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 analyze the basic characteristics of patients with acute myocardial infarction in a tertiary hospi-tal from 2014 to 2023,and provide references for the prevention,treatment,management,and quality control of this disease.Methods Based on the data from the medical records of patients with acute myocardial infarction admitted to a tertiary hospital from January 1,2014,to December 31,2023,the basic characteristics of hospitalized patients and trends in hospitalization costs were analyzed to summarize the development patterns.Results Over the past decade,the number of hospitalized patients with a-cute myocardial infarction has been increasing,while the average length of hospital stay,average cost per hospitalization,and mortality rate have been decreasing.Among the 19 937 patients,there were 16 037 male patients(80.44％)and 3 900 female patients(19.56％),with a male-to-female ratio of 4.11∶1.The median age for male patients was 60 years,while for female patients it was 68 years,indicating that males tend to develop the disease approximately 10 years earlier than females.Among pa-tients aged 60 and above,the mortality rate is positively correlated with age,while among patients below 60,the mortality rate is negatively correlated with age.The decision to undergo surgery has a significant impact on hospitalization costs.From the per-spective of cost structure,the proportion of consumables has decreased from 69.81％to 54.60％in the past decade but remains relatively high.Conclusion With the advancement of hospital management and medical insurance policies,the diagnosis,treat-ment,and quality of care for acute myocardial infarction have significantly improved.However,consumables management remains a key focus.Men and individuals aged 50 and above should be given special attention.During the diagnosis and treatment process,greater attention should also be given to younger or older patients and female patients to reduce the mortality rate.

Objective To investigate the therapeutic effect and underlying mechanism of action of a CXCR3 inhibitor in rheumatoid arthritis(RA)in mice model.Methods Thirty BALB/C mice were randomly divided into control,model,and treatment groups.RA model was established in both the model and treatment groups using a collagen induction method.Upon successful modeling,mice in the treat-ment group received a daily oral administration of 1 mg/kg SCH 546738(CXCR3 inhibitor)for 4 weeks,whereas those in the control and model groups received equivalent volumes of saline.During treatment,the weekly arthritis index scores of mice were recorded.The expres-sion of TNF-α,IFN-γ,and IL-1β in joint tissues was determined based on Western blotting and qRT-PCR analyses.In addition,we used flow cytometry to assess peripheral blood Th1/Th2 cell ratios,and serum levels of IFN-γ and IL-4 were measured using ELISA.Peripheral blood CD4+T cells were isolated and co-incubated with SCH 546738,and subsequently assessed as CD4+T and CD4+T+SCH 546738 groups.In addition,Th1/Th2 cell ratios were assessed using flow cytometry.Results Compared with the control group,mice in the model group were characterized by elevated weekly arthritic index scores,increases in the joint tissues expression of TNF-α,IFN-γ,and IL-1β,heightened peripheral blood Th1/Th2 cell ratios,and raised serum IFN-γ levels(P＜0.05).In contrast to the model group,the treatment group mice had lower weekly arthritis index scores,reductions in the joint tissue expression of TNF-α,IFN-γ,and IL-1β,diminished peripheral blood Th1/Th2 cell ratios,and lowered serum IFN-γ levels(P＜0.05).Moreover,compared with the CD4+T group,the CD4+T+SCH 546738 group was characterized reduced Th1/Th2 cell ratios(P＜0.001).Conclusion The CXCR3 inhibitor SCH 546738 can alle-viate the progression of RA in mice by reducing Th1/Th2 cell ratios,thereby ameliorating the immune response.

