BACKGROUND: Alpha-glucosidase inhibitors or dipeptidyl peptidase-4 inhibitors are both hypoglycemia agents that specifically impact on postprandial hyperglycemia. We compared the effects of acarbose and sitagliptin add on to metformin on time in range (TIR) and glycemic variability (GV) in Chinese patients with type 2 diabetes mellitus through continuous glucose monitoring (CGM). METHODS: This study was a randomized, open-label, active-con-trolled, parallel-group trial conducted at 15 centers in China from January 2020 to August 2022. We recruited patients with type 2 diabetes aged 18-65 years with body mass index (BMI) within 19-40 kg/m 2 and hemoglobin A1c (HbA1c) between 6.5% and 9.0%. Eligible patients were randomized to receive either metformin combined with acarbose 100 mg three times daily or metformin combined with sitagliptin 100 mg once daily for 28 days. After the first 14-day treatment period, patients wore CGM and entered another 14-day treatment period. The primary outcome was the level of TIR after treatment between groups. We also performed time series decomposition, dimensionality reduction, and clustering using the CGM data. RESULTS: A total of 701 participants received either acarbose or sitagliptin treatment in combination with metformin. There was no statistically significant difference in TIR between the two groups. Time below range (TBR) and coefficient of variation (CV) levels in acarbose users were significantly lower than those in sitagliptin users. Median (25th percentile, 75th percentile) of TBR below target level <3.9 mmol/L (TBR 3.9 ): Acarbose: 0.45% (0, 2.13%) vs . Sitagliptin: 0.78% (0, 3.12%), P = 0.042; Median (25th percentile, 75th percentile) of TBR below target level <3.0 mmol/L (TBR 3.0 ): Acarbose: 0 (0, 0.22%) vs . Sitagliptin: 0 (0, 0.63%), P = 0.033; CV: Acarbose: 22.44 ± 5.08% vs . Sitagliptin: 23.96 ± 5.19%, P <0.001. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV (group with small wave, moderate wave and big wave). No significant difference was found in the complexity of glucose time series index (CGI) between acarbose users and sitagliptin users. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV. CONCLUSIONS: Acarbose had slight advantages over sitagliptin in improving GV and reducing the risk of hypoglycemia. Time series analysis of CGM data may predict GV and the risk of hypoglycemia. TRIAL REGISTRATION Chinese Clinical Trial Registry: ChiCTR2000039424.
Humans ; Metformin/therapeutic use* ; Sitagliptin Phosphate/therapeutic use* ; Acarbose/therapeutic use* ; Diabetes Mellitus, Type 2/blood* ; Middle Aged ; Male ; Female ; Adult ; Blood Glucose/drug effects* ; Hypoglycemic Agents/therapeutic use* ; Aged ; Glycated Hemoglobin/metabolism* ; Adolescent ; Young Adult ; China ; East Asian People

