OBJECTIVE To investigate the improvement effect and potential mechanism of Qingxue xiaozhi jiangtang formula on insulin resistance （IR） in type 2 diabetes mellitus （T2DM） rats. METHODS T2DM rat model was established by intraperitoneal injection of 30 mg/kg streptozotocin combined with high-fat and high-sugar diet. The rats were randomly divided into normal control group， model group， Qingxue xiaozhi jiangtang formula low-dose and high-dose groups （6.525， 13.05 g/kg， calculated by raw material） and metformin group （positive control， 0.18 g/kg）， with 8 rats in each group. Administration groups were given relevant medicine intragastrically； normal control group and model group were given constant volume of normal saline intragastrically， once a day， for consecutive 6 weeks. Body mass and fasting blood glucose （FBG） were determined， and oral glucose tolerance test was conducted. Serum fasting insulin （FINS） level was measured to calculate the insulin resistance index （HOMA-IR） and insulin sensitivity index （ISI）. Additionally， the level of serum lipids， liver function， oxidative stress indicators and inflammatory factors were assessed. The phosphorylation levels of kinase R-like endoplasmic reticulum kinase （PERK） and forkhead box O1 （FOXO1） protein in liver tissue of rats were determined. RESULTS Compared with model group， the body weight， ISI， the levels of high-density lipoprotein cholesterol and superoxide dismutase were increased significantly in Qingxue xiaozhi jiangtang formula high-dose group and metformin group （P＜0.05）； FBG， blood glucose level at 120 minutes of glucose loading， area under the curve of glucose， FINS， HOMA-IR， low-density lipoprotein cholesterol， total cholesterol， triglyceride， alanine transaminase， aspartate transaminase， alkaline phosphatase， malondialdehyde， interleukin-6， tumor necrosis factor-α， and C-reactive protein levels were significantly reduced （P＜ Δ0.05）； the pathological damage of liver tissue had significantlyimproved， and the phosphorylation levels of PERK and FOXO1 proteins in liver tissue were significantly decreased （P＜0.05）. CONCLUSIONS Qingxue xiaozhi jiangtang formula can regulate glucose and lipid metabolism， inflammation factor and oxidative stress levels， and alleviate insulin resistance in T2DM rats. Its mechanism of action may be related to the inhibition of the PERK/FOXO1 signaling pathway.

Sensorineural hearing loss is one of the most common sensory disorders. In recent years, auditory neuropathy spectrum disorders caused by mutations in the OTOF gene have garnered significant attention worldwide, marking it as the first deafness gene with breakthroughs in gene therapy. Most patients with OTOF gene mutations present with stable, congenital, or prelingual onset of hearing loss, which can range from severe to profound and even complete hearing loss. However, a minority of patients may exhibit mild to moderate progressive hearing loss or temperature-sensitive hearing loss. This review further explores the genotype-phenotype relationship of the OTOF gene based on reported cases in China and abroad. Additionally, we analyze the characteristics of the natural history of OTOF gene mutations within the Chinese population. This study aims to provide a reference for the clinical diagnosis, evaluation, and treatment of hearing loss associated with OTOF gene mutations.
Humans ; Mutation ; Phenotype ; Genotype ; Hearing Loss, Sensorineural/genetics* ; Membrane Proteins/genetics*

