices, population density, and socioeconomic conditions to explore the temporal and spatial mechanism and influence the degree of extreme drought events on epidemics outbreaks. The results show that there is a clear positive link between drought and the spread of epidemics, with a notable one-year lag effect of drought. Drought impacts epidemics directly and indirectly through locust plague, famine, crop failure, and social turmoil, with famine being the most crucial factor. Official disaster management can mitigate epidemics. This study intuitively shows the relationship between extreme drought events and epidemics in ancient China and offering insights into the climate change-epidemic relationship. Placing the conclusions of this paper in a broader context has global implications, providing historical experience for polycrisis and modern challenges.

Infection with influenza A virus (IAV) may trigger excessive inflammatory responses, leading to severe viral pneumonia and accelerating disease progression. Therefore, controlling these excessive inflammatory responses is crucial for the prevention and treatment of pneumonia caused by IAV. Berberine (BBR), an isoquinoline alkaloid extracted from traditional Chinese medicine, possesses extensive pharmacological activities. However, its immunoregulatory effects and molecular mechanisms in the context of IAV infection require further investigation. This study explored the impact of BBR on macrophage pyroptosis and inflammatory responses induced by IAV infection. Our findings revealed that BBR effectively inhibits the release of IL-1β and TNF-α induced by IAV infection and suppresses gasdermin D (GSDMD)-mediated pyroptosis in a dose-dependent manner. Further research indicates that BBR alleviates macrophage pyroptosis and inflammatory responses in IAV-infected cells by reducing the release of mitochondrial reactive oxygen species (mtROS), inhibiting mitochondrial antiviral signaling protein (MAVS) expression and blocking the activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. Experiments using siRNA to knockdown MAVS further confirmed the pivotal role of MAVS in BBR’s inhibition of IAV-induced macrophage pyroptosis. This study provides a scientific basis for the application of BBR as an anti-inflammatory drug in the treatment of inflammatory diseases caused by IAV infection and directs future research endeavors.

Ethnopharmacological relevanceTanreqing injection (TRQ) is widely used, traditional Chinese medicine (TCM) injection used in China to treat respiratory infections. Modern pharmacological studies have confirmed that TRQ can protect against influenza viruses. However, the mechanism by which TRQ inhibits influenza viruses remains unclear.Aim of the studyTo explore the therapeutic effects and possible mechanisms of TRQ inhibition by the influenza virus.Materials and methodsUltra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) was used to determine the chemical composition of TRQ. Isobaric tags for relative and absolute quantification (iTRAQ) were used to define differential proteins related to TRQ inhibition of viruses. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed for functional annotation. For experimental validation, we established an in vitro model of the influenza virus infection by infecting A549 cells with the virus. The detection of the signaling pathway was carried out through qPCR,western blotting,and immunofluorescence.ResultsFifty one components were identified using UPLC/Q-TOF MS. We confirmed the inhibitory effect of TRQ on influenza virus replication in vitro. Ninety nine differentially expressed proteins related to the inhibitory effect of TRQ were identified using iTRAQ. KEGG functional enrichment analysis showed that the TRQ may inhibit influenza virus replication by affecting autophagy. Through network analysis, 29 targets were selected as major targets, and three key targets, HSPA5, PARP1, and GAPDH, may be the TRQ targets affecting autophagy. In vitro experiments showed that TRQ inhibits influenza virus replication by interfering with the expression and localization of STX17 and VAMP8 proteins, thereby promoting the fusion of autophagosomes with lysosomes.ConclusionTRQ inhibits influenza virus replication by promoting the fusion of autophagosomes with lysosomes. We additionally established potential gene and protein targets which are affected by TRQ. Therefore, our findings provide new therapeutic targets and a foundation further studies on influenza treatment with TRQ.

