ObjectiveTo investigate the antidepressant effect of Sinisan （SNS） by regulating glycogen aynthase kinase-3β （GSK-3β）/tumor necrosis factor alpha-induced protein 3（A20）/CCAAT enhancer binding protein β（C/EBPβ） to inhibit the activation of microglia. MethodA total of 72 male C57/6J mice were randomly divided into the normal group， model group， fluoxetine group （5.0 mg·kg^-1）， low-dose Sinisan group （4.9 g·kg^-1）， medium-dose Sinisan group （9.8 g·kg^-1）， and high-dose Sinisan group （19.6 g·kg^-1）， with 12 mice in each group. After one week of adaptive feeding， chronic unpredictable mild stress （CUMS） was performed to establish the depression model. In the fifth week， drug treatment was conducted for four weeks. In the ninth week， behavioral tests were performed， including sucrose preference test （SPT）， open field test （OPT）， elevated plus maze （EPM） test， and forced swimming test （FST）. Western blot was used to detect the expression levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， nitric oxide synthase （iNOS）， GSK-3β， A20， and C/EBPβ in the cortex. The expression of M1-polarized ionized calcium-binding adapter molecule 1 （Iba1） and cluster of differentiation 68 （CD68） in microglia was detected by immunofluorescence. ResultAfter eight weeks of CUMS， compared with the normal group， the mice in the model group had a significantly reduced sucrose preference rate （P<0.01）， and the activity in the central area of the OPT was significantly reduced （P<0.01）. The activity in the open arm area of the EPM test was significantly reduced （P<0.05）， and the immobility time of FST was increased （P<0.01）. The expression levels of inflammatory proteins IL-1β， IL-6， and iNOS were increased （P<0.01）， and the fluorescence co-localization index of Iba1 and CD68 was increased （P<0.05）. The protein expression levels of GSK-3β and C/EBPβ were significantly increased （P<0.05， P<0.01）. After four weeks of SNS intervention， compared with the model group， the mice in the SNS group had significantly increased sucrose preference rate （P<0.01）， significantly increased activities in the central area and the open arm area in the OPT and the EPM test （P<0.05）， and significantly reduced immobility time in the FST （P< 0.01）. The protein expression levels of IL-1β， IL-6， and iNOS were significantly decreased （P<0.05）， and the fluorescence co-localization index of Iba1 and CD68 was decreased in the high-dose SNS group （P<0.05）. The protein expression levels of GSK-3β and C/EBPβ in the medium-dose and high-dose SNS groups were significantly decreased （P<0.01）， and that of A20 was significantly increased （P<0.01）. ConclusionThe antidepressant effect of SNS is related to the regulation of GSK-3β/A20/C/EBPβ protein expression and the inhibition of M1-type activation of microglia.

Objective To investigate the expression of long non-coding RNA(lncRNA),surfactant associated 1 pseudogene(SFTA1P)in lung squamous carcinoma and its effect on the biological functions of SFTA1P in lung squamous carcinoma cell lines.Methods Based on the cancer genome atlas(TCGA)database,the differential expression of SFTA1P in tumor and normal tissues were compared in patients diagnosed with lung squamous cell carcinoma.Then,the expression of SFTA1P was detected in human normal lung epithelial cell line BEAS-2B and lung squamous cell lines SK-MES-1 and H520 with real-time quantitative polymerase chain reaction(RT-qPCR).SK-MES-1 and H520 cells with overexpression and/or knockdown of SFTA1P were constructed by transfecting the overexpression plasmids(pcDNA3.1-SFTA1P)and small interfering RNAs(si-SFTA1P-1 and si-SFTA1P-2).CCK-8 assay and Transwell assay were used to investigate the effect of SFTA1P on biological functions in lung squamous carcinoma cells.Differential gene expression analysis,correlation analysis and functional enrichment analysis were employed to explore the potential mechanism that SFTA1P may affect biological functions of lung squamous cells.Results Analysis of TCGA showed that the expression of SFTA1P was significantly lower in lung squamous cell carcinoma tissue than adjacent normal tissue(P＜0.05).RT-PCR results showed that the expression of SFTA1P was obviously lower in lung squamous carcinoma cells than the human normal lung epithelial cells(P＜0.05).And the expression level of SFTA1P was relatively lower in the SK-MES-1 cells than the H520 cells(P＜0.05).Overexpression of SFTA1P suppressed the proliferation,migration and invasion of lung squamous carcinoma cells(P＜0.05),while its knockdown promoted these abilities(P＜0.05).Differential gene expression analysis,correlation analysis and functional enrichment analysis indicated that SFTA1P may inhibit MYC,G2m checkpoints and E2f signaling pathways in lung squamous cell carcinoma.Conclusion SFTA1P shows anti-cancer function in lung squamous cell carcinoma,and it may affect the biological functions of lung squamous cell carcinoma cells through down-regulating MYC,G2m checkpoints and E2f signaling pathways.

