Objective: To investigate the effect of auricular therapy on sleep improvement and the GABAergic system pathway in a rat model of insomnia and to explore its possible mechanism. Methods: According to the random number table, 60 male SD rats were randomly divided into blank control, model, auricular point sticking, auricular bloodletting, and auricular bloodletting combined with sticking groups, with 12 rats per group. Insomnia was induced by intraperitoneal injection of p-chlorophenylalanine. After establishing the insomnia model, 36 rats were treated once a day with auricular point sticking or bloodletting for 5 consecutive days. After the intervention, the general condition and body weight of rats were observed; the righting reflex test was used to detect the sleep latency and duration; HE staining was used to observe the morphology of hypothalamic neuron cells; and an enzyme-linked immunosorbent assay was used to detect the GABA and glutamate content in rat serum. Immunohistochemistry(IHC) and real-time fluorescence quantitative PCR were used to detect GABA ARα1 and GABA ARγ2 protein and mRNA expression in the hypothalamus of rats, and Western blotting(WB) was used to detect GABA ARα1, GABA ARγ2, GAD65/67, GAT-1, and GABA-T protein expression in the hypothalamus of rats. Results: Compared with the blank control group, the model group had a lower body weight, a significantly shorter sleep duration (P<0.05), severe damage to the morphological structure of hypothalamic neurons with disordered cell arrangement, larger intercellular gaps, enlarged cell bodies, and a vacuolated appearance. All the intervention groups had significantly higher body weight and longer sleep duration than the model group (P<0.05). Compared with the other intervention groups, the auricular point sticking group had a longer sleep duration (P<0.05), and the hypothalamic neuron cells in all intervention groups improved, with the auricular point sticking group showing more apparent improvement. The model group had a lower GABA and higher glutamate contents, and GABA ARα1, GABA ARγ2, and GAD65/67 protein expression in the hypothalamus were lower than in the blank control group. In contrast, GAT-1 and GABA-T protein expression was higher, and GABA ARα1 and GABA ARγ2 mRNA expression was lower (P<0.05). The serum GABA content in the auricular point sticking and auricular bloodletting groups was higher, and the serum glutamate content in the auricular point sticking and auricular bloodletting combined sticking groups was lower than in the model group. GABA ARα1 mRNA expression in the hypothalamus of each intervention group was significantly increased, and GABA ARγ2 mRNA expression in the hypothalamus of the auricular point sticking and auricular bloodletting combined sticking groups increased. GABA ARα1(IHC, WB), GABA ARγ2(WB), and GAD65/67 protein expression in the hypothalamus of the auricular point sticking group increased, whereas GAT-1 and GABA-T protein expression decreased. GABA ARα1 and GABA ARγ2 protein expression(IHC, WB) in the hypothalamus of the auricular bloodletting group increased, whereas GABA-T protein expression decreased. GABA ARγ1(IHC) and GABA ARγ2(WB) protein expression in the hypothalamus of the auricular bloodletting combined sticking group increased, whereas GAT-1 and GABA-T protein expression decreased (P<0.05). Compared with in the inventation groups, the serum GABA content in the auricular point sticking group increased, the serum glutamate content decreased, GABA ARα1 and GABA ARγ2 mRNA expression in the hypothalamus increased, and GABA ARα1(IHC), GAD65/67 protein expression increased. In contrast, GABA-T protein expression decreased (P<0.05), and GABA ARγ2 protein expression(IHC) in the hypothalamus of the auricular bloodletting group increased (P<0.05). Conclusion Auricular therapy, particularly auricular point sticking, may have modulated the GABAergic system pathway by upregulating hypothalamic GABA ARα1, GABA ARγ2, and GAD65/67 protein expression while downregulating GAT-1 and GABA-T protein expression to alleviate symptoms in an insomnia rat model.

Objective:The aim is to construct an evaluation framework for clinical research benefits,and provide a reference for the formulate of evaluation standards for clinical research benefits.Methods:The Delphi method was used to carry out expert consultation,and the mean,score of importance,coefficient of variation and coordination,etc.of evaluation indicators were summarized and calculated,to screen evaluation indicators for clinical research benefits.Results:Twenty-three experts in this field were selected for correspondence,and their enthusiasm was 100%in both rounds,the authority coefficients were≥0.90,and Kendall's coefficients of concordance were<0.25(P<0.001).By referring to the mean and coefficient of variation of the indicators,as well as combining them with expert suggestions,an evaluation framework for clinical research benefits was ultimately formed with 2 primary indicators,5 secondary indicators,and 8 tertiary indicators.Conclusion:The evaluation framework for clinical research benefits constructed in this paper can comprehensively evaluate the research benefits,as well as provide a basis for reasonably determining the research risk-benefit ratio and developing quantitative evaluation tools for clinical research benefits.

