ObjectiveTo investigate the attenuating effect of Dioscoreae Bulbiferae Rhizoma（DBR） processed with Phaseoli Radiati Semen（PRS） juice， and explore the attenuating mechanism based on ferroptosis of the main toxic target organ. MethodSixty male ICR mice were randomly divided into blank group， DBR group， water roasted DBR group（hereinafter referred to as water group）， PRS juice-roasted DBR group 1（DBR-PRS 10∶1， stuffy moistening for 40 min， stir-fried at 130 ℃ for 18 min， hereinafter referred to as group 1）， PRS juice-roasted DBR group 2（DBR-PRS 10∶1， stuffy moistening for 80 min， stir-fried at 100 ℃ for 14 min， hereinafter referred to as group 2）， PRS juice-roasted DBR group 3（DBR-PRS=20∶3， stuffy moistening for 40 min， stir-fried at 160 ℃ for 14 min， hereinafter referred to as group 3）. The raw and processed groups of DBR were gavaged with their corresponding 95% ethanol extract at a dose of 3 g·kg^-1·d^-1， while the blank group was gavaged with an equal volume of 0.5% sodium carboxymethyl cellulose， once a day for 14 consecutive days. Hematoxylin-eosin（HE） staining was used to observe the histopathological changes of mouse liver. Alanine aminotransferase（ALT） and aspartate aminotransferase（AST） levels in serum， as well as malondialdehyde（MDA）， ferrous ions（Fe²⁺）， reduced glutathione（GSH） and superoxide dismutase（SOD） levels in liver tissue were detected by the biochemical detection. Western blot was used to detect the expression of iron key proteins such as ferritin heavy chain 1（FTH1） and glutathione peroxidase 4（GPX4）. ResultHE staining results showed that the liver tissue structure of the blank group was clear， the morphology of hepatocytes was normal， the cytoplasms of hepatocytes in the DBR group and water group were loose and vacuolar， with obvious pathological damages， and the pathologic damages of mice in the group 1-3 were significantly improved. Compared with the blank group， the levels of ALT， AST， MDA and Fe²⁺ in mice from the DBR group were significantly increased（P<0.01）， while GSH and SOD levels were significantly reduced（P<0.01）， and the protein expression levels of FTH1 and GPX4 were significantly decreased（P<0.01）. Compared with the DBR group， the ALT， AST，MDA and Fe²⁺ levels of mice in the group 1-3 were significantly reduced（P<0.05， P<0.01）， the GSH and SOD levels and the protein expression levels of FTH1 and GPX4 were significantly increased（P<0.01）. Compared with the water group， the AST and MDA levels of mice in the group 1-3 were significantly reduced（P<0.05， P<0.01）， the SOD level significantly increased（P<0.05， P<0.01）， the FTH1 protein expression significantly increased（P<0.01）， and the serum ALT level of mice in the group 2-3 significantly reduce（P<0.01）， Fe²⁺ level significantly reduced（P<0.01）， GSH level significantly increased（P<0.05， P<0.01）， and GPX4 protein expression significantly increased（P<0.05， P<0.01）. Among the group 1-3， the group 3 had the best detoxification effect. ConclutionProcessing with PRS juice can reduce the liver injury induced by DBR， and the mechanism may be related to the inhibition of ferroptosis in the liver.

