Promoting Sustainable Development Goals by Optimizing City-Level Solar Photovoltaic Deployment in China.

Solar photovoltaic (PV) installations, which enable carbon neutrality, are expected to surge in the coming decades. This growth will support sustainable development goals (SDGs) via reductions in power-generation-related environmental emissions and water consumption while generating new jobs. However, where and to what extent PVs should be utilized to support SDGs must be thoroughly addressed. Here, we use multiple PV deployment scenarios to compare the benefits of PVs and related SDGs progress in 366 prefectural-level cities in China. We developed an assessment framework that integrates a PV allocation model, an electricity system optimization model, and a benefit assessment approach. We identify vast differences in PV distribution and electricity transmission and elucidate trade-offs and synergies among the SDGs under various PV implementation scenarios. The water conservation-oriented scenario yields substantial carbon reduction, air pollutant mitigation, and water saving cobenefits, leading to the greatest SDGs improvements. Prioritizing employment creation enhances job-relevant SDGs but inhibits environmental resource benefits. SDGs in less developed cities present greater progress across all scenarios. This study highlights the need to consider spatial heterogeneity and the potential trade-offs between different SDGs and regions when designing energy transition strategies.

Construction and Validation of a Diagnostic Scoring System for Predicting Active Pulmonary Tuberculosis in Patients with Positive T-SPOT Based on Indicators Associated with Coagulation and Inflammation: A Retrospective Cross-Sectional Study.

Introduction: Tuberculosis (TB) is a life-threatening single infectious disease, which remains a major global public health concern. This study was to establish and validate a clinically practical diagnostic scoring system for predicting active pulmonary tuberculosis (APTB) in patients with positive tuberculosis T cell spot test [T-SPOT] using indicators associated with coagulation and inflammation. Methods: A single-center retrospective cross-sectional study was performed to include patients with positive T-SOPT registered and hospitalized at Wuhan Jinyintan Hospital between January 2017 and December 2019. All patients were separated into the active pulmonary tuberculosis (APTB) group and the inactive pulmonary tuberculosis (IPTB) group, according to the diagnostic criteria from China's Expert Consensus for APTB and IPTB. Subsequently, the patients were randomized into a training set and a validation set at a ratio of 2:1. Indicators associated with coagulation and inflammation, including prothrombin time activity (PTA), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen concentration (Fbg-C), C-reactive protein/albumin ratio (CAR), C-reactive protein/prealbumin ratio (CPR), neutrophils count/lymphocyte count ratio (NLR), platelet count/lymphocyte count ratio (PLR), monocyte count/lymphocyte count ratio (MLR), and erythrocyte sedimentation rate (ESR) were obtained from electronic medical record system (EMRS). Stepwise logistic regression was performed in the training set to build a diagnostic model for predicting APTB, which was transformed into an easily applicable scoring system via nomogram. Receiver operating characteristic (ROC) analysis, calibration curve (CC), and decision curve analysis (DCA) were conducted to evaluate the predictive performance of the established diagnostic scoring system. Results: A total of 508 patients [training set (211 cases of APTB and 116 cases of IPTB) and validation set (103 cases of APTB and 78 cases of IPTB)] with positive T-SPOT were recruited in the study. Stepwise logistic regression showed that CPR, MLR, ESR, APTT and Fbg-C were independent predictors for APTB. The scoring system was subsequently formulated based on the abovementioned predictors, which correspond to scores of 10, 6, 7, 5, and 5, respectively. In addition, patients are more likely to be diagnosed as APTB when the cut-off score was ≥16 scores, while patients with <16 scores are more likely to be diagnosed as IPTB. The scoring system showed good predictive efficacy in both the training set [area under the curve (AUC): 0.887] and the validation set (AUC: 0.898). Furthermore, both CC and DCA confirmed the clinical utility of the scoring system. Conclusion: The data suggest that the combination of indicators associated with coagulation and inflammation could serve as biomarkers to identify APTB in patients with positive T-SPOT. In addition, patients with positive T-SPOT were more prone to be diagnosed with APTB when having a combined total of scores ≥16 in the scoring system.

Risk Prediction for Rapidly Progressive Interstitial Lung Disease in Anti-MDA5-Positive Dermatomyositis: The CRAFT Model.

