Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)‍-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female ; Mice ; Demethylation/drug effects* ; Embryonic Stem Cells ; Estrogens/administration & dosage* ; Gene Expression/drug effects* ; Histones/metabolism* ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Mice, Inbred C57BL ; Oocytes ; Ovary/drug effects* ; Reproductive Techniques, Assisted ; Animals

Objective:To investigate the efficacy of low-methoxyl pectin (LMP) combined with early enteral nutrition (EEN) in patients with severe acute pancreatitis (SAP) complicated by acute kidney injury (AKI).Methods:A prospective study was conducted, enrolling 85 patients with SAP complicated by AKI admitted to the First Hospital of Qinhuangdao from January 2022 to December 2023. These patients were randomized into an LMP group ( n=42) and a control group ( n=43) using a random number table. The control group received traditional EEN, while the LMP group received traditional EEN combined with LMP. Nutritional indicators [total protein (TP), albumin (Alb), and prealbumin (PA)], inflammatory markers [C-reactive protein (CRP), interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor-α (TNF-α)], renal function indicators [creatinine (Cr), estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), uric acid (UA)], AKI stage, and fecal intestinal flora were compared between these two groups before and 7 days after intervention. Results:After 7 days of intervention, the TP, Alb, and PA levels significantly increased in both groups (all P<0.05); the increases in TP and PA were more significant in the LMP group (both P<0.05), whereas the increase in Alb did not differ significantly between groups ( P>0.05). The levels of CRP, IL-1, IL-6, IL-8, and TNF-α decreased significantly in both groups (all P<0.05),with more significant reductions in the LMP group (all P<0.001). The levels of Cr, eGFR, BUN, and UA improved significantly in both groups (all P<0.05),with more significant improvements in the LMP group (all P<0.05). The incidence of a higher AKI stage in the LMP group was significantly lower than that in the control group( P<0.05), and the incidence of a lower AKI stage was significantly higher than that in the control group ( P<0.001). The fecal counts of Bifidobacterium and Lactobacillus increased significantly while the fecal counts of Enterococcus and Enterobacter decreased significantly in both group (all P<0.001); notably, these changes in bacterial counts were significantly more pronounced in the LMP group ( P<0.001). Conclusions:EEN combined with LMP can significantly enhance nutritional status, reduce inflammatory response, and improve renal function in patients with SAP complicated by AKI.

Objective:To investigate the efficacy of low-methoxyl pectin (LMP) combined with early enteral nutrition (EEN) in patients with severe acute pancreatitis (SAP) complicated by acute kidney injury (AKI).Methods:A prospective study was conducted, enrolling 85 patients with SAP complicated by AKI admitted to the First Hospital of Qinhuangdao from January 2022 to December 2023. These patients were randomized into an LMP group ( n=42) and a control group ( n=43) using a random number table. The control group received traditional EEN, while the LMP group received traditional EEN combined with LMP. Nutritional indicators [total protein (TP), albumin (Alb), and prealbumin (PA)], inflammatory markers [C-reactive protein (CRP), interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor-α (TNF-α)], renal function indicators [creatinine (Cr), estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), uric acid (UA)], AKI stage, and fecal intestinal flora were compared between these two groups before and 7 days after intervention. Results:After 7 days of intervention, the TP, Alb, and PA levels significantly increased in both groups (all P<0.05); the increases in TP and PA were more significant in the LMP group (both P<0.05), whereas the increase in Alb did not differ significantly between groups ( P>0.05). The levels of CRP, IL-1, IL-6, IL-8, and TNF-α decreased significantly in both groups (all P<0.05),with more significant reductions in the LMP group (all P<0.001). The levels of Cr, eGFR, BUN, and UA improved significantly in both groups (all P<0.05),with more significant improvements in the LMP group (all P<0.05). The incidence of a higher AKI stage in the LMP group was significantly lower than that in the control group( P<0.05), and the incidence of a lower AKI stage was significantly higher than that in the control group ( P<0.001). The fecal counts of Bifidobacterium and Lactobacillus increased significantly while the fecal counts of Enterococcus and Enterobacter decreased significantly in both group (all P<0.001); notably, these changes in bacterial counts were significantly more pronounced in the LMP group ( P<0.001). Conclusions:EEN combined with LMP can significantly enhance nutritional status, reduce inflammatory response, and improve renal function in patients with SAP complicated by AKI.

