Objective:To investigate the effect of altitude on the risk of pre-eclampsia (PE).Methods:This cross-sectional study included 19 246 pregnant women who delivered in Gansu Provincial Hospital from January 2016 to December 2020. General clinical data, pregnancy outcomes and neonatal outcomes were collected. The diagnosis of PE was based on the disease diagnosis coding of medical record information system and the Chinese guidelines for the diagnosis and treatment of hypertensive disorders in pregnancy (2020). According to the altitude of residence, the subjects were divided into low altitude group (9 931 cases), middle altitude group (9 068 cases) and high altitude group (247 cases). Univariate and multivariate logistic regression analyses were used to evaluate the relationship between altitude and the risk of PE, after adjusting for confounding factors such as age, ethnicity, mode of conception, gestational diabetes mellitus, and hemoglobin level.Results:(1) Among the 19 246 pregnant women, 752 (3.91%, 752/19 246) were diagnosed with PE. The incidence of PE in the low altitude group, middle altitude group and high altitude group was 2.95% (293/9 931), 4.91% (445/9 068) and 5.67% (14/247), respectively. With the increase of living altitude, the incidence of PE increased significantly ( P<0.001). (2) The results of univariate logistic analysis showed that compared with the low altitude area, the risk of PE in pregnant women living in the middle altitude area and high altitude area increased by 70% ( OR=1.70, 95% CI: 1.46-1.97; P<0.001) and 98% ( OR=1.98, 95% CI: 1.14-3.43; P=0.016). (3) The results of multivariate logistic regression analysis showed that after fully adjusting for confounding factors, the risk of PE increased by 40% for every 500 meters of elevation ( OR=1.40, 95% CI: 1.25-1.57; P<0.001). Compared with those living in low altitude areas, the risk of PE in pregnant women living in middle altitude and high altitude areas increased by 72% ( OR=1.72, 95% CI: 1.47-2.00; P<0.001) and 100% ( OR=2.00, 95% CI: 1.07-3.74; P=0.030). Conclusion:In the high-altitude environment of Gansu Province, the risk of PE gradually increases with the increase of altitude.

Objective:Under the background of the"Healthy Shanxi 2030"strategy,it systematically analyzes the spatiotemporal evolution characteristics and equilibrium of health resource allocation in Shanxi Province,and explores the optimization path to promote the high-quality development of health care.Methods:Based on the health statistics of Shanxi Province from 2012 to 2023,it systematically analyzes the spatiotemporal evolution characteristics and equilibrium of health resource allocation in Shanxi Province by using Gini coefficient,Theil index and statistical description method.Results:The total number of health resources in Shanxi Province continues to grow steadily,and by the end of 2023,the total number of medical and health institutions in the province will reach to 37 838,the number of hospital beds will reach to 223 650,and the total number of health technicians will be 260 536.Despite this,the imbalance of regional allocation is still significant,showing a"core-periphery"structure.According to the calculation of the Gini coefficient and the Theil index,from 2011 to 2023,the overall equilibrium of the health resources allocation in Shanxi Province showed a gradual improvement trend,which was reflected in the fact that the Gini coefficient of the number of health institutions decreased from 0.287 to 0.268,and the Theil index decreased by 42.40％.However,the structural imbalance of key human resources such as registered nurses is still significant,and the Gini coefficient continues to be higher than 0.30.The regional differences are mainly due to the economic gradient differentiation,policy orientation and population aging pressure,among which the Gini coefficient in the Jinzhong region group is 0.33,and the contribution of regional differences to the overall imbalance is more than 51.00％.Conclusion:Promote the balanced allocation of health resources and help achieve the strategic goal of"Healthy Shanxi"by optimizing the spatial distribution of resources,strengthening the capacity of grassroots services,improving the talent training and mobility mechanism,and deepening the reform of the hierarchical diagnosis and treatment system.