Detrusor-sphincter dyssynergia (DSD) is a lower urinary tract dysfunction syndrome caused by disorders of the neural regulatory pathways for micturition. Its core feature is that the urethral sphincter fails to relax coordinately during detrusor contraction; instead, the persistent abnormal contraction leads to a series of severe complications such as dysuria, elevated intravesical pressure, and upper urinary tract damage.DSD is common in patients with central nervous system lesions, such as spinal cord injury and multiple sclerosis. This paper systematically reviews the latest research progress on the neural mechanisms of DSD, including ① loss of central regulation and excessive excitation of the spinal cord center, i.e., the loss of supraspinal inhibition leading to sacral spinal reflex hyperactivity; ② imbalance of key neurotransmitters and receptors, involving excessive glutamatergic excitation, weakened gamma-aminobutyric acid ergic/glycinergic inhibition, and the involvement of purinergic and endocannabinoid systems; ③ neuroimmunity and inflammatory response, where the activation of microglia and astrocytes after spinal cord injury releases pro-inflammatory factors, exacerbating neuronal excitability and circuit remodeling; ④ peripheral nerve and gut-bladder axis mechanisms, where sphincter structural remodeling and the gut microbiota-neuroimmunity crosstalk form a vicious cycle. The paper focuses on the sacral Onuf's nucleus as the“core hub”and key therapeutic target of DSD, discussing the central role of its dysfunction in the occurrence of synergistic disorders. In terms of therapeutic strategies, the paper summarizes existing traditional methods, such as drugs, botulinum toxin injection and neuromodulation, and envisions the cutting-edge directions of targeted intervention, such as precise strategies including gene therapy and neurotrophic support, as well as the challenges faced in clinical translation. Finally, the paper discusses the application prospects of precision medicine and artificial intelligence in the diagnosis and treatment of DSD, including precise classification based on multi-omics data, artificial intelligence-assisted recommendation of individualized treatment plans, and the development of dynamic closed-loop regulation systems. This paper aims to provide a theoretical basis and research direction for in-depth understanding of the neural mechanisms of DSD, and to promote the precise diagnosis, treatment and neural function remodeling.

The aim of this experiment is to investigate the mechanism of liver cell damage induced by nonylphenol(NP).After establishing an in vitro model of NP induced BRL-3A liver cell injury,changes of oxidative damage markers were evaluated,Fe2+content was determined,the ultrastruc-ture of BRL-3A was observed,and the expression level of iron death marker proteins were deter-mined.The results showed that NP could significantly increase ROS and MDA in BRL-3A cells(P＜0.05);the GSH content,GSH Px activity,and SOD activity were significantly reduced(P＜0.05);the Fe2+content significantly increased(P＜0.05)and showed a dose-dependent effect;the mitochondrial volume of BRL-3A cells significantly decreases,the mitochondrial cristae break or e-ven disappear,and some mitochondria show vacuolization;the expression levels of iron homeostasis related proteins TFR1 and FTH1 were significantly reduced(P＜0.05).The results indicate that ferroptosis is involved in the mechanism of NP induced liver cell damage,which bene-fits for further exploration of NP pathogenesis.

Objective:To explore the association between frailty index (FI) and the risk for cardiovascular disease (CVD) in adults in Inner Mongolia Autonomous Region, and provide new evidence for the prevention of CVD in adults in Inner Mongolia Autonomous Region.Methods:The FI was constructed by using the data from a prospective cohort with a sample size of 25 055 individuals in 6 years of follow-up, and the prevalence of frailty in adults in Inner Mongolia Autonomous Region was described by the FI, and Cox proportional hazard regression model was used to evaluate the association between the FI and the incidence of CVD in adults in Inner Mongolia Autonomous Region.Results:The FI of the study population was 0.24±0.09. The population in the pre-frail (FI: 0.21-0.27) and frail (FI≥0.28) phases had increased risk for CVD compared to non-frail (FI≤0.20) population [pre-frail: hazard ratio ( HR)=1.232, 95% CI: 1.127-1.347; frail phase: HR=1.418, 95% CI:1.299-1.548]. For every 0.10 increase in FI, the risk for cardiovascular disease increased by 20.3% ( HR=1.203,95% CI:1.156-1.252). Conclusions:In this study, we constructed a FI, which can suggest the risk for CVD. As the increase of frailty degree, the risk for CVD increases.

