Objective To investigate the impact of the interaction of fasting blood glucose(FBG)and serum uric acid(SUA)on diabetic retinopathy(DR).Methods A total of 306 diabetes mellitus(DM)patients diagnosed and re-ceived comprehensive ophthalmic examination in the First Affiliated Hospital of Gannan Medical University from January 2019 to January 2021 were selected.According to the presence or absence of DR,these patients were divided into the DR group(178 patients)and the non-DR(NDR)group(128 patients).The general clinical data of patients in the two groups were compared.The least absolute shrinkage and selection operator(LASSO)regression method and multivariate Logistic regression analysis were used to screen the independent influencing factors of DR in DM patients,and the odds ratio of risk factors was calculated.The sensitivity analysis of the results was performed using the E-value method.The interaction of FBG and SUA on DR in DM patients was analyzed by an additive interaction model.The Nomogram model to predict DR in DM patients was constructed and verified internally.The receiver operating characteristic curve(ROC)was used to evalu-ate the effects of FBG,SUA and both FBG and SUA on DR in DM patients.Results Compared with the NDR group,the course of DM in the DR group was significantly longer,the proportion of patients with history of oral medication was signif-icantly lower,the proportion of patients with history of insulin therapy was significantly higher,and the levels of total cho-lesterol,triglyceride,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,blood urea nitrogen,serum creatinine,SUA and FBG were significantly higher(all P＜0.05).The history of insulin therapy,course of DM≥9.66 years,TG≥2.07 mmol·L-1,SUA ≥ 297.73 μmol·L-1 and FBG ≥8.92 mmol·L-1 were the risk factors for DR in DM pa-tients,while the history of oral medication was the protective factor for DR in DM patients.The Nomogram model based on the above independent risk factors was accurate in predicting the occurrence of DR in DM patients.SUA and FBG had inter-active effects on DR in DM patients.The value of SUA-FBG interaction in the diagnosis of DR was greater than that of both alone.Conclusion SUA≥ 297.73 μmol·L-1 and FBG ≥8.92 mmol·L-1 are the risk factors for DR in DM patients.The value of interaction of FBG and SUA in the diagnosis of DM accompanied by DR is greater than that of both alone.

Objective To investigate the effects of calcitriol intervention on PI3K/AKT signaling pathway and wound healing in rats with diabetic foot ulcer(DFU).Methods Thirty-two male SD rats were divided into normal control(Con)group,DFU group,calcitriol low dose(L)group and calcitriol high dose(H)group.A circular wound of 5 mm in diameter and deep to the fascia was made on the dorsum of the left foot of rats in each group.HE staining was used to evaluate the histopathological changes of the wounds.Immunohistochemical method was selected to compare the distribution of CD34-positive cells and the expression of p-PI3K and p-AKT in traumatic tissues of each group.ELISA was adopted in the detection of serum IL-6,IFN-γ,TNF-α and IL-7.RT-PCR was used to detect the mRNA expression of PI3K and AKT in each group,and western blot was used to detect the protein expression of PI3K,p-PI3K,AKT,p-AKT and VEGF.Results Compared with Con group,the expressions of IL-6,IFN-γ,TNF-α,IL-7,CD34,PI3K mRNA,AKT mRNA,p-AKT protein,p-PI3K protein,p-PI3K/PI3K,p-AKT/AKT increased,while PI3K protein expression decreased in DFU,L and H groups(P<0.05),VEGF and AKT protein expression decreased in DFV and L groups(P<0.05).Compared with DFU group,the expressions of VEGF,AKT and PI3K protein increased(P<0.05),while the expressions of p-PI3K/PI3K,p-AKT/AKT decreased in L and H groups(P<0.05),IL-6 decreased in L group(P<0.05),and CD34 expression increased in H group(P<0.05),while IL-6,IFN-γ,TNF-α and IL-7,PI3K mRNA,AKT mRNA,p-AKT protein and p-PI3K protein expression decreased(P<0.05).Compared with L group,the expressions of CD34,VEGF,AKT and PI3K protein increased(P<0.05),while IL-6,PI3K mRNA,AKT mRNA,p-AKT protein,p-PI3K protein,p-PI3K/PI3K and p-AKT/AKT decreased in H group(P<0.05).Conclusions Calcitriol intervention may reduce the activity of the PI3K/AKT signaling pathway,inhibit inflammation,promote neovascularization,and facilitate wound healing in rats with DFU.