Objective:To investigate the effect of altitude on the risk of pre-eclampsia (PE).Methods:This cross-sectional study included 19 246 pregnant women who delivered in Gansu Provincial Hospital from January 2016 to December 2020. General clinical data, pregnancy outcomes and neonatal outcomes were collected. The diagnosis of PE was based on the disease diagnosis coding of medical record information system and the Chinese guidelines for the diagnosis and treatment of hypertensive disorders in pregnancy (2020). According to the altitude of residence, the subjects were divided into low altitude group (9 931 cases), middle altitude group (9 068 cases) and high altitude group (247 cases). Univariate and multivariate logistic regression analyses were used to evaluate the relationship between altitude and the risk of PE, after adjusting for confounding factors such as age, ethnicity, mode of conception, gestational diabetes mellitus, and hemoglobin level.Results:(1) Among the 19 246 pregnant women, 752 (3.91%, 752/19 246) were diagnosed with PE. The incidence of PE in the low altitude group, middle altitude group and high altitude group was 2.95% (293/9 931), 4.91% (445/9 068) and 5.67% (14/247), respectively. With the increase of living altitude, the incidence of PE increased significantly ( P<0.001). (2) The results of univariate logistic analysis showed that compared with the low altitude area, the risk of PE in pregnant women living in the middle altitude area and high altitude area increased by 70% ( OR=1.70, 95% CI: 1.46-1.97; P<0.001) and 98% ( OR=1.98, 95% CI: 1.14-3.43; P=0.016). (3) The results of multivariate logistic regression analysis showed that after fully adjusting for confounding factors, the risk of PE increased by 40% for every 500 meters of elevation ( OR=1.40, 95% CI: 1.25-1.57; P<0.001). Compared with those living in low altitude areas, the risk of PE in pregnant women living in middle altitude and high altitude areas increased by 72% ( OR=1.72, 95% CI: 1.47-2.00; P<0.001) and 100% ( OR=2.00, 95% CI: 1.07-3.74; P=0.030). Conclusion:In the high-altitude environment of Gansu Province, the risk of PE gradually increases with the increase of altitude.

Objective:Under the background of the"Healthy Shanxi 2030"strategy,it systematically analyzes the spatiotemporal evolution characteristics and equilibrium of health resource allocation in Shanxi Province,and explores the optimization path to promote the high-quality development of health care.Methods:Based on the health statistics of Shanxi Province from 2012 to 2023,it systematically analyzes the spatiotemporal evolution characteristics and equilibrium of health resource allocation in Shanxi Province by using Gini coefficient,Theil index and statistical description method.Results:The total number of health resources in Shanxi Province continues to grow steadily,and by the end of 2023,the total number of medical and health institutions in the province will reach to 37 838,the number of hospital beds will reach to 223 650,and the total number of health technicians will be 260 536.Despite this,the imbalance of regional allocation is still significant,showing a"core-periphery"structure.According to the calculation of the Gini coefficient and the Theil index,from 2011 to 2023,the overall equilibrium of the health resources allocation in Shanxi Province showed a gradual improvement trend,which was reflected in the fact that the Gini coefficient of the number of health institutions decreased from 0.287 to 0.268,and the Theil index decreased by 42.40％.However,the structural imbalance of key human resources such as registered nurses is still significant,and the Gini coefficient continues to be higher than 0.30.The regional differences are mainly due to the economic gradient differentiation,policy orientation and population aging pressure,among which the Gini coefficient in the Jinzhong region group is 0.33,and the contribution of regional differences to the overall imbalance is more than 51.00％.Conclusion:Promote the balanced allocation of health resources and help achieve the strategic goal of"Healthy Shanxi"by optimizing the spatial distribution of resources,strengthening the capacity of grassroots services,improving the talent training and mobility mechanism,and deepening the reform of the hierarchical diagnosis and treatment system.

Objective To rescue a recombinant oncolytic influenza virus chimeric with IL-21 and evaluate its inhibitory effects and safety against hepatocell ular carcinoma(HCC)both in vitro and in vivo,and to explore the mechanism by which this virus enhances antitumor effects when combined with anti-programmed cell death protein 1(anti-PD-1)antibody.Methods The IL-21 gene fragment was inserted into the nonstructural protein(NS)sequence of the influenza virus PR8 using reverse genetics(RG)technology to rescue the recombinant oncolytic influenza virus rOV-IL-21-NS.The virus titer and virulence were determined using the 50％tissue culture infectious dose(TCID50)and hemagglutination assays.The successful insertion of the exogenous gene into the NS sequence was verified using RT-qPCR,gel electrophoresis,and sequencing analysis.Viral morphology and size were observed with transmission electron microscopy.The impact of the virus on the viability of hepatocellular carcinoma cells was assessed with CCK-8 assay.A subcutaneous tumor model of HCC was established in 45 female C57BL/6 mice(8 weeks old,weighing 16～20 g),and then the mice were randomly assigned into PBS,PR8,anti-PD-1,rOV-IL-21-NS,and the rOV-IL-21-NS+anti-PD-1 treatment groups,with 9 mice in each group,to evaluate the anti-tumor effects of monotherapy versus combination therapy.Flow cytometry was conducted to assess the regulatory effects of monotherapy and combination therapy on the tumor immune microenvironment.Results RG technology successfully rescued the recombinant oncolytic influenza virus rOV-IL-21-NS.Sequencing confirmed the successful insertion of IL-21 into the target sequence,and the obtained virus could be stably propagated,with its sixth passage reaching a hemagglutination titer of 211,and a viral titer of 6 Log10(TCID50/mL).Oncolytic virus rOV-IL-21-NS,at a multiplicity of infection(MOI)of 3,selectively reduced the viability of HCC cells without significantly affecting normal liver cells.Compared to the control group,the combination of rOV-IL-21-NS and anti-PD-1 antibodies significantly inhibited tumor growth(P＜0.001)and increased the proportions of CD4+T and CD8+T cells in the spleen tissue of the mouse model of subcutaneous HCC tumor(P＜0.001).Conclusion The recombinant oncolytic influenza virus rOV-IL-21-NS chimeric with IL-21 can effectively and safely exert targeted killing to HCC cells,enhance T cell activation by synergizing with anti-PD-1 antibodies,and improve the immune microenvironment.

