BACKGROUND:Sclerostin can negatively regulate the bone metabolism, and the sclerostin monoclonal
antibody can antagonize the negative regulation effect, inhibit bone resorption and promote bone formation. OBJECTIVE:To explore the mechanism and application progress of sclerostin monoclonal antibody in the treatment of osteoporosis.
METHODS:An online search of PubMed database, CNKI database, VIP database and Wanfang database
between May 2005 and May 2013 was performed by the first author to search the related articles with the key words of“osteoporosis, antibody, sclerostin, Wnt, SOST”in both English and Chinese. Articles related to
sclerostin monoclonal antibody were included. For the articles in the same field, those published earlier or in the authorized journals were preferred.
RESULTS AND CONCLUSION:A total of 170 articles were obtained after initial search, and final y 54 articles related to sclerostin monoclonal antibody were included for review according to the inclusion criteria. The
sclerostin can block Wnt pathway through combining with low-density lipoprotein receptor-related protein 5/6, thus inhibiting the differentiation and mineralization of osteoblasts. By specifical y binding to sclerostin, the
sclerosin monoclonal antibody can indirectly promote bone formation and restrain bone absorption which has great significance in the treatment of osteoporosis. Meanwhile, compared with the other treatment method, the specific targeting of sclerostin and the binding specificity of sclerostin monoclonal antibody provide application advantages for the treatment of osteoporosis.

Objective To evaluate mono-and bi-exponential decay models in the diagnosis of hepatocellular carcinoma (HCC). Methods 28 patients with HCC who underwent conventional MRI imaging and diffusion-weighted imaging were collected,and all the HCC lesions were proved by operation pathology.The ADC values in mono-exponential decay model and ADCst ,ADCslow , ADCfast and ffast of the lesions in bi-exponential decay model were measured through the reconstruction of ADCmap ,ADCslow map, ADCfast map and fraction of fast ADC at a workstation.The relationships between the ADC values with low,medium and high b-val-ues and different differentiation degrees of HCC were analyzed.Moreover,the relationships between the ADCst ,ADCslow ,ADCfast , ffast values and HCC defferentiation grades were also explored.Results Significant differences in ADC value were found among differ-ent degrees of HCC differentiation in middle and high b-value groups (P <0.05).A positive correlation was found between the ADC value and the degree of HCC differentiation in middle (r=0.377,P <0.01)and high b-value group (r =0.81 5,P <0.01).There were no significant differences in ADC value among the different degrees of HCC differentiation in low b-value group.There were significant differences in the values of ADCst ,ADCslow and ADCfast among different degrees of HCC differentiation.Significant posi-tive correlations were found between the values of ADCst ,ADCslow and ADCfast and the degree of differentiation (P <0.01).There were no significant differences in the values of ffast among different degrees of HCC differentiation.Conclusion ADC value in mono-exponential decay model plays a potential role in the diagnosis of different differentiation degree of HCC with a b value ≥400 s/mm2 .Furthermore,the parameters in bi-exponential decay model,especially the values of ADCst ,ADCslow and ADCfast ,can provide new and unique information in the distinction of different degrees of HCC differentiation.

Objective:To evaluate the effect of anthracyclines on myocardial work in patients with breast cancer by left ventricular pressure strain loop (PSL).Methods:From April 2019 to June 2020, 30 breast cancer patients treated with AC-T regimen(Adriamycin/epirubicin+ cyclophosphamide+ docetaxel) in the Second Affiliated Hospital of Harbin Medical University were selected as case group, and 30 healthy volunteer were selected as control group. Transthoracic echocardiography was performed in the case group at 3 time points: before chemotherapy (T0 phase), after the third cycle of chemotherapy (T1 phase), and after the sixth cycle of chemotherapy (T2 phase) respectively. Conventional ultrasonic parameters were collected. Left ventricular PSL was used to evaluate the left ventricular myocardial work index, including global work index (GWI), global constructive work (GCW), global work waste (GWW) and global work efficiency (GWE). The same examination was performed in the control group, and the results between T0 phase and control group, among different phases were compared.Results:①There were no statistically significant differences of general information, conventional ultrasound parameters, left ventricular strain and myocardial work parameters between T0 phase and control group (all P>0.05). ②There were no statistically significant differences of LVEF, GLS, GWI, GCW, GWE and GWW between T1 phase and T0 phase (all P>0.05). ③There were no statistically significant differences in LVEF between T2 phase and T0 phase ( P>0.05). The absolute values of GLS, GWI, GCW and GWE decreased, but GWW increased, the difference was statistically significant (all P<0.05). ④There were no significant differences in LVEF between T2 phase and T1 phase ( P>0.05), but the absolute values of GLS, GWI, GCW and GWE decreased, while GWW increased (all P<0.05). Conclusions:Left ventricular PSL can effectively evaluate the myocardial work of anthracycline chemotherapy in breast cancer patients, which is superior to LVEF and provide a new evaluation method for asymptomatic patients.