The well-known insulin-like growth factor 1 (IGF1)/IGF-1 receptor (IGF-1R) signaling pathway is overexpressed in many tumors, and is thus an attractive target for cancer treatment. However, results have often been disappointing due to crosstalk with other signals. Here, we report that IGF-1R signaling stimulates the growth of hepatocellular carcinoma (HCC) cells through the translocation of IGF-1R into the ER to enhance sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2) activity. In response to ligand binding, IGF-1Rβ is translocated into the ER by β-arrestin2 (β-arr2). Mass spectrometry analysis identified SERCA2 as a target of ER IGF-1Rβ. SERCA2 activity is heavily dependent on the increase in ER IGF-1Rβ levels. ER IGF-1Rβ phosphorylates SERCA2 on Tyr⁹⁹⁰ to enhance its activity. Mutation of SERCA2-Tyr⁹⁹⁰ disrupted the interaction of ER IGF-1Rβ with SERCA2, and therefore ER IGF-1Rβ failed to promote SERCA2 activity. The enhancement of SERCA2 activity triggered Ca²⁺_ER perturbation, leading to an increase in autophagy. Thapsigargin blocked the interaction between SERCA2 and ER IGF-1Rβ and therefore SERCA2 activity, resulting in inhibition of HCC growth. In conclusion, the translocation of IGF-1R into the ER triggers Ca²⁺_ER perturbation by enhancing SERCA2 activity through phosphorylating Tyr⁹⁹⁰ in HCC.

Objective:To analyze the costs and effectiveness of five common screening modes and genetic screening for thalassemia in China in order to find the optimal way and provide evidence for the implementation of thalassemia prevention and control projects in Hunan Province.Methods:From June 2020 to April 2021, 12 971 couples from 14 cities and autonomous prefectures in Hunan Province were selected as the study population. The diagnosis of thalassemia was based on the results of genetic testing. Results of routine blood test and hemoglobin electrophoresis were collected and analyzed. The efficacy of five screening modes, at the cut-off value of <80 fl or 82 fl for the mean corpuscular volume (MCV), was analyzed by positive predictive value, negative predictive value, Jorden index and cost-effectiveness ratio. Sensitivity analysis was used to assess the feasibility of genetic screening at different costs after fixing the costs of routine blood and hemoglobin electrophoresis. The five thalassemia screening models are as follows: Mode 1: The woman had a blood routine test first. If the result was positive, the spouse required a blood routine test. If both results were positive, a thalassemia gene test should be offered to the couple. Mode 2: Both husband and wife were screened by blood routine and hemoglobin electrophoresis. If one or both of them were positive, both would be tested for thalassemia gene. Mode 3: The couple received blood routine tests initially. If either was positive, both should receive hemoglobin electrophoresis testing. If either was positive, both parties will conduct thalassemia gene testing. Mode 4: The woman was screened by blood routine and hemoglobin electrophoresis. If any one of them was positive, the woman would be tested for thalassemia gene. If the gene test result was positive, the spouse should receive thalassemia gene. Mode 5: Both spouses conducted a blood routine test. If either was positive, both would conduct hemoglobin electrophoresis test. If both were positive, both spouses should receive thalassemia gene testing. Gene testing mode: The woman would be tested for thalassemia, and her spouse would have thalassemia test too if her result was positive.Results:When using MCV<80 fl as the cut-off for diagnosing thalassemia, the Youden indices of the five prenatal screening modes in Hunan Province were 0.551, 0.639, 0.898, 0.555 and 0.356, while when using MCV<82 fl as the cut-off, the Youden indices were 0.549, 0.629, 0.851, 0.548 and 0.356. When the MCV cut-off value was <80 fl, the missed diagnosis rates of the five screening modes were 44.44%, 0.00, 0.00, 18.52% and 62.96%, and the cost-effectiveness ratios were 21 709, 250 939, 76 870, 138 463 and 92 860 yuan (RMB)/couple, respectively. When the price of genetic testing was lower than 55 yuan (RMB), the cost-effectiveness ratio of genetic screening was lower than that of Mode 3.Conclusions:MCV<80 fl can be considered as the positive criteria in blood routine screening for thalassemia in Hunan Province, and the cost-effectiveness ratio of Mode 3 (the couple received blood routine tests initially. If either was positive, both should receive hemoglobin electrophoresis testing. If either was positive, both parties will conduct thalassemia gene testing) is the best. Genetic screening has certain advantages with the decreasing price.

