Objective To investigate the effect of miR-217 on gefitinib resistance in non-small cell lung cancer(NSCLC),and to explore the downstream target genes and related pathways.Methods qRT-PCR was used to detect the expression of miR-217 in human lung normal epithelial cell lines BEAS-2B,NSCLC cell lines A549,HCC827,PC9,NCI-H1975 and gefitinib resistant strain PC9/GR.PC9/GR cells were selected and the cells of control group,NC-mimic group,miR-217 mimic group,miR-217 mimic+si-NC group,and miR-217 mimic+si-FOXO3 group were constructed using liposome transfection technique.CCK8 and clonal formation assay were used to detect changes in cell proliferation capacity,flow cytometry was used to detect changes in cell apoptosis capacity,and western blot was used to detect protein expression related to PI3K/AKT signaling pathway.The Targetscan bioinformatics website predicted the downstream target genes of miR-217,and the correlation between miR-217 and the target gene FOXO3 was detected by dual luciferase assay.Results Compared with BEAS-2B cells,the expression of miR-217 in A549,HCC827,PC9 and NCI-H1975 cells was significantly decreased(P＜0.05).With the increase of gefitinib concentration,the expression of miR-217 gene in PC9 cells was gradually decreased(P＜0.05),and the expression of miR-217 in PC9/GR cells was lower than that in PC9(P＜0.05).Compared with the control group and NC-mimic group,the cell proliferation capacity of miR-217 mimic group was significantly decreased(P＜0.05),the number of apoptosis was increased(P＜0.05),and the expression levels of p-PI3K and p-AKT were decreased(P＜0.05).Dual luciferase reporter gene assay proved that FOXO3 is the target of miR-217.Compared with miR-217 mimic group and miR-217 mimic+si-NC group,the cell drug resistance of miR-217 mimic+si-FOXO3 group was increased(P＜0.05),the proliferation ability was significantly increased(P＜0.05),and the number of apoptosis was decreased(P＜0.05).The expression levels of P-PI3K and P-AKT were increased(P＜0.05).Conclusion Overexpression of miR-217 reversed the resistance of PC9/GR to gefitinib in NSCLC cells and inhibited the proliferation and accelerated apoptosis of PC9/GR cells,which may be related to the regulation of PI3K/AKT signaling pathway by targeting FOXO3.

Background The effects of meteorological factors and air pollutants on ischemic heart disease (IHD) hospitalizations in Urumqi have not been fully understood. Objective To investigate the effects of meteorological conditions (temperature, relative humidity) and common air pollutants [fine particulate matter (PM_2.5), inhalable particulate matter (PM₁₀), ozone (O₃), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), and carbon monoxide (CO)] on the daily hospitalization volume of IHD, and to provide a scientific basis for the development of targeted prevention and management strategies. Methods Basic information of 90622 IHD hospitalized patients in Urumqi City was collected from January 1, 2014 to December 31, 2022, and daily air pollutant concentration data and meteorological data were collected during the same period. The meteorological data included daily mean temperature, daily maximum temperature, daily minimum temperature, and daily mean relative humidity, and the common air pollutants included PM_2.5, PM₁₀, daily maximum 8-h average concentration of O₃ (O₃_8 h), SO₂, NO₂, and CO. Descriptive statistical analyses (mean, standard deviation, and quartiles) were performed on the collected data. A distribution lag nonlinear model (DLNM) based on time-stratified case-crossover design was established to estimate the lagged effects (RR) as well as the cumulative lagged effects (RR_cum) of daily mean temperature, relative humidity, and different air pollutants on the number of IHD admissions, stratified by gender and age (<60 and ≥60 years). Subsequently, a generalized additive model (GAM) was used to explore the effects of cold waves (≤ P₅ of the daily minimum temperature and lasting ≥3 d) versus heat waves (≥ P₉₅ of the daily maximum temperature and lasting ≥3 d) on IHD hospitalizations and the potential interactions between temperature and the more influential air pollutants [particulate matter (PM) and O₃_8 h] on IHD hospitalizations. Results The maximum number of IHD hospitalizations in a single day in Urumqi from January 1, 2014 to December 31, 2022 was 100, and the average daily number of hospitalized IHD patients was 27. Daily mean temperature, relative humidity, and air pollutants had different nonlinear relationships and hysteresis with IHD hospitalizations. Extremely low temperatures (<P₁: −18 °C) showed the greatest risk to admission for the total IHD population at a cumulative lag of 31 d (lag0-31) (RR_cum=2.092, 95%CI: 1.261,3.471). Female [lag0-31, RR_cum and 95%CI: 3.416 (2.296,5.082)] and people ≥60 years old [lag0-31, RR_cum and 95%CI: 2.356 (1.681,3.303)] were more sensitive to extremely low temperatures. The risk of IHD hospitalization was greatest on lag20 for cold waves (RR=1.242, 95%CI: 1.053, 1.465), and no lagged effect of heat waves on the number of IHD hospitalizations was found. There was a positive interaction (SI >1, P<0.001) between temperature, PM, and O₃_8 h on the risk of IHD hospitalization, especially for low temperature-high PM and O₃_8 h. Conclusion Both low temperature and high pollutant concentrations associate with an increase in IHD hospitalizations with lagged effects in Urumqi from 2014 to 2022, while cold waves associate with a higher risk of IHD admissions. Females and people aged 60 years and older are at high risk.