Objective:To explore the pathological characteristics of adrenal masses based on various tumor diameter and unenhanced computed tomography(CT) attenuation value, and evaluate the value of the two parameters in the assessment of the benign and malignant nature of adrenal masses.Methods:The data of 1 367 patients who underwent adrenalectomy in Nanjing Drum Tower Hospital from January 2017 to October 2022 were retrospectively collected. The adrenal masses were divided into four groups according to tumor diameter and unenhanced CT attenuation value, and the clinical and histopathological characteristics of the four groups were compared respectively. Logistic regression was used to analyze the correlation between tumor diameter, non-contrast CT attenuation value and malignant adrenal masses, and receiver operating characteristic(ROC) curve was used to assess the diagnostic value of both in benign and malignant adrenal masses.Results:The proportion of adrenocortical carcinoma and other malignant tumors increased with the rise of tumor diameter or unenhanced CT attenuation value. After adjusting for age and gender, tumor diameter( OR=1.624, 95% CI 1.464-1.803, P<0.001) and unenhanced CT attenuation value( OR=1.108, 95% CI 1.079-1.138, P<0.001) were predictors of malignant adrenal masses. The tumor diameter and unenhanced CT attenuation value in diagnosing malignant adrenal masses had area under the ROC curve(AUC) of 0.838 and 0.892, respectively. With the optimal cut-off values of >3.4 cm and >30 HU, the sensitivity was 75.5% and 83.7%, and the specificity was 80.5% and 84.4%, respectively. The combination of tumor diameter >3.4 cm and unenhanced CT attenuation value >20 HU had an AUC of 0.927, with a sensitivity of 71.4% and a specificity of 90.1% in diagnosing malignant adrenal masses. Conclusions:Tumor diameter and unenhanced CT attenuation value has important significance in the differential diagnosis of benign and malignant adrenal masses. A combination of tumor diameter (>3.4 cm) and unenhanced CT attenuation value (>20 HU) demonstrates best diagnostic efficiency. Clinical application of this combined index can effectively diagnose malignant adrenal masses while avoiding unnecessary investigations or surgery.

Background::The clinical characteristics of patients with the comorbidities of hypertension and coronary artery disease (HT-CAD) and atrial fibrillation (AF) are largely unknown. This study aimed to investigate the prevalence of AF in patients with HT-CAD and clinical characteristics of patients with both HT-CAD and AF.Methods::This cross-sectional study was conducted in Chinese People’s Liberation Army General Hospital in Beijing, China, and included 20,747 inpatients with HT-CAD with or without AF from August 2008 to July 2018. We examined the overall prevalence, clinical characteristics, comorbidity profiles, treatment patterns, and blood pressure (BP) control of patients with both HT-CAD and AF. Multivariate logistic regression was used to investigate the associations of cardiovascular risk factors with AF in patients with HT-CAD.Results::The overall prevalence of AF in patients with HT-CAD was 4.87% (1011/20,747), and this increased with age; to be specific, the prevalence in women and men increased from 0.78% (2/255) and 1.02% (26/2561) at the age of <50 years to 8.73% (193/2210) and 10.28 % (298/2900) at the age of ≥70 years, respectively. HT-CAD patients who had AF had a higher prevalence of cardiovascular-related comorbidities than those without AF. Multivariate logistic regression showed that age, gender (male), body mass index, heart failure, and chronic kidney disease were independently associated with the risk of AF in patients with HT-CAD. For those with both HT-CAD and AF, 73.49% (743/1011) had a CHA 2DS 2-VASc score of ≥4, and only about half of them had the BP controlled at <140/90 mmHg, which indicated a high risk of thromboembolism and stroke. The use of oral anticoagulation increased during the study period (10.00% [20/200] in 2008 to 2011 vs. 30.06% [159/529] in 2015 to 2018, P < 0.01), but remained at a relatively low level. Conclusions::AF is highly prevalent among patients with HT-CAD. Patients with both HT-CAD and AF have a higher prevalence of cardiovascular-related comorbidities, lower BP control rate, and lower use of oral anticoagulation.