Objective To investigate the therapeutic effect and underlying mechanism of action of a CXCR3 inhibitor in rheumatoid arthritis(RA)in mice model.Methods Thirty BALB/C mice were randomly divided into control,model,and treatment groups.RA model was established in both the model and treatment groups using a collagen induction method.Upon successful modeling,mice in the treat-ment group received a daily oral administration of 1 mg/kg SCH 546738(CXCR3 inhibitor)for 4 weeks,whereas those in the control and model groups received equivalent volumes of saline.During treatment,the weekly arthritis index scores of mice were recorded.The expres-sion of TNF-α,IFN-γ,and IL-1β in joint tissues was determined based on Western blotting and qRT-PCR analyses.In addition,we used flow cytometry to assess peripheral blood Th1/Th2 cell ratios,and serum levels of IFN-γ and IL-4 were measured using ELISA.Peripheral blood CD4+T cells were isolated and co-incubated with SCH 546738,and subsequently assessed as CD4+T and CD4+T+SCH 546738 groups.In addition,Th1/Th2 cell ratios were assessed using flow cytometry.Results Compared with the control group,mice in the model group were characterized by elevated weekly arthritic index scores,increases in the joint tissues expression of TNF-α,IFN-γ,and IL-1β,heightened peripheral blood Th1/Th2 cell ratios,and raised serum IFN-γ levels(P＜0.05).In contrast to the model group,the treatment group mice had lower weekly arthritis index scores,reductions in the joint tissue expression of TNF-α,IFN-γ,and IL-1β,diminished peripheral blood Th1/Th2 cell ratios,and lowered serum IFN-γ levels(P＜0.05).Moreover,compared with the CD4+T group,the CD4+T+SCH 546738 group was characterized reduced Th1/Th2 cell ratios(P＜0.001).Conclusion The CXCR3 inhibitor SCH 546738 can alle-viate the progression of RA in mice by reducing Th1/Th2 cell ratios,thereby ameliorating the immune response.

Objective To analyze the basic characteristics of patients with acute myocardial infarction in a tertiary hospi-tal from 2014 to 2023,and provide references for the prevention,treatment,management,and quality control of this disease.Methods Based on the data from the medical records of patients with acute myocardial infarction admitted to a tertiary hospital from January 1,2014,to December 31,2023,the basic characteristics of hospitalized patients and trends in hospitalization costs were analyzed to summarize the development patterns.Results Over the past decade,the number of hospitalized patients with a-cute myocardial infarction has been increasing,while the average length of hospital stay,average cost per hospitalization,and mortality rate have been decreasing.Among the 19 937 patients,there were 16 037 male patients(80.44％)and 3 900 female patients(19.56％),with a male-to-female ratio of 4.11∶1.The median age for male patients was 60 years,while for female patients it was 68 years,indicating that males tend to develop the disease approximately 10 years earlier than females.Among pa-tients aged 60 and above,the mortality rate is positively correlated with age,while among patients below 60,the mortality rate is negatively correlated with age.The decision to undergo surgery has a significant impact on hospitalization costs.From the per-spective of cost structure,the proportion of consumables has decreased from 69.81％to 54.60％in the past decade but remains relatively high.Conclusion With the advancement of hospital management and medical insurance policies,the diagnosis,treat-ment,and quality of care for acute myocardial infarction have significantly improved.However,consumables management remains a key focus.Men and individuals aged 50 and above should be given special attention.During the diagnosis and treatment process,greater attention should also be given to younger or older patients and female patients to reduce the mortality rate.

Objective To analyze the basic characteristics of 1885 inpatients with rare diseases in a 3A hospital from January 1 to December 31,2023,so as to provide reference for the management of diagnosis and treatment of rare diseases and the formulation of policies.Methods Based on the medical record homepage data of rare disease inpatients in a tertiary hospital in 2023,analyze the basic characteristics and hospitalization cost structure of rare disease inpatients.Results The hospital ad-mitted 1 885 inpatients with rare diseases in 2023,accounting for 0.81％of the total number of discharged patients,with a male-to-female ratio close to 1:1.Patients aged over 60 accounted for 45.57％,followed by patients aged 45-59(26.47％),patients aged 19-44(20.9％)ranked third,and patients under 18 accounted for less.Rare diseases cover 11 disease classification sys-tems and including 80 diseases,which accounts for 38.65％of the rare diseases in the catalogue.The top ten diseases accounted for 70.56％of the total number of patients,and the top three diseases were progressive fibrosing interstitial lung disease,idio-pathic pulmonary fibrosis and primary biliary cholangitis.Patients under 1 year old accounted for 0.08％,patients aged 2-18 years accounted for 5.19％,patients aged 19-44 years accounted for 19.55％,patients aged 45-59 years accounted for 26.62％,and patients over 60 years old accounted for 48.57％.There was a large difference in the male-female ratio in four diseases:idio-pathic pulmonary fibrosis,amyotrophic lateral sclerosis,Takayasu's arteritis,and primary biliary cholangitis.From the perspec-tive of cost structure,the top ten rare diseases account for a high proportion of diagnosis fees,medicine fees and consumables fees.Conclusion Patients account for a high proportion of rare disease inpatients in the hospital and have a wide coverage of disease types.The overall male-female ratio of patients with rare diseases is similar,but the characteristics of the diseases are dif-ferent.The characteristics of rare diseases determine the structural characteristics of hospitalization expenses.Hospitals should improve the discipline construction and provide more resources for the diagnosis and treatment of rare diseases.To make guide-lines for the diagnosis and treatment of rare diseases and strengthen the training of doctors,so as to realize the early diagnosis and treatment of rare diseases.The state should continue to promote access to medication for rare diseases.