Objective:To automatically segment four body components at the T4 thoracic veertebra plane on chest CT in the newly diagnosed multiple myeloma(MM)patients by deep learning model,and to discuss the correlation between the four body components and the prognosis of the MM patients.Methods:The retrospective analysis was conducted on the clinical data of the MM patients diagnosed in our hospital from January 2017 to December 2021.The clinical informations such as age,gender,weight,height,and body mass index(BMI)of the patients were collected.The laboratory data of the patients were collected,including serum levels of lactate dehydrogenase(LDH),calcium(Ca),creatinine(Scr),albumin(Alb),hemoglobin(Hb),β2-microglobulin(β2-MG),and serum free light chains.The chest CT images of 79 regularly evaluated MM patients detected by deep learning model were divide into four body components:pectoralis major,pectoralis minor,subcutaneous fat,and mediastinal fat.Image J software was used to detect the areas of the four body components at the T4 thoracic vertebra plane,and their correlation with the prognosis of the MM patients was analyzed by Kaplan-Meier survival analysis.Results:The univariate analysis results showed that the area of subcutaneous fat,serum Ca levels,Scr levels,and International Staging System(ISS)stage were related to the overall survival(OS)of the MM patients(HR=2.260,95％CI:1.116-4.578,P=0.024;HR=2.088,95％CI:1.007-4.327,P=0.048;HR=2.209,95％CI:1.105-4.414,P=0.025;HR=1.730,95％CI:1.040-2.879,P=0.035).The multivariate analysis results showed that the area of subcutaneous fat among the four body components was an independent risk factor affecting the prognosis of the MM patients(95％CI:1.228-5.782,P=0.013).The Log-Rank test results showed that compared with high subcutaneous fat area group,the OS of the patients in low subcutaneous fat area group was decreased(P=0.018).There was no significant difference in OS of the patients with different genders between high subcutaneous fat area group and low subcutaneous fat area group(P＞0.05).In the patients without hematopoietic stem cell transplantation,compared with high subcutaneous fat area group,the OS of the patients in low subcutaneous fat area group was decreased(P=0.037).Conclusion:Among the four body components at the T4 thoracic vertebra plane,the area of subcutaneous fat is related to the OS of the MM patients and it is an independent risk factor for the prognosis of the MM patients,while the areas of mediastinal fat,pectoralis major,and pectoralis minor have no predictive value for the prognosis of the MM patients.

