Objective To explore the relationship between atherosclerosis(AS)and bone mineral density(BMD)as well as frac-ture risk in patients with type 2diabetes mellitus(T2DM).Methods A total of 380 T2DM patients aged 50-80 years were included and divided into AS group and non-AS group based on carotid intima-media thickness.Clinical indicators were compared between the two groups,and the relationship between AS and BMD as well as fracture risk was analyzed.Results The AS group had higher age,diabetes duration,incidence of osteopenia,10-year probability of major osteoporotic fracture(PMOF),and 10-year probability of hip fracture(PHF),while having lower femoral neck BMD than the non-AS group.In male T2DM patients,PMOF and PHF were positively correla-ted with age,diabetes duration,and AS lesions,and negatively correlated with total cholesterol,triglycerides,low-density lipoprotein,25-hydroxyvitamin D,type Ⅰ procollagen amino-terminal peptide,and BMD.In female T2DM patients,PMOF and PHF were posi-tively correlated with menopause duration,fasting insulin,and AS lesions,and negatively correlated with blood phosphorus and BMD.Regression analysis showed that osteopenia was an independent risk factor for AS lesions in male T2DM patients,AS lesions were an inde-pendent risk factor for BMD levels,and body mass index was an independent protective factor for BMD levels.In female T2DM patients,age,fasting insulin,and high-density lipoprotein were independent risk factors for BMD levels,and parathyroid hormone was an inde-pendent protective factor for BMD levels.Conclusion When T2DM patients have AS lesions,the incidence of low bone mass and osteo-porosis is higher,with decreased femoral neck BMD and increased PMOF and PHF.In male subjects,low bone mass and osteoporosis are independent risk factors for AS lesions,and AS lesions are also independent risk factors for BMD levels.

Objective To explore the relationship between atherosclerosis(AS)and bone mineral density(BMD)as well as frac-ture risk in patients with type 2diabetes mellitus(T2DM).Methods A total of 380 T2DM patients aged 50-80 years were included and divided into AS group and non-AS group based on carotid intima-media thickness.Clinical indicators were compared between the two groups,and the relationship between AS and BMD as well as fracture risk was analyzed.Results The AS group had higher age,diabetes duration,incidence of osteopenia,10-year probability of major osteoporotic fracture(PMOF),and 10-year probability of hip fracture(PHF),while having lower femoral neck BMD than the non-AS group.In male T2DM patients,PMOF and PHF were positively correla-ted with age,diabetes duration,and AS lesions,and negatively correlated with total cholesterol,triglycerides,low-density lipoprotein,25-hydroxyvitamin D,type Ⅰ procollagen amino-terminal peptide,and BMD.In female T2DM patients,PMOF and PHF were posi-tively correlated with menopause duration,fasting insulin,and AS lesions,and negatively correlated with blood phosphorus and BMD.Regression analysis showed that osteopenia was an independent risk factor for AS lesions in male T2DM patients,AS lesions were an inde-pendent risk factor for BMD levels,and body mass index was an independent protective factor for BMD levels.In female T2DM patients,age,fasting insulin,and high-density lipoprotein were independent risk factors for BMD levels,and parathyroid hormone was an inde-pendent protective factor for BMD levels.Conclusion When T2DM patients have AS lesions,the incidence of low bone mass and osteo-porosis is higher,with decreased femoral neck BMD and increased PMOF and PHF.In male subjects,low bone mass and osteoporosis are independent risk factors for AS lesions,and AS lesions are also independent risk factors for BMD levels.

