Objective To observe the effects of Gegen Qinlian Decoction on pancreatic endoplasmic reticulum stress in mice with type 2 diabetes mellitus(T2DM);To explore its mechanism of action in the treatment of T2DM.Methods Totally 75 SPF male db/db mice were randomly divided into model group,metformin group,and Gegen Qinlian Decoction high-,medium-,low-dosage groups,with 15 mice in each group.15 db/m mice were set as the blank group.The administration groups received corresponding medicine for gavage for 12 weeks.Body mass,fasting blood glucose(FBG)and glycated hemoglobin(HbA1c)in mice were detected,HE staining was used to observe the pathological changes of pancreatic tissue,the apoptosis of islet cells was determined by TUNEL staining,Western blot was used to detect pancreatic tissue glucose regulatory protein 78(GRP78),protein kinase R-like endoplasmic reticulum kinase(PERK),p-PERK,activated transcription factor 4(ATF4)and C/EBP homologous protein(CHOP)protein expression,RT-PCR was used to detect pancreatic tissue PERK,ATF4,CHOP mRNA expressions.Results Compared with the blank group,the body mass,FBG and HbA1c contents in the model group significantly increased(P<0.01);the pancreatic tissue structure was incomplete,with blurry boundaries and vacuoles inside,leading to a significant increase in pancreatic islet cells apoptosis(P<0.01);the expressions of GRP78,p-PERK,ATF4,and CHOP proteins in pancreatic tissue significantly increased(P<0.01),and the mRNA expressions of PERK,ATF4 and CHOP significantly increased(P<0.01).Compared with the model group,the body mass,FBG and HbA1c contents of mice in each administration group significantly decreased(P<0.05,P<0.01);pathological changes in pancreatic tissue was reduced,and islet cells apoptosis decreased to varying degrees(P<0.05,P<0.01);the expressions of GRP78,p-PERK,ATF4 and CHOP proteins in pancreatic tissue significantly decreased(P<0.01)in Gegen Qinlian Decoction high-and medium-dosage groups and the metformin group,and the expressions of PERK,ATF4 and CHOP mRNA significantly decreased(P<0.05,P<0.01).Conclusion Gegen Qinlian Decoction may decreased pancreatic islet cells apoptosis,protect pancreatic cell function,and delay the progression of T2DM by inhibiting the endoplasmic reticulum stress PERK/ATF4/CHOP signaling pathway,and down-regulating the expressions of related genes and proteins.

Objective To evaluate the angiogenesis of decidua in spontaneous abortion patients and to investigate the change of thyroid hormone receptor signal expression in decidua in miscarriage patients.Methods The decidua of pregnant women was collected.Patients with miscarriage were taken as the experimental group and healthy preg-nant women who underwent abortion by social factors were taken as the control group.The nuclear translocation of thyroid hormone receptor α(THR-α)and THR-β in decidua tissues was detected by Western blot method,and the distribution of THR-α and TH IR-β in decidua tissues was determined by immunohistochemistry.The expression of Deiodinase 2(DIO2)in decidua tissues was determined by Western blot.The distribution of DIO2 in decidua tissues was determined by immunofluorescence and the fluorescence intensity was measured.The decidual vessel density was determined by immunohistochemistry using CD34 as an endothelial marker.The protein expression of vascular endothelial growth factor receptor(VEGFR-1)was detected by Western blot.Results There was no sig-nificant difference in age,gestation days,TSH,T3,T4 and other basic data between the control group and the a-bortion group.The results of Western blot showed that the expression levels of THR-α and THR-β protein de-creased,and the results of immunohistochemical staining of decidual tissues showed that the nuclear translocation of decidual thyroid hormone receptor in patients with spontaneous abortion decreased(P＜0.05).Western blotting results showed that the expression of DIO2 protein in the abortion group was lower than that in the control group,suggesting that thyroid hormone metabolism in decidua of spontaneous abortion pregnant women was affected.The results of immunofluorescence test showed that the fluorescence intensity of DIO2 in the abortion group was weaker than that in the control group(P＜0.05).Immunohistochemical CD34 labeling of decidual small blood vessels showed that the number of CD34+blood vessels decreased in the abortion group with statistical difference(P＜0.05).Western blot results showed that there was no significant change in VEGFR-1 between the two groups,and the difference between the two groups was not statistically significant.Conclusion The abnormal signal of thyroid hormone receptors in decidua may decrease decidua angiogenesis and participate in spontaneous abortion.