Objective:To retrospectively analyze the bone marrow characteristics of methimazole-induced agranulocytosis and other hematologic damage, and to explore its correlation with clinical features and prognosis.Methods:The bone marrow and clinical parameters of 20 patients of Graves′ disease diagnosed with methimazole-induced agranulocytosis at the First Affiliated Hospital of Xi′an Jiaotong University from January 2000 to December 2022 were collected. The intergroup differences in bone marrow characteristics and granulocyte recovery time were analyzed. Differences in peripheral blood and bone marrow characteristics between patients with single agranulocytosis and pancytopenia were compared. Besides, literature review of the bone marrow characteristics of methimazole-induced hematologic diseases was conducted.Results:Compared to patients with bone marrow characteristics of granulocyte and precursor maturation disorders(Type Ⅱ), patients with aplastic marrow(Type Ⅰ) had significant decreases in the proportions of granulocytes in all phases( P<0.05). Patients with bone marrow characteristics of Type Ⅰ had a significant increase in the proportion of the lymphocyte system [51.00%(41.50%, 75.50%) vs 22.00%(14.00%, 35.00%), P=0.002], and got a longer to recovery time [(6.58±1.68)d vs(3.71±1.60)d, P=0.003]; Correlation analysis suggested the granulocyte to erythrocyte ratio was negatively correlated with the granulocyte recovery time( r=-0.520, P=0.023), and the proportion of the bone marrow lymphocyte was positively correlated with granulocyte recovery time( r=0.622, P=0.004). Compared to patients with single agranulocytosis, patients with pancytopenia had a markedly longer hospital stay duration [(27.14±5.27)d vs(14.15±7.36)d, P=0.001]. Literature review suggestsed that methimazole may cause various degrees of damage to blood system and bone marrow. Conclusion:Methimazole can induce a variety of hematologic damages. Analysis of bone marrow characteristics can aid in further prognosis assessment. Clinicians should be vigilant about potential hematologic adverse reactions when using methimazole and promptly diagnose and treat them to prevent serious consequences.

Objective:To understand the characteristics and trends of acute myocardial infarction (AMI) in Shandong Province and to provide evidence for formulating prevention and control strategies.Methods:Data were derived from the AMI incidence reports of Shandong Province's Chronic Disease Surveillance Information Management System in 2012-2021. The crude and standardized incidence rates were used as indicators to describe the incidence level of AMI. Joinpoint regression analysis was used to analyze the trends in the incidence and age of onset over the years. The contribution of population aging to the increase in AMI incidence was assessed using the rate difference decomposition method. The incidence of AMI in each district (county) in Shandong Province was visualized using ArcGIS 10.8 software, and global and local spatial autocorrelation analysis was performed using DeoDa 1.12 software.Results:From 2012 to 2021, 198 233 cases of AMI were reported from 19 provincial monitoring sites in Shandong Province, of which 53.13% were males and 97.12% were ≥45 years old. The reported crude incidence increased from 90.12 per 100 000 in 2012 to 176.54 per 100 000 in 2021, with an average annual increase of 7.01% ( Z=7.35 , P<0.001). There was no significant upward trend in standardized incidence ( Z=1.64 , P=0.140), but the standardized incidence of male residents showed an increasing trend ( Z=2.76 , P=0.028). Before 2014, the reported crude incidence of males was similar to that of females, but after 2014, the reported crude incidence of males was continuously higher than that of females. However, males' standardized incidence was higher than females in all years. Both crude and standardized incidence rates were higher in rural residents than in urban areas. The median onset of AMI increased from 71.6 years old in 2012 to 73.5 years old in 2021. The median age of onset in males was lower than that in females in all years, and in most years, the median age of onset in urban residents was lower than that in rural residents. The incidence of AMI in males showed a trend in younger age groups. According to the seasonal decomposition, the incidence peak of AMI was in January, and the trough was in September. The contribution of aging population to the increase in crude incidence of AMI increased from 8.63% in 2013 to 52.58% in 2021. The global spatial autocorrelation analysis showed that the incidence of AMI presented an obvious spatial clustering distribution. Local spatial autocorrelation analysis found that the high-incidence areas (counties) were mainly concentrated in Liaocheng City and Dezhou City in the northwest region of Shandong Province and Heze City in the southwest. Conclusions:The incidence of AMI among residents in Shandong Province was rising, with spatial clustering and seasonal clustering characteristics. People aged 45 years and older, male residents, and rural residents were at high risk of developing AMI. There was a certain trend of younger age at onset among men. Targeted prevention and control measures should be taken for high-incidence seasons, high-risk groups, and high-incidence clustering areas in northwestern Shandong Province.