Insulin-like growth factor-1 receptor (IGF-1R) has been made an attractive anticancer target due to its overexpression in cancers. However, targeting it has often produced the disappointing results as the role played by cross talk with numerous downstream signalings. Here, we report a disobliging IGF-1R signaling which promotes growth of cancer through triggering the E3 ubiquitin ligase MEX3A-mediated degradation of RIG-I. The active β-arrestin-2 scaffolds this disobliging signaling to talk with MEX3A. In response to ligands, IGF-1Rβ activated the basal βarr2 into its active state by phosphorylating the interdomain domain on Tyr64 and Tyr250, opening the middle loop (Leu130‒Cys141) to the RING domain of MEX3A through the conformational changes of βarr2. The models of βarr2/IGF-1Rβ and βarr2/MEX3A could interpret the mechanism of the activated-IGF-1R in triggering degradation of RIG-I. The assay of the mutants βarr2^Y64A and βarr2^Y250A further confirmed the role of these two Tyr residues of the interlobe in mediating the talk between IGF-1Rβ and the RING domain of MEX3A. The truncated-βarr2 and the peptide ATQAIRIF, which mimicked the RING domain of MEX3A could prevent the formation of βarr2/IGF-1Rβ and βarr2/MEX3A complexes, thus blocking the IGF-1R-triggered RIG-I degradation. Degradation of RIG-I resulted in the suppression of the IFN-I-associated immune cells in the TME due to the blockade of the RIG-I-MAVS-IFN-I pathway. Poly(I:C) could reverse anti-PD-L1 insensitivity by recovery of RIG-I. In summary, we revealed a disobliging IGF-1R signaling by which IGF-1Rβ promoted cancer growth through triggering the MEX3A-mediated degradation of RIG-I.

Objective To assess the clinical diagnosis value and treatment effect of anti-Müllerian hormone(AMH)and inhibin B(INHB)in polycystic ovary syndrome(PCOS)patients.Methods Total of 300 cases of PCOS patients were enrolled in this study from January 2014 to January 2016 in the First Affiliated Hospital,Hunan University of Chinese Medicine,and those patients were randomly divided into group A,group B and group C.There were 100 patients in every group.The patients in group A were interfered by traditional Chinese medicine.The patients in group B were treated with Western medicine and those in group C were treated with traditional Chinese medicine combined with western medicine.Total of 264 cases health volunteers were enrolled as the control group.The effect was evaluated.The level of AMH and INHB in serum of PCOS patients were detected by chemiluminescent assay before treatment and three months after treatment.Results The cutoffs of AMH and INHB were 6.98 ng/ml and 150 pg/ml,respectively.The AUC of AMH combined with INHB was significantly larger than that of AMH or INHB(0.945 vs.0.859,0.945 vs.0.784).In the PCOS group,the positive PCOS rate of AMH combined with INHB was significantly larger than that of AMH or INHB[87.00％(261/300)vs.83.33％(250/300)vs.93.67％(281/300),x2=15.593,P=0.000].The sensitivity[93.67％(281/300)],specificity[92.42％(244/264)],positive predictive value[93.36％(281/288)],negative predictive value[92.78％(244/264)]and Jordanian index(0.659)of AMH combined with INHB was significantly larger than that of AMH[87.00％(261/300),87.88％(232/264),89.08％(261/293),85.61％(232/271)and 0.612]or INHB[83.33％(250/300),90.15％(238/264),90.58％(250/276),82.64％(238/301)and 0.571].After treatment,AMH[(9.06±2.13)ng/ml vs.(6.34±1.12)ng/ml,t=10.595,P=0.000;(9.08±2.08)ng/ml vs.(6.02±1.02)ng/ml,t=13.209,P=0.000;(9.13±2.31)ng/ml vs.(3.53±0.83)ng/ml,t=22.814,P=0.000]and INHB[(173.13±14.22)pg/ml vs.(145.26±13.05)pg/ml,t=14.440,P=0.000;(174.28±13.82)pg/ml vs.(145.39±12.98)pg/ml,t=15.238,P=0.000;(174.98±13.77)pg/ml vs.(133.15±12.04)pg/ml,t=22.869,P=0.000]in 3 groups had decreased.After treatment,the AMH of group C [(3.53±0.83)ng/ml] was significantly lower than that of group A and B[(6.34±1.12)ng/ml and(6.02±1.02)ng/ml,F=237.936,P=0.000],and the level of AMH in group C [(133.15±12.04)pg/ml] was significantly lower than that in both group A and group B[(145.26±13.05)pg/ml and(145.39±12.98)pg/ml,F=30.645,P=0.000].Conclusions AMH combined with INHB can be used to diagnose PCOS.AMH and INHB can be used to evaluate PCOS efficacy.

