ObjectiveTo investigate the effects of Shengui Jiangtang Formula on insulin resistance and glucose-lipid metabolism in spontaneous type 2 diabetic db/db mice based on the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/forkhead box protein O1 （FoxO1） signaling pathway， and to provide theoretical foundation for its clinical application through fundamental experiments. MethodsA randomized controlled design was employed in this study. Thirty spontaneous type 2 diabetic db/db mice meeting the inclusion criteria （fasting blood glucose >7.0 mmol·L^-1 and random blood glucose on a different day≥11.1 mmol·L^-1） were selected as the subjects. After stratified block randomization by body weight and blood glucose levels， they were randomly assigned to a model group， a metformin group， and a Shengui Jiangtang formula group， with n=10 per group. Ten db/m mice were used as the normal group. During the 5-week intervention， general indicators （including general condition， fasting blood glucose （FBG）， body weight， and food intake） were recorded weekly. An oral glucose tolerance test （OGTT） was performed at week 5. After 5 weeks， serum was collected to measure glucose-lipid metabolism parameters. Liver tissues were analyzed as follows： Histopathology was observed through hematoxylin and eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Oil red O staining. The expression of proteins and genes related to the PI3K/Akt/FoxO1 signaling pathway was quantitatively analyzed using Western blotting （Western blot） and real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsGeneral observations： The mice in the normal group were generally healthy， exhibited agile responses and had smooth and glossy fur. Compared with the normal group， the mice in the model group displayed typical symptoms of polydipsia， polyphagia， and polyuria， along with listlessness and rough fur. Their food intake， initial body weight， liver weight， and liver index were all significantly higher than those in the normal group （P<0.01）. After 5 weeks of drug intervention， neither the Shengui Jiangtang Formula group nor the metformin group significantly affected the food intake of the model mice. Compared with the model group， no statistically significant difference was observed in liver weight or liver index in the Shengui Jiangtang formula group. Serum biochemical indicators： Compared with the normal group， the model group showed significantly elevated levels of FBG， fasting insulin， homeostatic model assessment of insulin resistance （HOMA-IR）， glycosylated serum protein， and blood lipids. After drug intervention， compared with the model group， the Shengui Jiangtang formula group significantly reduced FBG in the model mice （P<0.01）. The blood glucose levels at all time points during the OGTT in the Shengui Jiangtang Formula group were lower than those in the model group， with statistically significant differences in the 0 min blood glucose and the area under the curve for glucose compared to the model group （P<0.05）. Furthermore， the formula significantly reduced fasting insulin levels， HOMA-IR， and glycosylated serum protein levels （P<0.05）. It also showed a tendency to decrease blood lipids， liver enzymes （aspartate aminotransferase， alanine aminotransferase）， and blood urea nitrogen levels， and a tendency to increase creatinine levels， although these differences were not statistically significant. Liver histomorphology： HE staining indicated that Shengui Jiangtang formula improved the morphological structure of hepatocytes and attenuated steatosis in diabetic mice. Liver PAS staining showed that it increased hepatic glycogen content and promoted hepatic glycogen synthesis in diabetic mice. Oil red O staining demonstrated that it reduced lipid deposition within hepatocytes. Western blot： Compared with the normal group， the model group showed decreased protein expression of PI3K， Akt， p-Akt， and p-FoxO1， and increased FoxO1 protein expression. Compared with the model group， both the metformin and Shengui Jiangtang Formula groups showed increased protein expression of PI3K， Akt， p-Akt， and p-FoxO1， and decreased FoxO1 protein expression. Real-time PCR： Compared with the normal group， the mRNA expression of PI3K and Akt was downregulated （P<0.05）， and the mRNA expression of FoxO1 was downregulated （P<0.05） in the model group. ConclusionShengui Jiangtang Formula can improve insulin resistance and glucose-lipid metabolic disorders in db/db mice. It alleviates hepatic steatosis， promotes hepatic glycogen synthesis， and reduces lipid deposition in these mice. The mechanism by which Shengui Jiangtang Formula improves insulin resistance may be associated with the PI3K/Akt/FoxO1 signaling pathway.