Introduction:Non-small cell lung cancer (NSCLC) stands as one of the most prevalent malignancies, and chemotherapy remains the primary treatment for advanced stages. However, the high expression of ABC binding cassette transporters, including MRP, P-gp, and LRP, along with multidrug resistance proteins, has been identified as a significant factor contributing to decreased chemotherapy drug sensitivity. This study aims to explore the impact and underlying mechanisms of Curculiginis Rhizoma [Hypoxidaceae; Curculigo orchioides Gaertn.] (CR) in combination with cisplatin on improving chemoresistance mediated by ABC binding cassette transporters and multidrug resistance proteins in NSCLC.Methods and Results:To unravel the relationship between JNK, MRP, P-gp, and LRP in NSCLC and gain insights into the regulatory mechanism of CR, this study employs an integrated approach encompassing bioinformatics, molecular docking, molecular dynamics, animal and cellular experiments. Bioinformatics analysis revealed a significant increase in the expression levels of JNK, MRP, P-gp, and LRP subtypes in multidrug-resistant non-small cell lung cancer. Subsequent animal experiments have shown that the combination of CR with cisplatin can improve the survival rate of lung cancer mice. Molecular docking and molecular dynamics analyses demonstrated favorable binding interactions between curculigoside and the aforementioned subtypes of JNK, MRP, P-gp, and LRP. In cellular experiments, the combination of cisplatin with both curculigoside and CR extract resulted in a notable decrease in cell viability and downregulation of the expression of JNK1, JNK2, MRP1, MRP2, MRP4, P-gp, and LRP1 in A549/cis cells.Conclusion:Remarkably, curculigoside exerted a significant downregulation effect on the expression levels of JNK1, MRP1, MRP2, MRP4, and LRP1. CR, particularly its main effective metabolite, curculigoside, has the potential to enhance the sensitivity of non-small cell lung cancer to cisplatin by regulating levels of JNK/MRP/LRP/P-gp and mitigating multidrug resistance.

This study aims to develop and validate a machine learning (ML) predictive model for assessing mortality in patients with malignant tumors and hyperkalemia (MTH). We extracted data on patients with MTH from the Medical Information Mart for Intensive Care-IV, version 2.2 (MIMIC-IV v2.2) database. The dataset was split into a training set (75%) and a validation set (25%). We used the Least Absolute Shrinkage and Selection Operator (LASSO) regression to identify potential predictors, which included clinical laboratory indicators and vital signs. Pearson correlation analysis tested the correlation between predictors. In-hospital death was the prediction target. The Area Under the Curve (AUC) and accuracy of the training and validation sets of 7 ML algorithms were compared, and the optimal 1 was selected to develop the model. The calibration curve was used to evaluate the prediction accuracy of the model further. SHapley Additive exPlanations (SHAP) and Local Interpretable Model-agnostic Explanations (LIME) enhanced model interpretability. 496 patients with MTH in the Intensive Care Unit (ICU) were included. After screening, 17 clinical features were included in the construction of the ML model, and the Pearson correlation coefficient was <0.8, indicating that the correlation between the clinical features was small. eXtreme Gradient Boosting (XGBoost) outperformed other algorithms, achieving perfect scores in the training set (accuracy: 1.000, AUC: 1.000) and high scores in the validation set (accuracy: 0.734, AUC: 0.733). The calibration curves indicated good predictive calibration of the model. SHAP analysis identified the top 8 predictive factors: urine output, mean heart rate, maximum urea nitrogen, minimum oxygen saturation, minimum mean blood pressure, maximum total bilirubin, mean respiratory rate, and minimum pH. In addition, SHAP and LIME performed in-depth individual case analyses. This study demonstrates the effectiveness of ML methods in predicting mortality risk in ICU patients with MTH. It highlights the importance of predictors like urine output and mean heart rate. SHAP and LIME significantly enhanced the model’s interpretability.

