The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Objective:To explore the effect of different concentrations of Chinese herbal formula,Er-miao-san(EMS)immune regulatory gene on Gnαq expression in rats with collagen-induced arthritis(CIA).Methods:In the study,we established a CIA model,and randomly divided into model groups,EMS group with 1.5,3.0 and 4.5 g/kg(L-EMS,M-EMS,H-EMS)were adminis-tered to CIA rats by gavage,methotrexate was used as a positive control group(MTX).The rats in each group were given correspond-ing drugs for treatment,and the normal control group and model group were given the same amount of normal saline gavage.ELISA detects the expression of IL-1β,IL-6 and TNF-α in rats'serum.The mRNA and protein expression of Gnαq were analyzed using qRT-PCR and Western blot.The localization of Gnαq was performed by IHC.Results:The joint of rats in CIA group showed obvious damage,tissue hyperplasia and inflammatory infiltration;the joint tissue destruction and proliferation of MTX and EMS groups were reduced;the expressions of IL-1β,IL-6 and TNF-α in CIA group were extremely increased(P<0.01).The expressions of IL-1β(except H-EMS group),IL-6 and TNF-α in MTX and EMS groups were significantly lower than those in CIA group(P<0.05).The expressions of IL-1β,IL-6 and TNF-α in L-EMS group were lower than those in the M-EMS and H-EMS groups(P<0.05,P<0.01).The expression of Gnαq mRNA and protein in spleen and joints of CIA group were higher than those of Control group(P<0.01).The expression of Gnαq mRNA and protein in spleen and joints of EMS and MTX groups were lower than those of CIA group(P<0.05).The expression of Gnαq mRNA and protein in the dose of 1.5 g/kg of EMS group was lower than those of the other groups(P<0.01,P<0.05).Different degree of posi-tive signal was detected in spleen and joints in different groups.Conclusion:Gnαq is expressed in spleen and joints of CIA rats,may participate in the formation of inflammatory response in CIA rats,and then mediate the formation and development of RA by down-reg-ulating the expression of Gnαq.

Objective To explore the influencing factors of ecological momentary assessment(EMA)in the implementation of home rehabilitation exercise for middle-aged stroke patients,and to provide a basis for decision-making and practice of precision rehabilitation nursing for stroke.Methods This descriptive qualitative research utilized purposive sampling method to select 8 medical staff,4 information technicians,8 middle-aged stroke patients,and 5 caregivers from a tertiary A general hospital in Wuhan from January 2 to March 10,2024 as the research subjects.Semi-structured interview was conducted based on the framework of diffusion of innovations theory.The data were analyzed using directed content analysis.Results 5 themes and 10 sub-themes were extracted,including relative advantage factors(conducive to precise and dynamic evaluation of patient rehabilitation behavior and symptom trajectory by medical staff;enhancing patient self-management awareness,effectively reducing care burden),compatibility factors(new methods conflict with existing values;new methods are in line with clinical work practice),complexity factors(evaluation frequency affects the accuracy of rehabilitation tracking;limited limb function and social support increase user burden),experimental factors(pilot and real-time feedback improve user experience;experience summary and promotion,the strengthening of practical verification orientation),and observable factors(successful cases of mobile health help popularize new methods;visualization of new methods to enrich mobile health practice).Conclusion There are certain promoting and hindering factors in the implementation of EMA in the field of home rehabilitation exercise for middle-aged stroke patients.In the future,it is necessary to explore the potential of EMA in the field of precision rehabilitation and ensure its compatibility with clinical practice.