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Objective:To observe the differences in biochemical indexes and AIDS-related complications at baseline in HIV-infected patients with different levels of immune reconstitution to antiretroviral therapy (ART).Methods:The subjects were treat-na?ve adult HIV-infected patients who were followed up for more than 24 months in the Guangzhou Eighth People's Hospital affiliated infection clinic at Guangzhou Medical University from January 2010 to December 2017. CD4 + T lymphocyte count at baseline at <200, 200-350, and >350 cells/μl levels were divided into poor, partial, and good immune reconstitution groups. The Kruskal-Wallis H and chi-square tests were used to analyze the differences in baseline sociodemographic characteristics, biochemical indexes, and AIDS-related complications among different groups. The SPSS 20.0 software was used for statistical analysis. Results:Among the 3 900 HIV-infected individuals, 385 cases (9.9%), 1 206 cases (30.9%), and 2 309 cases (59.2%) were grouped into poor, partial and good immune reconstitution groups, respectively. The baseline biochemical indexes of leukocyte, platelet, hemoglobin, TG, TC, FPG, AST, ALT and total bilirubin in the poor immune reconstitution group were significantly different from those in the good immune reconstitution group (all P<0.05). The proportion of AIDS-related complications at baseline in the poor immune reconstitution group, such as tuberculosis, pneumocystis yeli pneumonia, disseminated mycosis, esophageal candidiasis, extrapulmonary tuberculosis, dermatitis, oral candidiasis, oral mucous leukoplakia, continuous diarrhea for more than 1 month and continuous or intermittent fever for more than 1 month, was significantly higher than that in the good immune reconstitution group (all P<0.05). Conclusions:The biochemical indexes and AIDS-related complications in HIV-infected patients with different levels of immune reconstitution were significantly different at baseline. Attention should be paid to monitoring abnormal biomedical indicators and AIDS-related complications at baseline.

Objective::Data comparing the outcomes of MiStent (Micell Technologies, Durham, North Carolina, USA) microcrystalline biodegradable polymer (BP) drug-eluting stent (DES) and those of another post-marketing BP-DES, TIVOLI (EssenTech, Beijing, China) are rare. This study sought to compare the angiographic efficacy and clinical outcomes of the microcrystalline BP sirolimus-eluting stent (SES) system MiStent and those of TIVOLI BP-SES.Methods::The DESSOLVE-C trial was a prospective, single-blinded, multicenter, randomized trial (NCT02448524), which randomly assigned patients with de novo coronary lesions to receive MiStent or TIVOLI BP-SES by a 1:1 ratio. The primary endpoint was a non-inferiority comparison of in-stent late lumen loss (LLL) by quantitative coronary angiography at 9 months. The secondary endpoint was device-related clinical cardiovascular composite events (target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction (MI), and clinically driven target lesion revascularization) and 1-year outcomes. Results::A total of 428 patients (216 patients in the MiStent group and 212 patients in the TIVOLI group) were enrolled and included in an intention-to-treat analysis. MiStent was not only non-inferior but superior to TIVOLI for in-stent LLL at 9 months ((0.23 ± 0.37) mm vs. (0.34 ± 0.48) mm, P for non-inferiority <0.001, P for superiority = 0.02). Although without significant difference, the rate of TLF in MiStent was quantitatively lower than that in TIVOLI (3.70% vs. 6.60%; P = 0.17). Conclusion::Compared with TIVOLI BP-SES, the MiStent system was superior in in-stent LLL at 9 months and had a comparable clinical benefit at 1 year in de novo coronary lesions.