BACKGROUND:Influenza viral pneumonia is a common complication after influenza virus infection. Xijiao Dihuang Decoction combined with Yinqiao Powder (XDY) is effective on improving influenza viral pneumonia. PURPOSE:This study further explores the anti-inflammatory mechanism of XDY in the treatment of influenza viral pneumonia. STUDY DESIGN:The effects of XDY on inflammation, autophagy, NACHT-LRR-PYD-containing protein 3 (NLRP3) inflammasome and pyroptosis were assessed in the mice with influenza viral pneumonia. In addition, the mouse macrophage cell line (J774A.1) infected with influenza virus was adopted to decode the in vitro effects of XDY on autophagy, reactive oxygen species (ROS), NLRP3 inflammasome and pyroptosis. We analyzed the XDY-induced autophagy, especially the mitophagy-related ROS clearance, and the subsequent inhibition of ROS/NLRP3 inflammasome/pyroptosis signaling in the infected macrophages by different assays based on quantitative polymerase chain reaction, western blot, flow cytometry, immunofluorescence and enzyme-linked immunosorbent assay. RESULTS:In vivo, XDY could effectively improve the lung inflammatory response in the mice with influenza virus pneumonia, due to an intact autophagy flux-promoting effect and the inhibiting roles on NLRP3 inflammasome and pyroptosis. Notably, in vitro, compared with the infected macrophages treated by the NLRP3 inflammasome agonist (Monosodium urate) or the mitochondrial-targeted antioxidant agent, the XDY-dependent treating could inhibit pyroptosis by negatively regulating the signaling axis of ROS/NLRP3 inflammasome/pyroptosis in the influenza virus-infected macrophages. More interestingly, XDY could promote an intact autophagy flux, inducing mitophagy eliminating the damaged mitochondria to reduce the intracellular ROS accumulation, and thus decrease the oxidative stress in the infected macrophages. Especially, the inhibitor of autophagy inition, 3-Methyladenine, could reverse the inhibitory effect of XDY on ROS-NLRP3 inflammasome-mediated pyroptosis, indicating an XDY-promoted mitophagy-dependent ROS scavenging. CONCLUSION:XDY can promote an intact autophagy flux to eliminate damaged mitochondria, namely mitophagy, which reduces the intracellular ROS accumulation contributing to NLRP3 inflammasome activation, restricting pyroptosis and eventually alleviating the influenza virus-induced inflammatory lesions. The obtained results provide new insights into the mechanism of action of XDY in alleviating influenza virus pneumonia, especially the roles of XDY in anti-oxidation, anti-inflammation and anti-pyroptosis, with potential therapeutic targets for future application in integrative medicine.

BackgroundSkin 16S microbiome diversity analysis indicates that the Staphylococcus genus, especially Staphylococcus aureus (S. aureus), plays a crucial role in the inflammatory lesions of acne. However, current animal models for acne do not fully replicate human diseases, especially pustular acne, which limits the development of anti-acne medications. AimsThe aim is to develop a mouse model for acne, establishing an animal model that more closely mimics the clinical presentation of pustular acne. This will provide a new research platform for screening anti-acne drugs and evaluating the efficacy of clinical anti-acne experimental treatments. MethodsBuilding upon the existing combination of acne-associated Cutibacterium acnes (C. acnes) with artificial sebum, we will inject a mixture of S. aureus and C. acnes locally into the dermis in a 3:7 ratio. ResultsWe found that the acne animal model with mixed bacterial infection better replicates the dynamic evolution process of human pustular acne. Compared to the infection with C. acnes alone, mixed bacterial infection resulted in pustules with a distinct yellowish appearance, resembling pustular acne morphology. The lesions exhibited redness, vascular dilation, and noticeable congestion, along with evident infiltration of inflammatory cells. This induced higher levels of inflammation, as indicated by a significant increase in the secretion of inflammatory factors such as IL-1 beta and TNF-alpha. ConclusionThis model can reflect the clinical symptoms and development of human pustular acne, overcoming the limitations of animal models commonly used in basic research to study this situation. It provides support for foundational research and the development of new acne medications.