Objective To develop and test the reliability and validity of the Intrinsic Capacity Assessment Scale for the Older People,so as to provide an effective tool for the assessment of the intrinsic capacity of the aged.Methods Based on the International Classification of Functioning,Disability and Health(ICF)as the theoretical framework,the initial version of The Intrinsic Capacity Assessment Scale for the Older People was developed through literature analysis,Delphi expert consultation and pre-survey.From July to September 2023,650 old people were selected by convenience sampling method to conduct a survey,and 20 old people were surveyed after 2 weeks again to test the reliability and validity of the scale.Results The effective questionnaire recovery rates of the 2 rounds of expert correspondence were 92.3％and 91.7％;the expert authority coefficients were 0.83 and 0.86;the mean importance scores of items were 2.04-3.79 and 3.50-3.82,and the full score ratios were 4.2％-83.3％and 54.6％-86.4％,respectively.The coefficients of variation were 0.11-0.42 and 0.11-0.23,respectively.A total of 5 common factors were extracted from exploratory factor analysis,and the cumulative variance contribution rate was 68.327％.The results of confirmatory factor analysis showed that the fit indexes were x2/df=1.908,RMSEA=0.054,CFI=0.931,IFI=0.932,TLI=0.922,indicating a good fit.The Cronbach's α coefficient of the scale was 0.944;the split half reliability was 0.806;the retest reliability was 0.933.The content validity index of item level was 0.82-1.00,and the content validity index of scale level was 0.91.The Intrinsic Capacity Assessment Scale for the Older People included 35 items in 5 dimensions:movement,vitality,sensation,cognition and psychology.Conclusion The Intrinsic Capacity Assessment Scale for the Older People has good reliability and validity,and it can be used as a reliable tool to evaluate the intrinsic capacity level of the aged.

Objective:To investigate the association between triglyceride-glucose (TyG) index and all-cause mortality in elderly patients with hypertension and coronary artery disease.Methods:This was a retrospective cohort study, a total of 5 640 elderly inpatients (≥65 years) with hypertension and coronary artery disease who were admitted to the Department of Cardiology, Liberation Army General Hospital from August 2008 to July 2018 were enrolled in this study. The baseline clinical data of the patients were collected and the TyG index was calculated. Patients were divided into four groups according to their TyG index quartiles: TyG index<8.31 ( Q1 group, n=1 392), 8.31≤TyG index<8.67 ( Q2 group, n=1 417), 8.67≤TyG index<9.07 ( Q3 group, n=1 427), and TyG index≥9.07 ( Q4 group, n=1 404). All patients were followed up by obtaining outpatient/rehospitalization records or by telephone. The primary endpoint was all-cause mortality. Log-rank test was used to compare the cumulative all-cause mortality among groups. Cox proportional hazard regression model was used to analyze the risk of all-cause mortality in each group (the Q2 group with the lowest all-cause mortality was used as a reference), after adjusting for confounding factors, Restricted cubic spline analysis (RCS) was used to determine the association between TyG index and risk of all-cause mortality. Results:During a follow-up of 6.44 (4.70, 8.85) years, 1 037 all-cause deaths (18.39 %) were documented. The cumulative all-cause mortality in Q1- Q4 groups was 16.52%, 16.51%, 17.59% and 22.93%, respectively, and the difference was statistically significant ( χ2=26.49, P<0.01). In the Cox regression model, compared with Q2 group (reference), the HR (95% CI) for all-cause mortality was 1.06 (0.88-1.28) in the Q1 group, 1.23 (1.02-1.48) in the Q3 group and 1.48 (1.23-1.77) in the Q4 group, respectively ( P for trend<0.01). RCS curve analysis showed that when the TyG index was greater than 8.67, the risk of all-cause mortality increased with the TyG index, and there was a linear relationship between TyG index and all-cause mortality in this patient cohort (non-linearity P=0.31). Conclusion:The elevated TyG index is significantly associated with a higher risk for all-cause mortality in elderly hypertension and coronary artery disease patients.