Objective::Data comparing the outcomes of MiStent (Micell Technologies, Durham, North Carolina, USA) microcrystalline biodegradable polymer (BP) drug-eluting stent (DES) and those of another post-marketing BP-DES, TIVOLI (EssenTech, Beijing, China) are rare. This study sought to compare the angiographic efficacy and clinical outcomes of the microcrystalline BP sirolimus-eluting stent (SES) system MiStent and those of TIVOLI BP-SES.Methods::The DESSOLVE-C trial was a prospective, single-blinded, multicenter, randomized trial (NCT02448524), which randomly assigned patients with de novo coronary lesions to receive MiStent or TIVOLI BP-SES by a 1:1 ratio. The primary endpoint was a non-inferiority comparison of in-stent late lumen loss (LLL) by quantitative coronary angiography at 9 months. The secondary endpoint was device-related clinical cardiovascular composite events (target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction (MI), and clinically driven target lesion revascularization) and 1-year outcomes. Results::A total of 428 patients (216 patients in the MiStent group and 212 patients in the TIVOLI group) were enrolled and included in an intention-to-treat analysis. MiStent was not only non-inferior but superior to TIVOLI for in-stent LLL at 9 months ((0.23 ± 0.37) mm vs. (0.34 ± 0.48) mm, P for non-inferiority <0.001, P for superiority = 0.02). Although without significant difference, the rate of TLF in MiStent was quantitatively lower than that in TIVOLI (3.70% vs. 6.60%; P = 0.17). Conclusion::Compared with TIVOLI BP-SES, the MiStent system was superior in in-stent LLL at 9 months and had a comparable clinical benefit at 1 year in de novo coronary lesions.

BACKGROUND: Intensive phototherapy (IPT) and exchange transfusion (ET) are the main treatments for extreme hyperbilirubinemia. However, there is no reliable evidence on determining the thresholds for these treatments. This multicenter study compared the effectiveness and complications of IPT and ET in the treatment of extreme hyperbilirubinemia. METHODS: This retrospective cohort study was conducted in seven centers from January 2015 to January 2018. Patients with extreme hyperbilirubinemia that met the criteria of ET were included. Patients were divided into three subgroups (low-, medium-, and high- risk) according to gestational week and risk factors. Propensity score matching (PSM) was performed to balance the data before treatment. Study outcomes included the development of bilirubin encephalopathy, duration of hospitalization, expenses, and complications. Mortality, auditory complications, seizures, enamel dysplasia, ocular motility disorders, athetosis, motor, and language development were evaluated during follow-up at age of 3 years. RESULTS: A total of 1164 patients were included in this study. After PSM, 296 patients in the IPT only group and 296 patients in the IPT plus ET group were further divided into the low-, medium-, and high-risk subgroups with 188, 364, and 40 matched patients, respectively. No significant differences were found between the IPT only and IPT plus ET groups in terms of morbidity, complications, and sequelae. Hospitalization duration and expenses were lower in the low- and medium-risk subgroups in the IPT only group. CONCLUSIONS In this study, our results suggest that IPT is a safe and effective treatment for extreme hyperbilirubinemia. The indication of ET for patients with hyperbilirubinemia could be stricter. However, it is necessary to have a contingency plan for emergency ET as soon as IPT is commenced especially for infants with risk factors. If IPT can be guaranteed and proved to be therapeutic, ET should be avoided as much as possible.
Child, Preschool ; Exchange Transfusion, Whole Blood/adverse effects* ; Humans ; Hyperbilirubinemia, Neonatal/therapy* ; Infant ; Infant, Newborn ; Kernicterus/therapy* ; Phototherapy/methods* ; Retrospective Studies

Skin is a kind of tissue that surrounds the surface of body, it is the first barrier for animals to resist mechanical, chemical and pathogenic microorganisms. Skin wound is one of the most common surgical diseases. The process of wound healing can be summarized as three stages: inflammation stage, fibrous tissue proliferation stage, and scar formation and repair stage. Incomplete repair of the wound leads to skin scarring, which causes the tissue to lose its normal structure and function, and seriously affects the aesthetic appearance. Traditional treatment methods can not restore the normal function of the skin and have obvious adverse reactions, which can not meet people's needs. Stem cell therapy, especially adipose derived stem cells (ADSCs) plays a essential rule in the process of wound healing making it a research hotspot in recent years. ADSCs can secrete a variety of growth factors during wound healing to reduce wound inflammatory response, promote wound regeneration epithelialization and vascular reconstruction, thereby promoting wound healing. In this paper, the wound healing process and its regulation mechanism were summarized, and the role of ADSCs in wound healing at home and abroad and its clinical application progress were reviewed.