OBJECTIVE To explore the renal protective mechanism of Shenbining granules on IgA nephropathy （IgAN） rats based on mitochondrial quality control system. METHODS IgAN rat model was established by the method of “bovine serum albumin+carbon tetrachloride+lipopolysaccharide”. The model rats were randomly divided into model group， prednisone acetate group （6.25 mg/kg）， Shenbining equal-dose group （4.1 g/kg） and Shenbining high-dose group （20.5 g/kg）. The normal rats were taken as the normal control group， with 12 rats in each group. Rats were given corresponding drugs or distilled water intragastrically in each group， once a day， for 4 consecutive weeks. After the last medication， the 24 h total urinary protein （24 h- UTP） and erythrocyte count in urine were determined， and the levels of serum creatinine （Scr）， blood urea nitrogen （BUN）， albumin （ALB） and alanine transaminase （ALT） were also detected. The histopathological changes in the kidneys and changes in IgA deposition in the mesangial area of the kidney were observed. mRNA and protein expression levels of PTEN-induced putative kinase 1 （PINK1）， E3 ubiquitin ligase（Parkin）， microtubule-associated protein 1 light chain-3 （LC3）， dynamin-related protein 1 （Drp1） and mitofusin 2 （Mfn2） were detected in the kidney tissues of rats. RESULTS Compared with model group， 24 h-UTP， urinary erythrocyte count， ALT， BUN and Scr levels， LC3-Ⅱ/LC3-Ⅰ mRNA ratio， mRNA and protein expressions of Drp1 were reduced significantly in prednisone acetate group， Shenbining equal-dose group and Shenbining high-dose group （P＜0.05）； ALB level， LC3-Ⅱ/LC3-Ⅰ protein ratio， mRNA and protein expressions of PINK1， Parkin and Mfn2 were increased significantly （P＜0.05）； the pathological morphology of kidney tissue in rats was significantly improved， and IgA deposition was significantly reduced. CONCLUSIONS Shenbining granule may reduce renal pathological injury in IgAN rats and protect renal function by activating the PINK1/Parkin pathway， enhancing mitochondrial autophagy， and correcting mitochondrial kinetic disorders.

High mobility group box 1 (HMGB1) has been reported to play an important role in experimental autoimmune encephalomyelitis (EAE). Astrocytes are important components of neurovascular units and tightly appose the endothelial cells of microvessels by their perivascular endfeet and directly regulate the functions of the blood-brain barrier. Astrocytes express more HMGB1 during EAE while the exact roles of astrocytic HMGB1 in EAE have not been well elucidated. Here, using conditional-knockout mice, we found that astrocytic HMGB1 depletion decreased morbidity, delayed the onset time, and reduced the disease score and demyelination of EAE. Meanwhile, there were fewer immune cells, especially pathogenic T cells infiltration in the central nervous system of astrocytic HMGB1 conditional-knockout EAE mice, accompanied by up-regulated expression of the tight-junction protein Claudin5 and down-regulated expression of the cell adhesion molecules ICAM1 and VCAM1 in vivo. In vitro, HMGB1 released from astrocytes decreased Claudin5 while increased ICAM1 and VCAM1 expressed by brain microvascular endothelial cells (BMECs) through TLR4 or RAGE. Taken together, our results demonstrate that HMGB1 derived from astrocytes aggravates EAE by directly influencing the immune cell infiltration-associated functions of BMECs.
Mice ; Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; HMGB1 Protein/metabolism* ; Endothelial Cells/metabolism* ; Mice, Inbred C57BL ; Mice, Knockout ; Blood-Brain Barrier/metabolism*