Objective To explore the influence of negative lymph node count (NLNC) on the prognosis of patients with gastric signet ring cell carcinoma (GSRC) and develop a prognostic nomogram based on NLNC. Methods On the basis of the SEER database, 2 101 patients diagnosed with GSRC were collected and randomly divided into the modeling group and validation group to test the relationship between clinicopathological characteristics and the prognosis of GSRC. The multivariate Cox proportional hazard regression model was used to analyze the independent risk factors affecting overall survival and establish a prognostic prediction model. The consistency index (C-index), calibration curve, net reclassification index (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA) were used to evaluate the accuracy and clinical applicability of the nomogram. Results All patients were divided according to the ratio of 7:3, with 1 473 in the modeling group and 628 in the validation group. NLNC > 10 (HR=0.578, 95%CI: 0.504-0.662, P < 0.001) was a protective factor for the prognosis of patients with GSRC, and the nomogram model was established based on multivariate Cox proportional hazards model. The C-index values of the nomogram were 0.737 (95%CI: 0.720-0.753) and 0.724 (95%CI: 0.699-0.749) in the modeling and validation groups, respectively, showing good discrimination. The calibration curves showed high consistency of the model. NRI=17.77%, continuous NRI=36.34%, and IDI=4.2% indicated that the model had positive returns compared with the traditional model. The DCA was far from the baseline, indicating that the model had good clinical applicability. Conclusion The increase in NLNC is a favorable factor for the prognosis of patients with GSRC, and a relatively accurate nomogram was established to predict the prognosis of patients with GSRC and help clinicians conduct individualized prognostic evaluations.

Objective:To investigate the effect of edaravone, a free radical scavenger, on the regulation of retinal autophagy and the protection of photoreceptor cells at the early stage of experimental retinal detachment (RD) in rats.Methods:Fifty-one adult male Sprague-Dawley rats were used for RD model establishment, and another 24 rats were served as PBS injection group.The RD model was established via subretinal injection of 0.5% sodium hyaluronate into the right eye of the rats and the rats with successful modeling were randomly divided into RD model group and edaravone treatment group.The rats in the edaravone treatment group were given edaravone of 3 mg/kg intraperitoneally, twice a day after modeling, and the rats in the PBS injection group and RD model group were given equal volume of normal saline.Rats were sacrificed on the 1st day, 3rd day and 7th day following modeling.The T-superoxide dismutase (T-SOD) activity and malondialdehyde (MDA) content in the intraocular fluid was detected.The expression levels of superoxide dismutase 2 (SOD2), nuclear factor E2-related factor 2 (Nrf2), autophagy related gene 4 (Atg4), microtubule-associated protein 1 light chain 3B (LC3B) and other proteins in retinal tissue were identified by Western blot analysis.TUNEL staining was performed on paraffin sections of the whole eyeball to analyze the apoptosis of photoreceptor cells.The study protocol was approved by an Ethics Committee of Xi'an Fourth Hospital (No. 2016016). The use and care of animals complied with the Regulations on the Administration of Experimental Animals.Results:The RD area was more than 60% in rat eyes of RD model.There were significant differences in MDA content and T-SOD activity among different groups at various time points (MDA: Fgroup=385.513, P<0.01; Ftime=13.021, P<0.01.T-SOD: Fgroup=48.865, P<0.01; Ftime=7.700, P=0.003). Compared with the PBS injection group, the MDA concentration was significantly increased and the T-SOD activity was significantly decreased in the RD group and edaravone treatment group on the 1st, 3rd and 7th day after modeling (all at P<0.05). The MDA concentration was significantly reduced and the T-SOD activity was significantly elevated in the edaravone treatment group on the 1st, 3rd and 7th day after modeling in comparison with those of the RD group (all at P<0.05). Compared with the PBS injection group, the relative expression levels of SOD2 and Nrf2 proteins were significantly increased in the RD group and edaravone treatment group on the 1st, 3rd and 7th day after modeling (all at P<0.05), and Atg4 and LC3B-Ⅱ/LC3B-Ⅰ were significantly increased on the 1st, 3rd and 7th day after modeling (all at P<0.05). The expression level of SOD2 in the edaravone treatment group was significantly higher than that in the RD group on the 1st, 3rd and 7th day after modeling (all at P<0.05), and the expression level of Nrf2 was significantly increased in the edaravone treatment group on the 1st and 3rd day after modeling compared with that of the RD group (both at P<0.05), and the expression levels of Atg4 and LC3B-Ⅱ/LC3B-Ⅰ were significantly increased in the edaravone treatment group on the 3rd day after modeling in comparison with those of the RD group (both at P<0.05). No significant TUNEL positive cells were observed in PBS injection group at all time points, and TUNEL positive cells were observed on the 1st, 3rd and 7th day after modeling in the RD group, and the expression level of caspase-3 in the RD group was significantly increased in comparison with that of the PBS injection group ( P<0.05). The apoptosis of photoreceptor cells and the expression level of caspase-3 in edaravone treatment group were significantly decreased in comparison with those of the RD group on the 1st, 3rd and 7th day after modeling (all at P<0.05). Conclusions:The intraperitoneal injection of edaravone, twice a day, can significantly improve the antioxidant capacity of the retina after experimental RD in rats, regulate retinal autophagy and reduce the apoptosis of photoreceptor cells in early-stage RD.