Background: Characterized by (3-amyloid (A(3) plaques, neurofibrillary tangles, and aberrant neuroinflammation in the brain, Alzheimer's disease (AD) is the most common neurodegenerative disease. Microglial polarization is a subtle mechanism which maintains immunological homeostasis and has emerged as a putative therapeutic to combat AD. Berberine (BBR) is a natural alkaloid compound with multiple pharmacological effects, and has shown considerable therapeutic potential against inflammatory disorders. However, BBR functions and underlying mechanisms in neuroinflammation remain unclear. Purpose: To examine BBR pharmacological effects and mechanisms in neuroinflammation with a view to treating AD. Methods: BBR effects on cognitive performance in 5 x FAD mice were assessed using open field, Y-maze, and Morris Water Maze (MWM) tests. Neuroinflammation-related markers and A(3 pathology were examined in brain sections from mice. Transcriptomic analyses of hippocampus tissues were also conducted. Microglial BV2 cells were also used to verify potential BBR mechanisms in neuroinflammation and microglial polarization. Results: BBR improved cognitive performance, reduced amyloid pathology, and alleviated aberrant neuroinflammation in an AD mouse model. BBR induced microglial polarization to an M2-like phenotype, which was manifested by lowered and elevated proinflammatory and anti-inflammatory cytokine production, respectively, improved microglial uptake and A(3 clearance. Mechanistically, BBR directly interacted with TYROBP and promoted its activation by stabilizing TYROBP oligomerization. TYROBP knockdown aggravated M1-like polarization and pro-inflammatory gene expression in microglial cells in the presence of lipopolysaccharide (LPS)+A(3, while blocked microglial M2-like polarization benefited from BBR administration. Conclusions: BBR modulated neuroinflammation by regulating microglial polarization via TYROBP activation. Our study provided new insight into BBR pharmacological actions in regulating microglial homeostasis and combating AD.

Androgenetic alopecia (AGA) is a prevalent disease in worldwide, local application or oral are often used to treat AGA, however, effective treatments for AGA are currently limited. In this work, we observed the promoting the initial anagen phase effect of pilose antler extract (PAE) on hair regeneration in AGA mice. We found that PAE accelerated hair growth and increased the degree of skin blackness by non-invasive in vivo methods including camera, optical coherence tomography and dermoscopy. Meanwhile, HE staining of sagittal and coronal skin sections revealed that PAE augmented the quantity and length of hair follicles, while also enhancing skin thickness and hair papilla diameter. Furthermore, PAE facilitated the shift of the growth cycle from the telogen to the anagen phase and expedited the proliferation of hair follicle stem cells and matrix cells in mice with AGA. This acceleration enabled the hair follicles to enter the growth phase at an earlier stage. PAE upregulated the expression of the sonic hedgehog (SHH), smoothened receptor, glioma-associated hemolog1 (GLI1), and downregulated the expression of bone morphogenetic protein 4 (BMP4), recombinant mothers against decapentaplegic homolog (Smad) 1 and 5 phosphorylation. This evidence suggests that PAE fosters hair growth and facilitates the transition of the growth cycle from the telogen to the anagen phase in AGA mice. This effect is achieved by enhancing the proliferation of follicle stem cells and matrix cells through the activation of the SHH/GLI pathway and suppression of the BMP/Smad pathway.

To investigate the inhibitory effect of Tanreqing Injection (TRQ) on the activation of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome in macrophages infected with influenza A virus and the underlying mechanism based on mitophagy pathway. The inflammatory model of murine macrophage J774A.1 induced by influenza A virus [strain A/Puerto Rico/8/1934 (H1N1), PR8] was constructed and treated by TRQ, while the mitochondria-targeted antioxidant Mito-TEMPO and autophagy specific inhibitor 3-methyladenine (3-MA) were used as controls to intensively study the anti-inflammatory mechanism of TRQ based on mitophagy-mitochondrial reactive oxygen species (mtROS)-NLRP3 inflammasome pathway. The levels of NLRP3, Caspase-1 p20, microtubule-associated protein 1 light chain 3 II (LC3II) and P62 proteins were measured by Western blot. The release of interleukin-1β (IL-1β) was tested by enzyme linked immunosorbent assay, the mtROS level was detected by flow cytometry, and the immunofluorescence and co-localization of LC3 and mitochondria were observed under confocal laser scanning microscopy. Similar to the effect of Mito-TEMPO and contrary to the results of 3-MA treatment, TRQ could significantly reduce the expressions of NLRP3, Caspase-1 p20, and autophagy adaptor P62, promote the expression of autophagy marker LC3II, enhance the mitochondrial fluorescence intensity, and inhibit the release of mtROS and IL-1β (all P<0.01). Moreover, LC3 was co-localized with mitochondria, confirming the type of mitophagy. TRQ could reduce the level of mtROS by promoting mitophagy in macrophages infected with influenza A virus, thus inhibiting the activation of NLRP3 inflammasome and the release of IL-1β, and attenuating the inflammatory response.