Objective: To investigate the current status of benefit finding among young and middle-aged patients with type 2 diabetes mellitus (T2DM) and analyze its influencing factors, so as to provide a reference for improving the level of benefit finding in this population. Methods: From November 2022 to May 2023, young and middle-aged patients with T2DM aged 18-59 years hospitalized in the endocrinology departments of 2 tertiary hospitals in Hengyang City, Hunan Province were selected as survey subjects by a convenience sampling method. Basic demographic information was collected using a general questionnaire survey. Benefit finding, resourcefulness, and stigma were evaluated using the Benefit Finding Scale, the Chinese Version of the Resourcefulness Scale, and the Type 2 Diabetes Stigma Assessment Scale, respectively. A multiple linear regression model was used to analyze the influencing factors of benefit finding among young and middle-aged patients with T2DM. Results: A total of 305 young and middle-aged patients with T2DM were investigated, including 222 males (72.79%) and 83 females (27.21%). There were 231 cases aged 45-59 years, accounting for 75.74%. The scores for benefit finding, resourcefulness, and stigma were (42.86±6.06), (75.12±11.30), and (41.20±10.10), respectively. Multiple linear regression analysis showed that young and middle-aged patients with T2DM who were male (β′=0.088), aged 18-<45 years (β′=0.083), absence of diabetes complications (β′=0.124), and had higher resourcefulness scores (β′=0.679) had higher levels of benefit finding, while patients with higher stigma scores (β′=-0.097) had lower levels of benefit finding. Conclusion The level of benefit finding among young and middle-aged patients with T2DM was moderate, and was related to gender, age, diabetes complications, resourcefulness, and stigma.

Background/Aims: The pathophysiology of refractory gastroesophageal reflux disease (RGERD), which differs from proton pump inhibitor dependent gastroesophageal reflux disease (DGERD), remains incompletely elucidated. This study aims to compare esophageal motility patterns, transdiaphragmatic pressure gradients (TPG), and reflux profiles between RGERD and DGERD patients, and to delineate dynamic pressure gradient-esophagogastric junction (EGJ) interactions in these patients. Methods: In this retrospective study, 274 patients who underwent 24-hour impedance-pH monitoring and high-resolution manometry, along with an assessment of proton pump inhibitor responsiveness, were classified as RGERD (32.5%), DGERD (54.4%), or non-GERD (13.1%). Clinical characteristics, TPG, esophageal motility, and reflux metrics were compared between RGERD and DGERD patients. Subgroup analysis excluding hiatal hernia (HH) was conducted to investigate the pathophysiology of RGERD. Results: The RGERD group exhibited a significantly higher proportion of chest pain compared to the DGERD group. Regarding reflux profiles, RGERD patients without HH (RGERDHH- group) experienced increased weakly acidic reflux (P < 0.001) and prolonged bolus exposure (P = 0.006) compared to their counterparts (DGERDHH- group). Mechanistically, the RGERDHH- group showed reduced lower esophageal sphincter basal pressure (P = 0.010) and EGJ contractile integral (P = 0.005). Notably, following a wet-swallow, the RGERDHH- group experienced the significant elevation in gastric pressure and TPG. Correlation analyses revealed weakly acidic reflux and bolus exposure were positively correlated with gastric pressure variation, and inversely correlated with lower esophageal sphincter basal pressure. Conclusions Transient gastric pressure elevation and compromised EGJ barrier function drive weakly acidic reflux and esophageal bolus exposure. This pressure gradient-barrier mismatch underpins the refractoriness of RGERD.

Objective To investigate the protective effect of Gynostemma pentaphyllum on memory of individuals rapidly ascending to high altitudes.Methods Twenty-one healthy subjects were randomly divided into a G.pentaphyllum food group(n=12)and a control group(n=9).The first group consumed G.pentaphyllum food for seven consecutive days while the control group received placebos.Both groups ascended from the plains to an altitude of 3600 m.Memory function was assessed using the matching memory and sequential memory tests of a cognitive evaluation system on day 1 and day 7 on the plains,and at 24 and 48 h after ascending to the high altitude.Scores of acute mountain sickness symptoms were also recorded.Results After 24 h of stay at the high altitude,the score of headache of the G.pentaphyllum food group was significantly lower than that of the control group(P＜0.05).Cognitive test results showed that the matching memory accuracy and sequential memory accuracy of the control group at 24 and 48 h were significantly lower than those on the plains(P＜0.05).In contrast,the G.pentaphyllum food group performed significantly better than the control group in these metrics(P＜0.05).Conclusion Regular consumption of G.pentaphyllum food can effectively alleviate headache symptoms in individuals rapidly ascending to high altitudes and mitigate the decline in working memory,short-term memory,and memory spans caused by acute hypoxic exposure.