Objective To develop and test the reliability and validity of the Intrinsic Capacity Assessment Scale for the Older People,so as to provide an effective tool for the assessment of the intrinsic capacity of the aged.Methods Based on the International Classification of Functioning,Disability and Health(ICF)as the theoretical framework,the initial version of The Intrinsic Capacity Assessment Scale for the Older People was developed through literature analysis,Delphi expert consultation and pre-survey.From July to September 2023,650 old people were selected by convenience sampling method to conduct a survey,and 20 old people were surveyed after 2 weeks again to test the reliability and validity of the scale.Results The effective questionnaire recovery rates of the 2 rounds of expert correspondence were 92.3％and 91.7％;the expert authority coefficients were 0.83 and 0.86;the mean importance scores of items were 2.04-3.79 and 3.50-3.82,and the full score ratios were 4.2％-83.3％and 54.6％-86.4％,respectively.The coefficients of variation were 0.11-0.42 and 0.11-0.23,respectively.A total of 5 common factors were extracted from exploratory factor analysis,and the cumulative variance contribution rate was 68.327％.The results of confirmatory factor analysis showed that the fit indexes were x2/df=1.908,RMSEA=0.054,CFI=0.931,IFI=0.932,TLI=0.922,indicating a good fit.The Cronbach's α coefficient of the scale was 0.944;the split half reliability was 0.806;the retest reliability was 0.933.The content validity index of item level was 0.82-1.00,and the content validity index of scale level was 0.91.The Intrinsic Capacity Assessment Scale for the Older People included 35 items in 5 dimensions:movement,vitality,sensation,cognition and psychology.Conclusion The Intrinsic Capacity Assessment Scale for the Older People has good reliability and validity,and it can be used as a reliable tool to evaluate the intrinsic capacity level of the aged.

Objective To explore the current status of clinical inertia in the treatment of patients with type 2 diabetes mellitus (T2DM) in the suburbs of Shanghai and analyze its risk factors. Methods A total of 1, 804 T2DM patients who visited the Endocrinology and Metabolism Clinic of Shanghai Sixth People's Hospital from November 2022 to November 2023 were selected as research objects. Patients were divided into clinical inertia group and non-clinical inertia group based on whether clinical inertia occurred during their treatment, and demographic and clinical data were collected. Logistic regression analysis was used to identify risk factors for clinical inertia in the treatment of T2DM patients. Results The incidence of clinical inertia in T2DM patients was 52.00% (938/1, 804). The results of multivariate Logistic regression analysis showed that longer diabetes duration, high level of glycated hemoglobin (HbA1c), high score of the Problem Areas in Diabetes Scale(PAID) score, taking over two oral medications, shorter life expectancy, and coexisting retinopathy were risk factors for clinical inertia in the treatment of T2DM patients (P < 0.05). Conclusion The incidence of clinical inertia is high in T2DM patients during treatment in the suburbs of Shanghai. T2DM patients with poor glycemic control, longer disease duration, high level of psychological distress, taking over two oral medications, shorter life expectancy, and coexisting retinopathy are more prone to occur clinical inertia.

