Practical guide:Glucagon-like peptide-1 and dual glucosedependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists in diabetes mellitus common second-line choice after metformin for treating T2...Practical guide:Glucagon-like peptide-1 and dual glucosedependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists in diabetes mellitus common second-line choice after metformin for treating T2DM.Various considerations can make selecting and switching between different GLP-1 RAs challenging.Our study aims to provide a comprehensive guide for the usage of GLP-1 RAs and dual GIP and GLP-1 RAs for the management of T2DM.展开更多
Type 1 diabetes(T1D)is a chronic autoimmune condition that destroys insulinproducing beta cells in the pancreas,leading to insulin deficiency and hyperglycemia.The management of T1D primarily focuses on exogenous insu...Type 1 diabetes(T1D)is a chronic autoimmune condition that destroys insulinproducing beta cells in the pancreas,leading to insulin deficiency and hyperglycemia.The management of T1D primarily focuses on exogenous insulin replacement to control blood glucose levels.However,this approach does not address the underlying autoimmune process or prevent the progressive loss of beta cells.Recent research has explored the potential of glucagon-like peptide-1 receptor agonists(GLP-1RAs)as a novel intervention to modify the disease course and delay the onset of T1D.GLP-1RAs are medications initially developed for treating type 2 diabetes.They exert their effects by enhancing glucose-dependent insulin secretion,suppressing glucagon secretion,and slowing gastric emptying.Emerging evidence suggests that GLP-1RAs may also benefit the treatment of newly diagnosed patients with T1D.This article aims to highlight the potential of GLP-1RAs as an intervention to delay the onset of T1D,possibly through their potential immunomodulatory and anti-inflammatory effects and preservation of beta-cells.This article aims to explore the potential of shifting the paradigm of T1D management from reactive insulin replacement to proactive disease modification,which should open new avenues for preventing and treating T1D,improving the quality of life and long-term outcomes for individuals at risk of T1D.展开更多
Background: The objective of this study was to compare and analyze the variations in clinical indices before and after treatment of type 2 mellitus (T2DM) combined with nonalcoholic fatty liver disease (NAFLD) that we...Background: The objective of this study was to compare and analyze the variations in clinical indices before and after treatment of type 2 mellitus (T2DM) combined with nonalcoholic fatty liver disease (NAFLD) that were treated with glucagon-like peptide 1 receptor agonists (GLP-1RAs). Methods: The electronic medical record system was utilized to search for a total of 16 patients with type 2 diabetes complicated by NAFLD who were hospitalized at the First Affiliated Hospital of Yangtze University from October 2022 to April 2023 and treated with GLP-1RA for the first time. The clinical indices were compared before and after 12 weeks of treatment with GLP-1RA. Results: The liver-spleen CT ratio (L/S), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) in all patients treated with GLP-1RA after 12 weeks were significantly different (P 0.05). The patients were categorized into two groups based on the types of GLP-1RAs. The changes in L/S, TC, TG, and LDL-C in the long-acting group after treatment were statistically significant (P Conclusions: GLP-1RAs can improve liver function, regulate lipid metabolism, and reduce the severity of fatty liver in patients with T2DM complicated by NAFLD, which demonstrates the importance of clinical applications.展开更多
[Objectives]The paper was to establish an ultra high performance liquid chromatography-quadrupole/linear ion trap complex mass spectrometry for the determination of 10 kinds ofα2-receptor agonists in animal derived f...[Objectives]The paper was to establish an ultra high performance liquid chromatography-quadrupole/linear ion trap complex mass spectrometry for the determination of 10 kinds ofα2-receptor agonists in animal derived food.[Methods]The samples were extracted with sodium carbonate buffer solution and ethyl acetate,and analyzed by mass spectrometry after solid phase extraction and high performance liquid chromatography separation.[Results]Ten kinds ofα2-receptor agonists showed a good linear relationship in the range of 1-100μg/mL,with the average recovery of over 69%and the relative standard deviation less than 8.32%.The detection limit of 10 kinds of α_(2)-receptor agonists was up to 1μg/kg.[Conclusions]The method has good selectivity and strong anti-interference ability,and can meet the requirements of 10 kinds ofα2-receptor agonists residues in animal derived food.展开更多