Objective:To explore the prevalence and risk factors of sarcopenia in patients with maintenance dialysis (MHD).Methods:It was a cross-sectional study. Patients who received MHD treatment in the Blood Purification Center of Hainan Provincial People's Hospital in October 2019 were included as study subjects. The patients were divided into sarcopenia group and non-sarcopenia group according to whether they had sarcopenia or not. Chest CT imaging and laboratory examination data were collected. Dual-energy X-ray absorptiometry was used to measure the skeletal muscle mass. Chi-square test or Mantel-Haenszel trend chi-square test was used to compare the clinical data of patients with and without sarcopenia. Multivariate logistic regression equation was used to analyze the risk factors of sarcopenia.Results:A total of 182 MHD patients were enrolled in the study, and the prevalence of sarcopenia was 33.5% (61/182). The proportions of age ≥60 years old, diabetic nephropathy, tunneled-cuffed catheter, body mass index <18 kg/m 2, serum albumin <40 g/L, low density lipoprotein cholesterol ≥3.37 mmol/L, left ventricular ejection fraction <50%, chest CT-suspected pulmonary tuberculosis (PTB) and PTB in sarcopenia group were higher than those in non-sarcopenia group (all P<0.05). Multivariate logistic regression analysis results showed that left ventricular ejection fraction <50% (≥50% as a reference, OR=3.250, 95% CI 1.035-10.206, P=0.044), low-density lipoprotein cholesterol ≥3.37 mmol/L (<3.37 mmol/L as a reference, OR=6.354 ,95% CI 1.675-24.108, P=0.007), chest CT-suspected PTB (normal as a reference, OR=7.433, 95% CI 1.531-36.083, P=0.013), and PTB (normal as a reference, OR=28.871, 95% CI 3.208-259.872, P=0.030) were independent influencing factors of sarcopenia in MHD patients. Conclusions:The prevalence of sarcopenia is higher in MHD patients. Blood low-density lipoprotein cholesterol ≥3.37 mmol/L, ejection fraction <50%, chest CT-PTB and suspected PTB are independent risk factors of sarcopenia in MHD patients. Correcting left ventricular systolic function, regulating blood lipids and preventing PTB as early as possible can reduce the prevalence of sarcopenia in MHD patients.

Bardet-Biedl syndrome (BBS) is an autosomal recessive hereditary rare disease with high heterogeneity in clinical phenotypes, which can affect multiple systems, such as six fingers/digits deformity, mental impairment, retinopathy, polycystic kidney, etc, and is easily diagnosed according to a single system disease, resulting in misdiagnosis. The paper reports a case of BBS, diagnosed with "renal cyst, developmental delay, chondrosis, and left foot hexadactylism" at 5 years old, "anemia, renal insufficiency, distal renal tubule poisoning, renal osteodystrophy" at 7 years old. At 10 years old, the patient received hemodialysis treatment for uremia. Cloudy vision appeared in both eyes at 14 years old. Because of the prominent manifestation of kidney damage, the patient was misdiagnosed as "polycystic kidney" for a long time, and other systemic damages were ignored. The result of gene sequencing showed that chromosome 16 NM_031885.5 exon17 had one homozygous nonsense mutation. Therefore, the patient was accurately diagnosed as BBS. This paper is the first report of BBS in Li nationality in China. The relevant literature of BBS were reviewed to strengthen clinicians' understanding of the disease and improve patients' prognosis.