Objective To investigate the correlation between the improvement of insulin resistance(IR)and T lymphocyte subsets in patients with type 2 diabetes mellitus(T2DM)after intensive insulin therapy.Methods A total of 160 patients with T2DM who were treated in the endocrinology department of our hospital from February 2020 to March 2023 were selected.They were divided into simple T2DM group(n=80)and T2DM combined with family history of diabetes mellitus(FHD)group(n=80)based on whether they had FHD.The changes in blood glucose,pancreatic islet cell function,T lymphocyte subsets,and inflammatory cytokine levels were compared before and after treatment between the two groups.Pearson correlation analysis was used to investigate the correlation between insulin resistance index(HOMA-IR)and T lymphocyte subsets,and multiple linear regression analysis was used to explore the influencing factors for IR in T2DM patients.Results After treatment,the FPG,2 hPG,and coefficient of variation(CV)of blood glucose were lower than before treatment in the T2DM group(P<0.05).In the FHD group,the FPG,2 hPG,bedtime blood glucose,and CV were lower after treatment than before treatment(P<0.05).After treatment,the FPG,2 hPG,and CV were lower in T2DM group than in FHD group(P<0.05).After treatment,FC-P,2 hC-P,HOMA-β and IL-10 were higher(P<0.05),while HOMA-IR,IL-21,IL-1β,CD3+,CD4+,CD8+,CD4+/CD8+were lower than before treatment in both groups(P<0.05).After treatment,FC-P,2 hC-P,HOMA-β and IL-10 were higher,while HOMA-IR,IL-21,IL-1β,CD3+,CD4+,CD8+,CD4+/CD8+were lower in T2DM group than in FHD group(P<0.05).Pearson correlation analysis showed that HOMA-IR was positively correlated with CD3+,CD4+,CD8+,CD4+/CD8+(P<0.05).Multiple linear regression analysis shows that BMI and CD8+are influencing factors for IR in T2DM patients.Conclusions Intensive insulin therapy can improve the islets β cell function inpatients with T2DM and IR.There is a correlation between IR and the increase of CD8+T lymphocyte level in patients.

Purpose The clinical and dual-layer detector spectral CT(DLCT)features of epidermal growth factor receptor(EGFR)mutation and anaplastic lymphoma kinase(ALK)rearrangement of lung adenocarcinoma were studied by DLCT multi-parameter imaging to explore a non-invasive prediction method for clinical diagnosis of lung adenocarcinoma gene expression.Materials and Methods A total of 98 cases of lung adenocarcinoma diagnosed by pathology in Gansu Provincial Hospital were prospectively collected from August 2020 to March 2022.Clinical parameters(gender,age,lesion morphology,number,mediastinal lymph node metastasis,EGFR and ALK mutations status)and DLCT parameters including slope of the spectrum curve of the arteriovenous phase(λHUA,λHUv),the standard iodine concentration of the arteriovenous phase(NICA,NICv),the 40 keV single-energy CT value of the arteriovenous phase(CTA 40 keV,CTv 40 keV),the active atomic number of the arteriovenous phases were collected,respectively.According to the expression of EGFR and ALK,all patients were divided into three groups:EGFR mutant group[EGFR(+)],ALK rearrangement group[ALK(+)],EGFR/ALK both negative group[EGFR/ALK(-)].Clinical and DLCT parameters of each group were analyzed.Results There were statistical difference in gender between the EGFR(+)group and EGFR/ALK(-)group(x2=11.010,P＜0.05).There were statistical differences in lesion morphology among the three groups(x2=12.858,P＜0.05).The value of CTv 40 keV in the EGFR(+)group was significantly higher than that in EGFR/ALK(-)group(t=1.997,P＜0.05),and the NICv in the ALK(+)group was significantly lower than that in EGFR/ALK(-)group(t=2.155,P＜0.05).The λHUv,NICv,CTv 40 keV of EGFR(+)group were significantly higher than those of ALK(+)group(t=2.613,3.149,3.218,all P＜0.05).The sensitivity and specifiicity to identify EGFR(+)and EGFR/ALK(-)adenocarcinoma were 62.7％and 70.0％,the area under curve(AUC)was 0.634(95％CI 0.516-0.756)when the CTv 40 keV value was 141.070 Hu.The sensitivity and specificity to identify ALK(+)and EGFR/ALK(-)adenocarcinoma were 76.7％and 64.2％,the AUC was 0.706(95％CI 0.536-0.853)when NICv value was 0.287.The sensitivity to identify EGFR(+)and ALK(+)adenocarcinoma were 70.6％,64.7％,72.5％and the specificity was 76.5％,76.5％,82.4％,respectively,the AUC was 0.734(95％CI 0.606-0.829),0.751(95％CI 0.610-0.832),0.773(95％CI 0.649-0.861)when the values of λHUv,NICv and CTv 40 keV were 1.335,0.320 and 132.350,respectively.Delong test showed that the AUC of CTv 40 keV and λHUv was statistically different(Z=2.327,P＜0.05),and the AUC of CTv 40 keV was 0.773.Conclusion The gender,lesion morphology and DLCT parameters(λHUv,CTv 40 keV,NICv)of lung adenocarcinoma have certain predictive value for EGFR and ALK genetic expression,which can help clinical judgment of lung adenocarcinoma gene mutation pattern.

