ObjectiveTo investigate the molecular mechanism by which the Bushen Kaixuan Tongluo prescription exerts a renal protective effect in mice with diabetic kidney disease （DKD） by regulating the cyclic adenosine monophosphate （cAMP） signaling pathway. MethodsThirty specific pathogen-free （SPF） male db/db mice were adaptively fed for three weeks. Mice with a random tail vein blood glucose level ≥ 11.1 mmol·L^-1 and urinary albumin-creatinine ratio （ACR） ≥ 30 mg·g^-1 were considered successfully modeled. The successfully modeled mice were randomly divided into five groups with six mice in each group： the model group， the low-， medium-， and high-dose Bushen Kaixuan Tongluo prescription groups （administered at doses of 7， 14， 28 g·kg^-1·d^-1 respectively）， and the positive drug irbesartan group （administered at a dose of 20 mg·kg^-1·d^-1）. Additionally， six db/m mice were selected as the blank group. Mice in each group were given intragastric administration of the Bushen Kaixuan Tongluo prescription at the corresponding concentrations， irbesartan， or an equal volume of pure water， and the intervention lasted for 12 weeks. During the experiment， the general conditions， body weight changes， and renal function indicators of the mice were dynamically monitored. After the intervention， a blood glucose meter was used to measure the fasting blood glucose （FBG） of the mice. An automatic biochemical analyzer was employed to detect the levels of serum creatinine （SCr）， blood urea nitrogen （BUN）， urinary microalbumin （uALB）， ACR， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglycerides （TG）， leptin （LEP）， glycosylated serum protein （GSP）， and insulin （INS） in the mice. Renal tissues were collected for hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson's trichrome staining to observe the histopathological changes. Immunohistochemistry （IHC） was used to detect the expressions of protein kinase A （PKA） and cAMP response element-binding protein （CREB） in the mice. Western blot analysis was performed to determine the expression levels of PKA， phosphorylated protein kinase A （p-PKA）， CREB， phosphorylated cAMP response element-binding protein （p-CREB）， and B-cell lymphoma-2 （Bcl-2） proteins in the renal tissues of the mice. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of PKA， CREB， and Bcl-2 in the renal tissues of the mice. ResultsCompared with the blank group， the mice in the model group showed listlessness， decreased activity， and a significant increase in body weight （P<0.01）. Biochemical indicators revealed that the levels of BUN， uALB， ACR， AST， ALT， TC， TG， FBG， LEP， GSP， and INS were significantly increased （P<0.01）， while SCr showed an increasing trend with no statistically significant difference. Compared with the model group， the mice in the Bushen Kaixuan Tongluo prescription intervention groups had improved general conditions and a decreasing trend in body weight. Biochemical indicators showed that the levels of BUN， uALB， ACR， TC， GSP， and INS were significantly decreased （P<0.05）， while SCr， AST， ALT， TG， and LEP showed a decreasing trend with no statistically significant difference. Renal histopathological analysis showed that the model group exhibited typical DKD pathological features such as thickening of the glomerular basement membrane， expansion of the mesangial matrix， and deposition of collagen fibers in the renal tubulointerstitium， and all treatment groups could alleviate the above pathological damages. The IHC results showed that compared with the blank group， the expression levels of p-PKA and p-CREB in the renal tissues of the model group were significantly decreased （P<0.01）. Compared with the model group， the expression level of p-PKA in the medium-dose Bushen Kaixuan Tongluo prescription group was significantly increased （P<0.01）， while the expression level of p-CREB showed an increasing trend with no statistically significant difference. Western blot results showed that compared with the blank group， the expression levels of p-PKA/PKA， p-CREB/CREB， and Bcl-2 in the model group were significantly decreased （P<0.05）. Compared with the model group， the expression levels of these proteins in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly increased （P<0.01）. Real-time PCR results showed that compared with the blank group， the mRNA expressions of PKA， CREB， and Bcl-2 in the model group were significantly down-regulated （P<0.05）. Compared with the model group， the mRNA expressions of these genes in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly up-regulated （P<0.05）. ConclusionThe Bushen Kaixuan Tongluo prescription can improve the liver and kidney functions of db/db mice， correct lipid metabolism disorders and glucose metabolism imbalance. Its renal protective effect is associated with up-regulating the cAMP signaling pathway to improve renal fibrosis and reduce the level of oxidative stress， thereby protecting renal function.