Objective:To construct and validate a three-level early warning model of moderate to severe ovarian hyperstimulation syndrome (OHSS) in assisted reproductive technology.Methods:A case-control study was conducted. Totally 10 181 infertility patients who underwent in vitro fertilization treatment in Reproductive Medicine Center, Women and Children's Medical Center Affiliated to Guangzhou Medical University from April 2013 to April 2023 were retrospectively analyzed and divided into modeling group (8 145 cases) and validation group (2 036 cases) by random number table method. The clinical data of the two groups were analyzed, and the risk factors affecting the occurrence of moderate and severe OHSS after oocytes retrieval were screened by multi-factor logistic regression analysis. The early warning model was established and the column diagram was drawn at three nodes which were before ovarian stimulation, before trigger and 3 d after oocyte retrieval. The receiver operating characteristic (ROC) curve and calibration curve were used to verify the models. Results:The antral follicle count (AFC, OR=1.045, 95% CI: 1.020-1.071, P<0.001), anti-Müllerian hormone (AMH)>3.36 μg/L ( OR=7.135, 95% CI: 2.084-24.432, P=0.002) and number of cycles ( OR=0.149, 95% CI: 0.022-1.026, P=0.049) were included in the pre-stimulation prediction model. AFC ( OR=1.046, 95% CI: 1.018-1.074, P=0.001), AMH>3.36 μg/L ( OR=5.780, 95% CI: 1.661-20.116, P=0.006), gonadotropin releasing hormone-agonist protocols ( OR=3.895, 95% CI=1.913-7.931, P<0.001), estrogen peak≥18 350 pmol/L ( OR=2.258, 95% CI: 1.092-4.666, P=0.028), the number of follicles with a diameter of ≥10 mm>20 ( OR=2.377, 95% CI: 1.092-5.172, P=0.029) were included in the pre-trigger prediction model. AMH>3.36 μg/L ( OR=8.374, 95% CI: 2.417-29.019, P=0.001), estrogen peak≥18 350 pmol/L ( OR=3.947, 95% CI: 1.533-10.167, P=0.004), total number of oocytes retrived ( OR=1.042, 95% CI: 0.996-1.090, P=0.025), abdominal distension ( OR=60.181, 95% CI: 22.515-160.854, P<0.001), fresh transplantation ( OR=21.766, 95% CI: 7.119-66.544, P<0.001), human chorionic gonadotropin trigger ( OR=17.752, 95% CI: 3.993-78.924, P<0.001) were included in the prediction model of 3 d after oocyte retrieval. The areas under ROC curves of the three models were 0.830 (95% CI: 0.782-0.878), 0.859 (95% CI: 0.812-0.906) and 0.948 (95% CI: 0.919-0.977), respectively. The areas under ROC curves of the validation groups of the three models were 0.922 (95% CI: 0.880-0.965), 0.936 (95% CI: 0.886-0.986), and 0.971 (95% CI: 0.938-0.999), respectively. The calibration curve indicated that the early-warning evaluation model has good stability. Conclusion:The three-level early warning model of moderate and severe OHSS has good differentiation, reliable predictability and clinical practicability, which is conducive to the dynamic and continuous assessment of the risk of moderate and severe OHSS, adjustment of treatment plan at any time, and timely adoption of effective preventive measures.

Objective:To construct and validate a three-level early warning model of moderate to severe ovarian hyperstimulation syndrome (OHSS) in assisted reproductive technology.Methods:A case-control study was conducted. Totally 10 181 infertility patients who underwent in vitro fertilization treatment in Reproductive Medicine Center, Women and Children's Medical Center Affiliated to Guangzhou Medical University from April 2013 to April 2023 were retrospectively analyzed and divided into modeling group (8 145 cases) and validation group (2 036 cases) by random number table method. The clinical data of the two groups were analyzed, and the risk factors affecting the occurrence of moderate and severe OHSS after oocytes retrieval were screened by multi-factor logistic regression analysis. The early warning model was established and the column diagram was drawn at three nodes which were before ovarian stimulation, before trigger and 3 d after oocyte retrieval. The receiver operating characteristic (ROC) curve and calibration curve were used to verify the models. Results:The antral follicle count (AFC, OR=1.045, 95% CI: 1.020-1.071, P<0.001), anti-Müllerian hormone (AMH)>3.36 μg/L ( OR=7.135, 95% CI: 2.084-24.432, P=0.002) and number of cycles ( OR=0.149, 95% CI: 0.022-1.026, P=0.049) were included in the pre-stimulation prediction model. AFC ( OR=1.046, 95% CI: 1.018-1.074, P=0.001), AMH>3.36 μg/L ( OR=5.780, 95% CI: 1.661-20.116, P=0.006), gonadotropin releasing hormone-agonist protocols ( OR=3.895, 95% CI=1.913-7.931, P<0.001), estrogen peak≥18 350 pmol/L ( OR=2.258, 95% CI: 1.092-4.666, P=0.028), the number of follicles with a diameter of ≥10 mm>20 ( OR=2.377, 95% CI: 1.092-5.172, P=0.029) were included in the pre-trigger prediction model. AMH>3.36 μg/L ( OR=8.374, 95% CI: 2.417-29.019, P=0.001), estrogen peak≥18 350 pmol/L ( OR=3.947, 95% CI: 1.533-10.167, P=0.004), total number of oocytes retrived ( OR=1.042, 95% CI: 0.996-1.090, P=0.025), abdominal distension ( OR=60.181, 95% CI: 22.515-160.854, P<0.001), fresh transplantation ( OR=21.766, 95% CI: 7.119-66.544, P<0.001), human chorionic gonadotropin trigger ( OR=17.752, 95% CI: 3.993-78.924, P<0.001) were included in the prediction model of 3 d after oocyte retrieval. The areas under ROC curves of the three models were 0.830 (95% CI: 0.782-0.878), 0.859 (95% CI: 0.812-0.906) and 0.948 (95% CI: 0.919-0.977), respectively. The areas under ROC curves of the validation groups of the three models were 0.922 (95% CI: 0.880-0.965), 0.936 (95% CI: 0.886-0.986), and 0.971 (95% CI: 0.938-0.999), respectively. The calibration curve indicated that the early-warning evaluation model has good stability. Conclusion:The three-level early warning model of moderate and severe OHSS has good differentiation, reliable predictability and clinical practicability, which is conducive to the dynamic and continuous assessment of the risk of moderate and severe OHSS, adjustment of treatment plan at any time, and timely adoption of effective preventive measures.