Objective To explore the effect of topical application of Fushan rheumatism external prescription on inflammatory cytokines and notch2 pathway in rats with collagen-induced arthritis(CIA).Methods 36 female Wistar rats were randomly divided into normal group(n=10)and model group(n=26).CIA model was successfully established in 20 rats,which were randomly divided into model group(n=10)and Fushan rheumatism external prescription group(n= 10).Treatment was initiated on day 14,and 0.4 mL ointment was evenly applied to the ankle joints of rats in Fushan rheumatism external prescription group.Normal group and model group were topical smeared with the same volume of normal saline.Activity was taken twice a day for 42 days.The joint swelling of rats was observed every week and the arthritis index was scored.Thereafter blood was collected from abdominal aorta,and then ankle joint,spleen,liver,and kidney of rats were taken out after the end of the interventions.The severity of arthritis and the pathological changes of ankle joint,liver and kidney were evaluated by HE staining;Inflammatory cytokines expression in serum were detected by ELISA;The expression of Notch2,Delta-like ligand protein 1(delta-like ligand protein-1,DLL1)and nuclear factor-κ Bp65(nuclear factor-κ Bp65,NF-κ Bp65)mRNA and protein in synovium of ankle joints and spleen were detected by qRT-PCR and Western blot,and its positive expression in ankle joints were detected by immunohistochemical method;The changes of liver and kidney function of rats in each group were detected in serum.Results Compared with normal group,the arthritis index score in model group were increased(P<0.01),joint injury and pathological score were increased(P<0.01),the levels of inflammatory cytokines TNF-α,IL-6,IL-17 and IFN-γ in serum were increased(P<0.01),the expression of Notch2,DLL1 and NF-κBp65 mRNA and protein in joints and spleen were increased(P<0.01),and the positive expression in joints were also increased(P<0.01);Compared with model group,the arthritis index score in Fushan rheumatism external prescription group were decreased(P<0.05,P<0.01),joint injury and pathological score were decreased(P<0.01),the levels of inflammatory cytokines TNF-α,IL-6,IL-17 and IFN-γ in serum were decreased(P<0.01),the expression of Notch2,DLL1 and NF-κBp65 mRNA and protein in joints and spleen were decreased(P<0.01),and the positive expression in joints were also decreased(P<0.01).In addition,no noticeable tissue damages were observed in liver and kidney in Fushan rheumatism external prescription group,and the levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),blood urea nitrogen(BUN)and creatinine(Cr)in serum were no changes(P>0.05).Conclusion Fushan rheumatism external prescription relieves arthritis symptoms and joint injury in CIA rats,and has no toxic and side effects on liver and kidney.Its mechanism may be related to the reduction of inflammatory cytokines and down-regulation of Nocth2 pathway.

Objective:To investigate the value of pulse oxygen saturation (SpO 2) monitoring in predicting children with moderate-to-severe obstructive sleep apnea (OSA). Methods:It was a retrospective study involving 341 children with snoring during nighttime sleep who had visited the Children′s Hospital of Soochow University from June 2017 to November 2020 and monitored for polysomnography (PSG) and SpO 2.The SpO 2 parameters mainly included oxygen desaturation index (ODI), oxygen desaturation index ≥3% (ODI3), oxygen desaturation index ≥4% (ODI4), mean pulse blood oxygen saturation (MSpO 2), lowest pulse blood oxygen saturation (LSpO 2), cumulative time spent with blood oxygen saturation below 95%, 92% and 90%(T95, T92 and T90). According to obstructive sleep apnea hypopnea index (OAHI), patients were divided into the snoring and mild OSA group (OAHI≤5 times/h) and moderate-to-severe OSA group (OAHI>5 times/h). Differences in SpO 2 parameters were compared between groups using the Chi- square test and Mann- Whitney U test. Spearman correlation analysis was used to analyze the correlation between SpO 2 parameters and OAHI in all children.The SpO 2 parameters were included in the Logistic regression model.Receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficiency of SpO 2 parameters on moderate-to-severe OSA. Results:A total of 341 patients were recruited, including 206 male and 135 female patients with the mean age, body mass index (BMI) and OAHI of 6.0 (4.0, 7.5) years, 16.2 (15.1, 18.0) kg/m 2 and 0.6 (0.1, 3.0) times /h, respectively.There were 283(83.0%) and 58 (17.0%) patients in the snoring and mild OSA group and moderate-to-severe OSA group.The ODI3[0.7 (0.3, 1.4) times/h vs.7.7 (4.4, 12.8) times/h], ODI4[0.4 (0.1, 0.8) times/h vs.5.3 (2.7, 9.1) times/h], T95[1.4 (0.3, 5.3) min vs.13.7 (7.0, 33.5) min], T92[0.1 (0, 0.5) min vs.1.8 (0.9, 6.0) min] and T90[0 (0, 0.1) min vs.0.6 (0.2, 2.2) min] were significantly lower in the snoring and mild OSA group than those of moderate-to-severe group, while LSpO 2[91.0 (89.0, 93.0)% vs.86.5 (82.0, 88.0)%] and MSpO 2[ 97.0 (97.0, 98.0)% vs.96.0 (96.0, 97.0)%] were significantly higher(all P<0.001). All SpO 2 parameters were significantly correlated with OAHI (all P<0.001), and the correlation coefficient between ODI3 and OAHI was 0.660.ODI3 was an independent predictor of moderate-to-severe OSA ( OR=3.117, 95% CI: 1.635-5.945, P=0.001). The area under the ROC curve of ODI3 in predicting the moderate-to-severe OSA was 0.957, and the cut-off value of 3.45 times/h and specificity of 95.4%.MSpO 2 was an independent predictor of moderate-to-severe OSA ( OR=2.917, 95% CI: 1.589-5.354, P=0.001). Conclusions:ODI3 can be used to predict the moderate-to-severe OSA in children.