ObjectiveTo investigate the mechanisms by which Bushen Tongluo Jiangzhuo prescription improves renal fibrosis in rats with chronic kidney disease （CKD） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsSeventy specific pathogen-free （SPF） Sprague-Dawley （SD） rats were randomly divided into a control group （n=15） and a modeling group （n=55）. Rats in the modeling group were administered a 2.5% adenine suspension at a dose of 200 mg·kg^-1·d^-1 by gavage for 4 weeks to establish a CKD model. Successfully modeled rats were randomly divided into a model group， an irbesartan group （20.25 mg·kg^-1·d^-1）， and Bushen Tongluo Jiangzhuo prescription low-， medium-， and high-dose groups （5.82， 11.64， and 23.28 g·kg^-1·d^-1， respectively）， with 10 rats in each group. Each group was administered an equal volume of physiological saline， the corresponding concentration of irbesartan， or Bushen Tongluo Jiangzhuo prescription by gavage for 12 weeks. Body weight and renal function indices were dynamically monitored. Serum creatinine （SCr）， blood urea nitrogen （BUN）， urine albumin-to-creatinine ratio （ACR）， 24-hour urinary total protein （24 hUTP）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） levels were measured using an automatic biochemical analyzer. Renal histopathological changes were observed by hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry （IHC） was used to detect the expression of PI3K， Akt， phosphorylated Akt （p-Akt）， and mTOR in renal tissues. Western blot was performed to assess the protein expression of PI3K， p-Akt， Akt， phosphorylated mTOR （p-mTOR）， and mTOR in renal tissues. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to determine the mRNA expression levels of PI3K， Akt， and mTOR in renal tissues. ResultsCompared with the model group， rats in the irbesartan group and the low-， medium-， and high-dose Bushen Tongluo Jiangzhuo prescription groups showed significantly decreased levels of SCr， BUN， ACR， 24 hUTP， IL-1β， IL-6， and TNF-α （P<0.01）. AST levels were significantly increased （P<0.01）， while no significant difference was observed in ALT levels. Histopathological examination revealed that， compared with the model group， renal tubular epithelial cell edema and necrosis and Bowman's capsule dilation were alleviated， inflammatory cell infiltration was reduced， and interstitial and glomerular fibrosis was markedly improved in all treatment groups， with the most pronounced effect observed in the high-dose Bushen Tongluo Jiangzhuo prescription group. Real-time PCR results showed that mRNA expression levels of PI3K， Akt， and mTOR were significantly downregulated in the high-dose group （P<0.01）. IHC results demonstrated that PI3K and p-Akt expression levels in renal tissues were significantly decreased in the high-dose group （P<0.01）. Western blot analysis further confirmed that the expression levels of PI3K， p-Akt/Akt， and p-mTOR/mTOR were significantly reduced in the high-dose group （P<0.01）. ConclusionBushen Tongluo Jiangzhuo prescription improves renal function indices in CKD rats， reduces collagen deposition in renal tissues， and decreases serum inflammatory factor levels. Its protective effect on renal function may be achieved by activating autophagy through downregulation of the PI3K/Akt/mTOR signaling pathway， thereby alleviating renal fibrosis.

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

Objective To investigate the clinical relevance and diagnostic or prognostic value of ST3β-galactoside α-2, 3-sialyltransferase 1 (ST3GAL1) in glioma and to confirm its role in promoting malignant phenotypes. Methods Using data from The Cancer Genome Atlas (TCGA) database, we analyzed the correlation between ST3GAL1 expression levels in glioma and clinical parameters to evaluate its diagnostic and prognostic value. The impact of ST3GAL1 on malignant phenotypes of glioma cells-including proliferation, cell cycle progression, apoptosis, and invasion was further validated through ST3GAL1 knockdown experiments. Results The expression level of ST3GAL1 was significantly higher in glioma tissues compared to healthy brain tissues and showed a strong correlation with clinical characteristics of glioma patients. Survival analysis and receiver operating characteristic (ROC) curve demonstrated that ST3GAL1 could serve as a potential diagnostic and prognostic biomarker for glioma. Knockdown of ST3GAL1 suppressed proliferation, invasion, and migration capabilities of glioma cell lines, and induced G1-phase cell cycle arrest. Conclusion ST3GAL1 promotes malignant phenotypes in glioma and plays a critical role in its malignant progression, suggesting its potential as a biomarker for glioma diagnosis and prognosis.
Humans ; Sialyltransferases/metabolism* ; Glioma/diagnosis* ; Cell Proliferation/genetics* ; Cell Line, Tumor ; Brain Neoplasms/enzymology* ; beta-Galactoside alpha-2,3-Sialyltransferase ; Disease Progression ; Prognosis ; Cell Movement/genetics* ; Apoptosis/genetics* ; Male ; Female ; Gene Expression Regulation, Neoplastic ; Biomarkers, Tumor/metabolism* ; Middle Aged