Objective:To determine whether a single dose of gonadotropin-releasing hormone(GnRH)agonist administered subcutaneously in addition to the regular progesterone supplementation could provide a better luteal support in ...Objective:To determine whether a single dose of gonadotropin-releasing hormone(GnRH)agonist administered subcutaneously in addition to the regular progesterone supplementation could provide a better luteal support in antagonist protocol fresh embryo transfer cycles.Methods:This prospective,multicentric,cohort study included total 140 women,70 in each group.Controlled ovarian stimulation was carried out as per fixed GnRH antagonist protocol.The trigger was given with hCG.In vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI)was performed and day-3 embryos were transferred.Patients were divided into groups 1 and 2 based on computer generated randomization sheet.Six days following oocyte retrieval,group 1 received 0.2 mg decapeptyl subcutaneously in addition to regular progesterone support while group 2 received progesterone only.Luteal support was given for 14 days to both groups;if pregnancy was confirmed luteal support was continued till 12 weeks of gestation.The clinical pregnancy rate was the primary outcome.The implantation rate,miscarriage rate,live birth delivery rate,and multiple pregnancy rates were the secondary outcomes.Results:A total of 140 patients were analysed,70 in each group.Clinical pregnancy rates(47.1%vs.35.7%;P=0.17),implantation rates(23.4%vs.18.1%,P=0.24),live birth delivery rates(41.4%vs.27.1%,P=0.08),and multiple pregnancy rates(21.2%vs.16.0%,P=0.74)were higher in group 1 than in group 2.Group 1 had a lower miscarriage rate than group 2(5.7%vs.8.6%;P=0.75).However,these differences were not statistically significant between the two groups.Conclusions:Administration of a single dose of GnRH agonist in addition to regular natural micronized vaginal progesterone as luteal support in GnRH antagonist protocol cycles marginally improves implantation rates,clinical pregnancy rates,and live birth delivery rates.However,more studies with higher sample sizes are needed before any conclusive statements about GnRH agonist as luteal phase support can be made.展开更多
Objective:CAR-T/NK cells have had limited success in the treatment of solid tumors,such as colorectal cancer(CRC),in part because of the heterogeneous nature of tumor-associated antigens that lead to antigen-negative ...Objective:CAR-T/NK cells have had limited success in the treatment of solid tumors,such as colorectal cancer(CRC),in part because of the heterogeneous nature of tumor-associated antigens that lead to antigen-negative relapse after the initial response.This barrier might be overcome by enhancing the recruitment and durability of endogenous immune cells.Methods:Immunohistochemistry and flow cytometry were used to assess the expression of CD133 antigen in tissue microarrays and cell lines,respectively.Retroviral vector transduction was used to generate CBLB502-secreting CAR133-NK92 cells(CAR133-i502-NK92).The tumor killing capacity of CAR133-NK92 cells in vitro and in vivo were quantified via LDH release,the RTCA assay,and the degranulation test,as well as measuring tumor bioluminescence signal intensity in mice xenografts.Results:We engineered CAR133-i502-NK92 cells and demonstrated that those cells displayed enhanced proliferation(9.0×10^(4)cells vs.7.0×10^(4)cells)and specific anti-tumor activities in vitro and in a xenogeneic mouse model,and were well-tolerated.Notably,CBLB502 secreted by CAR133-i502-NK92 cells effectively activated endogenous immune cells.Furthermore,in hCD133+/hCD133−mixed cancer xenograft models,CAR133-i502-NK92 cells suppressed cancer growth better than the counterparts(n=5,P=0.0297).Greater T-cell infiltration was associated with greater anti-tumor potency(P<0.0001).Conclusions:Armed with a CBLB502 TLR5 agonist,CAR133-NK92 cells were shown to be capable of specifically eliminating CD133-positive colon cancer cells in a CAR133-dependent manner and indirectly eradicating CD133-negative colon cancer cells in a CBLB502-specific endogenous immune response manner.This study describes a novel technique for optimizing CAR-T/NK cells for the treatment of antigenically-diverse solid tumors.展开更多