On plateaus,the low-oxygen and low-pressure environment is likely to lead to cognitive impairments,negatively impacting individuals newly exposed to high altitudes.This paper reviews how high-altitude environments impair cognitive functions and explores protective strategies in terms of oxygen-enriched and pressurization technologies,neuroregulation techniques,and approaches to endogenous protection.It is recommended that future research focus on personalized cognitive protection and training,the construction of integrated protection systems based on multi-technology convergence,and the investigation of long-term effectiveness and sustainability.These efforts are expected to result in more comprehensive strategies for cognitive protection and enhancement in high-altitude operations.

BACKGROUND: Asthma is a common chronic inflammatory airway disease and intermittent hypoxia is increasingly recognized as a factor that may impact disease progression. The present study investigated whether intermittent hypoxia (IH) could aggravate asthma by promoting hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3)/interleukin (IL)-1β-dependent pyroptosis and the inflammatory response and further elucidated the underlying molecular mechanisms involved. METHODS: A total of 49 patients diagnosed with severe bronchial asthma and diagnosed by polysomnography were enrolled at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, between January 2022 and December 2022, and their general data and induced sputum were collected. BEAS-2B cells were treated with IL-13 and subjected to IH. An ovalbumin (OVA)-treated mouse model was also used to assess the effects of chronic intermittent hypoxia (CIH) on asthma. Pyroptosis, the inflammatory response, and related signalling pathways were assessed in vivo and in vitro . RESULTS: In this study, as the apnoea and hypopnea index (AHI) increased, the proportion of patients with uncontrolled asthma increased. The proportions of neutrophils and the levels of IL-6, IL-8, HIF-1α and NLRP3 in induced sputum were related to the AHI. NLRP3-mediated pyroptosis, which could be mediated by the HIF-1α signalling pathway, was activated in IL-13 plus IH-treated BEAS-2B cells and in the lungs of OVA/CIH mice. HIF-1α downregulation significantly reduced lung pyroptosis and ameliorated neutrophil inflammation by modulating the NLRP3/IL-1β pathway both in vitro and in vivo . Similarly, pretreatment with LW6, an inhibitor of HIF-1α, effectively blocked the generation of inflammatory cytokines in neutrophils. In addition, administration of the NLRP3 activator nigericin obviously increased lung neutrophil inflammation. CONCLUSIONS Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is a risk factor for asthma exacerbation. IH aggravates neutrophil inflammation in asthma via NLRP3/IL-1β-dependent pyroptosis mediated by the HIF-1α signalling pathway, which should be considered a potential therapeutic target for the treatment of asthma with OSAHS.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Asthma/metabolism* ; Animals ; Pyroptosis/physiology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Mice ; Signal Transduction/physiology* ; Male ; Hypoxia/metabolism* ; Female ; Interleukin-1beta/metabolism* ; Adult ; Inflammation/metabolism* ; Middle Aged ; Mice, Inbred C57BL

[Purpose]To analyze the incidence,mortality and trends of bladder cancer worldwide and in China in 2022.[Methods]The incidence and mortality data of bladder cancer were ob-tained from the GLOBOCAN 2022 database by geographical regions,sex,age,and human deve-lopment index(HDI).The crude incidence/mortality rate,age-standardized incidence/mortality rate(ASIR/ASMR)of bladder cancer were calculated.Simple linear regression and Spearman's correla-tion test were used to analyze the correlation between the HDI and ASIR/ASMR,the trends of in-cidence and projection in 2050 were estimated.[Results]In 2022,the estimated numbers of new cases and deaths of bladder cancer worldwide were 614 298 and 220 596,respectively,with ASIR and ASMR of 5.6/105 and 1.8/105.ASIR and ASMR in Europe were the highest,with 12.0/105 and 3.0/105,respectively.The ASIR and ASMR for males were higher than those for females,and increased rapidly after 40 years old of age.A positive correlation was observed between HDI levels and ASIR and ASMR of bladder cancer(r=0.670 and 0.434,respectively,both P＜0.001).It was projected that the global incidence and mortality of bladder cancer would reach 1.229 million and 0.494 million by 2050,and 0.176 million and 0.103 million for China,respectively.[Conclusion]The incidence and mortality of bladder cancer varies significantly among different region,sex,age and HDI levels worldwide.With the population aging and the industrialization accelerating,the risk of bladder cancer in China has been increasing.The prevention and control efforts for bladder cancer should be further strengthened.