Objective To construct a Nomogram prediction model based on body position exercise training for patients with chronic constipation. Methods A total of 327 patients with chronic constipation from March 2021 to March 2023 were divided into qualified group (n=279) and unqualified group (n=48) according to their performance in body position exercises. General clinical materials of the patients were collected, and univariate and multivariate Logistic regression analyses were performed to identify risk factors for unqualified body position exercises in patients with chronic constipation; the R software was used to construct a Nomogram model for predicting unqualified body position exercises in patients with chronic constipation, and the receiver operating characteristic (ROC) curve and calibration curve were applied to verify the discrimination and consistency of the Nomogram model. Results There were no significant differences in gender, education level, history of smoking, history of alcohol abuse, history of hypertension, history of abdominal surgery, history of colonoscopy, and correct medication administration ratio between the two groups (P>0.05); the unqualified group had higher age, longer duration of chronic constipation, and a higher proportion of diabetes history compared to the qualified group (P < 0.05); age, duration of chronic constipation, and diabetes history were independent risk factors for unqualified body position exercises in patients with chronic constipation (P < 0.05). The constructed Nomogram prediction model demonstrated excellent discrimination (area under the curve was 0.923, 95%CI, 0.888 to 0.949, with sensitivity and specificity of 87.50% and 81.00% respectively) and consistency (H-L goodness-of-fit test χ²=2.246, P=0.973). The clinical value of this Nomogram model in predicting unqualified body position exercises for patients with chronic constipation was high when the high-risk threshold probability ranged from 0.06 to 0.80. Conclusion Age, duration of chronic constipation, and diabetes history are independent risk factors for unqualified body position exercises in patients with chronic constipation, and the Nomogram model constructed based on these multi-factor results has high discrimination and consistency in predicting unqualified body position exercises for patients with chronic constipation.

【Objective】 To construct the secretory expression system of insect cells to express the secretory TSHR A subunit protein in the ovarian cells of Spotoma oryzae (sf9). 【Methods】 A recombinant plasmid containing the target protein was constructed, and then the positive bacmid was screened out by the blue and white spots experiment. The verified bacmid was transfected into SF9 insect cells to obtain recombinant baculovirus. The virus was amplified, and the titer level was detected by virus plaque assay. Finally, Western blotting was used to identify the expression of the recombinant protein and optimize the expression conditions. 【Results】 During the construction of the protein expression system, PCR identification and sequencing results confirmed the correctness of the sequences of the recombinant plasmid and the recombinant bacmid. After the transfection of the bacmid, the signs of virus budding were observed in sf9 cells. The virus was collected and amplified. The titer of P1 generation virus was 2×10⁷ pfu/m according to the plaque assay. The recombinant protein was identified by Western blotting and confirmed to be exogenous into the culture medium. The optimal condition for virus infection and protein expression was 72 h after the infection when the multiplicity of infection (MOI) was 1. 【Conclusion】 We constructed an insect cell expression system secreting TSHR 22-289 (55 ku), and the protein could be successfully glycolyzed. This system provides a preliminary basis for the construction and production of its industrial platform and also provides a useful tool for studies on TSHR protein and prevention of GO in the future.