Objective:To investigate the clinical characteristics and correlation of sleep disturbances(SD)with cognitive impairment-associated cerebral small vascular disease(CSVD-CI)in elderly patients.Methods:In this cross-sectional study, 261 elderly CSVD-CI patients admitted to the Department of Neurology, Second Hospital of Tianjin Medical University between December 2019 and December 2021 were continuously enrolled.The Pittsburgh Sleep Index Scale(PSQI)was used to evaluate the overall sleep quality.Those with a PSQI score ≥7 was assigned to the CSVD-CI with sleep disturbances(CSVD-CI-SD)group, while those with a PSQI score <7 was assigned to the CSVD-CI without SD(CSVD-CI-NSD)group.The Montreal Cognitive Assessment(MoCA)was used to evaluate the cognitive function of patients with CSVD-CI, and scores on the overall cognitive function and various cognitive domains were compared between the CSVD-CI-SD group and the CSVD-CI-NSD group.Results:There were no significant differences between the CSVD-CI-SD group and the CSVD-CI-NSD group in sex ratio, age, education level and comorbidities( P>0.05). Compared with the CSVD-CI-NSD group, patients in the CSVD-CI-SD group took longer to fall asleep, had worse sleep efficiency, a shorter sleep duration, more obvious SD at night, worse sleep quality, more use of sleeping drugs, and more obvious daytime dysfunction(all P<0.05). Compared with the CSVD-CI-NSD group, the total MoCA score, attention score and orientation score in the CSVD-CI-SD group were significantly decreased( P<0.01). Correlation analysis results showed that the total MoCA score and attention in the CSVD-CI-SD group were negatively correlated with SD at night( r=-0.198, r=-0.115, P<0.05 for both), and orientation was negatively correlated with sleep quality( r=-0.170, P<0.05). Conclusions:The prevalence of SD is high in CSVD-CI patients, with CSVD-CI-SD patients showing more obvious overall cognitive, attention and orientation impairment in MoCA.Additionally, the total MoCA score and attention are negatively correlated with nighttime SD, and orientation is negatively correlated with sleep quality in CSVD-CI-SD patients.

Objective:To analyze the burden and changing trends of periodontal disease in adults of the mainland of China from 1990 to 2019, and to predict the incidence trends of periodontal disease in the next 25 years, with a goal to provide a basis for reducing the burden of periodontal disease and formulating relevant prevention and treatment measures.Methods:Data on the incidence, prevalence, and disability adjusted life years (DALY) rate of periodontal disease among adults in the mainland of China from 1990 to 2019 were extracted from the global burden of disease study 2019 (GBD 2019) database. The estimated annual percent change (EAPC) was used to estimate the temporal trend of periodontal disease, and the age-period-cohort model (APC) was used to predict the age-standardized incidence of periodontal disease in Chinese adults from 2020 to 2044.Results:From 1990 to 2019, the incidence, prevalence, and DALY rate of adult periodontal disease in the mainland of China showed an increasing trend, with EAPCs of 0.3 (95% CI: 0.1-0.6), 0.5 (95% CI: 0.1-0.8), and 0.5 (95% CI: 0.1-0.8), respectively. The incidence and prevalence of periodontitis among the population aged 35-39 years old and 40-44 years old increased the most significantly, with EAPCs of 0.8 and 0.7, respectively, whereas the change in periodontal disease prevalence tended to be stable and the increase trend in prevalence was lower in the elderly group (EAPC=0.4). The incidence (EAPC=2.1), prevalence (EAPC=2.6) and DALY rate (EAPC=2.6) of periodontal disease in females increased more than those in males (EAPC=1.9, 2.4, and 2.4, respectively), of which the prevalence had exceeded that of males in 2019. The APC model predicted that the prevalence of periodontal disease in the period of 2020-2044 in China would still be on an upward trend, and the increase rate would be higher in females than in males. Conclusions:The burden of periodontal disease among adults in China had been increasing over the past 30 years, especially among young and middle-aged adults as well as females, and the incidence of periodontal disease will continue to increase over the next 25 years.

ObjectiveTo determine the characteristics and influencing factors of hepatitis C virus （HCV） co-infection among HIV concordant couples in Dehong Prefecture. MethodsUsing the data of newly reported HIV concordant couples in Dehong Prefecture from 2016 to 2019， we collected the demographic characteristics， exposure history， and HCV infection to determine the characteristics of HCV co-infection among HIV concordant couples. ResultsAmong the 160 HIV concordant couples included in the study， 46 （28.8%） males and 14 （8.8%） females were co-infected with HCV. The prevalence of HIV-HCV co-infection was higher among the male spouses who were diagnosed less than 40， Jingpo ethnic， Burmese， illiteracy， farmers， and intravenous drug users. In contrast， the prevalence of HIV-HCV co-infection was higher among the female spouses who were diagnosed less than 40， Jingpo ethnic， and Burmese. Logistic regression analysis among male spouses showed that the Jingpo ethnic and intravenous drug users had higher risk of HCV co-infection. ConclusionHIV concordant couples in Dehong Prefecture have high prevalence of HIV-HCV co-infection. Effective intervention strategies should be developed based on ethnic-specific factors and exposure characteristics among male and female spouses of HIV concordant couples.