Alzheimer’s disease(AD)is a typical neurodegenerative disease that leads to irreversible neuronal degeneration,and effective treatment remains elusive due to the unclear mechanism.We utilized biocompatible mesenchyma...Alzheimer’s disease(AD)is a typical neurodegenerative disease that leads to irreversible neuronal degeneration,and effective treatment remains elusive due to the unclear mechanism.We utilized biocompatible mesenchymal stem cell-derived extracellular vesicles as carriers loaded with the CB2 target medicine AM1241(EVs-AM1241)to protect against neurodegenerative progression and neuronal function in AD model mice.According to the results,EVs-AM1241 were successfully constructed and exhibited better bioavailability and therapeutic effects than bare AM1241.The Morris water maze(MWM)and fear conditioning tests revealed that the learning and memory of EVs-AM1241-treated model mice were significantly improved.In vivo electrophysiological recording of CA1 neurons indicated enhanced response to an auditory conditioned stimulus following fear learning.Immunostaining and Western blot analysis showed that amyloid plaque deposition and amyloidβ(Aβ)-induced neuronal apoptosis were significantly suppressed by EVs-AM1241.Moreover,EVs-AM1241 increased the number of neurons and restored the neuronal cytoskeleton,indicating that they enhanced neuronal regeneration.RNA sequencing revealed that EVs-AM1241 facilitated Aβphagocytosis,promoted neurogenesis and ultimately improved learning and memory through the calcium-Erk signaling pathway.Our study showed that EVs-AM1241 efficiently reversed neurodegenerative pathology and enhanced neurogenesis in modelmice,indicating that they are very promising particles for treating AD.展开更多
BACKGROUND The prevalence of female infertility between the ages of 25 and 44 is 3.5%to 16.7%in developed countries and 6.9%to 9.3%in developing countries.This means that infertility affects one in six couples and is ...BACKGROUND The prevalence of female infertility between the ages of 25 and 44 is 3.5%to 16.7%in developed countries and 6.9%to 9.3%in developing countries.This means that infertility affects one in six couples and is recognized by the World Health Organization as the fifth most serious global disability.The International Committee for Monitoring Assisted Reproductive Technology reported that the global total of babies born as a result of assisted reproductive technology procedures and other advanced fertility treatments is more than 8 million.Advancements in controlled ovarian hyperstimulation procedures led to crucial accomplishments in human fertility treatments.The European Society for Human Reproduction and Embryology guideline on ovarian stimulation gave us valuable evidence-based recommendations to optimize ovarian stimulation in assisted reproductive technology.Conventional ovarian stimulation protocols for in vitro fertilization(IVF)–embryo transfer are based upon the administration of gonadotropins combined with gonadotropin-releasing hormone(GnRH)analogues,either GnRH agonists(GnRHa)or antagonists.The development of ovarian cysts requires the combination of GnRHa and gonadotropins for controlled ovarian hyperstimulation.However,in rare cases patients may develop an ovarian hyper response after administration of GnRHa alone.CASE SUMMARY Here,two case studies were conducted.In the first case,a 33-year-old female diagnosed with polycystic ovary syndrome presented for her first IVF cycle at our reproductive center.Fourteen days after triptorelin acetate was administrated(day 18 of her menstrual cycle),bilateral ovaries presented polycystic manifestations.The patient was given 5000 IU of human chorionic gonadotropin.Twenty-two oocytes were obtained,and eight embryos formed.Two blastospheres were transferred in the frozen-thawed embryo transfer cycle,and the patient was impregnated.In the second case,a 37-year-old woman presented to the reproductive