Objective:To investigate the iodine content distribution of drinking water in Jiangsu Province.Methods:In 2017, the iodine content in drinking water of residents in townships (streets, hereinafter referred to as townships) of Jiangsu Province was investigated. Administrative villages (neighborhood committees, hereinafter referred to as administrative villages) of Jiangsu Province were selected as units for the investigation of townships with the median water iodine greater than 10 μg/L. Delimitation criteria: the median iodine content of water < 40 μg/L was iodine deficiency area, 40-100 μg/L was suitable iodine area, and > 100 μg/L was high iodine area.Results:A total of 1 285 townships were surveyed in 101 counties (cities, districts) in 13 cities, and the median water iodine in townships was 7.28 μg/L. Among them, there were 875 townships with median water iodine < 10 μg/L, accounting for 68.09%; 315 townships 10-< 40 μg/L, accounting for 24.51%; 56 townships 40-100 μg/L, accounting for 4.36%; 39 townships > 100 μg/L, accounting for 3.04%. The water iodine survey at the administrative village level was conducted in 5 864 administrative villages in 410 townships in 6 cities. Among them, 769 administrative villages with median water iodine < 10 μg/L, accounting for 13.11%; 3 558 administrative villages 10 - < 40 μg/L, accounting for 60.68%; 613 administrative villages 40 - 100 μg/L, accounting for 10.45%; and 924 administrative villages > 100 μg/L, accounting for 15.76%.Conclusion:According to the water iodine, there are iodine deficiency, suitable iodine and high iodine areas in Jiangsu Province, mainly in iodine deficiency areas.

Objective:To analyze the disease burden of liver cancer in China.Methods:Based on eight data sources, including the series of Chinese Cancer Registry Annual Report, three national death cause surveys in China, China Health Statistical Yearbook, China Death Cause Surveillance Datasets, GLOBOCAN, Cancer Incidence in Five Continents (CI5), WHO Mortality Database and the Global Burden of Disease (GBD), the information on incidence, mortality and disability-adjusted life year (DALY) of liver cancer, were extracted for the analysis on the past, current and future disease burden caused by liver cancer in China.Results:1) Past situation: The long-term data from 1973 to 2012 reported by the CI5 showed that in urban populations in China (taking Shanghai as an example), the incidence rate of liver cancer in males and females decreased by 41.3 % and 36.3 %, respectively, and that in rural areas (taking Qidong as an example) decreased by 32.3 % and 12.2 %, respectively. The Chinese Cancer Registry Annual Reports showed that the national incidence and mortality rates of liver cancer decreased by 8.1 % and 12.8 % respectively from 2005 to 2015. The Joinpoint analysis based on the data from the China Health Statistics Yearbook also showed a declining trend: the average annual percentage change of liver cancer mortality in China from 2002 to 2017 was -3.0 % ( P<0.05), and that in rural areas was -3.1 % ( P<0.05). 2) Current status: GLOBOCAN estimates that the rates of incidence, mortality and prevalence of liver cancer in China in 2018 were 18.3 per 100 000, 17.1 per 100 000 and 10.8 per 100 000, respectively. According to the latest annual report, the incidence and mortality rates of liver cancer in cancer registration areas in 2015 were 17.6 per 100 000 and 15.3 per 100 000, respectively, and both increased with age. The mortality rate was similar to that reported in 2017 (16.7 per 100 000) by the China Death Cause Surveillance Datasets, and the male to female ratio of live cancer deaths was estimated as 3.1. The GBD 2017 reports that the DALYs caused by liver cancer in China reached 11 153.0 thousand in 2017 (accounting for 53.7 % of the global DALYs) and hepatitis B virus infection was always the leading cause. 3) Prediction: The GLOBOCAN 2018 predicts that, by 2040, the number of liver cancer cases and deaths in China would reach 591 000 and 572 000 (with an increase of 50.5 % and 54.9 %, respectively, compared with those in 2018), with a more significant increase in people over 70 years old. 4) Economic burden: According to the literature review of economic burden data on liver cancer, the direct medical expenditure per patient with liver cancer generally showed a rising trend. Conclusions:Multiple data sources indicate that the incidence and mortality rates of liver cancer in populations in China decreased in the past decades, indicating the effect of population interventions. However, the population-level disease burden are still substantial, and comprehensive intervention strategies need to be continually strengthened and optimized, especially the primary and secondary prevention.