Objective To investigate the regulatory mechanism of apurnic/apyrimidinic endonuclease 1(APE1)in the transformation of chronic intestinal inflammation to colitis-associated colorectal cancer(CAC).Methods C64S mutant(APE1C64S)mice and APE1 wild type(APE1WT)mice were randomly divided into experimental group and control group.In vivo CAC model was established by azoxymethane(AOM)and dextran sulfate sodium salt(DSS)solution.Immunohistochemistry(IHC)and multiple IHC(mIHC)assays were used to observe the expression of APE1 and immune cell infiltration in colon tissues of each group.A mouse colon cancer cell line MC38 with stable knockdown of APE1 was constructed by lentivirus transfection,and subcutaneous tumor bearing experiments were performed in APE1WT and APE1C64S mice to confirm that tumor cell-derived APE1 caused immunosuppressive tumor microenvironment.The expression of APE1 and CXCL1[chemokine(C-X-C motif)ligand 1]and the infiltration of immune cells in tumor-bearing specimens were analyzed by IHC and mIHC assays.The tumor specimens of a 28-year-old female patient with CAC from Army Medical Center of PLA were analyzed for the expression of APE1 and CXCL1 and the infiltration of immune cells in the tumor and adjacent inflammatory tissues by IHC and mIHC assays.Results Compared with the control group and APE1WT erperimental group,APE1C64S erperimental group had significantly reduced disease activity index and tumor formation,polymorphonuclear myeloid-derived suppressor cells(PMN-MDSCs)infiltration,and CD4+and CD8+T cells(P＜0.05).No significant differences were observed in tumor growth and immune cells between APE1WT and APE 1C64S mice bearing subcutaneous tumors.However,in the tumor-bearing experiment using tumor cells with knockdown of APE1,the tumor growth was significantly lower and the number of infiltrated PMN-MDSCs was reduced,while those of CD4+and CD8+T cells were significantly increased(P＜0.05).Furthermore,high expression of APE1 and increased infiltration of PMN-MDSCs were found in the tumor tissues of the young CAC patient,and CD8+T cells were significantly reduced in the tumor tissues compared with the inflammatory tissues(P＜0.05).Conclusion APE1-redox in tumor cells can promote the infiltration of PMN-MDSCs and reduce the number of T cells,thereby forming an immunosuppressive tumor microenvironment and mediating the occurrence and development of CAC.

Objective To explore the effect of deep learning image reconstruction(DLIR)algorithm combined with"double low"[low voltage(kV)and low contrast agent dosage]technique on the image quality of coronary computed tomography angiography(CCTA)in overweight patients compared with adaptive statistical iterative reconstruction(ASIR-V)and filtered back projection(FBP).Methods Fifty-two patients with body mass index(BMI)between 25.1 kg/m2and 28 kg/m2 who underwent CCTA scanning were prospectively selected,all of whom scanned on a GE Revolution APEX-CT with a tube voltage of 80 kV,a smart mA(500-1 300 mA),a noise index of 30,and a contrast dosage of 0.5 mL/kg;four groups of images were reconstructed for each patient,FBP,50％ASIR-V,DLIR-M,and DLIR-H.The CT and SD values of the aorta(AO)root,the proximal segment of the right coronary artery(RCA),the left circumflex(LCX),the left anterior descending branch(LAD)and the pericardial fat were measured,and the signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were calculated.Two doctors experienced in the diagnosis of cardiovascular disease were selected to subjectively score the reconstructed images using a double-blind method.The SD value,SNR value,CNR value and subjective scores of images in the four groups were compared.Results In the objective image quality evaluation,there were statistically significant differences in SD value,SNR value and CNR value of reconstructed images in the four groups(P＜0.05).As the four groups of reconstruction algorithms FBP,50％ASIR-V,DLIR-M,and DLIR-H were changed sequentially,the image SD value gradually decreased,the SNR value and CNR value gradually increased,and the DLIR-H group had the lowest SD value and the highest SNR and CNR values.In the subjective image quality evaluation,the subjective scores of the two doctors had good consistency(Kappa value=0.900),and the difference between them was statistically significant(P＜0.001).The subjective scores of DLIR-M and DLIR-H groups were higher.Conclusion DLIR algorithm combined with"double-low"technique can significantly improve the CCTA image quality of overweight patients,which is better than 50％ASIR-V and FBP.