Backgroud Beta-cypermethrin and emamectin benzoate are widely used for the prevention and control of pests in the greenhouse planting industry, and their combined exposure may increase the accumulation of beta-cypermethrin and emamectin benzoate in organisms and affect human health. Objective Based on the changes in reproductive hormone levels in the hypothalamic-pituitary-ovarian (HPO) axis, to investigate the effect of combined exposure to beta-cypermethrin and emamectin benzoate on the estrous cycle of female mice. Methods Twenty-four healthy adult SD rats were randomly divided into a blank control group, a beta-cypermethrin group (Beta-CYP, 53 mg·m⁻³), an emamectin benzoate group (EMB, 8 mg·m⁻³), and a beta-cypermethrin and emamectin benzoate combined exposure group (Beta-CYP+EMB, Beta-CYP 53 mg·m⁻³ + EMB 8 mg·m⁻³). Six rats in each group were exposed to the designed treatment protocol by aerosol inhalation 6 d a week for 13 weeks. The general condition of the rats was observed in real time during the treatment. From the 12th week of exposure, a 10-day reproductive tract smear was performed on the rats to observe the estrous cycle. The rats were neutralized on the second day after the end of the treatment protocol, and the ovarian tissues were stained with HE to observe histopathological changes. Serum levels of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were measured by ELISA. Experimental results were expressed as mean ± standard deviation (\begin{document}$ \overline{x}\pm s $\end{document}). One-way ANOVA was used for comparison among groups, and LSD test for pairwise comparison between groups. The significance level was α=0.05. Results After four weeks of the treatment protocol, the rats in the Beta-CYP group and the Beta-CYP+EMB group continued to be hyperactive and irritable, while the EMB group showed symptoms of mental disorder, decreased activity, and slow response. On the 90th day of the treatment protocol, the body weight of rats in the control group increased to (314.51±2.44) g, and that in the Beta-CYP+EMB group only increased to (253.47±1.50) g. There was no abnormal cellular morphology in the control group; however, small deeply stained nuclei appeared in the Beta-CYP group, the EMB group, and the Beta-CYP+EMB group, and abnormal morphological development of keratinized epithelial cells in the Beta-CYP+EMB group was found. The estrous cycle of rats in the control group was (97.83±4.17) h, and compared with the control group, the estrous cycles of rats in the Beta-CYP group, the EMB group, and the Beta-CYP+EMB group were prolonged to (134.33±7.53) h, (126.50±5.28) h, and (156.00±6.66) h, respectively. The results of ANOVA showed that the numbers of leukocytes (527.17±15.83), keratinized epithelial cells (35.67±4.32), and non-keratinized epithelial cells (70.50±4.51) in the vaginal smears during diestrus in the Beta-CYP+EMB group were significantly lower than those in the control group (752.50±28.89, 50.50±2.74, 101.33±7.92) (P<0.001). The hormone levels of GnRH and FSH in the control group were (5.13±0.59) and (0.76±0.09) IU·L⁻¹ respectively, while the levels in the Beta-CYP+EMB group were increased to (16.86±0.59) and (3.80±0.19) IU·L⁻¹ respectively (P<0.05). The levels of LH and E2 in the control group were (12.93±0.81) IU·L⁻¹ and (22.23±1.44) pmol·L⁻¹ respectively, and the levels in the Beta-CYP+EMB group were decreased to (5.63±0.41) IU·L⁻¹ and (10.45±0.78) pmol·L⁻¹ respectively (P<0.05). Conclusion The combined exposure to beta-cypermethrin and emamectin benzoate may ultimately affect the estrous cycle of female rats by interfering with the secretion of reproductive hormones involved in the HPO axis.

Objective:To observe the effects of different doses of Gegen Qinlian Decoction on nucleotide oligomeric domain-like receptor protein 3 (NLRP3)/Caspase-1/IL1β inflammatory signaling pathway in liver of db/db mice with type 2 diabetes mellitus (T2DM).Methods:Totally 75 SPF male db/db mice were randomly divided into model group, metformin group (0.2 g/kg), Gegen Qinlian Decoction high-, medium-, and low-dosage groups (61.80, 30.90, 15.45 g/kg), with 15 mice in each group. Another 15 db/m male mice were selected as blank control group. Each administration group was given relevant medicine for gavage, while the blank group and model group were given 0.9% sodium chloride solution for gavage, once a day, for 12 weeks. The body weight, fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) contents of each group were measured after treatment. The mRNA expression levels of NLRP3, Caspase-1 and interleukin-1β (IL-1β) in liver were detected by real-time quantitative PCR. The expression levels of NLRP3, Caspase-1, IL-1β and IL-18 in liver tissues were detected by Western Blot. HE staining was used to observe the morphology of liver tissues.Results:Compared with model group, body weight, fasting blood glucose and HbA1c contents of mice in Gegen Qinlian Decoction high- and medium-dosage groups and metformin groups decreased ( P<0.05), the body weight and fasting blood glucose levels of mice in Gegen Qinlian Decoction low-dosage group decreased ( P<0.05); the mRNA levels of NLRP3 and IL-1β in liver tissues of all treatment groups decreased ( P<0.05), the mRNA level of Caspase-1 in liver tissue decreased in Gegen Qinlian Decoction high- and medium-dosage groups ( P<0.05); the expression of NLRP3, Caspase-1, and IL-18 in liver tissue of each treatment group decreased ( P<0.05), while the expression of IL-1β in Gegen Qinlian Decoction high- and medium-dosage groups and the metformin group decreased ( P<0.05); compared with the metformin group, the body weight and fasting blood glucose of mice in the Gegen Qinlian Decoction high-dosage decreased ( P<0.05), while the HbA1c levels in the Qinlian Decoction high- and medium-dosage decreased ( P<0.05); the expressions of NLRP3, Caspase-1 and IL-18 in liver tissues of Gegen Qinlian Decoction high-dosage group decreased ( P<0.05), the expression of IL-1β, NLRP3, Caspase-1, IL-1β, and IL-18 decreased ( P<0.05); HE staining showed that the pathological changes of liver tissue were reduced in all treatment groups. Conclusion:Gegen Qinlian Decoction may reduce blood sugar by inhibiting the activation of NLRP3/Caspase-1/IL-1β inflammatory signaling pathway in liver of db/db mice, thereby improving the inflammatory damage of T2DM.