Ovarian cancer poses a significant threat to women's health, necessitating effective therapeutic strategies. Emd-D, an emodin derivative, demonstrates enhanced pharmaceutical properties and bioavailability. In this study, Cell Counting Kit 8 (CCK8) assays and Ki-67 staining revealed dose-dependent inhibition of cell proliferation by Emd-D. Migration and invasion experiments confirmed its inhibitory effects on OVHM cells, while flow cytometry analysis demonstrated Emd-D-induced apoptosis. Mechanistic investigations elucidated that Emd-D functions as an inhibitor by directly binding to the glycolysis-related enzyme PFKFB4. This was corroborated by alterations in intracellular lactate and pyruvate levels, as well as glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) expression. PFKFB4 overexpression experiments further supported the dependence of Emd-D on PFKFB4-mediated glycolysis and SRC3/mTORC1 pathway-associated apoptosis. In vivo experiments exhibited reduced xenograft tumor sizes upon Emd-D treatment, accompanied by suppressed glycolysis and increased expression of Bax/Bcl-2 apoptotic proteins within the tumors. In conclusion, our findings demonstrate Emd-D's potential as an anti-ovarian cancer agent through inhibition of the PFKFB4-dependent glycolysis pathway and induction of apoptosis. These results provide a foundation for further exploration of Emd-D as a promising drug candidate for ovarian cancer treatment.
Female ; Humans ; Ovarian Neoplasms/physiopathology* ; Phosphofructokinase-2/genetics* ; Apoptosis/drug effects* ; Glycolysis/drug effects* ; Animals ; Cell Line, Tumor ; Mice ; Cell Proliferation/drug effects* ; Emodin/administration & dosage* ; Mice, Nude ; Mice, Inbred BALB C ; Hexokinase/metabolism* ; Xenograft Model Antitumor Assays

OBJECTIVE To explore the therapeutic effect of hearing aids on chronic subjective tinnitus with moderate to severe sensorineural hearing loss.METHODS Ninety-five patients were enrolled in this prospective study.Pure tone audiometry,acoustic immittance and tinnitus were performed before hearing aids were worn.The tinnitus handicap inventory(THI),hospital anxiety and depression scale(HADS)and visual analogue scale(VAS)were completed before and after 3 and 6 months after wearing the device.SPSS 22 was used for statistical analysis.RESULTS After 3 months and 6 months of hearing aid wearing,THI,HADS and VAS scores of the patients were significantly decreased,and there were significant differences before and after wearing the hearing aid(P<0.05).The THI score of patients in the catastrophic group decreased the most,reaching 44.5 points.Age,gender,duration of tinnitus,the side of tinnitus and the degree of hearing loss have no effect on the treatment effect of hearing aids.CONCLUSION Hearing aids can not only improve the hearing of patients,but also reduce tinnitus,relieve anxiety and depression.

Objective To explore the correlation of body mass index,urinary protein and tumor necrosis factor-like weak inducer of apoptosis(sTWEAK)during pregnancy with the severity of preeclampsia and pregnancy outcome.Methods A total of 63 patients with preeclampsia who were examined in Xingtai People's Hospital from April 2022 to April 2023 were enrolled in the study,33 patients with mild preeclampsia were included in the mild group and 30 patients with severe preeclampsia were included in the severe group.Physi-cal characteristics,urinary protein and sTWEAK levels between the groups were recorded,and the patients were followed up to explore the correlation with pregnancy outcome.Results The systolic and diastolic blood pressure of patients in the mild group were lower than those in the severe group,and the plasma albumin was higher than that in the severe group(P＜0.05).There was no statistically significant difference in pre preg-nancy weight and pre pregnancy body mass index between the mild and severe groups of patients(P＞0.05).The delivery weight and weight gain during pregnancy in the mild group were lower than those in the severe group(P＜0.05).The 24-hour urinary protein quantification in the mild group was lower than that in the se-vere group,and the sTWEAK expression level was higher than that in the severe group(P＜0.05).The pre pregnancy weight,pre pregnancy body mass index,delivery weight,and weight gain during pregnancy in the good pregnancy outcome group were all lower than those in the adverse pregnancy outcome group(P＜0.05).The 24-hour urinary protein quantification in the good pregnancy outcome group was lower than that in the adverse pregnancy outcome group,and the sTWEAK expression level was higher than that in the adverse pregnancy outcome group(P＜0.05).Receiver operating characteristic(ROC)curve analysis revealed that the area under the curve(AUC)of pre pregnancy body mass index,pre pregnancy weight,delivery weight,gestational weight gain,24-hour urinary protein quantification,and sTWEAK expression levels for predicting adverse pregnancy outcomes in patients were 0.906,0.690,0.919,0.664,0.908,and 0.793,respectively.The AUC for predicting adverse pregnancy outcomes in patients by combining pre pregnancy body mass index,de-livery weight,24-hour urinary protein quantification,and sTWEAK expression level was 0.932.Conclusion Body mass index,urinary protein and sTWEAK levels during pregnancy are closely associated with the severity of pre-eclampsia and pregnancy outcomes,and these indicators may help identify high-risk pregnant women early and take appropriate interventions to improve pregnancy outcomes.