Objective:To explore the risk factors of autogenous arteriovenous fistula (AVF) aneurysms (AVFAs) in maintenance hemodialysis (MHD) patients.Methods:The patients who used internal arteriovenous fistula (end to side anastomosis) of cephalic vein-radial artery at wrist as vascular access in Hainan Provincial People′s Hospital from June 1 to June 30, 2021 were selected as the research objects. The patients were divided into AVFAs group and non-AVFAs group according to whether AVF formed AVFAs. The clinical data and laboratory examination results between the two groups were compared. Binary logistic regression model was used to analyze the risk factors for the formation of AVFAs.Results:A total of 170 MHD patients were enrolled in this study, including 111 males (65.3%) and 59 females (34.7%), with age of (51.65±12.70) years old and dialysis age of (57.03±49.25) months. There were 33 cases in AVFAs group and 137 cases in non-AVFAs group. The incidence of AVFAs was 19.4%. Compared with non-AVFAs group, the proportion of males ( χ2=4.934, P=0.026) and the levels of serum uric acid ( t=2.547, P=0.012) and serum albumin ( t=2.122, P=0.010) in AVFAs group were higher; The age ( t=-2.210, P=0.028), the proportion of diabetes nephropathy ( χ2=11.788, P=0.001), systolic blood pressure ( t=-1.994, P=0.048) and total cholesterol ( t=-2.174, P=0.031) were lower; The diameter of anastomosis was wider ( Z=-3.224, P=0.001); Mantel-Haenszel chi square test analysis showed that dialysis age ( χ2=53.832, OR=0.518, P<0.001), AVF service time ( χ2=51.355, OR=0.516, P<0.001), and brachial artery blood flow ( χ2=25.315, OR=0.331, P<0.001) were correlated to the formation of AVFAs. The results of multivariate logistic regression analysis showed that males ( OR=10.005, 95% CI 1.875-53.394, P=0.007), longer dialysis age ( OR=1.341, 95% CI 1.104-1.628, P=0.003), longer AVF use time ( OR=1.187, 95% CI 1.002-1.405, P=0.047), higher brachial artery blood flow ( OR=1.002, 95% CI 1.000-1.004, P=0.028) and lower total cholesterol ( OR=0.388, 95% CI 0.172-0.875, P=0.022) were the independent risk factors for the formation of AVFAs. Conclusions:The incidence of AVFAs in MHD patients is 19.4%. Males, long dialysis age, long AVF use time, high brachial artery blood flow and low total cholesterol level are the independent risk factors for the formation of AVFAs.

Objective:To compare the effects of different intraocular infusion solutions on histology and function of retina.Methods:Human corneal endothelial cells (HCEC), human retinal pigment epithelium (HRPE) cells and rat retinal ganglion cells (RGC) were divided into normal control group, balanced saline solution (BSS) group and compound electrolyte intraocular irrigating solution (CEIIS) group, and the cells were cultured in 10% DMEM/F12 medium, BSS and CEIIS for 12, 24 and 48 hours, respectively, according to grouping.The proliferation absorbance value of cultured cells was measured by cell counting kit-8 (CCK8) method.The expression of apoptosis related proteins in cultured cells was detected by cellular immunofluorescence staining.The cell apoptosis rate and cell cycle were measured by flow cytometry.The mitochondrial damage was detected by lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) quantitative detection kit.Fifteen New Zealand white rabbits were randomly divided into control group ( n=3), BSS group ( n=6) and CEIIS group ( n=6). The left eyes were taken for vitrectomy and different intraocular perfusion fluids were used during vitrectomy according to grouping.The retinal function of operative eyes was measured by flash electroretinogram (ERG) before operation and 24 hours after operation, and the structural changes of each layer of retina were detected by optical coherence tomography (OCT). The early apoptosis of retinal cells was detected by TUNEL staining.The expressions of cytochrome C and bax protein in retina were detected by immunohistochemical staining.The ultrastructural changes of retina were observed under a transmission electron microscope.The use and care of animals complied with the ARVO statement.This study protocol was approved by an Ethics Committee of Peking University People's Hospital (No.2019PHE059). Results:The three kinds of cultured cells in BSS and CEIIS groups were damaged in various degrees.With the extension of culture time, proliferated cells were decreased and the number of apoptotic cells was increased.Compared with the BSS group, cultured cells in the CEIIS group were dense and in orderly arrangement with uniform morphology and size.The apoptosis rates of HRPE cells and RGC in the BSS group were (37.157±6.918)% and (29.993±12.330)%, respectively, which were significantly higher than (4.163±1.310)% and (6.337±1.903)% in the CEIIS group ( P=0.003, 0.045). There was no significant difference in G0/G1+ S phase ratio of HCEC and HRPE cells among the normal control