Background: Seasonal influenza infection is a major challenge in public health. Previous studies have shown that the timing of seasonal influenza epidemics varies with latitude, indicating that meteorological and environmental conditions are involved in the spread of influenza. We sought to investigate the link between the onset of influenza and meteorological factors in Gansu Province, to build an accurate forecasting model. Methods: We conducted time series analysis based on selected weather variables and influenza incidence data from 2006 to 2016 in Gansu Province. First, the cross-correlation function (CCF) was applied to explore the correlation between meteorological variables and influenza incidence. Then, a seasonal autoregressive integrated moving average model with additional covariates (SARIMAX) was performed to fit and predict influenza incidence. Results: After fitting the SARIMAX model, minimum temperature at lag 1 (β = −0.067, P < 0.05, 95% confidence interval: −0.119, −0.015) was negatively associated with loginfluenza incidence. SARIMAX (1, 1, 1) (0, 1, 1)12 with minimum temperature at lag 1 was the optimal model, with good prediction accuracy. Conclusions: Meteorological factors showed different effects on influenza incidence in Gansu Province. Our results verify the idea that climate is an important factor in the spread of influenza. Keywords: influenza; meteorological factor; time series; SARIMAX; Gansu Province

The dual strategy of inhibiting the viral life cycle and reducing the host inflammatory response should be considered in the development of therapeutic drugs for influenza A virus (IAV). In this study, an extract of Scutellaria baicalinase (SBE) containing seven flavonoids was identified to exert both antiviral and anti-inflammatory effects in macrophages infected with IAV. We performed transcriptome analysis using high-throughput RNA sequencing and identified 315 genes whose transcription levels were increased after IAV infection but were able to be decreased after SBE intervention. Combined with Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, these genes were mainly involved in TLR3/7/8, RIG-I/MDA5, NLRP3 and cGAS pattern recognition receptor (PRR)-mediated signaling pathways. SBE inhibited the transcription of essential genes in the above pathways and nuclear translocation of NF-κB p65 as confirmed by RT-qPCR and immunofluorescence, respectively, indicating that SBE reversed PR8-induced over-activation of the PRR signaling pathway and inflammation in macrophages. This study provides an experimental basis for applying Scutellaria baicalensis and its main effects in the clinical treatment of viral pneumonia. It also provides novel targets for screening and developing novel drugs to prevent and treat IAV infectious diseases.

目的 探究犀角地黄汤对流感病毒性肺炎小鼠炎症反应的作用及作用机制.方法 BALB/c小鼠,随机分为正常组、模型组、犀角地黄汤组、达菲组,除正常组外其余小鼠以流感病毒滴鼻感染,1小时后给药.各组分别以对应的水煎剂或溶液灌胃,每日1次,连续6天.BALB/c小鼠分别在感染后第2、4、6天取材,观察小鼠肺大体病变情况;计算肺指数;光镜下观察肺组织病理切片;RT-PCR法检测肺组织中NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)、凋亡相关斑点样蛋白(apoptosis-associated speck-like protein,ASC)、半胱天冬氨酸酶1前体(Pro-Caspase-1)和gasdermin D(GSDMD)mRNA水平;ELISA法检测小鼠血清中肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素1β(interleukin-1β,IL-1β)和白细胞介素6(interleukin-6,IL-6)水平.Western blot检测肺组织中NLRP3、Caspase-1 p20、GSDMD和gasdermin D N端片段(GSDMD-N)蛋白表达量.结果 犀角地黄汤组和达菲组均可在第2、4、6天改善小鼠肺脏充血、红肿和坏死现象,且不同程度的减轻感染小鼠肺组织炎性病理改变.第6天,犀角地黄汤组的肺指数显著降低.模型组小鼠肺组织NLRP3、ASC、Pro-Caspase-1、GSDMD mRNA表达增多,NLRP3、Caspase-1 p20、GSDMD和GSDMD-N蛋白表达亦增多,肺组织IL-1β、IL-6、TNF-α水平升高;犀角地黄汤可显著减少上述分子mRNA、蛋白表达及炎症因子水平.结论 犀角地黄汤通过调控NLRP3-Caspase1介导的细胞焦亡抑制流感病毒性肺炎小鼠的炎症反应,是其截断疾病的传变的机制之一.