ObjectiveTo validate the alleviating effect of Gegen Qinliantang （GGQLT） on insulin resistance in db/db diabetic mice by regulating the silent information regulator 1 （SIRT1）/forkhead transcription factor O1 （FoxO1） autophagy pathway. MethodSeventy-five SPF-grade spontaneous type 2 diabetic db/db mice and 15 control db/m mice were selected and maintained on regular feed for one week before measuring blood glucose. They were randomly divided into six groups， with 15 mice in each group. The groups included a normal group （physiological saline， 0.2 g·kg^-1）， a metformin group （0.2 g·kg^-1）， high-， medium-， and low-dose GGQLT groups （31.9， 19.1， 6.9 g·kg^-1）， and a model group （physiological saline， 0.2 g·kg^-1）. They were orally treated with corresponding drugs for eight weeks， once daily. Fasting blood glucose （FBG） was measured using a Roche glucometer. Serum levels of high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， triglyceride （TG）， and total cholesterol （TC） were measured using an automated biochemical analyzer. Fasting serum insulin （INS） levels were determined using enzyme-linked immunosorbent assay （ELISA）， and the homeostasis model assessment of insulin resistance （HOMA-IR） was calculated. Western blot was used to detect the expression of Beclin-1， microtubule-associated protein 1 light chain 3 （LC3）， and SIRT1/FoxO1 autophagy pathway-related proteins in liver tissues. Immunohistochemistry was performed to assess the expression of SIRT1， FoxO1， Beclin-1， and LC3B proteins in liver tissues. Transmission electron microscopy was used to observe the formation of autophagosomes in the liver. ResultCompared with the normal group， the model group showed significant increases in FBG， FINS， HOMA-IR， TC， TG， LDL-C， and HDL-C levels （P<0.01）， and significant increases in the expression of SIRT1， Beclin-1， LC3， and FoxO1 proteins in liver tissues （P<0.01）. Transmission electron microscopy revealed the highest number of autophagosomes in the model group. Compared with the model group， the metformin group and the low-， medium-， and high-dose GGQLT groups showed significant decreases in serum FBG， FINS， HOMA-IR， TC， TG， LDL-C， and HDL-C levels （P<0.05， P<0.01）， significant decreases in the expression of SIRT1， Beclin-1， LC3 （P<0.05， P<0.01）， and up-regulated FoxO1 protein （P<0.01）. Transmission electron microscopy showed a reduction in the degree of autophagy in the treatment groups. Compared with the metformin group， the medium- and high-dose GGQLT groups showed significant decreases in FBG， FINS， and TG levels （P<0.01）， significant decreases in the expression of SIRT1， Beclin-1， and LC3 in liver tissues （P<0.05， P<0.01）， and reduced FoxO1 protein （P<0.01）. The high-dose GGQLT group showed reduced HOMA-IR， TC， LDL-C， and HDL-C levels （P<0.05， P<0.01）. Transmission electron microscopy revealed a significant reduction in autophagosomes in the medium- and high-dose GGQLT groups. ConclusionGGQLT can significantly improve glucose and lipid metabolism disorders， alleviate insulin resistance in db/db mice， and prevent and treat type 2 diabetes by activating the SIRT1/FoxO1 autophagy pathway.

Objective:To assess the reliability, constructive validity and item characteristics of the general self-efficacy scale (GSES) among Chinese medical postgraduates using classical test theory and item response theory.Methods:A questionnaire survey was conducted among 1 021 medical postgraduates from 6 comprehensive level Ⅲ A hospitals in Beijing. Demographic characteristics and general self-efficacy were investigated. SPSS 24.0 software was used for statistical analysis. Internal consistency of the GSES was evaluated using Cronbach’s α coefficient and intraclass correlation coefficient. Factor analyses were implemented to test the structure of the scale. An item response theory (IRT) framework with a graded response model was performed to estimate the parameters of each item. Results:The overall Cronbach’s α coefficient of the GSES was 0.92. Parallel analysis and confirmatory factor analysis supported the unidimensional structure of the GSES. The discrimination parameter of the 10 items ranged from 1.82 to 3.65, and the difficulty parameter ranged from -3.51 to 1.66, with a monotonically increasing trend. The maximum test information of the scale among medical postgraduates was 19.16. Conclusion:The GSES has good reliability, validity and measurement precision, showing a good applicability in the survey of medical postgraduates. However, the difficulty of specific items is relatively low, and the scale may be further optimized and improved.