Hepatitis E virus(HEV)is one of the most common pathogens in acute viral hepatitis.There are at least eight distinct genotypes of HEV.Only humans can contract HEV genotypes 1 and 2,but zoonotic viruses like genotypes 3 and 4 are mostly spread by eating undercooked or in-fected pork in some affluent nations.As a result,boars,both domestic and wild,are typically regar-ded as primary hosts of HEV.Nevertheless,during the past few years,a growing body of research has demonstrated that a number of other wild ruminant animals,such as wild deer and goats,are also susceptible to HEV infection.Determining their participation in the epidemiological cycle of hepatitis E thus requires an understanding of the risk variables that influence the transmission be-tween wild ruminants and humans.With an emphasis on published serological and molecular re-search,this review offers a broad summary of the body of knowledge currently available on the epi-demiology of HEV in wild ruminants.It addresses potential risk factors that could impact the spread of HEV among animals as well as their potential to serve as a source of infectious zoonotic illnesses.It presents an overview of the most recent developments in the epidemiology of HEV in wild ruminants and offers a framework for HEV prevention and management based on science.

Objective:To analyze the expression levels and clinical significance of interferon (IFN)-α/β in the renal cortex and serum of children with lupus nephritis (LN).Methods:A total of 32 children with LN diagnosed in the pediatric nephrology department of the Second Xiangya Hospital of Central South University from December 2017 to September 2020 were selected as the study subjects (LN group). The normal kidney control group consisted of 3 normal kidney transplant volunteers who underwent biopsy of kidney tissue (normal kidney control group), while 14 healthy children who underwent physical examination were collected as the normal control group. According to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), LN patients were divided into mild activity group ( n=8), moderate activity group ( n=9), and severe activity group ( n=15). According to the International Society of Nephrology/Society of Nephrology (ISN/RPS) 2003 LN classification criteria, pathological classification was performed (3 cases in the mild pathological damage group, 8 cases in the moderate pathological damage group, and 11 cases in the severe pathological damage group); Immunohistochemistry was used to detect the expression and distribution of IFN-α/β in glomeruli and renal interstitium; Enzyme linked immunosorbent assay (ELISA) was used to detect the concentration of IFN-α/β in serum samples and analyze its correlation with the pathological classification and disease activity of LN patients. Results:The serum and renal cortex IFN-α/β levels in the LN group were higher than those in the normal control group and normal kidney control group, respectively (all P<0.05). The average level of serum IFN-α/β in the heavy activity group was higher than that in the light and moderate activity groups (all P<0.05). The serum and renal cortex IFN-α/β levels in the severe pathological damage group were significantly higher than those in the mild and moderate pathological damage groups (all P<0.05). Conclusions:IFN-α/β in the renal cortex is closely related to renal injury in LN; Serum IFN-α/β can assist in evaluating the disease activity level of LN to a certain extent.

Objective To explore the pharmacokinetic changes of single dose of fentanyl in rats in a simulated high-altitude and contributing factors.Methods Thirty-six healthy female SD rats(6～8 weeks old,250±20 g)were randomly divided into high-altitude-acute-exposure group(group A),high-altitude-chronic-exposure group(group S)and control group(group C)through random number table,with 12 rats in each group.The group A and S were housed in a low-pressure chamber simulating the high altitude of 5000 m above sea level for 3 and 30 d respectively,and the group C was housed out of the chamber(at an altitude of 300 m).A single dose of fentanyl was administered through the femoral vein to 6 rats randomly selected from each group.Liquid chromatography tandem mass spectrometry(LC-MS/MS)was used to detect blood concentrations of fentanyl and WinNonlin 8.2 software was used to calculate the pharmacokinetic parameters,while blood samples were taken through the femoral artery before and in 1,2,4,8,15,30,60,120 and 180 min after administration.The remaining 6 rats were ultrasonographically assessed for portal vein internal diameter(PVD),peak flow velocity(PVV)and blood flow(PVF),and liver tissues were collected for CYP3A1 protein content assay.Results The blood drug concentrations of fentanyl in the group A and group S were significantly lower than those in the group C at 60,120,and 180 min(P=0.002,P＜0.001,P= 0.001).Compared with the group C,the clearance rate(CL)of the group A was increased by 54.06%(P=0.021),and the mean residence time(MRTlast)was shortened by 24.21%(P=0.033);CL of the group S was increased by 50.10%(P=0.041),the area under the concentration-time curve(AUC0-t,AUC0-∞)and MRTlast were reduced by 18.92%(P=0.039),27.54%(P=0.018)and 33.61%(P= 0.004),respectively.PVD and PVF in the group S increased by 10.87%(P=0.006)and 42.50%(P= 0.006)when compared with the group C.The CYP3A1 protein content in the group A was 28.74%,which was higher than that in the group C(P=0.048).Conclusion Fentanyl is cleared significantly faster after a single dose in rats in simulated high-altitude,which may be related to the increased liver blood flow and increased CYP3A1 protein expression in liver.