目的:探究小檗碱(BBR)对过氧化氢(H2O2)诱导的巨噬细胞焦亡的影响及mtROS-NLRP3通路在其中的调控作用.方法:以巨噬细胞J774A.1为研究对象,设置正常对照组(control组)、模型组(H2O2作用24 h)、BBR干预组(H2O2+BBR作用24 h)和ROS清除剂NAC干预组(H2O2+NAC作用24 h).流式细胞术检测各组细胞活性氧簇(ROS)的生成,免疫荧光检测ROS与线粒体的共定位情况,实时荧光定量PCR检测各组细胞NLRP3、IL-1β的基因转录水平,Western blot检测NLRP3蛋白表达量,流式细胞术检测caspase-1的活化及其介导的细胞焦亡率,乳酸脱氢酶(LDH)试剂盒检测各组细胞LDH的释放量,ELISA检测IL-1β分泌水平.结果:与模型组相比,BBR干预后显著减少了H2O2诱导的巨噬细胞线粒体ROS(mtROS)的生成,下调了NLRP3和IL-1β的基因表达水平,减少了NLRP3蛋白的表达,降低了caspase-1活化水平及其介导的细胞焦亡率,同时减少了细胞上清液中LDH和IL-1β的释放.结论:小檗碱可能通过下调mtROS水平进而抑制NLRP3炎症体介导的细胞焦亡以减轻炎症反应.

目的:探究犀角地黄汤合银翘散(XDY)对自噬调节的流感病毒感染小鼠巨噬细胞线粒体活性氧(mtROS)水平的影响.方法:以流感病毒PR8感染小鼠巨噬细胞J774A.1为模型,进行下列实验:(1)分为正常组、模型组(PR8感染24 h)、XDY干预组(PR8感染及162.5 mg/L XDY干预24 h)、3-甲基腺嘌呤(3-MA)干预组(5 mmol/L 3-MA预处理3 h+PR8感染24 h)、3-MA对照组(5 mmol/L 3-MA预处理3 h再继续培养24 h)和PR8+3-MA+XDY组(5 mmol/L 3-MA预处理3 h+PR8感染及162.5 mg/L XDY干预24 h),Western blot法检测细胞微管相关蛋白1轻链3-II(LC3-II)和P62蛋白水平,ELISA检测细胞培养上清液白细胞介素1β(IL-1β)的分泌水平;(2)分为正常组、模型组和XDY干预组,免疫荧光观察细胞线粒体膜电位、自噬体与线粒体共定位;(3)分为正常组、模型组、XDY干预组、Mito-TEMPO干预组(PR8感染及500μmol/L Mito-TEMPO干预24 h)、Mito-TEMPO对照组(500μmol/L Mito-TEMPO干预24 h)、3-MA干预组、3-MA对照组和PR8+3-MA+XDY组,流式细胞术检测mtROS水平.结果:流感病毒感染后,J774A.1细胞内LC3-II和P62蛋白水平显著升高,线粒体膜电位下降,mtROS生成增多,IL-1β分泌显著增多;与模型组相比,XDY可降低P62的表达,促进线粒体自噬,升高线粒体膜电位,减少mtROS产生及IL-1β分泌;以3-MA抑制细胞自噬可加重mtROS累积,XDY降低mtROS的作用也受到抑制.结论:XDY可通过促进流感病毒感染的小鼠巨噬细胞自噬而降低mtROS水平,从而抑制炎症反应.