Objective:To investigate the regulation effect of miR-125b in the gastric cancer cell growth mediated by apoptosis related protein (Fas)/apoptosis related protein ligand (FasL) signal.Methods:Gastric cancer SGC-7901 cells were cultured in vitro. MiR-125b inhibitor sequence, NC sequence and transfection reagent were transfected into SGC-7901 cells and divided into three groups: miR-125b inhibited group, NC group and control group. The expression of miR-125b in transfected cells was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR), and cell proliferation was detected by cell counting kit-8 (CCK-8) method. The colony formation was detected by plate cell clone formation assay. Cell apoptosis and cycle were detected by flow cytometry. The protein expression of Fas and FasL was detected by Western blot. The targeted regulation of Fas by miR-125b was detected by luciferase activity assay. Results:The expression level of miR-125 and the number of cell colony in miR-125b inhibited group was significantly lower than those in control group and NC group, and the inhibition rate of cell proliferation and apoptosis rate were significantly higher than that in control group and NC group (all P<0.05). The DNA content in G 1 phase in miR-125b inhibited group was significantly higher than that in control group and NC group, and the DNA content in S phase in miR-125b inhibited group was significantly lower than that in control group and NC group (all P<0.05). The expression of Fas and FasL protein in miR-125b inhibited group was significantly higher than that in control group and NC group (all P<0.05). The target site of miR-125b was found in 3′-UTR of Fas mRNA, and compared with the NC+ Fas 3′UTR-Wt group, the activity of luciferase in the miR-125b inhibited group+ Fas 3′-UTR-Wt group decreased significantly ( P<0.05). Conclusions:Inhibition of miR-125b expression can activate Fas/FasL signal and inhibit SGC-7901 cell proliferation, induce G 1 phase arrest of cell cycle and promote apoptosis.

Objective:To investigate the effects of piperine on experimental colon carcinogenesis induced by 1, 2-dimethylhydrazine (DMH)/sodium dextran sulfate (DSS) and its mechanism.Methods:36 mice were divided into control group, model group and piperine group, 12 mice in each group. The control group was given normal saline by gavage; The model group and piperine group were given 3.6 mg/(kg·d) of normal saline and piperine respectively after establishing the experimental colon cancer model induced by DMH/DSS. Tumor load and volume were observed. Hematoxylin and eosin (HE) staining was used to observe the histological change of colon in mice. RAS/PI3K/AKT related pathway protein expression was detected by Western blot.Results:The body weight gain, protein expression levels of cleaved poly-ADP ribose polymerase (PARP), cleaved caspase-3 in model group were significantly lower than those in the control group (all P<0.05). The protein expression levels of Bcl-2, Bax, pan-Ras, p-MEK, p-ERK, PI3K, p-AKT, NF-κBP65, c-Myc and cyclin D1 in model group were significantly higher than those in the control group (all P<0.05). The body weight gain, protein expression levels of cleaved PARP and cleaved caspase-3 in piperine group were significantly higher than those in model group (all P<0.05). The protein expression levels of Bcl-2, Bax, pan-Ras, p-MEK, p-ERK, PI3K, p-AKT, NF-κBP65, c-Myc and cyclin D1 in piperine group were significantly lower than those in model group (all P<0.05). Conclusions:Piperine can inhibit the occurrence of experimental colon cancer induced by DMH/DSS, which may involve multiple components of RAS/PI3K/AKT signal axis.