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.

Objective To explore the effect and mechanism of local administration of thymosin β4 (Tβ4) on bone regeneration in a distraction osteogenesis model of rat fenur.Methods Sixty Sprague-Dawley rats were randomly divided into groups A,B and C in this study.A distraction osteogenesis model was established in the left femur after osteotomy.At the end of distraction period,the bone regeneration area in group A was subjected to no treatment,that in group B to injection of phosphate buffer saline (PBS),and that in group C to injection of Tβ4.On days 22,29 and 43 postoperatively,the rats from each group were randomly sacrificed and processed for observation of bone regeneration in the distraction osteogenesis area using radiography,Micro-CT,histology and immunohistochemical staining.RT-PCR was used to detect the expression of related genes as well.Results Radiography revealed that the bone regeneration in group C was superior to that in groups A and B on days 22,29 and 43 postoperatively.Micro-CT examination showed significantly increased bone volume (BV),bone mineral density (BMD) and ratio of bone volume to tissue volume (BV/TV) in group C on days 22,29 and 43 postoperatively,and significantly decreased ratio of bone surface area to bone volume on postoperative day 43 in comparison with groups A and B(P ＜ 0.05).HE staining indicated that local capillary density was significantly higher in group C than in groups A and B after local administration of Tβ4 in the distraction osteogenesis.Immunohistochemical staining showed that the capillary density and osteoblasts in group C were higher than in groups A and B.RT-PCR results revealed significantly higher expression of eNOS and Osterix mRNA in the local callus in group C on postoperative day 22 than in groups A and group B (P ＜ 0.05).Conclusion Local administration of thymosin β4 may promote bone formation,which is probably related to the increased expression of eNOS and Osterix.

Objective To investigate the nutritional management level of Department of Clinical Nutrition in elderly inpatients through analyzing the actual hospital dietary intakes in elderly inpatients in Peking Union Medical College Hospital from 2013-2015.Methods Using continuous sampling, the nutrients contents and the eating rates of hospital meals ordered by the elderly inpatients on the 1st, 15th, 29th of every month from May 2013 to October 2015 were selected.The intake levels of energy, protein, calcium, vitamin A, vitamin B1 , and vitamin C were calculated and compared with the Chinese dietary reference intakes (DRIs).The nutritional in-take differences between diabetes diet and the basic hospital diet were also compared.Results A total of 90 days of hospital dietary data from 8 402 elderly inpatients were included in the study.The average eating rate was (50.1 ±4.2)%, which was lower than the general eating rate of the hospital [ (59.0 ±4.0)%, P<0.001]. Only protein intake from hospital diet reached the requirement target [male (103.1 ±47.3)%, femal (98.3 ± 33.8)%].Individual compliance rates were 63.2%and 59.8%, respectively, while the other kinds of nutrients were lower.The compliance rates of energy [ (73.3 ±26.3)%vs.(62.1 ±38.2)%, P<0.001] and ma-jor nutrient intake [ protein: ( 119.1 ±41.2 )% vs.( 93.3 ±65.1 )%, P <0.001; calcium: ( 55.5 ± 26.7)% vs.(34.3 ±34.2)%, P <0.001; vitamin A: (75.2 ±48.3)% vs.(57.4 ±97.1)%, P<0.001;vitamin B1:(76.4 ±38.2)%vs.(52.1 ±46.6)%, P<0.001;vitamin C:(92.2 ±51.4)%vs. (49.3 ±55.0)%, P<0.001) in diabetes diet group were significantly higher than those in the basic hospi-tal diet group.Conclusions The nutritional intakes from hospital diets may not meet the nutritional require-ments based on DRIs in elderly inpatients.Medical diet designed by physicians and dietitians should be ex-panded to improve the nutritional management level for these patients.