In the context of global climate change, the impact of ambient temperature change on cardiovascular health has become increasingly significant. Epidemiological studies have shown that both high and low temperature can lead to the occurrence of adverse cardiovascular outcomes. For example, exposure to low temperature and high temperature, and diurnal temperature difference can increase the risk of cardiovascular diseases (CVD) mortality. Exposure to cold and heat, heatwaves and cold spells may induce myocardial infarction. Low temperature, high temperature and variations in temperature can increase the risk of heart failure. There are complex interactions among the effects of temperature and humidity, wind speed, radiation, precipitation and air pollution on adverse cardiovascular outcomes. Valnerable groups such as the elderly, patients with chronic diseases, and outdoor workers are particularly susceptible to temperature-related CVD risks. The mechanisms by which temperature affects adverse cardiovascular outcomes involves hemodynamic changes, autonomic nervous system dysregulation, blood rheology alterations, as well as inflammation and metabolic abnormalities, but many research gaps remain. Future studies should conduct in-depth research on mechanisms, individual differences, climate change impacts, and public health interventions to provide more effective policies and interventions to reduce the burden of CVD.

Hypertriglyceridemia （HTG） is the second leading cause of acute pancreatitis in China and can be caused by primary factors， namely gene mutations， which may lead to recurrent hypertriglyceridemic acute pancreatitis （HTG-AP） and difficulties in effective control of triglyceride. This article reports an adult Chinese male patient who experienced eight attacks of HTG-AP and was found to carry a de novo heterozygous mutation， p.K327N， of the GPD1 gene， which may cause the persistent high level of triglyceride and recurrent attacks of HTG-AP.

Objective To investigate the characteristic volatile organic compounds(VOCs)in exhaled breath and their diagnostic value in mice with early stage radiation injury.Methods The thermal desorption gas chromatography-mass spectrometry(TD-GC/MS)technique was used to analyze VOCs in exhaled breath of irradiated mice by 60Coγ-ray with 800 cGy.The characteristic VOCs in the early stage of radiation injury were identified,and a diagnostic model was established.Results The 30-day survival rate of mice was 4.2%.There were significant differences in characteristic VOCs at 7 hours after radiation injury,and thirty characteristic VOCs related to early-stage radiation injury were identified.The diagnostic value of differential metabolites in mice after irradiation was evaluated via the ROC curve,and the area under the ROC curve(AUC)of a single compound exceeded 0.8.The diagnostic model was constructed by screening 9 potential biomarkers of exhalation through Fisher discriminant analysis,and its sensitivity and specificity were close to 100%.Conclusion Analysis of VOCs in exhaled breath is expected to provide a non-invasive diagnostic method for early screening and diagnosis of radiation injury.

AIM:To investigate the effect of Bushen formulae(BHF)on bone metabolism and its possible mechanism in ovariectomized rats with high salt intake.METHODS:According to the random number table method,80 SPF-grade Sprague-Dawley rats were divided into sham group,ovariectomy(OVX)group,medium-high-salt diet(MSD)group,high-salt diet(HSD)group,BHF group,BHF with normal saline(BHF+NS)group,BHF+MSD group,and BHF+ HSD group,with 10 rats in each group.After modeling,different diets and BHF formula interventions were administered,and the concentrations of sodium chloride added to MSD group and HSD group were 2%(w/w)and 8%(w/w),respective-ly.The dose of BHF was 7.8 g·kg-1·d-1,once a day,and the treatment lasted for 12 weeks.Bone density,bone microar-chitecture,bone parameters,bone metabolism biomarkers,bone histopathological changes,the expression of epithelial sodium channel α(ENaCα),Na-Cl cotransporter(NCC),and voltage-gated chloride channel 3(ClC-3)proteins in bone tissue were detected in each group.RESULTS:Compared with sham group,the rats in OVX group had reduced bone density and destroyed bone microstructure.Compared with OVX group,the bone microstructure in MSD and HSD groups was more significantly damaged,while the levels of bone formation markers,bone glycoprotein(BGP)and type Ⅰ procolla-gen N-terminal peptide(PINP),were significantly increased in HSD group(P<0.05).Moreover,the levels of bone re-sorption markers,such as amino-terminal cross-linked telopeptides of type Ⅰ collagen(NTX),carboxy-terminal cross-linked telopeptides of type Ⅰ collagen(CTX)and tartrate-resistant acid phosphatase(TRACP),were significantly in-creased(P<0.05),indicating that bone metabolism was in high-conversion state.High-salt diet accelerated the structural destruction of bone trabeculae,and Western blot results showed that high-salt diet caused decreases in the protein expres-sion levels of ENaCα and ClC-3 and an increase in the protein expression level of NCC in femoral tissues(P<0.05).After BHF intervention,the expression of relevant ion channels caused by high salt could be regulated to different degrees.CONCLUSION:Bushen formulae could differentially regulate the expression of relevant ion channels ENaCα,ClC-3,and NCC induced by high salt to different degrees,which has certain ameliorative and therapeutic effects on the imbalance of bone metabolism.

