Objective:To determine the incidence of adrenal incidentalomas(AIs) in patients with diabetes mellitus and the metabolism profiles.Methods:A total of 615 hospitalized patients with diabetes mellitus in the Department of Endocrinology and Metabolism of Peking University People′s Hospital from March 2020 to May 2021 were retrospectively included in this study. AIs were screened by unenhanced chest computed tomography(CT) retrospectively and subsequently confirmed by multiplanar reconstruction. Participants′ physical indicators, metabolic profiles, and adrenal function parameters were collected. Unpaired t test, Mann-Whitney U test, and Chi-Square test were adopted to compare the metabolism profiles between diabetes mellitus patients with or without AIs. Regression models were used to estimate the correlations between AIs and the metabolism profiles such as blood glucose, blood lipids, blood pressure, and the adrenal function parameters.Results:Twenty-seven out of 615 participants were detected with AIs(4.4%). Patients with AIs had higher body mass index, waist circumference, and hip circumference than patients without AIs [(29.4±5.1)kg/m 2vs(26.8±3.8)kg/m 2,P=0.018; (102.3±11.7)cm vs(95.8±10.3)cm, P=0.002; (107.3±10.1)cm vs(101.4±7.6)cm, P=0.008]. The levels of serum uric acid and urinary albumin/creatinine ratio were also significantly increased in patients with AIs [(409.6±118.1)μmol/L vs(357.4±100.6)μmol/L, P=0.009; 21.25(7.49, 180.24)mg/g vs 8.60(4.71, 34.56)mg/g, P=0.010]. Besides, individuals with AIs were also associated with a higher risk of co-existing hypertension( P=0.045). Conclusion:The incidence of AIs in patients with diabetes is 4.4%. The presence of AIs in patients with diabetes may associated with increased risk of obesity and hypertension.

Bladder cancer remains the 10th most common cancer worldwide. In recent years, metformin has been found to have potential anti-bladder cancer activ-ity while high concentration of IC50 at millimolar level is needed, which could not be reached by regular oral administration route. Thus, higher efficient agent is urgently demanded for clinically treating bladder cancer. Here, by conjugating artesunate to metformin, a novel artesunate-metformin dimer triazine derivative AM2 was designed and synthesized. The inhibitory effect of AM2 on bladder cancer cell line T24 and the mechanism underlying was determined. Anti-tumor activity of AM2 was assessed by MTT, cloning formation and wound healing assays. Decreasing effect of AM2 on lipogenesis was determined by oil red O staining. The protein expressions of Clusterin, SREBP1 and FASN in T24 cells were evaluated by Western blotting. The results show that AM2 significantly inhibited cell proliferation and migration at micromolar level, much higher than parental metformin. AM2 reduced lipogenesis and down-regulated the expressions of Clusterin, SREBP1 and FASN. These results suggest that AM2 inhibits the growth of bladder cancer cells T24 by inhibiting cellular lipogenesis associated with the Clusterin/SREBP1/FASN signaling pathway.

Mammalian bone is constantly metabolized from the embryonic stage, and the maintenance of bone health depends on the dynamic balance between bone resorption and bone formation, mediated by osteoclasts and osteoblasts. It is widely recognized that circadian clock genes can regulate bone metabolism. In recent years, the regulation of bone metabolism by non-coding RNAs has become a hotspot of research. MicroRNAs can participate in bone catabolism and anabolism by targeting key factors related to bone metabolism, including circadian clock genes. However, research in this field has been conducted only in recent years and the mechanisms involved are not yet well established. Recent studies have focused on how to target circadian clock genes to treat some diseases, such as autoimmune diseases, but few have focused on the co-regulation of circadian clock genes and microRNAs in bone metabolic diseases. Therefore, in this paper we review the progress of research on the co-regulation of bone metabolism by circadian clock genes and microRNAs, aiming to provide new ideas for the prevention and treatment of bone metabolic diseases such as osteoporosis.
Animals ; Circadian Clocks/genetics* ; Circadian Rhythm/genetics* ; Mammals/genetics* ; MicroRNAs/genetics* ; Osteogenesis/genetics* ; Osteoporosis/genetics*