BACKGROUND:Previous studies by the research team have shown that the neuroprotective effect of ginsenoside Rb1 on improving cerebral ischemia-reperfusion injury may be related to the Wnt/β-catenin signaling pathway,but the specific mechanism of action remains unclear.OBJECTIVE:To explore the molecular mechanism of ginsenoside Rb1 in alleviating cerebral ischemia-reperfusion injury in mice.METHODS:100 C57BL/6 mice were randomly divided into four groups.The sham operation group(n=25)did not undergo model establishment.In the cerebral ischemia-reperfusion injury group(n=25),the middle cerebral artery occlusion model was established by thread embolism.In the ginsenoside Rb1 group(n=25),the middle cerebral artery occlusion model was established by thread embolism and ginsenoside Rb1 was intraperitoneally injected every day for 3 days before the establishment.In ginsenoside Rb1+inhibitor group(n=25),the middle cerebral artery occlusion model was established by thread embolism and ginsenoside Rb1 and Wnt/β-catenin signaling pathway inhibitor XAV939 were intraperitoneally injected every day for 3 days before the establishment.Three days after modeling,Zea Longa score and balance beam test were used to evaluate the neurological deficits of mice.TTC staining was used to observe the volume of cerebral infarction.The dry-wet mass method was used to detect the degree of brain edema in mice.The activities of superoxide dismutase and glutathione peroxidase and the concentration of malondialdehyde in the parietal lobe of the ischemic side were detected by colorimetry.The co-expression of microglial marker Iba1 and inducible nitric oxide synthase(or arginase 1)was detected by immunofluorescence.The levels of aquaporin AQP4,inflammatory-related factors,and phosphorylation of Wnt/β-catenin pathway proteins glycogen synthase kinase 3β and β-catenin were detected by western blot assay.The mRNA expression of inflammatory factors was detected by q-PCR.RESULTS AND CONCLUSION:(1)Compared with cerebral ischemia-reperfusion injury group,the neurological deficit symptoms,cerebral infarction foci and brain tissue edema,oxidative stress and inflammatory response of the mice were alleviated;the number of M1 microglia(Iba1 and inducible nitric oxide synthase co-expressed)decreased;the number of M2 microglia(Iba1 and arginase 1 co-expressed)increased;the expression of phosphorylated glycogen synthase kinase 3β and phosphorylated β-catenin protein decreased in ginsenoside Rb1 group.Compared with ginsenoside Rb1 group,the neurological deficit symptoms,cerebral infarction foci and brain tissue edema,oxidative stress and inflammatory response of the mice were aggravated;the number of M1 microglia increased;the number of M2 microglia decreased;the expression of phosphorylated glycogen synthase kinase 3β and phosphorylated β-catenin protein increased in ginsenoside Rb1+inhibitor group.(2)The results indicate that ginsenoside Rb1 can regulate the polarization of microglia to M2 type and alleviate oxidative stress damage and inflammatory response after cerebral ischemia-reperfusion injury.Its mechanism may be related to the nuclear translocation of β-catenin mediated by the Wnt/β-catenin signaling pathway.

Cognitive decline is one of the most common adverse symptoms following acute high-altitude exposure(AHAE).MRI can reveal the structural and functional changes in brain caused by AHAE,thereby deeply understanding the specific mechanism of its cognitive decline,which is of great significance for early prevention and intervention.Research progresses on MRI assessment of cognitive function after AHAE and related intervention methods were reviewed in this article.