The expression levels of serum tenascin-C, osteopontin(OPN), and transforming growth factor-β1(TGF-β1) in the patients of diabetic mellitus were measured by ELISA. With the increase of the UACR, the expression of tenascin-C, osteopontin, and transforming growth factor-β1 showed a trend of increase and hypertension will argument this phenomenon. Pearson correlation analysis showed that levels of tenascin-C were positively correlated with HbA1C , body mass index, systolic blood pressure, diastolic blood pressure, UACR, osteopontin, and transforming growth factor-β1.

Objective To investigate the association of adaptor protein,phosphotyrosine interacting with PH domain and leucine zipper 1(APPL1)with urinary albumin excretion rate in patients with type 2 diabetes mellitus (T2DM),and to explore the role of APPL1 in the development of diabetic kidney disease(DKD). Methods According to the urinary albumin/creatinine ratio(UACR),288 newly-diagnozed patients with T2DM were divided into normal albuminuria group(UACR<30 mg/g,n=116),microalbuminuria group(UACR 30 ~300 mg/g,n=95),and macroalbuminuria group(UACR>300 mg/g,n=77). 130 healthy subjects with matched sex and age were used as control group. Serum APPL1,tumor necrosis factor α(TNF-α),and adiponectin levels were measured by ELISA method. Results Serum APPL1 level in T2DM patients was significantly higher than that in control subjects (P<0.01), and increased with the rising of UACR. In patients with T2DM, serum APPL1 level was negatively correlated with estimated glomerular filtration rate(r=-0.246, P<0.01) while it was positively correlated with HbA1C, low density lipoprotein cholesterol, total cholesterol, triglycerides, insulin resistance index, serum creatinine,blood urea nitrogen, systolic blood pressure, TNF-α, and adiponectin(r=0. 119, 0. 167, 0. 209, 0.194,0.273,0.242,0.131,0.144,0.365, and 0.952, respectively, P<0.05 or P<0.01). Conclusion Serum APPL1 level in patients with T2DM was increased with the rising of UACR, suggesting that APPL1 may be involved in the development of DKD.

267 newly-diagnosed patients with type 2 diabetes were divided into normoalbuminuria group [group N-UAlb, urinary albumin to creatinine ratio (UACR)<30 mg/g, n=103], microalbuminuria group(group M-UAlb, UACR 30~300 mg/g, n=88 ) , and macroalbuminuria group ( group L-UAlb, UACR>300 mg/g, n=76). The control group(group NC) consisted of 114 healthy individuals. Serum betatrophin, adiponectin(APN), and interleukin-1β( IL-1β) levels were determined with ELISA methods and the parameters of body mass index (BMI), estimated glomerular filtration rate(eGFR), HbA1C, fasting plasma glucose(FPG), OGTT 2h plasma glucose(2hPG), fasting insulin(FINS), OGTT 2h postprandial insulin(2hPINS), fasting C-peptide(FCP), homeostasis model assessment insulin resistant index(HOMA-IR), and blood lipid were collected. Compared with group NC, the serum betatrophin levels in patients with type 2 diabetes were obviously increased. In patients with type 2 diabetes, betatrophin levels increased along with the increase of UACR and there were significant differences in betatrophin among the three groups(P<0. 01). Betatrophin positively correlated with UACR, HbA1C, FPG, 2hPG, FINS, 2hPINS, HOMA-IR, TC, LDL-C, and TG( r were 0. 785, 0. 225, 0. 136, 0. 241, 0. 386, 0. 223, 0. 411, 0.216,0.193,and0.298,allP<0.05),and betatrophin were also positively correlated with APN and IL-1β(rwere 0. 643 and 0. 710, both P<0. 01). Stepwise multiple regression analysis showed that UACR, HbA1C, FINS, and TG were independent relevant factors affecting betatrophin levels.