生物仪器分析是生物工程专业的一门专业必修课。本文根据课程的培养目标，从课程定位、优化教学内容及方法、 改革考核模式和增设课后实践环节几个方面探索生物仪器分析课程体系建设，以期培养学生的科研思维和实践技能。

Background: Tanreqing injection (TRQ) has been widely used in the treatment of viral pneumonia in China. However, the effectiveness and safety of TRQ in the treatment of viral pneumonia have not been scientifically and systematically evaluated so far.Methods: We searched eight databases and conducted six studies, including effective rate, antipyretic time, cough stopping time, antiasthmatic time, rale reduction time, length of stay. We evaluated the methodological bias risk of all included trials using the Cochrane evaluation handbook of randomized controlled trials (RCTs) (5.1.0),.Results: A total of 37 randomized controlled trials were included, including 2997 patients. The statistical results of six clinical indicators show that,effective rate, part A, [RR = 1.20, 95% CI (1.15-1.25), P < 0.00001]; part B, [RR = 1.19, 95% CI (1.14-1.25), P < 0.00001]. Antipyretic time, part A, [MD = -0.99, 95% CI (- 1.20, - 0.78), P < 0.00001]; part B, [MD = -0.57, 95% CI (- 0.70, - 0.44), P < 0.00001]. Cough stopping time, part A, [MD = -1.48, 95% CI (- 1.88, - 1.07), P < 0.00001]; part B, [MD = -0.45, 95% CI (- 1.95, 1.04), P = 0.55]. Antiasthmatic time, part A, [MD = -1.28, 95% CI (- 1.52, - 1.04), P < 0.00001]. Rale reduction time, part A, [MD = -1.35, 95% CI (- 1.68, - 1.01), P < 0.00001]; part B, [MD = -0.88, 95% CI (- 1.73, - 0.03), P = 0.04]. Length of stay, part A, [MD = -1.87, 95% CI (- 2.43, - 1.31), P < 0.00001]; part B, [MD = -2.23, 95% CI (- 2.40, - 2.06), P < 0.00001).Conclusion: Six studys show that TRQ has certain advantages over conventional drugs in the treatment of viral pneumonia. TRQ has no serious adverse reactions and has safety.

Viral pneumonia is a common complication caused by Influenza A virus infection and is characterized by severe pulmonary inflammation. A previous study showed that berberine (BBR) significantly ameliorated the pulmonary inflammation in mice with influenza viral pneumonia but its underlying mechanism is not entirely understood. In this study, we reproduced the mouse model of influenza viral pneumonia through intranasal infection of A/Puerto Rico/8/34 (H1N1), to further investigate the anti-inflammatory mechanism of BBR based on nucleotide-binding oligomerization domain-like receptor protein (NLRP) 3 inflammasome activation and Gasdermin D (GSDMD)-mediated pyroptosis. Consistent with MCC950 (10 mg/kg, a specific NLRP3 inflammasome inhibitor), BBR (10 mg/kg) obviously improved the weight loss and survival rate of infected mice, alleviated their pulmonary inflammation, and suppressed the accumulation of tumor necrosis factor and interleukin (IL)-6 in lungs without obvious inhibition on viral multiplication (hemagglutinin titer and nucleoprotein messenger RNA). Moreover, BBR (10 mg/kg) reduced the expressions of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and cysteinyl aspartate-specific proteinase (Caspase)1 (Caspase1 precursor [Pro-caspase1] + Caspase1p20 subunit) and the ratio of Caspase1p20 subunit to Caspase1, thus inhibiting the NLRP3 inflammasome activation and resulting in the decreased contents of mature IL-1 beta and IL-18 in lungs. The GSDMD expression (GSDMD precursor [Pro-GSDMD] + GSDMD-N terminal [NT]) and the ratio of GSDMD-NT to GSDMD were also declined by BBR (10 mg/kg). These evidence indicate that BBR may ameliorate pulmonary inflammation in mice with influenza viral pneumonia through inhibiting NLRP3 inflammasome activation, as well as depressing GSDMD-mediated pyroptosis via declining GSDMD expression and restraining NLRP3 inflammasome-mediated GSDMD activation.