Objective To analyze the basic characteristics of 1885 inpatients with rare diseases in a 3A hospital from January 1 to December 31,2023,so as to provide reference for the management of diagnosis and treatment of rare diseases and the formulation of policies.Methods Based on the medical record homepage data of rare disease inpatients in a tertiary hospital in 2023,analyze the basic characteristics and hospitalization cost structure of rare disease inpatients.Results The hospital ad-mitted 1 885 inpatients with rare diseases in 2023,accounting for 0.81％of the total number of discharged patients,with a male-to-female ratio close to 1:1.Patients aged over 60 accounted for 45.57％,followed by patients aged 45-59(26.47％),patients aged 19-44(20.9％)ranked third,and patients under 18 accounted for less.Rare diseases cover 11 disease classification sys-tems and including 80 diseases,which accounts for 38.65％of the rare diseases in the catalogue.The top ten diseases accounted for 70.56％of the total number of patients,and the top three diseases were progressive fibrosing interstitial lung disease,idio-pathic pulmonary fibrosis and primary biliary cholangitis.Patients under 1 year old accounted for 0.08％,patients aged 2-18 years accounted for 5.19％,patients aged 19-44 years accounted for 19.55％,patients aged 45-59 years accounted for 26.62％,and patients over 60 years old accounted for 48.57％.There was a large difference in the male-female ratio in four diseases:idio-pathic pulmonary fibrosis,amyotrophic lateral sclerosis,Takayasu's arteritis,and primary biliary cholangitis.From the perspec-tive of cost structure,the top ten rare diseases account for a high proportion of diagnosis fees,medicine fees and consumables fees.Conclusion Patients account for a high proportion of rare disease inpatients in the hospital and have a wide coverage of disease types.The overall male-female ratio of patients with rare diseases is similar,but the characteristics of the diseases are dif-ferent.The characteristics of rare diseases determine the structural characteristics of hospitalization expenses.Hospitals should improve the discipline construction and provide more resources for the diagnosis and treatment of rare diseases.To make guide-lines for the diagnosis and treatment of rare diseases and strengthen the training of doctors,so as to realize the early diagnosis and treatment of rare diseases.The state should continue to promote access to medication for rare diseases.

As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44-CXCR2- neutrophils as tumor-specific neutrophils (tsNeus) in both mouse and human gastric cancer (GC). We uncovered a Hippo regulon in neutrophils with unique YAP signature genes (e.g., ICAM1, CD14, EGR1) distinct from those identified in epithelial and/or cancer cells. Importantly, knockout of YAP/TAZ in neutrophils impaired their differentiation into CD54+ tsNeus and reduced their antitumor activity, leading to accelerated GC progression. Moreover, the relative amounts of CD54+ tsNeus were found to be negatively associated with GC progression and positively associated with patient survival. Interestingly, GC patients receiving neoadjuvant chemotherapy had increased numbers of CD54+ tsNeus. Furthermore, pharmacologically enhancing YAP activity selectively activated neutrophils to suppress refractory GC, with no significant inflammation-related side effects. Thus, our work characterized tumor-specific neutrophils in GC and revealed an essential role of YAP/TAZ-CD54 axis in tsNeus, opening a new possibility to develop neutrophil-based antitumor therapeutics.
Humans ; Animals ; Mice ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Stomach Neoplasms/pathology* ; Neutrophils/pathology* ; Signal Transduction/genetics* ; YAP-Signaling Proteins ; Tumor Microenvironment ; Hyaluronan Receptors/genetics*