Objective To explore the application value of deep learning image reconstruction(DLIR)with coronary computed tomography angiography(CCTA)using 100 kV.Methods Sixty patients who underwent CCTA were selected.The tube voltage of 100 kV,noise index of 24 were applied.The 60％adaptive statistical iterative reconstruction-Veo(ASIR-V)and DLIR-low(DLIR-L),DLIR-medium(DLIR-M)and DLIR-high(DL1R-H)were reconstructed.The CT values and standard deviation(SD)values of the aortic root,left main artery,left anterior descending artery,left circumflex artery,right coronary artery and pericardial fat of the four groups of images were measured,and the signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were calculated.Two radiologists with five-year working experience subjectively evaluated the image quality using a five-point method double-blindly.Results The differences in noise(SD values),SNR values and CNR values among the four groups of images were statistically significant(P＜0.001).As the reconstruction gradually changed of 60％ASIR-V,DLIR-L,DLIR-M and DLIR-H,the coronary SD values gradually decreased,while the SNR values and CNR values gradually increased,among which the DLIR-H had the lowest SD values and the highest SNR values and CNR values.The subjective scores of the four groups of images by two radiologists showed good consistency(Kappa value=0.929,P＜0.001),and the subjective scores were all above 3 points which met the clinical diagnosis criteria.The subjective scores of DLIR-L,DLIR-M and DLIR-H were significantly higher than those of 60％ASIR-V(P＜0.001),with the DLIR-H achieving the highest subjective score.Conclusion DLIR can significantly reduce image SD value and improve image quality of CCTA with 100 kV,among which DLIR-H has the best effect on improving CCTA image quality.

Objective:Clarify the correlation between the Centralized Drug Volume-based Purchasing Policy,changes in physical&mental health status,and health inequalities among the older adults,as well as exploring whether this correlation differs between urban and rural areas so as to determine the role played by the total cost of healthcare.Methods:Based on CFPS 2018 and 2020,DID and PSM-DID were used to verify the impact of the Centralized Drug Volume-based Purchasing Policy on physical&mental health status and health inequalities of the elderly in urban and rural China.Three-step method and Sobel test were used to verify the mediating effect of total medical costs.Results:The pilot effect of the Centralized Drug Volume-based Purchasing Policy was first realized among the urban elderly population,promoting their physical and mental health through the intermediary mechanism of reducing the total medical costs,but for the time being did not show a significant correlation with health inequalities within this group.Among the rural elderly population,none of the three dependent variables was significant(P＞0.1).Conclusion:The underlying logic of the Centralized Drug Volume-based Purchasing Policy is right,but its future reform should focus on the rural elderly group,and consider the fairness of the effect within the group and between urban and rural areas,so as to improve the health level of the whole society in the longer term.

Objective:Clarify the correlation between the Centralized Drug Volume-based Purchasing Policy,changes in physical&mental health status,and health inequalities among the older adults,as well as exploring whether this correlation differs between urban and rural areas so as to determine the role played by the total cost of healthcare.Methods:Based on CFPS 2018 and 2020,DID and PSM-DID were used to verify the impact of the Centralized Drug Volume-based Purchasing Policy on physical&mental health status and health inequalities of the elderly in urban and rural China.Three-step method and Sobel test were used to verify the mediating effect of total medical costs.Results:The pilot effect of the Centralized Drug Volume-based Purchasing Policy was first realized among the urban elderly population,promoting their physical and mental health through the intermediary mechanism of reducing the total medical costs,but for the time being did not show a significant correlation with health inequalities within this group.Among the rural elderly population,none of the three dependent variables was significant(P＞0.1).Conclusion:The underlying logic of the Centralized Drug Volume-based Purchasing Policy is right,but its future reform should focus on the rural elderly group,and consider the fairness of the effect within the group and between urban and rural areas,so as to improve the health level of the whole society in the longer term.