OBJECTIVE: To explore the genetic basis for two children with sporadic neurofibromatosis type 1 (NF1) complicated with nephrotic syndrome (NS). METHODS: Clinical data of the children were collected. Both children were subjected to high-throughput sequencing, and candidate variants were verified by Sanger sequencing. RESULTS: Both children had café-au-lait macules, subaxillary freckle and Lisch nodules. Child 1 also had congenital tibiofibular pseudarthrosis on the left side. Genetic testing revealed that child 1 has harbored a heterozygous c.844C>T variant in the exon 8 of the NF1 gene, whilst child 2 has harbored a heterozygous c.1246C>T variant in the exon 11 of the NF1 gene. Both children were diagnosed with NF1 and have developed pronounced proteinuria, hypoalbuminemia, hypercholesterolemia and pitting edema at the ages of 3 and 10, respectively. Renal biopsy of child 2 has revealed minimal change nephropathy, and the diagnosis of nephrotic syndrome was established. Child 1 was treated with glucocorticoid, and child 2 was treated with glucocorticoid in combination with mycophenolate mofetil. The NS was relieved with no recurrence during 1 year's follow-up. CONCLUSION NF1 combined with NS is rare in the clinical settings. The prognosis of children with NF1 combined with minimal change nephropathy is relatively good. Detection of NF1 gene variant can facilitate early identification and diagnosis of NF1.
Child ; Humans ; Neurofibromatosis 1/genetics* ; Nephrotic Syndrome/genetics* ; Nephrosis, Lipoid ; Glucocorticoids ; Genetic Testing

Chinese medicine enema is an effective guiding method to treat diabetic kidney disease, a common chronic complication of diabetes, by regulating the function of the intestines to increase clearing and lower turbidity. We reviewed the treatment of diabetic kidney disease (DKD) with traditional Chinese medicine enemas and found that commonly used traditional Chinese medicines included Rhei Radix Et Rhizoma (Rheum palmatum L.), Ostrea concha (Ostrea gigas Thunberg), Taraxaci Herba (Taraxacum mongolicum Hand.-Mazz.), Astmgali Radix (Astragalus membranaceus Bge. var.mongholicus(Bge.) Hsiao), Salviae Miltiorrhizae Radix Et Rhizoma (Salvia miltiorrhiza Bge.), and Aconiti Lateralis Radix Praeparata (Aconitum carmichaelii Debx). The mechanism of the adjuvant therapeutic effect on DKD may relate to regulating intestinal flora, inhibiting inflammation and oxidative stress and protecting against kidney injury.

Objective To set up the proteomic protein profiling of adenomyotic tissue and normal uterine muscle and identify the abnormally expressed proteins in adenomyotic tissue. Methods Samples of adenomyotic tissue (adenomyosis group) and age-matched healthy uterine muscle (control group) were collected from totally 10 patients undergoing transabdominal hysterectomy for adenomyosis and cervical diseases at Peking Union Medical College Hospital from January 2007 to October 2007. The proteomics profiling of adenomyotic tissue and normal uterine tissue were established using two dimensional gel electrophoresis (2-DE) and gel staining method. The differently expressed protein spots were detected by gel comparison using image analysis software and identified using matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Results In Coomassie blue stained gels there were on average (512 ± 36) spots and compared with the reference gel the matching rate was 83.7%. In silver stained gels there were (762 +54) spots and compared with the reference gel the matching rate was 81.1%.Compared with normal uterine muscle, there were 15 protein spots disregulated in adenomyotic tissue.Among them 10 protein spots were successfully identified by mass spectrometry. The functions of these disregulated proteins included cell skeleton, oxidation, apoptosis and immune reaction. Conclusions Comparative proteomics analysis is a useful approach for the study of adenomyosis. Compared with normal uterine muscle there are abnormalities in cell skeleton, oxidation, apoptosis and immune reaction. These life processes may participate in pathophysiology of adenomyosis.