BACKGROUND Anti-melanoma differentiation-associated protein 5-positive dermatomyositis (MDA5⁺ DM) is characterized by a life-threatening complication of rapidly progressive interstitial lung disease (RP-ILD). Early prediction of RP-ILD can enhance diagnostic accuracy and therapeutic efficacy. This study was conducted to develop a nomogram model for predicting RP-ILD in patients with MDA5⁺ DM. MATERIAL AND METHODS We retrospectively analyzed 53 patients with MDA5⁺ DM, of whom 21 patients were diagnosed with RP-ILD between January 2018 and January 2021. Univariate analysis (t test, Mann-Whitney U test, chi-squared test, or Fisher's exact test) and receiver operating characteristic (ROC) analysis were used to select candidate variables. Multivariate logistic regression analysis was conducted to construct a prediction model, which was subsequently transformed into a nomogram. ROC analysis, calibration curve and decision curve analysis were performed to evaluate the model's performance. The bootstrapping method (resampling=500) was used for internal validation. RESULTS We successfully established a nomogram, called the CRAFT model, to predict RP-ILD in MDA5⁺ DM patients. The model included 4 variables, namely C-reactive protein-to-albumin ratio, red blood cell distribution width-coefficient of variation, fever status, and CD3⁺ T cells. The model presented high predictive power and a good performance in calibration curve and decision curve analysis. In addition, the model had a good predictive ability in internal validation. CONCLUSIONS The CRAFT model could help to predict RP-ILD in patients with MDA5⁺ DM.

Inhibition of miR338 rescues cleidocranial dysplasia in Runx2 mutant mice partially via the Hif1a-Vegfa axis.

Haploinsufficiency of Runt-related transcription factor-2 (RUNX2) is responsible for cleidocranial dysplasia (CCD), a rare hereditary disease with a range of defects, including delayed closure of the cranial sutures and short stature. Symptom-based treatments, such as a combined surgical-orthodontic approach, are commonly used to treat CCD patients. However, there have been few reports of treatments based on Runx2-specific regulation targeting dwarfism symptoms. Previously, we found that the miR338 cluster, a potential diagnostic and therapeutic target for postmenopausal osteoporosis, could directly target Runx2 during osteoblast differentiation in vitro. Here, we generated miR338-/-;Runx2+/- mice to investigate whether inhibition of miR338 could rescue CCD defects caused by Runx2 mutation in vivo. We found that the dwarfism phenotype caused by Runx2 haploinsufficiency was recovered in miR338-/-;Runx2+/- mice, with complete bone density restoration and quicker closure of fontanels. Single-cell RNA-seq analysis revealed that knockout of miR338 specifically rescued the osteoblast lineage priming ability of bone marrow stromal cells in Runx2+/- femurs, which was further confirmed by Osterix-specific conditional knockout of miR338 in Runx2+/- mice (OsxCre; miR338 fl/fl;Runx2+/-). Mechanistically, ablation of the miR338 cluster in Runx2+/- femurs directly rescued the Hif1a-Vegfa pathway in Runx2+/- osteoblasts, as proven by gene expression profiles and ChIP and Re-ChIP assays. Collectively, our data revealed the genetic interaction between Runx2 and the miR338 cluster during osteoblast differentiation and implied that the miR338 cluster could be a potential therapeutic target for CCD.

Klf4 haploinsufficiency in Sp7+ lineage leads to underdeveloped mandibles and insufficient elongation of mandibular incisor.

The mandible is an important component of the craniofacial bones, whose development is regulated by complex molecular networks and involves the well-coordinated development of the bone, cartilage, and teeth. Previously, we demonstrated that Krüppel-like factor 4 (KLF4) promoted dentinogenesis and osteogenesis, but it was enigmatic whether Klf4 participated in the development of the mandible. In this study, the Sp7-Cre; Klf4f/+ mice exhibited underdeveloped mandibles and insufficient elongation of the mandibular incisor when compared with Klf4f/+ and Sp7-Cre mice. Moreover, morphological and molecular analysis showed that the alveolar bone mass was significantly decreased in KLF4 deficient mice, accompanied by reduced expression of osteoblast-related genes. Meanwhile, the KLF4 deficient mice had decreased expression of receptor activator of nuclear factor kappa-Β ligand (RANKL) and no significant change of osteoprotegerin (OPG) in the alveolar bone near the mandibular incisor. Simultaneously, the osteoclastogenesis in the alveolar bone of KLF4 deficient mice was attenuated, which was demonstrated by a diminished number of tartrate-resistant acid phosphatase positive (TRAP+), matrix metallopeptidase 9 positive (MMP9+), and cathepsin K positive (CTSK+) multinucleated osteoclasts, respectively. Collectively, our study suggested that Klf4 participated in mandibular development, and Klf4 in Sp7+ lineage affected osteogenesis directly and osteoclastogenesis indirectly.