group, BSS group and CEIIS group (HCEC: F=2.226, P=0.189; HRPE: F=2.634, P=0.151), and the proportion of G2/M division arrest phase of RGC in the BSS group was significantly higher than that in the normal control group and CEIIS group ( P=0.047, 0.024). The proliferation absorbance values of HCEC, HRPE cells and RGC in the CEIIS group were significantly higher than those in the BSS group at each culture time point (all at P<0.05). The fluorescence intensity of cytochrome C, bax, caspase-3 and caspase-9 proteins in the BSS group was stronger than that in the normal control group and CEIIS group, and the fluorescence intensity of bcl-2 was weaker than that in the CEIIS group, and the fluorescence intensity of zonula occluden-1 (ZO-1) was weaker than that in the normal control group and CEIIS group.The release level of LDH in the BSS group was significantly higher than that in the CEIIS group at different time points (all at P<0.001). After 48 hours of culture, the release level of SDH in the BSS group was significantly higher than that in the CEIIS group ( P<0.05). No retinal histological abnormalities was found through OCT examination of rabbit eyes after vitrectomy in the two groups, but transmission electron microscopy showed that there were different degrees of loose arrangement of retinal photoreceptor cells, a large number of photoreceptor outer membrane discs falling off and vacuolar degeneration in the two groups, especially in the BSS group.TUNEL staining showed that the apoptotic cells were mainly located in the inner nuclear layer and RGC layer.The number of apoptotic retinal cells was (135.2±22.8)/high-power field of vision in the BSS group, which was significantly higher than (81.3±17.7)/high-power field of vision in the CEIIS group ( t=4.175, P=0.002). Full field flash ERG showed that the amplitudes of scotopic 3.0 ERG a- and b-wave in the CEIIS group after operation were significantly lower than those before operation, but the differences were not statistically significant (all at P>0.05). The amplitudes of scotopic 3.0 ERG a- and b-wave in the BSS group after operation were significantly lower than those before operation ( P=0.026, 0.010). Conclusions:In vivo and in vitro research results show that compared with BSS, there were few apoptotic cells in retinal tissue after vitrectomy perfused by CEIIS.

Objective:To explore the effect of long-term exposure to ambient particulate matter (PM 10) on the prevalence of diabetes and fasting plasma glucose (FPG). Methods:The subjects of the study were from the baseline population of "Jinchang Cohort", and 24 285 subjects were finally included after excluding incomplete home address information and diabetic diagnosis information. The demographic characteristics, lifestyle and health status of the survey subjects were collected through questionnaire, physical examination and laboratory tests. ArcGIS software was used to match the nearest environmental monitoring stations for each subject according to residential address. Two-year average concentrations of PM 10 were calculated to estimate exposure level. The logistic regression and the multiple linear regression were conducted to assess the effects of ambient PM 10 on the prevalence of diabetes and FPG. The restricted cubic spline was used to quantify the dose-response relationship. Stratified analysis and effect modification analysis were also performed. Results:The age of 24 285 participants was (49.32±8.60) years, and the BMI was (24.22±6.09) kg/m 2. There were 13 950 (57.44%) males and 2 066 (8.51%) diabetic patients. After adjusting for confounders, for every 10 μg/m 3 increase in the average PM 10 concentration in the first two years of the survey, the prevalence of diabetes increased [ OR (95% CI) =1.05 (1.01-1.09)]and the FPG level elevated [β (95% CI) = 0.061 (0.047-0.076) mmol/L]. The results of the restricted cubic spline analysis showed a nonlinear relationship between PM 10 concentration and FPG level ( P<0.001). Further subgroup analysis showed that female [ OR (95% CI) =1.10 (1.03-1.18)], people over 50 years old [ OR (95% CI) =1.06 (1.02-1.11) ], subjects with family history of diabetes [ OR (95% CI) = 1.13 (1.04-1.23) ], and with hypertension [ OR (95% CI) = 1.07 (1.02-1.12) ] had a stronger association between the prevalence of diabetes and PM 10 exposure (all P interaction values were<0.05). The effects of PM 10 on FPG were more significant in people older than 50 years[β (95% CI) = 0.080 (0.050-0.109) mmol/L], with family history of diabetes [β (95% CI) = 0.087 (0.036-0.137) mmol/L], and hypertension [β (95% CI) = 0.077 (0.046-0.108) mmol/L] (all P interaction values were<0.05). Conclusions:Long-term exposure to ambient PM 10 increases the diabetes prevalence and FPG. People older than 50 years old, with family history of diabetes and hypertension could be more sensitive to the effects of PM 10 exposure.