Objective Screening for sensitive biomarkers for predicting and analyzing drug-induced renal toxicity,accelerates drug early development.Methods Focuses on epithelial cells of proximal convoluted tubules in human renal cortex(human kidney-2,HK-2)cells as the research object,screening for highly sensitive biomarkers using three nephrotoxic drugs(cisplatin,gentamicin,and aristolochic acid Ⅰ).Results The sensitivity of biomarkers in intracellular fluid is higher than in extracellular fluid,compared to detecting a single biomarker in the intracellular fluid.The combined detection of β2-microglobulin(β2-MG)and neutrophil gelatinase-associated lipocalin(NGAL)improved the accuracy of renal toxicity evaluation.Conclusion Based on the HK-2 cell model,the combined detection of β2-MG and NGAL in intracellular fluid can be used to predict renal toxicity in the drug's early development stage.

Owing to the increasing incidence and prevalence of inflammatory bowel disease (IBD) worldwide, effective and safe treatments for IBD are urgently needed. Hydrogen sulfide (H₂S) is an endogenous gasotransmitter and plays an important role in inflammation. To date, H₂S-releasing agents are viewed as potential anti-inflammatory drugs. The slow-releasing H₂S donor 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH), known as a potent therapeutic with chemopreventive and cytoprotective properties, has received attention recently. Here, we reported its anti-inflammatory effects on dextran sodium sulfate (DSS)-induced acute (7 days) and chronic (30 days) colitis. We found that ADT-OH effectively reduced the DSS-colitis clinical score and reversed the inflammation-induced shortening of colon length. Moreover, ADT-OH reduced intestinal inflammation by suppressing the nuclear factor kappa-B pathway. In vivo and in vitro results showed that ADT-OH decreased intestinal permeability by increasing the expression of zonula occludens-1 and occludin and blocking increases in myosin II regulatory light chain phosphorylation and epithelial myosin light chain kinase protein expression levels. In addition, ADT-OH restored intestinal microbiota dysbiosis characterized by the significantly increased abundance of Muribaculaceae and Alistipes and markedly decreased abundance of Helicobacter, Mucispirillum, Parasutterella, and Desulfovibrio. Transplanting ADT-OH-modulated microbiota can alleviate DSS-induced colitis and negatively regulate the expression of local and systemic proinflammatory cytokines. Collectively, ADT-OH is safe without any short-term (5 days) or long-term (30 days) toxicological adverse effects and can be used as an alternative therapeutic agent for IBD treatment.
Humans ; Mice ; Animals ; Gastrointestinal Microbiome ; Intestinal Barrier Function ; Mice, Inbred C57BL ; Colitis/metabolism* ; Inflammatory Bowel Diseases/drug therapy* ; Inflammation ; Anti-Inflammatory Agents/pharmacology* ; Disease Models, Animal