BMP2-dependent gene regulatory network analysis reveals Klf4 as a novel transcription factor of osteoblast differentiation.

Transcription factors (TFs) regulate the expression of target genes, inducing changes in cell morphology or activities needed for cell fate determination and differentiation. The BMP signaling pathway is widely regarded as one of the most important pathways in vertebrate skeletal biology, of which BMP2 is a potent inducer, governing the osteoblast differentiation of bone marrow stromal cells (BMSCs). However, the mechanism by which BMP2 initiates its downstream transcription factor cascade and determines the direction of differentiation remains largely unknown. In this study, we used RNA-seq, ATAC-seq, and animal models to characterize the BMP2-dependent gene regulatory network governing osteoblast lineage commitment. Sp7-Cre; Bmp2fx/fx mice (BMP2-cKO) were generated and exhibited decreased bone density and lower osteoblast number (n > 6). In vitro experiments showed that BMP2-cKO mouse bone marrow stromal cells (mBMSCs) had an impact on osteoblast differentiation and deficient cell proliferation. Osteogenic medium induced mBMSCs from BMP2-cKO mice and control were subjected to RNA-seq and ATAC-seq analysis to reveal differentially expressed TFs, along with their target open chromatin regions. Combined with H3K27Ac CUT&Tag during osteoblast differentiation, we identified 2338 BMP2-dependent osteoblast-specific active enhancers. Motif enrichment assay revealed that over 80% of these elements were directly targeted by RUNX2, DLX5, MEF2C, OASIS, and KLF4. We deactivated Klf4 in the Sp7 + lineage to validate the role of KLF4 in osteoblast differentiation of mBMSCs. Compared to the wild-type, Sp7-Cre; Klf4fx/+ mice (KLF4-Het) were smaller in size and had abnormal incisors resembling BMP2-cKO mice. Additionally, KLF4-Het mice had fewer osteoblasts and decreased osteogenic ability. RNA-seq and ATAC-seq revealed that KLF4 mainly "co-bound" with RUNX2 to regulate downstream genes. Given the significant overlap between KLF4- and BMP2-dependent NFRs and enriched motifs, our findings outline a comprehensive BMP2-dependent gene regulatory network specifically governing osteoblast differentiation of the Sp7 + lineage, in which Klf4 is a novel transcription factor.

Hypoxia, acidification and nutrient accumulation in the Yellow Sea Cold Water of the South Yellow Sea.

Hypoxia and acidification in coastal waters are of global concern. However, the complex hydrodynamic processes and human interferences are major challenges for the diagnosis of their mechanism. The role of seasonal water masses involved still remains unknown. We herein investigated the dynamics of dissolved oxygen (DO), pH, inorganic and organic nutrients in the South Yellow Sea (SYS) in autumn, aiming for a better understanding of the biogeochemical processes of the Yellow Sea Cold Water (YSCW). Low DO, pH and organic nutrients were observed in the YSCW, while the apparent oxygen utilization and dissolved inorganic nutrients were relatively high. Quantitative assessment shows that although the water volume of the YSCW accounts for only 16.4% that of the SYS, the reservoirs of dissolved inorganic nitrogen, phosphate and silicate were 30.8%, 52.1% and 33.0%, respectively. Our results suggest that organic matter mineralization and water stratification are important driving forces for hypoxia, acidification and nutrient accumulation in the YSCW. The upwelling of the YSCW can bring abundant nutrients and stimulate the algal blooms, which are detrimental to the ecology. As global warming continues, the hypoxia and acidification in the YSCW will likely intensify in the near future in response to a projected slowdown of overturning circulation.

[Compound-specific carbon and nitrogen isotope analysis of amino sugars and their applications]. / æ°¨åŸºç³–å•ä½“ç¢³æ°®åŒä½ç´ çš„åˆ†æžåŠå ¶åº”ç”¨.