Objectives Brain atrophy plays a key role in post-stroke dementia. The current study aims to explore risk factors for brain atrophy in different regions in order to find the ultimate therapeutic strategy. Methods Consecutive stroke and/or transient ischemic attack (TIA) patients were recruited from July 2012 to June . The clinical features, neuro?imaging findings and risk factors were collected during hospitalization. Logistic regression analysis showed that, except for age, female gender (Odds ratio, OR=2.447, P=0.007) and the number of silent lacuna infarcts (OR=1.414, P=0.027) were independent risk factors for frontal lobe atrophy. Ischemic stroke history (OR=2.224, P=0.024) was the independent risk factor for parietal lobe atrophy. All of extra-/intracranial larger artery diseases (OR=2.584, P=0.015) and white mat?ter severity score (OR=1.112, P=0.007) as well as the number of silent lacuna infarcts (OR=1.158,P=0.042) were inde?pendent risk factors for medial temporal lobe atrophy. Moreover, diabetes (OR=2.109, P=0.001),atrial fibrillation (OR=1.934, P=0.015) and white matter severity score (OR=1.098, P=0.002) were independent risk factors for global brain atro? phy. Conclusion Risk factors for brain atrophy included diabetes,atrial fibrillation, silent lacuna infarcts and white mat?ter changes. We should pay more attention to those patients with above risk factors in order to slow down the progression of brain atrophy and also prevent them from dementia by early interventions.

Objetive The present study was aimed to explore the risk factors of mid-term cognitive decline in pa?tients with indexed TIA/minor stroke (NIHSS≤3) in a Chinese hospital-based cohort. Methods We recruited all consec?utive Chinese TIA/minor stroke patients from July to December in 2012 and followed them up in stroke clinics at 3 and 18 months after indexed TIA/minor stroke. The outcome was defined as significantly cognitive decline at 18 months com?pared with that at 3 months. Results A total of 209 consecutive Chinese TIA/minor stroke cases completed their fol?low-up investigation. Among them, 24 (11.5%) exhibited significantly cognitive decline. The independent risk factors of cognitive decline post TIA/minor stroke were education years (OR=0.869,P=0.021), atrial fibrillation(OR=5.950, P=0.001) and multiple silent lacunar infarcts (OR=5.179,P=0.020). Conclusion It is necessary to evaluate the cognition among TIA/minor stroke cases and a close follow-up is required for patients with atrial fibrillation and multiple silent la?cunar infarcts frequently in order to decrease the risk of cognitive decline post TIA/minor stroke.

Objective To analyze the behavioral characteristics and mental health status for patients with chronic hepatitis B,to explore the correlation between them and analyze the influence of behavioral characteristics of patients with chronic hepatitis B on their mental health.And provide a reference of clinical mental health intervention for patients with chronic hepatitis B.Methods 216 cases of patients with chronic hepatitis B in our hospital from October 2010 to October 2011 were chosen as the research object.Symptom checklist-90(SCL-90)and Eysenck personality questionnaire(EPQ)were used for evaluation.The correlation of behavioral characteristics and mental health status for patients with chronic hepatitis B and the effect of behavioral characteristics of patients with chronic hepatitis B for their mental health were analyzed.Results The SCL-90 score for 216 cases of chronic hepatitis B patients showed that its total score was significantly higher than the norm,the difference was statistically significant.The results of EPQ score showed that the neurotic or emotional stability of personality scores were significantly higher than the norm,the difference was significant.The psychotic scores were significantly lower than the norm,the difference was significant.The analysis of the correlation for nine projects in the SCL-90 scale and four items in the EPQ scale showed that introversion had a significant positive correlation with compulsion,depression,anxiety,fear and paranoia.The nervous or emotion had a significant positive correlation with compulsion,interpersonal sensitivity,paranoid,psychotic.Conclusions The behavioral characteristics of chronic hepatitis B patients have a relation with the mental health.The mental health status changes according to the changes of behavioral characteristics.

Objective To investigate influence of nursing intervention on quality of life of hospitalized patients with peptic ulcer. Methods l00 cases of peptic ulcer patients from October 2009 to September 2011 were chosen as the object.50 patients of hospitalized patients were defined as the ward group,and 50 cases of patients in outpatient were defined as the outpatient group.The life quality questionnaire was adopted to evaluate life quality before and after treatment between two groups. Results After intervention,number of patients whose score ranged 5～7 grades were more in the ward group than those in the outpatient group. Conclusions Nursing intervention for patients with peptic ulcer has significant effect on life quality and treatment effect of them.