ObjectiveTo investigate the regulatory effects and underlying mechanisms of Liuhuang Zhike prescription （LHZK） on blood glucose in type 2 diabetic db/db mice based on the AMP-activated protein kinase/protein kinase B/glycogen synthase kinase-3β （AMPK/Akt/GSK-3β） signaling pathway. MethodsDb/db mice were used as the model animals， and db/m mice served as the blank control. Forty db/db mice were randomly divided into the model group， metformin group （0.14 g·kg^-1）， and low-， medium-， and high-dose （4.11， 8.21， 16.43 g·kg^-1） LHZK groups， with 8 mice in each group. The db/db mice in the metformin and LHZK groups were administered the corresponding drugs by gavage， while the blank control and model groups were given distilled water by gavage once daily for 8 consecutive weeks. Food intake， water consumption， body weight， and fasting blood glucose （FBG） were measured weekly. An automatic biochemical analyzer was used to determine glycated serum protein （GSP）， serum triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） levels. Hematoxylin-eosin （HE） staining was used to observe pathological morphological changes in the liver and pancreatic tissues. Oil red O staining was used to assess lipid accumulation in liver tissue. The anthrone colorimetric method was used to determine hepatic glycogen content. Real-time quantitative PCR （Real-time PCR） was used to detect the mRNA expression levels of insulin receptor substrate-1 （IRS-1）， Akt2， phosphoenolpyruvate carboxykinase （PEPCK）， and glucose-6-phosphatase （G6Pase） in liver tissue. Western blot was used to detect the protein expression of AMPKα， phosphorylated AMPKα （p-AMPKα）， GSK-3β， p-GSK-3β， glycogen synthase （GS）， and phosphorylated GS （p-GS） in liver tissue. ResultsCompared with the blank control group， the model group showed significantly increased food intake， water consumption， body weight， FBG， and GSP levels （P<0.01）. Pancreatic islets exhibited marked parenchymal cell hyperplasia and interstitial inflammatory cell infiltration. Liver tissue showed obvious steatosis， accompanied by a compensatory increase in hepatic glycogen content （P<0.01）. Hepatic G6Pase mRNA expression was increased， while IRS-1 and Akt2 mRNA expression levels were significantly decreased （P<0.01）. The p-AMPKα/AMPKα protein expression ratio showed a decreasing trend， whereas the p-GSK-3β/GSK-3β and p-GS/GS protein expression ratios were significantly increased （P<0.01）. Compared with the model group， food intake and water consumption showed decreasing trends in all treatment groups. Food intake was significantly reduced in the low- and high-dose LHZK groups and in the metformin group （P<0.05， P<0.01）， and water consumption was significantly reduced in the low-dose LHZK group and in the metformin group （P<0.05， P<0.01）. No statistically significant differences in body weight were observed among the LHZK groups， whereas body weight in the metformin group was significantly increased （P<0.05， P<0.01）. FBG showed a decreasing trend in all treatment groups， with significant decreases in the low-dose LHZK group and the metformin group （P<0.05， P<0.01）. GSP levels were significantly reduced in the low-dose LHZK group and in the metformin group （P<0.05， P<0.01）. Hepatic steatosis and pancreatic pathological injury were alleviated to varying degrees in all treatment groups. Hepatic glycogen content further increased in all treatment groups， with significant increases in the medium- and high-dose LHZK groups （P<0.05）. Real-time PCR results showed that all treatment groups downregulated the mRNA expression of G6Pase and PEPCK in the liver tissues of db/db mice， with significant downregulation of PEPCK mRNA in the low-dose LHZK and metformin groups （P<0.01）. Meanwhile， all treatment groups upregulated IRS-1 and Akt2 mRNA expression， with the most pronounced upregulation observed in the medium-dose LHZK group （P<0.01）. The p-AMPKα/AMPKα protein expression ratio was significantly increased in the low- and medium-dose LHZK groups （P<0.01）. The p-GSK-3β/GSK-3β protein expression ratio was significantly increased in all treatment groups （P<0.05， P<0.01）， whereas the p-GS/GS protein expression ratio was significantly decreased in all treatment groups （P<0.01）. ConclusionLHZK effectively reduces FBG and GSP levels in type 2 diabetic mice and improves hepatic steatosis and pancreatic islet pathological injury. Its hypoglycemic mechanism may be associated with regulation of the AMPK/Akt/GSK-3β signaling pathway and promotion of hepatic glycogen synthesis.

Risk prediction models for postoperative pulmonary complications (PPCs) can assist healthcare professionals in assessing the likelihood of PPCs occurring after surgery, thereby supporting rapid decision-making. This study evaluated the merits, limitations, and challenges of these models, focusing on model types, construction methods, performance, and clinical applications. The findings indicate that current risk prediction models for PPCs following lung cancer surgery demonstrate a certain level of predictive effectiveness. However, there are notable deficiencies in study design, clinical implementation, and reporting transparency. Future research should prioritize large-scale, prospective, multi-center studies that utilize multiomics approaches to ensure robust data for accurate predictions, ultimately facilitating clinical translation, adoption, and promotion.

GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

OBJECTIVE: To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases. METHODS: TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases. RESULTS: Increased TB risk was linked to PM _2.5, PM ₁₀, and rainfall, whereas NO ₂, SO ₂, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM _2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM ₁₀ ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO ₂ ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO ₂ ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM _2.5 on TB. CONCLUSION Exposure to PM _2.5, PM ₁₀, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology* ; Humans ; Air Pollutants/analysis* ; Tuberculosis/epidemiology* ; Incidence ; Meteorological Concepts ; Particulate Matter/adverse effects* ; Environmental Exposure ; Male ; Female ; Adult ; Air Pollution ; Middle Aged

[Purpose]To analyze the causes of death and potential life loss of malignant tumors in Sichuan Province from 2017 to 2022.[Methods]Data were collected from the death information registration and management system of China Disease Prevention and Control Information System,and national cause of death monitoring sites in Sichuan Province from 2017 to 2022.SAS 9.4 and Joinpoint 4.9.1.0 software were used to calculate crude cancer mortality rate,age-standardized mortality rate by Chinese standerd population(ASMRC),annual percentage change and potential years of life lost(PYLL)and potential years of life lost rate(PYLLR).[Results]From 2017 to 2022,the crude cancer mortality rate in Sichuan Province was 169.32/105,and the ASMRC was 111.26/105.The cancer mortality rate in the general population and that stratified by sex showed an increasing trend(all P＜0.05).The top 5 causes of cancer death were lung cancer,liver cancer,esophageal cancer,gastric cancer and colorectum cancer.The mortality rates of lung cancer,colorectum can-cer,female breast cancer,pancreatic cancer,lip,oral and pharyngeal malignancies all increased(all P＜0.05).From 2017 to 2022,the PYLL caused by malignant tumors in Sichuan Province was 1 520 175.00 person-year,the PYLLR was 13.98‰.[Conclusion]In Sichuan Province,the mortali-ty rate of malignant tumors is on the rise.Lung cancer and gastrointestinal cancers are the main malignancies causing life loss.Early diagnosis and treatment of key cancers should be strengthened to reduce cancer mortality.

Objective:To investigate the application value of multi-parameter ultrasound in the non-invasive assessment of renal fibrosis in patients with chronic kidney disease（CKD）.Methods:From December 2023 to April 2024，77 CKD patients（CKD group）and 30 healthy individuals（control group）from Renmin Hospital of Wuhan University were prospectively collected. The CKD group was further classified into mild（ n = 30），moderate（ n = 25）and severe（ n = 22）groups according to pathological assessment of renal fibrosis. Ultrasound parameters and clinical data of all patients were collected for group comparisons. Ultrasound parameters that showed statistically significant differences in univariate analysis were incorporated into a Logistic regression model to identify independent influencing factors. ROC curve was constructed，and the area under the curve（AUC）was calculated for statistical evaluation. Results:① The moderate and severe groups compared to control group，as well as the severe group compared to the mild and moderate groups，showed increased levels of SCr and BUN，and decreased level of eGFR，with statistically significant differences（all P < 0.05）. The kidney length and renal parenchymal thickness in the moderate group were smaller than those in the control group，while the kidney length，renal parenchymal thickness，and renal cortical thickness in the severe group were smaller than those in the control，mild，and moderate groups，with statistically significant differences among the groups（all P < 0.05）. The Vmax in the severe group was lower than those in the control，mild，and moderate groups，while the RI was higher than those in the control，mild，and moderate groups，with statistically significant differences（all P < 0.05）. ②In superb microvascular imaging，perfusion levels were predominantly grade 5 in the control and mild groups（83.3%，25/30；70.0%，21/30），grade 4 in the moderate group（48.0%，12/25），and grade 3 in the severe group（63.6%，14/22）. No significant differences were observed between the mild and control groups，or between the moderate and severe groups（all P>0.05），significant differences in blood flow perfusion were found between other groups（ P < 0.05）.③Shear wave elastography and super-resolution imaging revealed that mean of Young's modulus（Emean）in renal cortex increased progressively from the mild to the severe group，while microvascular density decreased. Except for Emean，which did not show significant differences between the moderate and severe groups（ P > 0.05），all other parameters showed significant differences between groups（ P < 0.05）. ④ROC curve analysis indicated that differentiating the control group from the mild group using Emean and microvascular density，the AUC was 0.769（95% CI = 0.631 - 0.872， P<0.001），with a sensitivity of 0.821 and specificity of 0.539. For the combined use of Emean，microvascular density，peak inter-arterial velocity，and resistance index for distinguishing mild from moderate-to-severe fibrosis resulted in an AUC of 0.902（95% CI = 0.843 - 0.972，P < 0.001），with a sensitivity of 0.967 and specificity of 0.755. These multi-parameter combined diagnostic approaches outperformed single ultrasound parameters. Conclusions:Multi-parameter ultrasound technology can display multidimensional renal changes in patients with CKD and effectively assess the degree of renal fibrosis. It is expected to become a non-invasive，highly sensitive tool for evaluating renal fibrosis in CKD.