Amino sugars (AS) are one of the important biochemical components in the natural organic matter pool. Clarifying the sources and transformations of AS would facilitate our understan-ding of the microbial regulation of organic matter. As an emerging technology, compound-specific isotope analysis of amino sugars (CSIA-AS) provides more detailed dynamic information of indivi-dual AS in natural environment. Here, we systematically summarized the determination methods of CSIA-AS and gave an overview on innovative applications in the cycling of AS. CSIA-AS can be performed by gas chromatography-isotope ratio mass spectrometry (GC-IRMS) and ion chromatography-isotope ratio mass spectrometry (IC-IRMS). Each method has its own advantages and disadvantages, but reliable results can be achieved after calibration. The mean residence time of AS is relatively low in soil organic matter, and the bacterial-derived muramic acid possesses a higher minera-lization rate than glucosamine, galactosamine, and mannosamine. The source and metabolic transformation of AS are affected by the substrate, which is related to the specific response of microbial community to different carbon and nitrogen sources. The promotion of CSIA-AS technology requires further optimization of method and integration with other approaches such as microbial screening to decipher the source, transformation, fate and regulatory mechanisms of organic matter.

Physicochemical changes in liver and Hsc70 expression in pikeperch Sander lucioperca under heat stress.

The pikeperch Sander lucioperca is an economically important freshwater species that is currently threatened by higher summer temperatures caused by global warming. To clarify the physiological state of pikeperch reared under relatively high temperatures and to acquire valuable biomarkers to monitor heat stress in this species, 100 fish were subjected to five different temperature treatments, ranging from 23 °C (control) to 36 °C. The physiological and biochemical indexes of liver and blood were determined, and heat-shock cognate 70 kDa protein (Hsc70) mRNA expression profiles were analyzed. The results showed that the activities of superoxide dismutase, catalase, and glutathione peroxidase in heat-stressed pikeperch first increased and then decreased, exhibiting peaks at 34 °C, 28 °C, and 28 °C, respectively. The level of thiobarbituric acid-reactive substances (TBARS) in all experimental groups was significantly higher than that of the control. The numbers of red blood cells, the packed-cell volume, and the contents of hemoglobin were significantly higher in the 34 °C and 36 °C treatment groups. Under heat stress, the albumin, cholesterol, and triglycerides contents decreased with increasing temperatures. Real-time fluorescence-based quantitative RT-PCR showed that Hsc70 mRNA levels increased in all eight of the tested tissues under heat stress. Expression reached maximum levels at 34 °C in the muscle, heart and gill tissues, and at 36 °C in the other five tissues. These results demonstrate that several physiological and biochemical phenotypes, such as oxidative stress, antioxidant enzymes and molecular chaperones, could be important biomarkers of heat stress in pikeperch, and are potentially valuable to uncover the mechanisms of heat-stress responses in fish.

Long-term variations of the riverine input of potentially toxic dissolved elements and the impacts on their distribution in Jiaozhou Bay, China.

The concentrations of the potentially toxic dissolved elements (PTEs) As, Hg, Cr, Pb, Cd, and Cu in the main rivers into Jiaozhou Bay (JZB) during 1981-2006 were measured, and the impact of the fluvial PTE fluxes on their distributions in the bay was investigated. The overall average concentration in the rivers into JZB ranged from 8.8 to 39.6 µg L-1 for As, 10.1 to 632.6 ng L-1 for Hg, 4.1 to 3003.6 µg L-1 for Cr, 8.5 to 141.9 µg L-1 for Pb, 1.1 to 34.2 µg L-1 for Cd, and 13.2 to 1042.8 µg L-1 for Cu. The interannual average concentration variations of the PTEs in these rivers were enormous, with maximum differences of 41-21,680 times, while their relative seasonal changes were far smaller with maximum differences of 3-12 times. The total annual fluvial fluxes for As, Hg, and Cr into JZB exhibited the inverse "U" pattern, while those for Pb and Cd showed the "N" pattern. As a whole, the total annual Cu flux presented a growing tendency from 1998 to 2006. In general, the changing trends of the PTE concentrations in JZB were similar to those of their annual fluxes from the rivers, indicating a great impact of their fluvial fluxes on their distributions in JZB. The annual concentration of Cd in the bay almost remained constant and differed from the fluvial flux of Cd. The diversified pattern of the environmental Kuznets curve (EKC) represented China's approach to industrialization as "improving while developing."

Infection by the nematode Angiostrongylus cantonensis induces differential expression of miRNAs in mouse brain.