Objective To investigate the serum interleukin-17A(IL-17A)and chemokine CXC motif ligand 13(CXCL13)levels in children with cough variant asthma and their clinical significance.Methods A total of 108 children with cough variant asthma admitted to Meihe Maternity Hospital from November 2021 to Febru-ary 2023 were selected as the study group,and 86 healthy children who underwent physical examinations dur-ing the same period were selected as the control group.The levels of serum IL-17A and CXCL13 in the two groups were detected by enzyme-linked immunosorbent assay.Multivariate Logistic regression was used to an-alyze the factors influencing the occurrence of cough variant asthma.Receiver operating characteristic(ROC)curve was plotted to analyze the diagnostic value of serum IL-17A and CXCL13 expressions for cough variant asthma.Results The levels of serum IL-17A and CXCL13 in the study group were both higher than those in the control group(P＜0.05).The levels of serum IL-17A and CXCL13 in children with cough variant asthma were negatively correlated with forced vital capacity(FVC),forced expiratory volume in one second(FEV1),maximal expiratory flow rate(PEF),and FEV1/FVC and basal respiratory conductivity(Grs cont),while positively correlated with initial resistance value(Rrs cont).Multivariate Logistic regression analysis indicated that FVC,FEV1,PEF,FEV1/FVC,and Grs cont were protective factors influencing the occurrence of cough variant asthma(P＜0.05).However,Rrs cont,IL-17A and CXCL13 were risk factors affecting the occurrence of cough variant asthma(P＜0.05).The area under the curve(AUC)of serum IL-17A and CXCL13 levels for diagnosing cough variant asthma were 0.920 and 0.867,respectively.The AUC of the combined diagnosis of the two was 0.937,which was significantly greater than that of the diagnosis of CXCL1 alone(Z=2.194,P=0.028).Conclusion The levels of serum IL-17A and CXCL13 in children with cough variant asthma are upreg-ulated,and both are related to the lung function and airway responsiveness of children with cough variant asthma.The combined detection of serum IL-17A and CXCL13 levels has a high diagnostic value for cough variant asthma.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

OBJECTIVE T o establish the automatic diagnosis system for varicella pneumonia based on multi-slice spiral computed tomography(MSCT)and verify its application value.METHODS The clinical data were collected from 295 patients with varicella who were treated in the hospital from Jan.2016 to Mar.2023 and assigned as the training set,the pulmonary imaging findings were acquired from the MSCT chest scanning.The automatic diagno-sis system for varicella pneumonia was established based on MSCT with the use of convolutional neural network technology.Totally 279 patients with varicella who were treated during the same period were chosen as the valida-tion set,the result of comprehensive diagnosis was set as gold standard,and the efficiency of the above system in diagnosis of varicella pneumonia was observed.RESULTS Totally 279 patients with varicella were included in the validation group,243 of whom had varicella pneumonia,and 36 had simple varicella infection.The sensitivity of the automatic diagnosis system established based on MSCT was 97.53％in diagnosis of the varicella pneumonia of the validation group,with the specificity 91.67％,the accuracy 96.77％,respectively higher than 93.83％,83.33％and 92.47％of MSCT,and it was highly consistent with the gold standard(Kappa=0.919,P＜0.001);there was consistency between MSCT and the gold standards(Kappa=0.675,P＜0.001).CONCLUSION The au-tomatic diagnosis system for varicella pneumonia established based MSCT can raise the sensitivity,specificity and accuracy in diagnosis of varicella pneumonia and have the advantages of automation and convenience,and serve as a new tool for clinical diagnosis of varicella pneumonia.