Objective:Taking emergency department (ED) as a starting point, to analyze the epidemiological characteristics and mortality risk factors of sepsis, and to provide evidences for ED to carry out the strategy of "three early and two lower" for sepsis.Methods:Based on the ED and inpatient medical record management information platform of Tianjin Medical University Gernal Hospital, adult ED patients with sepsis from January 1, 2017 to December 31, 2020 were included according to the third international consensus definitions for sepsis and septic shock in 2016 and the consensus of Chinese experts on early prevention and blocking of sepsis in 2020. The epidemiological characteristics of patients were retrospectively analyzed. Chi-square test was used to compare the difference of age, sex, hospitalization times, length of stay, hospitalization cost and infection location between dead patients and survival patients, and a stepwise logistic regression model was used to analyze the influencing factors of mortality in hospitalized patients with ED sepsis.Results:A total of 7 494 patients with sepsis in ED were included in this study, and the annual and monthly component ratios varied from 3.8‰ to 6.1‰ and 2.0‰ to 9.0‰, respectively. The main characteristics of patients with sepsis in ED were as follows: 40-69 years old (46.0%), male (59.0%), mostly diagnosed with sepsis (96.8%), mainly treated with urban health insurance (59.6%), and ED diagnosis and treatment fees of 2 000-8 000 Yuan (51.1%). The mortality of hospitalized patients with ED sepsis was 24.4% and that of hospitalized patients with septic shock was 28.8%. The main characteristics of hospitalized patients with ED sepsis were as follows: most of them were male (56.2%) patients over 70 years old (56.0%), most of them were diagnosed with sepsis (94.0%) and hospitalized for the first time (76.0%), the median hospitalization time was 15 d, most of them were hospitalized under urban health insurance (65.2%), and the median hospitalization fees was 47 000 Yuan. The risk factors of death were influenced by age and length of stay. Patients aged 70 years or older had a higher risk of death than those aged from 18 to 39 years, and patients with a length of stay of more than 7 d had a lower risk of death than those with a length of stay of shorter than 7 d. The primary infection focus were mainly respiratory and urinary systems, while the death rate of patients with hematological and abdominal infections was relatively high, and the difference was statistically significant ( P<0.01). Respiratory and abdominal infections were risk factors for death in patients with ED sepsis. Conclusions:The composition ratio of sepsis in ED patients is not regular in time, so vigilance of sepsis in elderly men and patients with respiratory system, blood system, urinary system and abdominal infections should be constantly raised. Patients with sepsis who are older, hospitalized more frequently, hospitalized for a shorter time, and infected in the respiratory system or abdomen have a higher risk of death.

Objective:To study the incidences of postoperative complications and nutritional status following different timings of stoma reversal in necrotizing enterocolitis (NEC).Method:From January 2017 to December 2019, NEC patients receiving enterostomy surgery and later stoma reversal in our hospital were retrospectively analyzed. They were assigned into three groups according to the timing of stoma reversal: early group (reversal within 8 weeks of stoma formation), middle group (reversal at 8~12 weeks from stoma formation) and late group (reversal after 12 weeks from stoma formation). Weight-for-age-Z-score (WAZ) was used to evaluate nutritional status.Result:A total of 56 infants were enrolled, including 6 cases in the early group, 11 cases in the middle group, and 39 cases in the late group. The gestational age and birth weight were (33.4±3.4) weeks and (1 894±640) g, respectively. The median age of stoma formation and the interval between stoma formation and reversal were 16.5 (8.0, 28.2) days and 94.0 (76.5, 126.5) days. No significant differences existed on gestational age, birth weight, age of stoma formation and complications of stoma reversal among the three groups ( P>0.05). The incidence of growth retardation (WAZ<-2) was 14.3% at stoma formation, and significantly increased to 62.5% at stoma reversal ( P<0.05). The WAZ at stoma reversal in early, middle and late groups were (-3.2±1.9), (-3.0±1.6) and (-2.3±1.5), without significant differences( P>0.05). The WAZ gradually increased to (-0.7±1.2), (-0.1±2.0) and (-0.1±0.8) at 42~48 weeks after reversal, respectively. Conclusion:The timing of stoma reversal may not influence the complications of reversal. Growth retardation are common in NEC infants with stoma formation and stoma reversal may improve the nutritional status of the infants. Early reversal of stoma is suggested to improve the nutritional status of patients with poor weight gain after stoma formation.