center for her first donor IVF cycle.Fourteen days after GnRHa administration,the transvaginal ultrasound revealed six follicles measuring 17-26 mm in the bilateral ovaries.The patient was given 10000 IU of human chorionic gonadotropin.Three oocytes were obtained,and three embryos formed.Two high-grade embryos were transferred in the frozen-thawed embryo transfer cycle,and the patient was impregnated.CONCLUSION These two special cases provide valuable knowledge through our experience.We hypothesize that oocyte retrieval can be an alternative to cycle cancellation in these conditions.Considering the high progesterone level in most cases of this situation,we advocate freezing embryos after oocyte retrieval rather than fresh embryo transfer.展开更多
Acute Kidney Injury (AKI) is a condition that causes nephrotoxicity in kidney tissues due to cisplatin-induced cancer treatments. Hence, it is proposed in this review that AVE0991 (a MAS-receptor Angiotensin II (1-7) ...Acute Kidney Injury (AKI) is a condition that causes nephrotoxicity in kidney tissues due to cisplatin-induced cancer treatments. Hence, it is proposed in this review that AVE0991 (a MAS-receptor Angiotensin II (1-7) agonist) may reduce cisplatin-induced acute kidney injury by promoting nitric oxide production.展开更多
BACKGROUND Currently,the lack of comparative studies between weekly and daily formulations of glucagon-like peptide-1 receptor agonists(GLP-1RAs)for glucose excursion is worth investigation.AIM To investigate the effe...BACKGROUND Currently,the lack of comparative studies between weekly and daily formulations of glucagon-like peptide-1 receptor agonists(GLP-1RAs)for glucose excursion is worth investigation.AIM To investigate the effects of weekly and daily formulations of GLP-1RA on glucose excursion and inflammation in overweight and obese patients with type 2 diabetes.METHODS Seventy patients with type 2 diabetes mellitus who were treated at our hospital between January 2019 and January 2022 were enrolled in this retrospective analysis.All patients were treated with metformin.We evaluated changes in blood glucose levels and a series of important indicators in patients before and after treatment with either a weekly or daily preparation of GLP-1RA(group A;n=33 and group B;n=37).RESULTS The degree of decrease in the levels of fasting blood glucose,mean blood glucose,mean amplitude of glycemic excursions,total cholesterol,triglycerides,tumor necrosis factor-α,interleukin-6,and high-sensitivity C-reactive protein after treatment in group A was higher than that in group B(P<0.05),whereas the 2-h postprandial blood glucose levels decreased more so in group B than in group A(P<0.001).However,there were no statistically significant differences in the levels of glycated hemoglobin,standard deviation of blood glucose,coefficient of variation,absolute mean of daily differences,percentage of time with 3.9 mmol/L<glucose<10 mmol/L,and high-and low-density lipoproteins between the two groups(P>0.05).The incidence of adverse reactions was significantly lower in group A than in group B(P<0.05).CONCLUSION The effect of the weekly preparation of GLP-1RA in controlling blood glucose levels in the patients,suppressing inflammation,and reducing adverse reactions was significantly higher than that of the daily preparations,which is worthy of clinical promotion.展开更多
BACKGROUND Breast cancer in young women has been shown to have an aggressive behavior and poor prognosis.AIM To evaluate the outcomes of young hormone receptor(HR)-positive patients with breast cancer treated with neo...BACKGROUND Breast cancer in young women has been shown to have an aggressive behavior and poor prognosis.AIM To evaluate the outcomes of young hormone receptor(HR)-positive patients with breast cancer treated with neoadjuvant chemotherapy(NAC),and the oncologic efficacy of gonadotropin-releasing hormone(GnRH)agonists.METHODS This retrospective study involved a prospectively enrolled cohort.We included patients diagnosed with invasive breast cancer who were treated with NAC followed by curative surgery at the Samsung Medical Center and Samsung Changwon Hospital between January 2006 and December 2017.Among patients with HR-positive and human epidermal grow factor 2(HER2)-negative breast cancer,we analyzed the characteristics and oncology outcomes between