Objective:To determine the expression and diagnostic value of peripheral blood lymphocytes and functional activation status in non-Hodgkin lymphoma with hemophagocytic lymphohistiocytosis (NHL-HLH) .Methods:We retrospectively analyzed clinical data from 30 newly diagnosed NHL-HLH patients admitted to Jiangsu Province Hospital from September 2022 to September 2023. We assessed peripheral blood lymphocytes and activation status by flow cytometry. Forty newly diagnosed patients with NHL who received treatment at our hospital during the same period and had lymphocyte and functional activation indexes were selected as the control group. The differences in relative and absolute lymphocyte counts and functional activation indexes between the two groups were compared. The optimal cutoff values for continuous variables were calculated from the receiver operating characteristic curve and logistic regression analysis was used to evaluate the risk factors in NHL patients with HLH.Results:A total of 30 NHL-HLH patients were evaluated, including 12 T-cell lymphoma and 18 B-cell lymphoma patients. Forty individuals were in the control group, which included 19 T-cell lymphoma and 21 B-cell lymphoma patients. The absolute counts of CD3 + T, CD4 + T, CD8 + T, and NK cells, along with the relative count of NK cells, were significantly lower in the HLH group compared with that in the control group (all P values<0.01) . The expression of CD38 and HLA-DR on CD8 + T-cell activated subgroups was significantly higher in the NHL-HLH group compared with that in the control group (CD8 +CD38 +/CD8 + T expression median: 57.4% vs 21.5%, P<0.001; CD8 +CD38 +/CD8 + T expression median: 49.7% vs 33.5%, P=0.028, respectively) . In addition, CD28 expression on CD4 + and CD8 + T cells was significantly higher in NHL-HLH patients ( P<0.01) . ROC curve and multivariate logistic regression analyses revealed that absolute NK cell count ≤72.0 cells/μl, CD4 +CD28 +/CD4 + T >94.2%, and CD8 +CD28 +/CD8 + T >38.4% were risk factors for predicting the occurrence of NHL-HLH patients. The sensitivity and specificity of the regression model were 86.7% and 86.1%, respectively, with an area under the curve of 0.94 ( P<0.001) . Conclusions:In NHL patients with HLH, there was a significant reduction in the absolute number of peripheral blood lymphocyte subpopulations, whereas T-cell function was notably activated. Specifically, absolute counts of NK cells ≤72.0 cells/μl, CD4 +CD28 +/CD4 + T >94.2%, and CD8 +CD28 +/CD8 + T >38.4% were identified as risk factors for predicting the development of NHL-HLH patients. This will assist in early clinical diagnosis and treatment.