In order to evaluate the efficacy and side effects of the non-insulin antidiabetes medications as an adjunct treatment in type 1 diabetes mellitus (T1DM), we conducted systematic searches in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials published between the date of inception and March 2020 to produce a systematic review and meta-analysis. Overall, 57 studies were included. Compared with placebo, antidiabetes agents in adjunct to insulin treatment resulted in significant reduction in glycosylated hemoglobin (weighted mean difference [WMD], –0.30%; 95% confidence interval [CI], –0.34 to –0.25%; P<0.01) and body weight (WMD, –2.15 kg; 95% CI, –2.77 to –1.53 kg; P<0.01), and required a significantly lower dosage of insulin (WMD, –5.17 unit/day; 95% CI, –6.77 to –3.57 unit/day; P<0.01). Compared with placebo, antidiabetes agents in adjunct to insulin treatment increased the risk of hypoglycemia (relative risk [RR], 1.04; 95% CI, 1.01 to 1.08; P=0.02) and gastrointestinal side effects (RR, 1.99; 95% CI, 1.61 to 2.46; P<0.01) in patients with T1DM. Compared with placebo, the use of non-insulin antidiabetes agents in addition to insulin could lead to glycemic improvement, weight control and lower insulin dosage, while they might be associated with increased risks of hypoglycemia and gastrointestinal side effects in patients with T1DM.

OBJECTIVE：To study t he effects of bro mophenylcurcumin（GL63）on the apoptosis ，migration and invasion of human cholangiocarcinoma RBE cells ，and to investigate its mechanism based on JAK/STAT signaling pathway. METHODS ：MTT assay was used to detect the effects of different concentrations of GL 63 [0（blank control ，similarly hereinafter ），1.25，2.5，5，10， 20，40 μ mol/L] on the proliferation of RBE cells after 48 h treatment ；the IC 50 was calculated. The effects of different concentrations of GL 63（0，5，10，20 μmol/L）on colony formation were detected by crystal violet staining after 48 h treatment. Flow cytometry ，Hoechst 33342 staining，cell scratch test and Transwell chamber invasion test were used to detect the effects of different concentrations of GL 63（0，5，10，20 μmol/L）on cell cycle distribution ，apoptosis，migration and invasion ability after 24 h treatment. Western blotting assay was adopted to detect the effects of different concentration of GL 63（0，5，10，20 μmol/L） on the expression of JAK 2/STAT3 signal pathway associated proteins. RESULTS ：The proliferation inhibition rates of RBE cells in different concentrations of GL 63 groups（1.25-40 μmol/L）were significantly increase d，compared with blank control group （P＜ 0.01），and showed a dose-dependent trend ，with IC 50 of （8.46±1.30）μmol/L. Compared with blank control group， 85917439。E-mail：zhaoji-an-88@163.com inhibition rates of RBE cell colony formation were significantly decreased in different concentrations （5，10，20 μmol/L）of GL 63 groups（P＜0.01）. The percentage of RBE cells at G 0/G1 phase increased significantly ，while that at S phase decreased significantly （P＜0.01）. The apoptotic rate increased significantly（P＜0.01），and the nucleus showed dense pyknosis and apoptotic bodies. The rate of cell migration and healing was significantly decreased （P＜0.01），and the number of invasive cells through basement membrane was significantly decreased （P＜ 0.01）. The protein expression of p-JAK 2， p-STAT3， Bcl-2， MMP-2， MMP-9， Pro-caspase-9 and P ro-caspase-3 were down-regulated significantly while the expression of Bax ，Cyt-c，Cleaved-caspase-9 and Cleaved-caspase- 3 were up-regulated significantly（P＜0.01）. CONCLUSIONS ：GL63 may inhibit the proliferation ，migration and invasion of RBE cells and promote its apoptosis by inhibiting JAK 2/STAT3 signal pathway.