Objective:To explore the effect of long-term exposure to ambient particulate matter (PM 10) on the prevalence of diabetes and fasting plasma glucose (FPG). Methods:The subjects of the study were from the baseline population of "Jinchang Cohort", and 24 285 subjects were finally included after excluding incomplete home address information and diabetic diagnosis information. The demographic characteristics, lifestyle and health status of the survey subjects were collected through questionnaire, physical examination and laboratory tests. ArcGIS software was used to match the nearest environmental monitoring stations for each subject according to residential address. Two-year average concentrations of PM 10 were calculated to estimate exposure level. The logistic regression and the multiple linear regression were conducted to assess the effects of ambient PM 10 on the prevalence of diabetes and FPG. The restricted cubic spline was used to quantify the dose-response relationship. Stratified analysis and effect modification analysis were also performed. Results:The age of 24 285 participants was (49.32±8.60) years, and the BMI was (24.22±6.09) kg/m 2. There were 13 950 (57.44%) males and 2 066 (8.51%) diabetic patients. After adjusting for confounders, for every 10 μg/m 3 increase in the average PM 10 concentration in the first two years of the survey, the prevalence of diabetes increased [ OR (95% CI) =1.05 (1.01-1.09)]and the FPG level elevated [β (95% CI) = 0.061 (0.047-0.076) mmol/L]. The results of the restricted cubic spline analysis showed a nonlinear relationship between PM 10 concentration and FPG level ( P<0.001). Further subgroup analysis showed that female [ OR (95% CI) =1.10 (1.03-1.18)], people over 50 years old [ OR (95% CI) =1.06 (1.02-1.11) ], subjects with family history of diabetes [ OR (95% CI) = 1.13 (1.04-1.23) ], and with hypertension [ OR (95% CI) = 1.07 (1.02-1.12) ] had a stronger association between the prevalence of diabetes and PM 10 exposure (all P interaction values were<0.05). The effects of PM 10 on FPG were more significant in people older than 50 years[β (95% CI) = 0.080 (0.050-0.109) mmol/L], with family history of diabetes [β (95% CI) = 0.087 (0.036-0.137) mmol/L], and hypertension [β (95% CI) = 0.077 (0.046-0.108) mmol/L] (all P interaction values were<0.05). Conclusions:Long-term exposure to ambient PM 10 increases the diabetes prevalence and FPG. People older than 50 years old, with family history of diabetes and hypertension could be more sensitive to the effects of PM 10 exposure.