BACKGROUND: The parasitic nematode Angiostrongylus cantonensis is the primary pathogen causing eosinophilic meningitis and meningoencephalitis in nonpermissive hosts. The larval parasites are eliminated by the host's immune responses in the central nervous system (CNS) through infiltration of eosinophils and lymphocytes. This study aimed to determine primary alterations of microRNA (miRNA) during A. cantonensis infection in mice. METHODS: miRNA array was used to analyze the expression of miRNA in uninfected and A. cantonensis-infected mouse brains at 21 days postinfection (dpi). Target genes were predicted by miRDB software, and protein-protein interaction network was analyzed using STRING v9.1. Expression levels of selected miRNAs and cytokine production were verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: Twenty-five mature miRNAs showed differential expression in infected mouse brains, of which 24 were upregulated and one was downregulated compared to the uninfected control. These 25 miRNAs were divided into five clusters, and the first upregulated cluster was selected for further bioinformatics analysis. Target gene prediction and gene ontology (GO) enrichment analysis revealed that the miRNAs were mainly related to the immune response. Furthermore, six target genes of mmu-miR-146a-5p were predicted to interact with tumor necrosis factor alpha (TNF-α). The in vitro study suggested that transfected mmu-miR-146a-5p inhibitor upregulated TNF-α and its target gene Traf6 in microglia following stimulation with A. cantonensis larval antigen. CONCLUSION: This study suggested a critical role of miRNAs in the host defense during A. cantonensis infection, providing new insights into the molecular mechanisms underlying the interaction between mmu-miR-146a-5p and TNF-α in angiostrongyliasis in nonpermissive hosts.

Green tea polyphenol epigallocatechin-3-gallate ameliorates insulin resistance in non-alcoholic fatty liver disease mice.

AIM: Epigallocatechin-3-gallate (EGCG) is a major polyphenol in green tea. In this study, we investigated the effects of EGCG on insulin resistance and insulin clearance in non-alcoholic fatty liver disease (NAFLD) mice. METHODS: Mice were fed on a high-fat diet for 24 weeks. During the last 4 weeks, the mice were injected with EGCG (10, 20 and 40 mg·kg(-1)·d(-1), ip). Glucose tolerance, insulin tolerance and insulin clearance were assessed. After the mice were euthanized, blood samples and tissue specimens were collected. Glucose-stimulated insulin secretion was examined in isolated pancreatic islets. The progression of NAFLD was evaluated histologically and by measuring lipid contents. Insulin-degrading enzyme (IDE) protein expression and enzyme activity were detected using Western blot and immunocapture activity assays, respectively. RESULTS: The high-fat diet significantly increased the body weight and induced grade 2 or 3 liver fatty degeneration (steatosis, lobular inflammation and ballooning) accompanied by severe hyperlipidemia, hyperglycemia, hyperinsulinemia and insulin resistance in the model mice. Administration of EGCG dose-dependently ameliorated the hepatic morphology and function, reduced the body weight, and alleviated hyperlipidemia, hyperglycemia, hyperinsulinemia and insulin resistance in NAFLD mice. Furthermore, EGCG dose-dependently enhanced insulin clearance and upregulated IDE protein expression and enzyme activity in the liver of NAFLD mice. CONCLUSION: EGCG dose-dependently improves insulin resistance in NAFLD mice not only by reducing body weight but also through enhancing the insulin clearance by hepatic IDE. The results suggest that IDE be a potential drug target for the treatment of NAFLD.

Effects and mechanisms of vitamin A and vitamin E on the levels of serum leptin and other related cytokines in rats with rheumatoid arthritis.

Leptin has been identified as an important cytokine in the inflammatory networks of rheumatoid arthritis (RA). Higher serum leptin levels may accelerate the development of RA. This study aimed to examine the effects of vitamin A (VitA) and vitamin E (VitE) on the levels of leptin and other related experimental and clinical indices, and to explore the mechanisms of these effects through the Janus kinase/signal transducer and activator of transcription (STAT) signal transduction pathway in rats with collagen-induced arthritis (CIA). CIA model rats were established by the intradermal injection of bovine type II collagen emulsified in incomplete Freund's adjuvant, followed by a booster intradermal injection. Four weeks later, the CIA model rats were treated with 42.86 µg retinol equivalents/kg body weight (b.w.) VitA or 200 mg/kg b.w. VitE for four weeks. The levels of leptin, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-10, IL-4, C-reactive protein (CRP) and rheumatic factor were measured by ELISA using commercial kits, and the erythrocyte sedimentation rate (ESR) was determined. In addition, the expression levels of phosphorylated (p)-STAT1, p-STAT3 and leptin in the synovium were evaluated by western blot analysis. The results indicated that VitA and VitE significantly reduced the levels of leptin, TNF-α, IL-6 and CRP and the ESR and significantly increased the levels of IL-10 compared with those of the model group. Furthermore, significantly reduced p-STAT3 protein expression levels were observed in the VitA and VitE groups. In conclusion, VitA and VitE reduced the levels of serum leptin protein and other cytokines. Furthermore, VitA and VitE also reduced the p-STAT3 protein levels. The present study may provide a novel approach for the treatment of RA.