Objective:To study the efficacy and influencing factors of ursodeoxycholic acid (UDCA) in the treatment of cholesterol gallstone, so as to provide reference for the treatment of cholesterol gallstone by internal medicine.Methods:From March 1, 2017 to March 31, 2018, at outpatient department of gastroenterology of 9 Beijing medical centers including Peking University People′s Hospital, the Sixth Medical Center of PLA General Hospital, Beijing Huaxin Hospital, PLA Rocket Force Characteristic Medical Center, Peking University Aerospace Center Hospital, Beijing Youan Hospital of Capital Medical University and Beijing Tiantan Hospital of Capital Medical University, Beijing Tongren Hospital of Capital Medical University, and Beijing Shijitan Hospital of Capital Medical University, the data of patients with cholesterol gallstone treated by UDCA were collected. The inclusion criteria were that the largest diameter of stone was ≤10 mm and the stone was not detected under X-ray. The treatment plan was taking UDCA orally for 6 months at a dose of 10 mg·kg -1·d -1. The basic information of patients, the ultrasound examination results before treatment and 6 months after treatment, and scores of biliary abdominal pain and dyspepsia symptom were collected. Univariate and multivariate logistic regression were used to analyze the influencing factors of the efficacy in gallstrone dissolution by UDCA, and Wilcoxon signed rank test was used for statistical analysis. Results:A total of 215 patients were enrolled. The complete dissolution rate of gallstone was 19.5% (42/215) and partial dissolution rate was 50.7% (109/215), and the total effective rate was 70.2% (151/215). The complete dissolution rate of sandy stone was significantly higher than that of lumped stones (37.0%(17/46) vs. 14.8%(25/169); OR=3.377, 95% confidence interval (95% CI) 1.621 to 7.035, P=0.001). In lumped stones, the complete dissolution rate of the stones with diameter ≤5 mm was significantly higher than that of the stones with diameter >5 mm (37.5%(9/24) vs. 11.0%(16/145); OR=4.837, 95% CI 1.823 to 12.839, P=0.002). The complete dissolution rate of patients with higher body mass index ( OR=0.872, 95% CI 0.764 to 0.995, P=0.043) and longer disease course ( OR=0.942, 95% CI 0.912 to 0.973, P<0.001) was low. The results of multivariate logistic analysis indicated that long disease course of gallstone ( OR=0.940, 95% CI 0.908 to 0.974, P=0.001), rough gallbladder wall ( OR=0.438, 95% CI 0.200 to 0.962, P=0.040) and lumped stone ( OR=0.236, 95% CI 0.101 to 0.550, P=0.001) were independent risk factors of influencing the efficacy of stone dissolution by UDCA. As for lumped stones, the independent risk factors included long disease course of gallstone ( OR=0.926, 95% CI 0.877 to 0.978, P=0.006) and stone diameter >5 mm ( OR=0.142, 95% CI 0.043 to 0.470, P=0.001). After 6 months of UDCA treatment, score of biliary abdominal pain decreased from 0 (0 to 6) to 0 (0 to 0) and the score of dyspepsia symptom decreased from 1 (0 to 2) to 0 (0 to 0), and the differences between before treatment and after treatment were statistically significant ( Z=-8.50, and -9.13, both P<0.001). Conclusions:UDCA has a certain efficacy in cholesterol gallstone dissolution and can ease biliary abdominal pain and dyspepsia symptom. Long disease course of gallstone, rough gallbladder wall and stone diameter >5 mm are independent risk factors of poor efficacy in gallstone dissolution by UDCA.

Objective:To analyze the incidence and epidemiological characteristics of traumatic spinal cord injury in China in 2018.Methods:Multi-stage stratified cluster sampling was used to randomly select hospitals capable of treating patients with spinal cord injury from 3 regions，9 provinces and 27 cities in China to retrospectively investigate eligible patients with traumatic spinal cord injury admitted in 2018. National and regional incidence rates were calculated. The data of cause of injury，injury level，severity of injury，segment and type of fracture，complications，death and other data were collected by medical record questionnaire，and analyzed according to geographical region，age and gender.Results:Medical records of 4，134 patients were included in this study，with a male-to-female ratio of 2.99∶1. The incidence of traumatic spinal cord injury in China in 2018 was 50.484 / 1 million （95% CI 50.122-50.846）. The highest incidence in the Eastern region was 53.791 / 1 million （95% CI 53.217-54.365）. In the whole country，the main causes of injury were high falls （29.58%），as well as in the Western region （40.68%），while the main causes of injury in the Eastern and Central regions were traffic injuries （31.22%，30.10%）. The main injury level was cervical spinal cord in the whole country （64.49%），and the proportion of cervical spinal cord injury in the Central region was the highest （74.68%），and the proportion of lumbosacral spinal cord injury in the Western region was the highest （32.30%）. The highest proportion of degree of injury was incomplete quadriplegia （55.20%），and the distribution pattern was the same in each region. A total of 65.87% of the patients were complicated with fracture or dislocation，77.95% in the Western region and only 54.77% in the Central region. In the whole country，the head was the main combined injury （37.87%），as well as in the Eastern and Central regions，while the proportion of chest combined injury in the Western region was the highest （38.57%）. A total of 32.90% of the patients were complicated with respiratory complications. There were 23 patients （0.56%） died in hospital，of which 17（73.91%） died of respiratory dysfunction. Conclusions:The Eastern region of China has a high incidence of traumatic spinal cord injury. Other epidemiological features include high fall as the main cause of injury cervical spinal cord injury as the main injury level，incomplete quadriplegia as the main degree of injury，head as the main combined injury，and respiratory complications as the main complication.