Objective:To study the effect of rapamycin on the disorder of CD4 + T cell subsets in Graves′ ophthalmopathy(GO) mice, as well as the ophthalmopathy and hyperthyroidism phenotype, providing new possibilities for the treatment of GO. Methods:6-8 weeks old female Balb/c mice were injected intramuscularly with adenovirus expressing the A-subunit of TSHR(A-sub-Ad) 9 times. Rapamycin was given by embedding in the feed(14 ppm). The animals were euthanized 4 weeks after the final injection to obtain blood, spleen cells, thyroid glands, and orbital tissue. TT 4, thyrotropin receptor antibody(TRAb), thyroid, and orbital pathologic changes were detected, and the CD4 + T cell subgroup was evaluated by flow cytometry and immunohistochemistry. Results:After final immunization, the mice showed characteristics of GO: increased retrobulbar fibrosis and retrobulbar adipogenesis that indicated ophthalmopathy, increased autoantibodies, and serum total thyroxin that indicated hyperthyroidism. After the intervention of rapamycin, retrobulbar fibrosis and retrobulbar adipogenesis were significantly improved, and the incidence of ophthalmopathy was reduced from 80%-90% to 20%. Moreover, the increase of total thyroxin was reduced from 80% to 20%, and the metabolic condition and thyroid pathology were also improved. Flow cytometry of the spleen, immunohistochemistry of the thyroid and orbital tissue revealed that GO mice exhibited Th1 dominance in Th1/Th2 balance and reduction of Treg cells. After the intervention of rapamycin, flow cytometry showed that the ratio of Th1 and Th17 cells decreased and the ratio of Th2 and Treg cells increased. Immunohistochemistry of thyroid and orbital tissues also confirmed improvement of Th1/Th2 cell imbalance and Treg cell reduction.Conclusion:GO mouse model showed a significant imbalance of CD4 + T cell subsets, and rapamycin could not only regulate the disorder of CD4 + T cell subsets in GO mice, but also effectively improve the phenotype of ophthalmopathy and hyperthyroidism. Therefore, the imbalance of CD4 + T cell subsets is one of the etiological intervention targets of GO, and rapamycin is a potential intervention mode of GO, which can be further explored by randomized clinical studies in the future.

Objective:To understand the epidemiological characteristics and trends of syphilis in Kashgar area of Xinjiang Uygur Autonomous Region and provide a basis for formulating syphilis control measures.Methods:A descriptive epidemiological method was used to analyze the epidemiological characteristics of syphilis cases reported in Kashgar from 2005 to 2020, and the Joinpoint 4.8.0.1 software was used to calculate the annual percent change (APC) and perform trend testing.Results:From 2005 to 2020, 75 331 syphilis cases were reported in Kashgar. The number of syphilis cases increased from 720 in 2005 to 4 275 in 2020. The reported incidence increased from 19.57/100 000 in 2005 to 93.86/100 000 in 2020 in two stages. From 2005 to 2014, the reported incidence increased from 19.57/100 000 to 188.17/100 000, with an average annual increase of 28.24%. From 2014 to 2020, the reported incidence decreased from 188.17/100 000 to 93.86/100 000, with an average annual decrease of 12.58%. The reported incidence of primary syphilis, secondary syphilis, tertiary syphilis and fetal-transmitted syphilis increased first and then decreased with time. However, the reported incidence of recessive syphilis has been on the rise. Since 2018, the ratio of recessive syphilis has exceeded that of primary syphilis, becoming the main epidemic type. The incidence ratio of male to female was 0.97∶1 (37 097∶38 234); all age groups had reported cases, with 20-49-year-old group the most, accounting for 55.65% (41 921/75 331) of the total number of reported cases; occupational distribution was dominated by farmers, accounting for 71.15% (53 595/75 331) of all reported cases, and the proportion of farmers was increasing year by year, from 35.00% in 2005 to 79.04% in 2020.Conclusions:The situation of syphilis in Kashgar was serious in 2005-2020. We should strengthen the publicity of health knowledge and health education,especially strengthen the health education and prevention of young and middle-aged people, farmers, women of childbearing age and other key groups. Additional, the screening that raises syphilis ceaselessly even and detects level, accomplish early discovery, standard report and cure, in order to curb the popularity of syphilis.

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. Conclusion The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.