Objective To explore the associations of serum Mir-217 with silent information regulator 1 (Sirt1)and hypoxia-inducible factor-1α(HIF-1α)in type 2 diabetic patients with different urinary albumin excretion rates. Methods A total of 479 patients with type 2 diabetes were divided into normoalbuminuric(D1, n=181), microalbuminuric(D2, n=165), and macroalbuminuric(D3, n=133)subgroups. 192 normal subjects served as control group. Serum level of Mir-217 was detected by realtime PCR. Serum Sirt1, HIF-1α, and vascular endothelial growth factor ( VEGF ) levels were determined by enzyme-linked immunosorbent assay. Results Compared with control subjects, serum Mir-217 level was significantly increased in type 2 diabetic patients and gradually increased in D1, D2, and D3 groups(P<0. 01). The parameters of age, diabetes duration, body mass index, fasting plasma glucose, fasting insulin, homeostasis model assessment of insulin resistant index(HOMA-IR), HbA1C, low density lipoprotein-cholesterol( LDL-C) , total cholesterol ( TC ) , triglyceride ( TG ) , serum uric acid ( SUA ) , blood urea nitrogen(BUN), HIF-1α, VEGF, and Mir-217 all were positively correlated with ACR(all P<0. 05). High density lipoprotein-cholesterol(HDL-C)and Sirt1 were negatively correlated with ACR(both P<0. 05). VEGF, HIF-1α, Mir-217, BUN, diabetes duration, LDL-C, Sirt1, and SUA were independent factors that influenced ACR(all P<0. 01). Additionally, diabetes duration, HOMA-IR, HbA1C, ACR, LDL-C, TC, TG, SUA, BUN, HIF-1α, and VEGF were positively correlated with Mir-217(all P<0. 05), while Sirt1 was negatively correlated with Mir-217(P<0. 01). Conclusion Serum Mir-217, as a possible biomarker for early diagnosis of diabetic nephropathy, may be involved in the development of diabetic nephropathy by promoting chronic inflammatory reaction, renal fibrosis, and angiogenesis.

Objective To investigate the expression levels of serum vasohibin-1(VASH-1)in type 2 diabetes mellitus(T2DM)patients at different stages of urinary albumin to creatinineratio(UACR)and to attempt to investigate the relationship between VASH-1 and inflammation and fibrosis in the pathogenesis of diabetic nephropathy(DN), one of the microvascular complications of T2DM. Methods 486 patients with T2DMwere divided into four groups:normal albuminuria [ UACR<30 mg/ g, n = 134], microalbuminuria [ UACR at 30-300 mg/ g, n = 122], clinical albuminuria [UACR > 300 mg/ g, n = 106 ], and clinical albuminuria hypertensive [ UACR > 300 mg/ g, with hypertension, n=124] groups. Age, course, serum levels ofVASH1, inflammation markers(CRP, ESR)and fibrosis marker( TGF-β1) with other biochemical indicators were measured, and 130 normal control subjects were also included. Results Compared with normal control group, the levels of UACR, HbA1C ,ESR, CRP, TGF-β1 and VASH-1 in groups ofnormal albuminuria, microalbuminuria, clinical albuminuria, and clinical albuminuria hypertensive were significantly higher(P<0. 05). Pearson correlation analysis showed that levels of VASH-1 were positively correlated with UACR, HbA1C ,ESR, CRPand TGF-β1( r = 0. 521, 0. 261, 0. 519, 0. 523, 0. 479, P<0. 001), while multivariate regression analysis showed that levels of UACR, HbA1C ,ESR, CRP and TGF-β1 were important factors affecting serum VASH-1 levels. Conclusion Serum levels of VASH-1 may become new biomarkers of early diagnosis of DN. Consequently, VASH-1 level may provide a new pattern and direction of inflammation and fibrosis for consideration in diabetic kidney damage.