Objective To investigate the incidence and related risk factors of delirium in elderly patients with hip frac-ture. Methods From October 2014 to February 2017, 306 patients with femoral neck fracture or intertrochanteric fracture more than 65 years old underwent elective hip arthroplasty (hip arthroplasty, proximal femoral nail fixation) were retrospective-ly analyzed. Patients' general information was recorded: age, sex, body mass index (BMI), history of diabetes mellitus, history of coronary heart disease, cerebral infarction, preoperative biochemical tests, left ventricular ejection fraction, thrombosis of both lower extremities, intraoperative status (ASA score, NYHA heart function score, anesthesia, anesthesia time, etc.), periop-erative blood transfusion, biochemical examination on the first day after surgery, perioperative albumin consumption, etc.; ac-cording to whether delirium happened after surgery, those patients were divided into delirium group and non-delirium Group and analyzed the incidence of postoperative delirium. Using univariate logistic regression analysis screened factors associated with postoperative delirium. The results were entered into the multivariate logistic regression analysis, screening the high risk factors for postoperative delirium.Results The incidence of delirium was 59(19.29%) after perioperative hip fracture, includ-ing 23 males and 36 females, ranging in age from 70 to 93 years with an average of (81.9±5.4) years. 247 cases had no deliri-um,including 81 males and 166 females,aged 65-96 years,with an average(76.4±8.1)years.The factors of age,length of hos-pital stay, days before surgery, preoperative hematocrit, perioperative albumin consumption, perioperative blood transfusion, preoperative leukocyte levels, preoperative albumin levels, preoperative creatinine, urea level, Mallampati classification (Mar-kov grade), cardiac function score (NYHA score), ASA score, intraoperative blood loss, postoperative leukocyte level, left ven-tricular ejection fraction, previous cerebral infarction, history of coronary heart disease, and diabetes were statistically signifi-cant different; univariate logistic regression analysis showed that the factors of age, ASA score, history of diabetes mellitus, length of hospitalization, and perioperative albumin consumption were demonstrated to have relationship with the occurrence of postoperative delirium. Multivariate regression analysis showed that age, history of diabetes and ASA score are the high risk factors of postoperative delirium.Conclusion Age,history of diabetes mellitus and ASA score are risk factors of delirium in el-derly patients with hip fracture.Those patients older than 75 years,with the history of diabetes mellitus or ASA score> 2 points were at higher risk of postoperative delirium,which prolongs hospitalization and increases protein consumption.

Objective To investigate the role and mechanism of nico-tinamide adenine dinucleotide phosphate oxidase 4 (NAPHD oxidase 4,Nox4)-mediated reactive oxygen species (ROS) generation on high-dose dexamethasone (DEX) induced apoptosis in osteoblasts.Methods According to culture conditions,3rd passage of murine osteoblastic MC3T3-E 1 cells were divided into control group,Dexamethasone group,Dexamethasone+NAC (N-acetyl-L-cysteine) group,NAC group,Dexamethasone+DPI (Diphenyleneiodonium) group and DPI group.24 hours after culture,the morphology of osteoblasts was observed by inverted phase contrast microscope.Cell viability was determined by MTT assay.The generation of ROS in osteoblasts was measured using a fluorescent probe DCFH-DA.The apoptosis of each group was observed through Hoechst staining.The mRNA level and protein expression of Nox4 were detected by real-time quantitative PCR and Western Blot.In addition,after silence of Nox4 with small interfering RNA (siRNA),the ROS generation was further detected by a fluorescent probe DCFH-DA.Results After treatment with 1000 nmol DEX for 24 hours,compared to control group,the results of inverted phase contrast microscope and MTT showed that osteoblasts in DEX group exhibited more obvious signs of shrinkage and deformation with decreased cell viability.After intervene with NAC and DPI,morphology of osteoblasts was good with increased viability of osteoblasts.Compared to control group (5.86％± 0.28％),the production of ROS in DEX group (45.14％±1.49％) was significantly increased (P=0.000).The apoptotic rates in DEX group (29.60％± 1.52％) was significantly increased compared with control group (4.12％±0.67％) (P=0.000).Compared to DEX group,the production of ROS generation in DEX+NAC group (28.06％±1.61％) and DEX+DPI group (23.70％±1.28％) was significantly decreased (P=0.000).It presented that NAC or DPI significantly decreased the formation of ROS.Compared to DEX group,the apoptotic rate in DEX+NAC group (8.94％± 1.47％) and DEX+DPI group (12.96％±2.03％) was significantly decreased (P=0.000).It presented that NAC or DPI significantly decreased osteoblast apoptosis.In addition,the Nox4 mRNA level in DEX group was 2.67-fold compared with control group (t=-10.301,P=0.009).The difference had statistically significance.The protein expression of Nox4 in DEX group was 2.37-fold compared with control group (t=-15.542,P=0.004).The difference has statistically significance.After silence of Nox4 by siRNA,the generation of ROS in DEX+Nox4 siRNA group (14.53％± 1.00％) was decreased by 16.92％ compared with DEX group 31.45％±0.72％ (P=0.000).The difference had statistically significance.Conclusion Nox4-mediated ROS generation plays an important role in osteoblasts apoptosis induced by high-dose dexamethasone.It provided us the new target in the management of Nox4 to provide possible therapy for steroid-induced avascular necrosis of the femoral head (SANFH).