Objective To evaluate the role of tumor budding in the prognostic value of intrahepatic cholangiocarcinoma(ICC) after radical resection.Methods The clinicopathological data of patients undergoing radical resection for intrahepatic cholangiocarcinoma between 2011 and 2016 were retrospectively analyzed.The number of tumor budding was counted in a ×200 microscopic field (0.785mm2).Based on receiver operation curve (ROC),the number of tumor budding ≥ 15 was defined as high-grade group,and ＜ 15 was low-grade group.Multivariate analysis were performed on predictors of the tumor.Results Low-grade group was observed in 32 cases and high-grade group in 50.High-grade group appeared to develop tumors with higher CA199,poor differentiation,larger tumor diameter,advanced stage and high risks of lymphnode metastasis (respectively x2 =5.470,4.359,5.101,4.696,5.960,all P ＜ 0.05).Univariate analysis showed that tumor budding,CA199,differentiation,tumor diameter,T classification and lymphnode metastasis were related to the overall survival of patients with ICC (respectively x2 =11.704,4.876,5.056,5.152,8.442,16.725,all P ＜ 0.05).On multivariable analysis,high-grade group was a significant independent predictor of worse OS (HR =2.707 95％ CI 1.558-4.705,P ＜ 0.001).Conclusions High-grade tumor budding is an important negative prognostic factor for ICC.

Objective To explore the association of nocturnal serum cortisol levels with diabetic microvascular complications in overweight or obese patients with type 2 diabetes mellitus. Methods Serum cortisol levels of 316 overweight or obese type 2 diabetic patients were tested at midnight by the method of chemiluminescence. Diabetic microvascular complications were compared among various groups according to nocturnal serum cortisol levels. All the patients with nocturnal serum cortisol level > 50 nmol/L were asked to undergo overnight low-dose dexamethasone suppression test to rule out the possibility of subclincal Cushing's syndrome. The incidences of diabetic nephropathy ( DN ) , diabetic retinopathy ( DR ) , and diabetic peripheral neuropathy ( DPN ) were examined in all the patients. Results (1)The incidence of DN was gradually increased from 13.3％to 27.7％and 44.2％in patients with low, medium, and high cortisol level groups, showing a statistical difference among 3 groups ( P<0.05) . The incidences of DR in medium and high cortisol level groups were higher than that in low cortisol level group (40.6％and 47.7％vs 22.7％, both P<0.01). The incidence of DPN in high cortisol level group was higher as compared with low cortisol level group (60.5％ vs 38.7％, P<0.01). (2) Nocturnal serum cortisol level in patients with diabetic microvascular complications was higher than that in patients without complications [ (136.87 ± 105.78 vs 97.55 ± 93.48) nmol/L, P<0.01]. Nocturnal serum cortisol level in patients with multiple diabetic microvascular complications was higher than that in patients with single diabetic microvascular complication [ (151.66±114.54vs117.69±90.26)nmol/L,P<0.05].(3)Singlefactorlogisticregressionanalysisshowedthat higher nocturnal serum cortisol level was a risk factor for diabetic microvascular complications in addition to female, age, longer diabetic duration, higher fasting plasma glucose ( FPG ) . Multivariate logistic regression analysis showed that higher nocturnal serum cortisol level was still a risk factor for diabetic microvascular complications after adjusted by diabetic duration, FPG, HbA1C, and the use of insulin (P=0.013). Conclusion Nocturnal serum cortisol level seems to be a risk factor for diabetic microvascular complications in overweight or obese patients with type 2 diabetes mellitus.

BACKGROUND: The proliferation of peripheral blood stem cells among peripheral blood mononuclear cells (PBMCs) invitro remains unclear. There is no optimal marker for tracing PBMCs transplanted in vivo.OBJECTIVE: To observe the degree of PBMC proliferation in stem cell medium by EdU labeling and to explore thefeasibility of EdU-labeled peripheral blood stem cells.METHODS: New Zealand rabbit PBMCs were isolated and cultured for 1 to 5 days in stem cell medium supplementedwith EdU. The cells were observed and counted at 0, 1, 2, 3, 4 and 5 days in culture. The cells were harvested at eachtime point and stained with EdU fluorescent reagents. Then, confocal microscopy and flow cytometry were used to detectEdU-labeled cells.RESULTS AND CONCLUSION: (1) Freshly isolated rabbit PBMCs were rounded and showed clear outline. After 1 dayculture, most of the cells were suspended in the medium, spherical or round. There were also a few cell clusters andadherent cells scattered in a triangle or polygon shape; after 2 days culture, more cell debris were observed, and mostcells were round; when cultured for 3-5 days, increased cell debris, smaller cell mass and decreased cell densitysignificantly were observed. (2) With the prolongation of culture time, the cell count decreased gradually. (3) Whencultured for 1 day, EdU labeled cells in red were scattered. The number of cells marked with EdU red label increasedsignificantly at day 2 and remained unchanged after 3 days of culture. At 5 days of culture, the number of red cellsmarkedly decreased; the highest positive rate of EdU-labeled cells was (2.38±0.10)% at 2 days after culture. To conclude,these results showed that the proportion of proliferating cells in rabbit PBMCs was very low. EdU is capable of labelingproliferative cells among PBMCs.