OBJECTIVE AMPK activator,act as exer-cise mimetics,effective in preventing or ameliorating met-abolic diseases,including obesity and diabetes.Systemic activating of AMPK represents an important therapeutic strategy to treat metabolic diseases.However,whether far-infrared(FIR)hyperthermia therapy could be used as exercise mimetic to realize wide-ranging metabolic regu-lation,and its underling mechanisms remain unclear.METHODS The mice were subjected to hyperthermia in the FIR chamber(30±1)℃for 14 d.Exercise endurance was determined using a treadmill.Blood flow were mea-sured by the laser speckle contrast imaging.Combina-tion of microbiomic and metabolomic analysis,diversity of microbiota and metabolic profiling in muscle were detected.The microbiota disorder model via treatment with different cocktails of antibiotics(ABX).RESULTS The material characterization shows that the graphene synthesized by chemical vapour deposition(CVD)is dif-ferent from carbon fi ber,with single-layer structure and high electrothermal transform efficiency.The emission spectra generated by graphene-FIR device would maxi-mize matching those adsorbed by tissues(≈8.0 μm).Gra-phene-FIR improves core and epidermal temperature,and increases blood flow in femoral muscle and abdo-men.The diversity of gut microbiota was increased by graphene-FIR exposure.Graphene-FIR reduced the bac-teroidetes/firmicutes(B/F)ratio and increased the abun-dance of short-chain fatty acids(SCFA)-producing bac-teria,including Allobaculum,Blautia and Anaerostipes.Additionally,graphene-FIR stimulated the expression of SCFAs-sensing receptor(GPR 43),p-AMPK Thr172 and GLUT4,and increased the AMP/ATP ratio,thus enhanc-ing muscle glucose uptake.Metabolomic analyses revealed the significant changes in 25 metabolites,with twenty increased(eg.creatinine and phosphate)and five decreased(eg.lactic acid),and the marked impact of five metabolic pathways,including galactose metabo-lism,glycolysis,gluconeogenesis,fatty acid biosynthesis,butanoate metabolism,pyruvate metabolism.Further-more,a microbiota disorder model also demonstrates that the graphene-FIR effectively restore the exercise endurance with enhanced p-AMPK and GLUT4.CON-CLUSION Our results provide convincing evidence that graphene-based FIR therapy promoted exercise capacity and glucose metabolism via AMPK in gut-muscle axis.These novel insights into graphene-FIR therapy suggest a potential as an exercise mimetic for the treatment of metabolic disease in clinical.

Hyperaldosteronism is a common disease that is closely related to endocrine hypertension and other cardiovascular diseases. Cytochrome P450 11B2 (CYP11B2), an important enzyme in aldosterone (ALD) synthesis, is a promising target for the treatment of hyperaldosteronism. However, selective inhibitors targeting CYP11B2 are still lacking due to the high similarity with CYP11B1. In this study, atractylenolide-I (AT-I) was found to significantly reduce the production of ALD but had no effect on cortisol synthesis, which is catalyzed by CYP11B1. Chemical biology studies revealed that due to the presence of Ala320, AT-I is selectively bound to the catalytic pocket of CYP11B2, and the C8/C9 double bond of AT-I can be epoxidized, which then undergoes nucleophilic addition with the sulfhydryl group of Cys450 in CYP11B2. The covalent binding of AT-I disrupts the interaction between heme and CYP11B2 and inactivates CYP11B2, leading to the suppression of ALD synthesis; AT-I shows a significant therapeutic effect for improving hyperaldosteronism.

Objective: To explore the clinical application value of mixed reality technology in locating perforator vessels and assisting perforator vessel dissection to harvest anterolateral thigh flaps. Methods: Six patients who needed anterolateral thigh flap repair after resection of oral and maxillofacial tumors were recruited from the Department of Oral and Maxillofacial Surgery of Nanchong Central Hospital from January 2020 to January 2021. Before surgery, the CT angiography data of the lower limbs of the patients carrying the calibration points were imported into the data workstation to perform 3D reconstruction of the perforator vessels and surrounding tissues of the thigh, and the reconstruction results were imported into Microsoft HoloLens 2 glasses. During the operation, calibration was performed at the calibration point of the operative area so that the preoperative reconstruction results were superimposed on the operative area through Microsoft HoloLens 2 glasses. The clinical application value of mixed reality technology assisted perforator vessel location and anatomy of anterolateral femoral perforator flap was discussed from six aspects: whether the perforator vessel was reconstructed preoperatively, intraoperative calibration time, whether the actual position of the perforating vessels passing through the fascia lata fulcrum deviated from the preoperative reconstruction result within 1 cm, time required to harvest the flap, and whether the actual route of the perforator vessel was consistent with the reconstruction result, and whether the postoperative flap survived. Results : The position and course of perforating vessels were successfully reconstructed in 6 cases before the operation. The actual course of perforating vessels during the operation was consistent with the reconstruction results. The deviation between the actual position of the perforating points and the preoperative reconstruction results was within 1 cm, which met the requirements of the actual asisting of the anterolateral thigh flap. The average time of flap harvest was (70.50 ± 7.20) min. The average calibration time was (13.33 ± 5.50) min. All flaps survived. Conclusions Mixed reality technology projects the reconstruction results of anterolateral femoral perforator vessels directly into the operative area, which provides a new method for asisting localization and anatomy of anterolateral femoral flap perforator vessels and reduces the possibility of injury to perforator vessels.