Test performance of sputum microRNAs for lung cancer: a meta-analysis.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide. Early detection and precise diagnosis are critical for the patients with lung cancer. Increasing evidence has suggested that microRNAs (miRNAs) play important roles in the diagnosis of lung cancer. To evaluate the overall diagnostic performance of sputum miRNAs for the detection of lung cancer, a meta-analysis was performed. METHODS: A systematic search for published literature evaluating the diagnostic accuracy of sputum miRNAs in lung cancer was performed to determine pooled sensitivity and specificity. A summary receiver operating characteristic curve was constructed to assess the overall test performance. Subgroup analysis was utilized to explore potential sources of heterogeneity in the included studies. RESULTS: Eight studies with a total of 514 patients and 491 controls were included in this meta-analysis. Sputum miRNAs had a pooled sensitivity of 0.70 (95% confidence interval [95% CI]: 0.66-0.70) and a pooled specificity of 0.89 (95% CI: 0.86-0.91) for the detection of lung cancer, with an area under the summary receiver operating characteristics curve of 0.83. Significant interstudy heterogeneity for specificity was observed, with miRNA profiles being a possible source. CONCLUSION: Sputum miRNAs are potentially useful noninvasive markers for diagnosis of lung cancer. The diagnostic specificity of sputum miRNAs may be influenced by the miRNA profiles. It would be important for further work to evaluate the generalizability of our results by methodologically rigorous studies on a well-defined patient population.

[Establishment of a murine model of hepatic steatosis induced by chronic viral hepatitis].

OBJECTIVE: To establish a animal model of hepatic steatosis induced by chronic viral hepatitis in C(57)BL/6 mice. METHODS: C(57)BL/6 mice were randomly assigned to control group, high-fat diet group, mouse hepatitis virus strain A59 (MHV-A59) virus infection group, and high-fat diet plus virus infection group. At 13 weeks of the experiment, serum samples were collected to detect MHV antibodies and transaminase and lipid levels. The hepatic pathologies of the mice were examined with Oil red O staining of the frozen sections the and HE staining of paraffin-embedded sections. RESULTS: The mice in the two virus infection groups showed strong positivity of MHV antibodies in the serum. Compared with the control group, the mice in high-fat diet group and the two virus infection groups had significantly increased AST and ALT levels with also elevated TC and LDL-C levels. The two virus infection groups both exhibited obvious pathologies in the liver characteristic of chronic viral hepatitis with increased lipid accumulation in the hepatocytes. CONCLUSION: We have successfully established a mouse model of hepatic steatosis induced by chronic viral hepatitis, which provides the basis for further study of the disease mechanism.

Pathological changes in the lung and brain of mice during heat stress and cooling treatment.

BACKGROUND: Heatstroke often leads to multiple organ dysfunction syndrome (MODS) with a death rate of 40% or a neurological morbidity of 30%. These high rates in patients with heatstroke are largely due to the progression of heat stress to MODS, resulting in no specific treatment available. This study aimed to develop a mouse model of heat stress and determine the pathological changes in the lung and brain during heat stress and cooling treatment. METHODS: A mouse model of heat stress was established in a pre-warmed incubator set at 35.5 ± 0.5°C and with a relative humidity of 60% ± 5%. Rectal temperature was monitored, and at a temperature of 39 °C, 40 °C, 41 °C, or 42 °C, the mice were sacrificed. The remaining animals were removed from the incubator and cooled at an ambient temperature of 25 ± 0.5 °C and a humidity of 35% ± 5% for 12 or 24 hours at a temperature of 41 °C or for 6 hours at a temperature of 42 °C. The control mice were sham-heated at a temperature of 25 ± 0.5 °C and a humidity of 35% ± 5%. The lungs and brains of all animals were isolated. Hematoxylin and eosin staining and light microscopy were performed to detect pathological changes. RESULTS: All mice demonstrated a uniform response to heat stress. A low degree of heat stress induced marked pathological changes of the lungs. With the rise of the temperature to 42°C, progressively greater damage to the lungs with further congestion of the lung matrix, asystematic hemorrhage of alveolar space, abscission of alveolar epithelial cells, and disappearance of pulmonary alveolus tissue structure were detected. However, absorption of congestion and hemorrhage as well as recovery of pulmonary alveolus tissue structure was observed following cooling treatment at an ambient temperature. With a low degree of heat stress, the brain only showed moderate edema. Neuronal denaturation and necrosis were detected at a temperature of 42°C. Interestingly, the lesions in the brain were further aggravated at 42 °C regardless of cooling treatment, but recovery was observed after cooling treatment at 41 °C. CONCLUSIONS: The pathological changes of the lungs and brain of mice showed distinctive lesions following heat stress and cooling treatment, and they were correlated with the time and duration of cooling treatment. The results of this study are helpful for further study of the mechanisms linking heatstroke.