Objective:To investigate the characteristics of gene mutation by using whole exome sequencing (WES) and its relationship with therapeutic efficacy in patients with acute myeloid leukemia (AML).Methods:The data of 30 patients with AML from the Second Hospital of Anhui Medical University between December 2014 and September 2019 were retrospectively analyzed; the result of WES, disease type and classification, genetic prognostic stratification and therapeutic efficacy were summarized. The mutation types and mutation frequency of AML patients stratified by the different clinical characteristics and genetic prognosis were compared.Results:Among 30 AML patients, 26 cases (86.7%) had 1 gene mutation at least. The genes with a mutation frequency more than 10.0% were NRAS, RUNX1, TET2, CEBPA, IDH2 and ASXL1. The function of the mutated genes was involved in signaling pathways, transcription factors, epigenetics, and RNA splicing and other biological functions; in terms of mutation pattern, 19 cases (63.3%) of all AML patients mainly presented combined mutations of many combinations. There were no significant differences in mutation rates among age, gender, disease type, disease classification and genetic prognosis stratification groups (all P > 0.05). Of the 8 fusion gene positive cases, 7 were mutated, the average mutation frequency was 175.0% (14/8). There were 19 mutations in 22 patients with negative fusion gene, the average mutation frequency was 213.6% (47/22), and the difference in mutation frequency between the two groups was statistically significant ( P = 0.001). Of the 14 cases of continuous remission, 11 had mutations, with average mutation frequency of 157.1% (22/14); there were 9 cases of mutations in 10 relapsed patients, and the average mutation frequency was 200.0% (20/10); mutations occurred in 5 patients with primary drug resistance, and the average mutation frequency was 300.0% (15/5); and the difference of mutation frequency among the three groups was statistically significant ( P = 0.009). Conclusions:Through WES analysis, it is found that most AML patients have complex and variable gene mutations; and the higher the gene mutation frequency is, the worse the prognosis of the disease is.

Objective:To investigate the relationship of blood lipid levels with bone mass and fracture risk in elderly patients with type 2 diabetes mellitus (T2DM).Methods:A total of 744 elderly patients with T2DM who were treated in Tangshan Second Hospital from November 2018 to May 2020 were divided into normal bone mass group, low bone mass group and osteoporosis group according to bone mass levels. The total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels in the three groups were compared, and the relationship between lipid indexes and bone mass was analyzed. The risk of fracture was calculated in the low bone mass group, and the relationship between lipid index and fracture risk was analyzed by linear regression. The blood lipid index between subjects with fracture and without fracture in osteoporosis group was compared, and the relationship between blood lipid index and fracture was analyzed by logistic regression.Results:There were significant differences in gender and age among the three groups (χ 2=38.80, F=4.94, P<0.05). The normal bone mass group had the smallest proportion of women and the youngest average age, while the osteoporosis group had the largest proportion of women and the average age. maximum. The LDL-C level in normal bone mass group was higher than those in the low bone mass group and the osteoporosis group, and LDL-C level in the low bone mass group was higher than that in the osteoporosis group ( F=3.38, P<0.05). In the low bone mass group, the risk of systemic fracture was 3.50% (2.40%, 4.10%) and hip fracture was 0.99% (0.80%, 1.20%). Linear regression showed that LDL-C and TG were positively correlated with the risk of systemic fractures in the low bone mass group (LDL-C: B=0.98, P=0.006;TG: B=0.23, P=0.024);TG was positively correlated with the risk of hip fracture in the low bone mass group ( B=0.16, P=0.002). In the osteoporosis group, the levels of HDL-C and LDL-C were lower in the patients with fractures than those without fractures ( t=3.24, P=0.001; t=2.98, P=0.003). Logistic regression analysis showed that higher HDL-C and LDL-C levels were protection factors for fracture risk in the osteoporosis group ( β=-2.73, P=0.009, OR=0.06, 95 %CI=0.04-0.10; β=-0.15, P=0.033, OR=0.83, 95 %CI=0.74-0.99). Conclusion:The relationship of serum lipid index with bone mass and fracture risk in hospitalized elderly T2DM patients is complicated, it is suggested to set individual blood lipid control targets according to the bone mass of patients.