Liver diseases have a high prevalence rate worldwide with relatively poor long-term clinical outcomes and have become one of the leading causes of disease burden and death around the world,which poses significant challenges to public health.Eosinophils(Eos)are a class of highly conserved multifunctional immune cells that play critical effector roles in allergic diseases.In recent years,an increasing amount of evidence has shown that Eos plays an important role in the pathogenesis of liver diseases,exerting a protective or harmful effect in different liver diseases,which has become a research hotspot in this field.This article elaborates on the role and potential mechanism of action of Eos in liver diseases,in order to provide a new perspective for in-depth research on the pathogenesis of liver diseases and lay the foundation for developing therapeutic strategies targeting Eos.

OBJECTIVE To standardize the strategies for prevention and control of Chikungunya(CHIK)in healthcare in-stitutions so as to reduce the risk of transmission in the institutions.METHODS A working group comprising the ex-perts in hospital infection control,infectious diseases,and microbiology systematically reviewed domestic and international evidence and current guidelines,integrated China's vector ecology and healthcare realities,conducted two rounds of Delphi to achieve expert consensus,and graded the evidence and recommendation strength using the Oxford Centre for Evidence Based Medicine system.RESULTS The consensus issues 18 actionable recommendations on triage,patient mosquito-proof isolation,integrated vector control,protection of susceptible populations,environmental cleaning and disinfection,specimen management,medical textile handling,and outbreak emergency response,with each statement assigned an evi-dence level and recommendation strength.CONCLUSION This consensus is for the first time in China to provide evidence-graded strategies for control of CHIK in healthcare institutions,offering work flow-oriented,implementable guidance for clinicians,laboratorians,and infection-control personnel under different risk scenarios and enhancing the comprehensive coping capacity of the healthcare institutions.

Objective:To develop an ultrasound multi-view fusion recognition model and evaluate its clinical value in diagnosing fetal conotruncal defects (CTD).Methods:This prospective study collected cardiac ultrasound images from fetuses at 20-32 weeks of gestation undergoing prenatal ultrasound at Dongguan Maternal and Child Health Hospital between September 2022 and May 2024. The case group comprised fetuses diagnosed with CTD, while controls with normal cardiac structures were collected at a 1∶2 ratio. Both groups were divided into modeling training and validation sets at a 3∶1 ratio. One optimal standard image each from the four-chamber view, left ventricular outflow tract view, right ventricular outflow tract view, and three vessels and trachea view was included per fetus. A deep learning-based multi-view fusion recognition model was developed to differentiate normal conotruncal anatomy from CTD. Model performance was validated against post-abortion pathology or postnatal echocardiography results. SAS software was used for statistical analysis to calculate the sensitivity and specificity of three fusion models (based on positivity in any two, three, or four views, and were designated as Fusion Model 1, Fusion Model 2, and Fusion Model 3, respectively), with the optimal model determined by the maximum Youden index. Senior, intermediate, and junior prenatal sonologists independently diagnosed cases in the validation set under blinding conditions. Their diagnostic results were compared with those of the optimal model. Paired Chi-square test (Cochran's Q test) was employed to compare the differences between the diagnostic accuracy rates of sonologists at different experience levels and the sensitivity of the optimal model, thereby analyzing the auxiliary diagnostic value of the multi-view fusion recognition model. Results:The study included 88 CTD cases, excluding six cases (non-CTD diagnosed by post-abortion pathology or postnatal echocardiography or poor image quality), divided into 60 training and 22 validation cases (12 tetralogy of Fallot, four double outlet right ventricle, three transposition of great arteries, three persistent truncus arteriosus). The control group included 176 cases, excluding 15 cases (other cardiac abnormalities confirmed postnatally or poor image quality after re-evaluation), divided into 120 training and 41 validation cases. The sensitivities of Fusion Model 1, Fusion Model 2, and Fusion Mudel 3 were 0.86, 0.64, and 0.27, while their specificities were 0.76, 0.95, and 1.00, respectively. Fusion Model 1 demonstrated the highest Youden index (0.62) and was selected as optimal. Its diagnostic sensitivity showed no significant difference from senior sonologists [86% vs. 91% (20/22), Bonferroni-corrected P>0.999], but was significantly higher than intermediate [55% (12/22), Bonferroni-corrected P=0.049] and junior sonologists [32% (7/22), Bonferroni-corrected P=0.003]. Conclusion:The deep learning multi-view fusion model achieved diagnostic performance comparable to senior sonologists, demonstrating potential value in assisting CTD diagnosis, training less experienced sonologists, and supporting research and education.