[Construction of MHV-A59 damp-heat mouse model and analysis of the relevant indices].

OBJECTIVE: To explore the impact of inflammation, water metabolism and immune function on the establishment of a mouse model of damp-heat syndrome with MHV-A59 infection. METHODS: Twenty-four mice were randomly divided into control group, virus group, damp-heat group and model group. The peripheral blood CD4(+) and CD8(+) lymphocytes were detected by flow cytometry, and the serum levels of IFN-γ and IL-4 were assayed by ELISA. The expressions of NF-κB and AQP4 in the liver and stomach were determined using immunohistochemistry. RESULTS: The expression of NF-κB and CD4(+)/CD8(+) ratio in the virus and model groups were significantly higher than those in the damp-heat and control groups, while the expression of AQP4 was significantly higher in the model and damp-heat groups than in the other groups. Compared with the control group, the model group showed a significantly higher ratio of IFN-γ/IL-4. CONCLUSIONS: MHV-A59 virus is the main cause of elevated NF-κB expression and CD4(+)/CD8(+)/ ratio, while damp-heat syndrome is responsible for increased AQP4 expression, and their synergistic effect results in increased IFN-γ/IL-4 ratio. The mouse model established using MHV-A59 virus and the damp-heat factors can mimic damp-heat syndrome described in traditional Chinese medicine theory.

[The mechanism of signal extension in Haoqin Qingdan decoction immunity activity in Damp-heat syndrome of pneumonia disease infected by influenza virus].