Objective: To create a model for early prediction of essential hypertension (EH) based on the TreeNet algorithm, so as to provide a tool for early monitoring of EH. Methods: The health examination data were collected from individuals receiving health examinations in Hangzhou Haiqin Health Examination Center or Shanghai Yibao Health Management Co., Ltd from 2014 to 2016, and a predictive model for EH was created based on the TreeNet algorithm. The effectiveness of the model for early prediction of EH was evaluated using root mean square error (RMSE), mean absolute deviation (MAD), coefficient of determination (R2) and receiver operating characteristic (ROC) curve. Results: A total of 12 variables were included in the model, and the highest contributing variable was body mass index (BMI), followed by BMI difference, two-year BMI difference, two-year triglyceride (TG) difference, two-year total cholesterol (TC) difference, high-density lipoprotein cholesterol (HDL-C) in 2014, TG in 2014, low-density lipoprotein cholesterol (LDL-C) in 2014, body weight in 2015, fasting blood glucose in 2015, TG in 2015, urea nitrogen difference and platelet in 2015. The highest predictive accuracy was 100.00%, and the lowest was 56.89%. The risk of EH significantly increased among individuals with BMI in 2015 of >25 kg/m2, two-year BMI difference of >0.5 kg/m2, two-year TG difference ranging from 1.3 to 3.3 mmol/L, TC in 2015 of 2.0 to 2.4 mmol/L and HDL-C in 2014 of <0.52 mmol/L. The model presented RMSE of 0.082, MAD of 0.064, R2 of 0.811, area under the ROC curve of 0.788 (95%CI: 0.741-0.815), sensitivity of 69.05% and specificity of 66.21% for prediction of EH Conclusion The TreeNet algorithm-based model is effective for early monitoring of high-risk individuals for EH.

Objective: To analyze the association between the concentration of metalloestrogens ( MEs ) in seminal plasma and sperm quality in infertile patients, so as to provide the basis for the study of MEs on human sperm quality. Methods: The spermatozoa concentration, progressive rate ( PR ), normal morphology rate ( NMR ) and DNA fragmentation index ( DFI ) were determined in the infertile male patients from Zhejiang Provincial People's Hospital from March to April, 2020. The contents of As, Cd, Co, Cr, Cu, Hg and Ni in seminal plasma were determined by inductively coupled plasma mass spectrometry ( ICP-MS ). The distribution of MEs in seminal plasma and the sperm quality in different concentration of MEs ( grouped by quartiles ) were analyzed. Results: Among 105 cases recruited, 28 cases were normal in sperm parameters and 77 cases were abnormal, including 22 cases of oligospermia, 47 cases of asthenospermia, 54 cases of dysspermia and 30 cases of abnormal DFI. As, Cr, Cu, Hg and Ni were detected in all samples, the detection rates of Cd and Co were 78.57%-90.91%. Compared with the normal group, the concentration of As in oligospermia group was higher [( 18.96±12.56 ) µg/L vs. (13.67±4.19) µg/L, P<0.05],the concentration of Cr was higher in asthenospermia, dysspermia and abnormal DFI in Q3 and Q4 groups groups [( 386.62±81.92 ), ( 378.02±81.46 ), ( 393.88±77.03 ) µg/L vs. ( 343.12±55.08 ) µg/L,P<0.05]. The PRs in Q3 and Q4 groups of Cr were lower than that in Q2 group [( 32.95±18.22 )%, ( 27.74±22.77 )% vs. ( 54.18±24.64 )%, P<0.05], the DFI in Q3 and Q4 groups was higher than that in Q2 group [( 26.91±14.77 )%, ( 29.91±16.93 )% vs. ( 9.87±10.93 )%, P<0.05], and the NMR in Q4 group was lower than that in Q2 group [( 1.62±1.72 )% vs. ( 3.36±1.97 )%, P<0.05]. The concentration of sperm in Q3 group of Cu was higher than that in Q2 group [( 115.87±88.22 )×106/mL vs. (61.91±66.16)×106/mL, P<0.05]. Conclusion As and Cu in seminal plasma are associated with abnormal sperm concentration, and Cr is associated with NMR, PR and DFI.

Objective:To study the patterns of tocilizumab (TCZ) use, its efficacy and safety in patients with rheumatoid arthritis (RA) in routine clinical practice.Methods:A total of 407 patients with RA were enrolled from 23 centers and treated with TCZ within 8 weeks prior to the enrollment visit, and were followed for 6-month. The patterns of TCZ treatment at 6 months, the effectiveness and safety outcomes were recorded. Statistical analysis was performed using SAS version 9.4.Results:A total of 396 patients were included for analysis, in which 330 (83.3%) patients received TCZ combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and 16.7%(66/396) received TCZ monotherapy. At baseline, TCZ was initiated in 56.6%(224/396) and 9.6%(38/396) of patients after failure of DMARDs and other biological agents (bDMARDs) respectively. During the 6-month follow-up period, the mean frequency of TCZ administration was (3.7±1.6), the mean TCZ dosage was (7.4±1.2) mg/kg, and the mean interval between doses was (40±13) days. 120(25.8%) patients were on TCZ treatment at the end of the study. Improvements in disease activity, systemic symptoms and patient report outcomes were observed at the end of the study. 22.7%(90/396) patients experienced at least one treatment related adverse event, and 8 patients experienced at least one serious adverse event.Conclusion:This study demonstrates that TCZ treatment is effective in patients with RA when being treated for 6 months with an acceptable safety profile. The duration of TCZ treatment needs to be extended.