Objective:To explore the value of different machine learning models based on Gd-EOB-DTPA enhanced MRI hepatobiliary phase radiomics features in preoperative prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC).Methods:The data of 132 patients with HCC confirmed by pathology in the First Affiliated Hospital of Soochow University from January 2015 to May 2020 were retrospectively analyzed, including 72 cases of positive MVI and 60 cases of negative MVI. According to the proportion of 7∶3, the cases were randomly divided into training set and validation set. The radiomics features of hepatobiliary phase images for HCC were extracted by PyRadiomics software. The clinical and radiomics features of the training set were screened by the least absolute shrinkage and selection operator (LASSO) regression with 5 fold cross-validation, and then the optimal feature subset was obtained. Six machine learning algorithms, including decision tree, extreme gradient boosting, random forest, support vector machine (SVM), generalized linear model (GLM) and neural network, were used to build the prediction models, and the ROC curves were used to evaluate the prediction ability of the models. DeLong test was used to compare the differences of area under the curve (AUC) for 6 machine learning algorithms.Results:Totally 14 features selected by LASSO regression were obtained to form the optimal feature subset, including 2 clinical features (maximum tumor diameter and alpha-fetoprotein) and 12 radiomics features. The AUCs of decision tree, extreme gradient boosting, random forest, SVM, GLM and neural network based on the optimal feature subset were 0.969, 1.000, 1.000, 0.991, 0.966, 1.000 in the training set and 0.781, 0.890, 0.920, 0.806, 0.684, 0.703 in the validation set, respectively. There were significant differences in the AUCs between extreme gradient boosting and GLM or neural network ( Z=2.857, 3.220, P=0.004, 0.001). The differences in AUCs between random forest and SVM, GLM, or neural network were significant ( Z=2.371, 3.190, 3.967, P=0.018, 0.001,<0.001). The difference in AUCs between SVM and GLM was statistically significant ( Z=2.621 , P=0.009). There were no significant differences in the AUCs among the other machine learning models ( P>0.05). Conclusion:Machine learning models based on Gd-EOB-DTPA enhanced MRI hepatobiliary phase radiomics features can be used to preoperatively predict MVI of HCC, particularly the extreme gradient boosting and random forest models have high prediction efficiency.

Objective:To analyze the longitudinal characteristics of CD4 +T lymphocytes (CD4) among the adult HIV/AIDS on antiretroviral therapy (ART) and the related factors. Methods:A retrospective cohort of adult HIV/AIDS starting ART in Dehong Dai and Jingpo Autonomous Prefecture (Dehong) in 2007-2016 was followed up to December 31, 2018. Group-based trajectory models were utilized to identify CD4 subgroups based on immune recovery (whether and when CD4 reached the average level of >500 cells/μl). The demographics and information at ART baseline were described, and the related factors were analyzed with polytomous logistic regression. The SAS 9.4 software was used for statistical analysis.Results:A total of 7 605 adults with HIV/AIDS were included, of which the median ( P 25, P 75) age at ART were 36 (30,43) years old, 61.0% were male, 42.5% were Han nationality, and 60.8% with the education of primary school or below. The follow-up duration M ( P 25, P 75) was 6.1 (4.1,8.1) years. HIV/AIDS in Dehong showed four CD4 trajectory subgroups from low to high: below the average level, primary recovery to a normal level, full recovery to a moderate level, and normal steady level, accounting for 34.4%, 39.8%, 20.6%, and 5.2%, respectively. When compared with corresponding control groups, age <35 years at ART, female, education of middle school or above, sexual transmission, no opportunistic infection, CD4 ≥200 cells/μl, baseline regimen with tenofovir (TDF) and time from HIV diagnosis to ART <1 year were the related factors facilitating the higher CD4 subgroups. Conclusions:The various CD4 immune recoveries of HIV/AIDS were changing patterns after ART. Starting ART with a high CD4 level was beneficial to CD4 recovery to normal level during the follow-up period. Early initiation of ART and exceptional attention to CD4 immune recovery should be encouraged after the ART.

Gestational diabetes mellitus is one of the most common complications of pregnancy. Poor control of maternal blood glucose during pregnancy seriously threatens the short-term and long-term health of pregnant women and fetuses. Standardized blood glucose monitoring during pregnancy can significantly reduce the short-term and long-term complications of gestational diabetes mellitus mothers and infants, and blood glucose self-monitoring is currently the most widely used and most convenient blood glucose monitoring method in clinical practice. This article reviews the related concepts, main monitoring content, current situation, influencing factors and improvement strategies of blood glucose self-monitoring in patients with gestational diabetes mellitus. The aim is to raise the attention of medical and nursing staff to blood glucose self-monitoring in patients with gestational diabetes mellitus, and provide a theoretical basis for the prevention and treatment of adverse outcomes of gestational diabetes mellitus.