OBJECTIVE: To explore the immunoregulation existing signal transduction mechanism, to evaluate the role of lay its experimental basis By using Haoqin Qingdan decoction for treatments on the mouse models. METHODS: A total of 40 NIH Mice were randomly divided into five groups: control group, virus group (infecting by influenza virus), complex model group (richly fatty and sweet diet + Humid heat environment + infecting by influenza virus), virazole group (mouse of model group was treated by virazole), and Haoqin Qingdan decoction group (mouse of complex model group was treated by decoction of Haoqin Qingdan). When the complex model was established, determination of the mice lung indexes in each group and calculate the inhibition of lung indexes. The level of TLR2 mRNA and NF-κB mRNA expressions of peritoneal macrophages in each group of mice were quantitated by reverse transcription-polymerase chain reaction (RT-PCR). The level of IL-4 and IFN-γ in mouse serum was detected by ELISA to calculate the Th1/Th2 (IFN-γ/IL-4). RESULTS: The lung index of control group, virus group, complex model group, virazole group and Haoqin Qingdan decoction group were separately: (0.79 ± 0.11)%, (1.93 ± 0.38)%, (1.41 ± 0.26)%, (1.10 ± 0.26)% and (1.02 ± 0.16)%; The mice of virazole group and Haoqin Qingdan decoction group lung index were decreased (t = 0.322, P < 0.05). TLR2 mRNA expression The results showed that the control group, virus group, complex model group, virazole group and Haoqin Qingdan decoction group were: 0.145 ± 0.017, 0.991 ± 0.149, 0.903 ± 0.124, 0.257 ± 0.03 and 0.413 ± 0.031; Compared to the complex model group, Haoqin Qingdan decoction group and virazole group were decreased (t = 0.422, F = 112.834, P < 0.05). Control group, virus group, complex model group, virazole group and Haoqin Qingdan decoction group NF-κB mRNA expression were separately: 0.075 ± 0.148, 0.379 ± 0.019, 0.291 ± 0.012, 0.169 ± 0.026 and 0.175 ± 0.033; the expression in virazole group and Haoqin Qingdan decoction group were decreased (t = 0.422, F = 112.834, P < 0.05). The level of IFN-γ in mice serum of control group, virus group, complex model group, virazole group and Haoqin Qingdan decoction group were: (7434.06 ± 323.27) pg/ml, (8679.77 ± 198.70) pg/ml, (8068.78 ± 113.8) pg/ml, (7454.66 ± 301.30) pg/ml and (7484.56 ± 229.85) pg/ml respectively; the IFN-γ level in serum of Haoqin Qingdan decoction group and virazole group were decreased (t = 0.201, F = 5.390, P < 0.05). Each group of mice IL-4 contents were (3701.74 ± 256.00) pg/ml, (3569.64 ± 161.35) pg/ml, (3530.88 ± 334.63) pg/ml, (3481.84 ± 282.25) pg/ml and (3618.00 ± 262.16) pg/ml; there were no significant difference between each group (t = 0.414, F = 0.505, P > 0.05). Th1/Th2 type cells in state of equilibrium (means IFN-γ/IL-4) were: 2.02 ± 0.19, 2.38 ± 0.10, 2.36 ± 0.14, 2.22 ± 0.17 and 2.07 ± 0.15; and complex model group Haoqin Qingdan decoction group and virazole group were decreased, and there was no significant difference observed (t = 0.587, F = 3.684, P > 0.05). CONCLUSION: The effect of Haoqin Qingdan decoction on treatment of damp-heat syndrome of pneumonia infected by influenza virus was observed. Through reducing the expressions of TLR2, it decreases the levels of NF-κB mRNA and the proportionality of Th1/Th2 are obviously descend (P < 0.05). Haoqin Qingdan decoction can reduce the lung index and relieve the pathogenic changes.

[Reproduction of a murine model of hyperthermic treatment].

OBJECTIVE: To find out the most suitable conditions for a whole body hyperthermia (WBH) model and the influence of these conditions on the blood brain barrier (BBB) disruption and brain edema in rats. METHODS: Forty male Sprague-Dawley (SD) rats were randomly assigned to four groups (n=10 in each group): control group, group A, group B and group C. After anesthesia with pentobarbital, rats were subjected to femoral artery and vein cannulation. Rats of control group were housed at a controlled room temperature (25-26 degrees C) for 4 hours. Rats of group A, group B and group C were exposed to WBH in a biological oxygen supply heated container (relative humidity 65%, wind velocity 25 cm/s) maintained at 34, 36 and 38 degrees C for 3 hours, respectively. Then the rats were removed from the heated container and their body temperature was cooled down for 1 hour. During heating, rectal temperature, heart rate (HR), mean arterial pressure (MAP), pH, partial pressure of oxygen in artery (PaO(2)), partial pressure of carbon dioxide in artery (PaCO(2)), the dosage of anesthetic, and the mortality rate in each group were recorded. Evans blue (EB) was administered into the femoral vein and allowed to circulate for 5 minutes. At the end of the experiment, the animals were perfused with 0.9% saline and heparin through the heart, and the brain was harvested for the examination of BBB permeability, water content and morphological alterations in brain tissues and neurons. RESULTS: The total dosage of pentobarbital was not significantly different among all groups. After WBH for 3 hours, the average rectal temperature was higher than rats without WBH, and the mortality rate was 0, 10%, 10% and 40% in groups control, A, B, C, respectively. HR of groups A, B and C were significantly higher than those of control group; MAP, pH of group A, B and C were significantly lower than those of control group (all P<0.05). Compared to that of control group, water content of the brain and permeability of EB in groups A, B and C were significantly increased (P<0.05 or P<0.01), but there was no marked difference on PaO(2), PaCO(2) and haematocrit (HCT) among groups A, B and C. Morphological investigation showed that there were different degrees of structural changes in brain tissue in groups A, B and C under light microscopy. Under transmission election microscopy, the structure of nerve cells and BBB in group B and group C showed moderate to profound alterations, but there were no changes in group A. CONCLUSION: Rats housed in a biological oxygen supply heat container with the temperature maintained at 36 degrees C for 3 hours could establish an ideal WBH model with notable BBB breakdown, moderate brain edema, and histological changes in brain.