Objective To establish the 3D hydrogel cell model and apply compressive stress with different intensities, frequencies and durations on osteoclasts, so as to observe the effect of compressive stress on osteoclast differentiation and investigate the appropriate compressive stress solution for inhibiting osteoclast differentiation. Methods M-CSF and RANKL were used to induce bone marrow mononuclear cells into osteoclasts. After the 3D cell-agarose mixture was seeded in compression culture plate, compressive stress was applied on osteoclasts with different intensities, frequencies and durations the next day. The cells in control group were not interfered. The cells were divided as following: G0 (control group), G1 (1%, 0.5 Hz, 4 h), G2 (2%, 0.5 Hz, 4 h), G3 (3%, 0.5 Hz, 4 h), G4 (1%, 1.0 Hz, 4 h), G5 (2%, 1.0 Hz, 4 h), G6 (3%, 1.0 Hz, 4 h). After the loading plan with the most effective intensity and frequency was calculated by statistical analysis, compressive stresses were applied on cells with different durations as following: D1(4 h), D2(8 h), D3(12 h), D4(16 h), and each group had two samples. Once compressive loading was finished, the total RNA extraction from cell-gel constructs were performed and Ctsk mRNA, NFATc1 mRNA, TRACP mRNA, M-CSF mRNA and RANK mRNA were measured by quantitative testing. Results RANK and TRACP mRNA expression significantly depended on intensities and frequencies of the compressive stress (P<0.01), and Ctsk mRNA significantly depended on intensities(P<0.01) while it differed notably with different frequencies (P<0.01). M-CSF mRNA expression with 8 h was much lower than that with 12 h (P<0.01) and 16 h (P<0.05). RANK mRNA expression with 8 h was lower than that with 12 h (P<0.05) and 16 h (P<0.01). In addition, Ctsk and NFATc1 mRNA expression with 16 h was higher than that with 4 h and 8 h (P<0.05). Conclusions In the 3D hydrogel model, 1% intensity, frequency of 0.5 Hz, cyclic compression intervention with 8 h can suppress the differentiation of osteoclasts. The research findings provide the theoretical basis for preventing osteoporosis and improving the peak bone mass by appropriate exercise.

Objective:3D hydrogel cell model was established,and cyclic compressive loading on MC3T3-E1 cell with different intensities,frequencies and durations was applied,in order to research the suitable solution about promoting the osteoblast differentiation with cyclic compression.Methods:Cyclic compressive loading on MC3T3-E1 cell was applied with different intensity,frequency and time.After compressive loading finished,the total RNA extraction from cell-gel constructs were performed and quantified ATF4,ALP,Runx2,Osteocalcin,RANKL and RANK mRNA.Results:RANKL and RANK mRNA expression significantly with different frequencies cyclic compressive loading (P ＜ 0.05),and ALP mRNA (P ＜ 0.05) and Runx2 mRNA (P ＜ 0.01) expression significantly with different intensities and frequencies cyclic compressive loading (P ＜ 0.05).Meanwhile,Runx2 mRNA expression with 4h significant higher than 12h (P ＜ 0.05),and RANKL mRNA expression with 4h significant lower than 12h (P ＜ 0.05).Conclusion:Determine the stress intensity and frequency,1％ intensity,frequency of 0.5 Hz,4 h of cyclic compression intervention could promote the growth of osteoblasts-like cells in the 3D hydrogel model.

The process of exercise regulating bone metabolism is complicated, which involves a number of signaling pathways. A large number of studies in vitro have indicated that mechanical stress regulates bone metabolism by Wnt, bone morphogenetic protein (BMP), and osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL)/receptor activator of NF-κB (RANK) signaling pathways. Both the in-tensity and frequency of mechanical stress have varing impact on bone tissue and cells. Plenty of studies in vivo also have shown that exer-cise regulates bone metabolism by key factors in bone metabolism signaling pathways. This paper reviewed the effects of exercise on bone metabolism pathways and their mechanisms.

Objective To study early diagnosis and treatment of Wernicke's encephalopathy(WE) in allogeneic peripheral blood stem cell transplantation recipients.Method A 17 years old patient with acute B-lymphocytic leukemia received HLA-matched nonrelative allogeneic peripheral blood stem cell transplantation after conditioning with total-body irradiation/idamycin/cyclophosphamide (TBI/IDA/Cy) regimen.CD25 monoclonal antibody and cyclosporine A+mycophenolate mofetil + methotrexate were administrated for graft versus host disease prophylaxis.Result On the day 8,the platelet was over 20 × 109/L; On the day 10,the neutrophile granulocyte was over 0.5 × 109/L; On the day 28,full engraftment was confirmed by a bone marrow medicolegal identification.The continued nausea and vomiting after HSCT resulted in deficiency of intake and malabsorption.On the day 54,illusion and tremor occurred,and the follow-up brain MRI suggested WE,but the patient died before thiamine replacing therapy.Conclusion WE is also a rare neurologic complication of HSCT,however,it can easily be overlooked.So early radiologic surveillance and treatment for patients with WE is very important to minimize central nervous system complications and unwanted mortality.