Driven by demand and policy guidance, the construction of Internet hospitals is on a fast track mode in China. To address such a situation, the state requires that before Internet hospitals are admitted, the provincial health authorities should establish an Internet medical service supervision platform to interconnect with the Internet hospital information platform for real-time supervision. This study discussed and introduced the Internet medical service supervision platform in Henan province, covering its system architecture, functions, regulatory indicators and operation mode. The platform is officially in operation and has completed docking with 7 medical institutions. It can implement entire process supervision with a total of 186 indicators in five categories in Henan, providing a reference for the construction of Internet medical service supervision platforms in other provinces.

OBJECTIVE：To e xplore the health economic burden of hypertension patients at county-level areas and its influential factors in China. METHODS ：A questionnaire survey was conducted on hypertension patients in 7 county-level public hospitals from 6 provinces as Hebei ，Shandong，Shanxi provinces by using a convenient sampling method. Catastrophic health expenditure was defined by the standard of “medical and health expenditure exceeding 10％ of household income ”. The incidence ， average gap and relative gap of catastrophic health expenditure were analyzed. A multi-factor Logistic regression model analysis was used to analyze the influential factors that lead to catastrophi c health expenditure. RESULTS ：A total of 1 378 questionnaires were sent out ，and 925 valid questionnaires were collected with effective rate of 67.13％ . The incidence of catastrophic health expenditure，average gap and relative gap among hypertension patients were 23.03％，19.37％ and 84.12％，respectively. At different income levels ，the incidence of catastrophic health expenditure，average gap and relative gap were 72.67％ ， 96.79％ and 133.18％ in the poorest household group ，and were 1.94％ ，0.47％ and 24.23％ in the richest household group. Among different types of medical insurance ，the incidence of catastrophic health expenditure in patients covered by “New Rural Cooperative Medical Scheme （NRCMS）”the highest （31.30％）. The household income ，complications and the type of health insurance had significant impacts on the incidence of catastrophic health expenditure in hypertension patients （P＜0.05）. CONCLUSIONS：The incidence of catastrophic health expenditure in hypertension patients with different income levels is different. As the income level raised ，the incidence of catastrophic health expenditures continued to decrease. But the protection of household health expenditure by NRCMS is weak. It is suggested that a certain policy preference should be given to families with low income and patients with chronic diseases ，so as to ensure the rights and interests of patients with hypertension .

OBJECTIVE： To evaluate the economics of the full coverage policy for hypoglycemic essential medicines in Taizhou city， and to provide reference for improving medicine accessibility and essential medicine system in China. METHODS： The electronic health records and financial input data of diabetic patients were extracted from different districts and counties of Taizhou city during 2009-2016. In cohort study design， taking the implementation time of each district and county’s policies as the breakpoint， the data recorded annually were processed as annual data， forming the cohort data for 1 year before （baseline year） and 3 years after the implementation of the policies. According to the choice of free medicines after the implementation of the policy， they were divided into policy group and control group. Propensity score matching was used to balance the differences between two groups to get the final sample， and then the economics of the policy was evaluated with the methods of difference-in-differences. The cost and benefit of implementation policy were calculated. RESULTS： Totally 14 744 people of each group were got by propensity score matching. The mean annual financial expenses on free medicine per capita were 263.8 yuan. Compared with baseline year， mean annual medicine expenses per capita reduced by the policy were 649.2 yuan， and mean annual hospitalization expenses per capita were 624.7 yuan. Thus the input-output ratio of the policy was 1 ∶ 4.8. CONCLUSIONS： The implementation of the policy is beneficial to reduce the cost burden of patients and economical. It can be popularized and sustained through scientific design combined with relevant policies.