Objective:To compare the clinical utility of 18F-fibroblast activating protein inhibitor (FAPI)-42 and 18F-fluorodeoxyglucose (FDG) PET/CT imaging in newly diagnosed lung cancer patients. Methods:From May 2020 to September 2021, the images of 43 lung cancer patients (32 males, 11 females, age: 37-80 years) who pathologically confirmed and received 18F-FDG and 18F-FAPI-42 PET/CT within 2 weeks in the First Affiliated Hospital of Guangzhou Medical University were prospectively analyzed. The maximum standardized uptake value (SUV max) of 18F-FDG and 18F-FAPI-42 and the number of lesions detected by 2 imaging methods were compared by using paired t test and Wilcoxon rank sum test. Results:The 43 newly diagnosed lung cancer patients included 35 adenocarcinoma, 2 squamous cell carcinoma, 4 small cell lung cancer, and 2 high-grade neuroendocrine tumors. 18F-FAPI-42 had a very high tumor uptake (SUV max: 12.24±3.97) and lesion detection rate (positive rate: 100%(37/37)) in primary lung adenocarcinoma and squamous cell carcinoma. The uptake of 18F-FAPI-42 in lymph node (10.13±5.43), pleura (6.75(4.96, 8.58)) and bone lesion (7.18(4.33, 9.66)) were significantly higher than those of 18F-FDG (6.35±3.30, 2.69(1.81, 5.00), 4.38(2.96, 6.36); t=12.19, z values: 5.47, 5.79, all P<0.001). In lung adenocarcinoma and squamous cell carcinoma, although the uptake of 18F-FAPI-42 in brain metastases was significantly lower than that of 18F-FDG (0.72(0.15, 1.82) vs 6.53(4.65, 9.34); z=6.42, P<0.001), the tumor/background (T/B) ratio was significantly higher than that of 18F-FDG (3.54(1.15, 14.88) vs 0.96(0.77, 1.04); z=6.05, P<0.001). In lung adenocarcinoma and squamous cell carcinoma, the number of lesions detected by 18F-FAPI-42 PET/CT was significantly more than that of 18F-FDG (lymph node: 6.0(2.3, 11.5) vs 4.5(2.0, 10.8); brain: 2.0(1.0, 3.0) vs 0.0(0.0, 0.0); pleura: 6.0(2.8, 10.0) vs 4.0(0.8, 5.5); z values: 2.16, 3.10, 2.04, all P<0.05). However, in high-grade neuroendocrine tumors and small cell lung cancer, the SUV max of 18F-FAPI-42 in primary lesions (8.05±2.60), lymph node lesions (5.98±2.21) and brain lesions (0.44(0.13, 0.82)) were lower than those of 18F-FDG (16.28±5.17, 12.30±5.47, 4.94(4.84, 6.25); t values: 3.58, 7.52, z=3.06, all P<0.05). Conclusions:In lung adenocarcinoma and squamous cell carcinoma, 18F-FAPI-42 has a very high tumor uptake and lesion detection rate in primary tumor. In addition, compared with 18F-FDG PET/CT, 18F-FAPI-42 PET/CT shows clearer tumor contours and more lesions. Therefore, 18F-FAPI-42 is more suitable for preliminary staging of lung adenocarcinoma and squamous cell carcinoma than 18F-FDG, while the opposite is true in small cell lung cancer and high-grade neuroendocrine tumors.