Background Research on non-target organ damage of biological pesticides has attracted much attention. Rotenone exposure may be far beyond the occupational environment, and the exposureduring pregnancy may be increased through bioaccumulation, fruit or vegetable residues, and other forms of oral intake. At present, the effects of rotenone on placental development and its mechanism are still unknown. Objective To investigate the developmental damage of rat placenta and evaluate the expression levels of glycogen synthase kinase (GSK-3β) and beta catenin (β-catenin) followed by rotenone exposure through the placental barrier during pregnancy, as well as to propose possible associated mechanisms. Methods Eighteen sexually mature SD female infertile rats without specific pathogens were selected and divided into three groups: blank control group (0.9% saline), corn oil group, and rotenone group (corn oil + 2 mg·kg⁻¹ rotenone) by random number method, six female animals in each group. Another six male rats were selected and mated to the female rats at night with a female to male ratio of 3:1 per cage. Pregnant rats were given 0.9% saline, corn oil, and 2 mg·kg⁻¹ rotenone preparation by isovolumetric gavage once daily for the entire gestation period (19 d), and their conditions were observed after the last dose. The pregnant rats were anesthetized, and the size of the placenta and blood perfusion were detected by ultrasound the next day of the last dose of rotenone. Then, 3 pregnant rats in each group were sacrificed immediately and the placenta and umbilical cord tissues were dissected. The remaining 9 pregnant rats gave birth naturally, and the fetuses were observed for developmental evaluation and weighed. The histopathological changes of umbilical cord and placenta were observed by hematoxylin-eosin staining. The reactive oxygen species levels of placenta tissues were detected by flow cytometry. The Ca²⁺-ATPase activity of placenta tissues was detected by colorimetric method. The localization and levels of GSK-3β and β-catenin expression of placenta were detected by immunohistochemistry. The p-GSK-3β/GSK-3β and p-β-catenin/β-catenin protein expression in placental tissues were measured by Western blotting. Results No injury or death was recorded during the pregnant rats receiving rotennon administration. Adverse pregnancy outcomes such as fetal absorption and postpartum stillbirth were found in the rotenone group, and the weight of the fetal mice decreased (P<0.05). The B-ultrasound showed disc-shaped placenta with a thick middle and thin edge, smooth fetal surface, rough maternal surface, visible placental lobules, granular echotexture of the placenta with comma-like echogenic densities, and chorionic plate showing deep indentations, no calcification, degeneration, or necrosis in each group. Compared with the corn oil group, the fetal surface diameter of the placenta was reduced in the rotenone group (P<0.05). The Doppler color ultrasound showed that interplacental blood flow was reduced in the rotenone group, while interplacental blood flow was abundant in the blank control and the corn oil groups. The hematoxylin-eosin staining results showed that smooth muscle cells in the umbilical cord tissues of rats were loosely arranged, with fuzzy nuclei and inflammatory infiltration in the rotenone group. The placental trophoblast cells were small in size, disorderly arranged with nuclear fragmentation and cytoplasm turbidity. The tissue reactive oxygen species level in the rotenone group was higher than those in the other two groups (P<0.05). The Ca²⁺-ATPase activity of placental tissues was reduced in the rotenone group (P<0.05). The immunofluorescence low-magnification observation showed that GSK-3β and β-catenin were expressed in placental tissue, weak fluorescence expression in the decidua basalis, strong fluorescence expression in the labyrinthine layer structure. The labyrinthine layer under high magnification showed that compared with the blank control group and the corn oil group, the brightness of β-catenin fluorescence expression in the rotenone group decreased (P<0.05), and the brightness of GSK-3β expression increased (P<0.05). The Western blotting results showed that the expression of β-catenin and p-GSK-3β proteins decreased (P<0.01), and the expression of GSK-3β protein increased (P<0.01) in the rotenone group. No significant expression of p-β-catenin protein was detected in the placenta tissue of each group. Conclusion Rotenone exposure during pregnancy induces placental hypoperfusion, growth retardation, and oxidative stress in rats, as well as down-regulation of β-catenin and p-GSK-3β protein expression, and up-regulation of GSK-3β protein expression, which may further lead to abnormal pregnancy and fetal restricted growth.

Objective:To explore the value of adrenocorticotrophic hormone (ACTH) stimulation in adrenal vein sampling (AVS) with its effect on the sampling success rate and lateralization determination.Methods:The clinical data of 54 patients with primary aldosteronism (PA) who underwent AVS in Nanjing Drum Tower Hospital from July 2018 to June 2020 were collected retrospectively. Blood samples from bilateral adrenal veins were collected simultaneously at baseline and after ACTH stimulation. The selectivity index (SI), lateralization index (LI), and relative aldosterone secretion index (RASI) were examined.Results:The concentration of serum cortisol level in left and right adrenal vein and peripheral vein increased significantly after ACTH stimulation ( P<0.001). SI of left adrenal vein increased from 18.00 (2.29, 20.29) to 34.76 (12.10, 46.86) , and the SI of right adrenal vein increased from 26.61(5.24, 31.85) to 28.40 (27.65, 56.05, P<0.001). The bilateral vein sampling success rate increased from 80%(43/54) to 93%(50/54). LI decreased from 2.85(1.78, 6.20) at baseline to 2.45(1.40, 6.10) after ACTH stimulation without significant difference( P>0.05). Eleven patients who identified unilateral secretion at baseline demonstrated bilateral after ACTH stimulation, and the RASI of these patients decreased from 0.50 (0.38, 1.25 ) to 0.37 (0.22, 0.84, P=0.019). Conclusion:ACTH stimulation significantly increased SI and the AVS success rate in patients with PA: ACTH stimulation decreased the relative aldosterone secretion in the dominant side of some patients with aldosterone producing adenoma, thus reduced the proportion of identified unilateral PA.