the patients equal to or younger than 35 years and the patients older than 35 years.RESULTS Among 431 patients with NAC and HR-positive/HER2-negative breast cancer,78 were 35 years old or younger,and 353 patients were older than 35 years.The median follow-up was 71.0 months.There was no statistically significant difference in disease free survival(DFS,P=0.565)and overall survival(P=0.820)between the patients equal to or younger than 35 years and the patients older than 35 years.The two groups differed in that the GnRH agonist was used more frequently in the group of patients equal to or younger than 35 years than in the other group(52.4%vs 11.2%,P<0.001).Interestingly,for the DFS according to the GnRH agonist in the group of patients equal to or younger than 35 years,patients treated with the GnRH agonist had better DFS(P=0.037).CONCLUSION Administration of GnRH agonists might improve the DFS rate of HR-positive/HER2-negative breast cancer in the equal to or younger than 35 years group of patients with NAC.展开更多
[Objectives]A high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method was established for the determination of 14β-receptor agonist residues in mutton.[Methods]Samples were hydrolyzed byβ-g...[Objectives]A high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method was established for the determination of 14β-receptor agonist residues in mutton.[Methods]Samples were hydrolyzed byβ-glucuronidase and extracted with 5%acetic acid-acetonitrile(1:99,V/V)solution.An Eclipse plus C 18 column was used for separation,and the MRM mode was used for qualitative analysis,and the external standard method was used for quantitative analysis of matrix standard solutions.[Results]Under the optimal conditions,the retention time of the 14 kinds ofβ-receptor agonists ranged from 1.0 to 9.5 min.When the mass concentration was in the range of 0.05-0.50μg/ml,the linear relationship ofβ-receptor agonists was good,with correlation coefficients(r)≥0.9992.The detection limits of the method were in the range of 0.04-0.87μg/kg,and the quantitative limits were in the range of 0.35-1.86μg/kg.The average recovery values were in the range of 82.8%-108.9%,with RSDs(n=6)in the range of 1.9%-6.7%.[Conclusions]The method is simple,sensitive,reproducible,accurate,and can be used for simultaneous determination of the 14 kinds ofβ-receptor agonist residues in mutton.展开更多
An agonistic display by a white shark was observed and photographed during a cage dive at Guadalupe Island in November 2015. Exhibiting exaggerated pectoral fin depression, agonistic behaviors have been previously obs...An agonistic display by a white shark was observed and photographed during a cage dive at Guadalupe Island in November 2015. Exhibiting exaggerated pectoral fin depression, agonistic behaviors have been previously observed and described in several shark species. This account may be the first record of a white shark in close proximity to a caged diver, exhibiting strong pectoral fin depression significantly dipped, in the mid-agonistic display. Such displays should be considered as aggressive and potentially life-threatening by those using the ocean for recreational or professional purposes.展开更多
This observational study included 21 patients at remarkably high risk of ovarian hyperstimulation syndrome(OHSS),characterized by more than 30 follicles measuring≥11 mm in diameter on trigger day and/or pre-trigger p...This observational study included 21 patients at remarkably high risk of ovarian hyperstimulation syndrome(OHSS),characterized by more than 30 follicles measuring≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL.which was also the feature of women with established severe early OHSS followed by gonadotrophin-releasing hormone agonist(GnRHa)trigger and freeze-all policy that previously have been reported.All patients received a second dose of GnRHa 12 h after the first GnRHa trigger combined with administration of GnRH antagonist at 0.25 mg/day for a period of 3 days from the day of oocyte retrieval onwards.The in vitro fertilization(IVF)outcomes may be preferable compared with a bolus of GnRHa trigger and none of the included patients developed moderate-to-severe OHSS.Moreover,patients'symptoms,reproductive honnone levels and ultrasound findings were improved significantly.This new strategy seems to be efficacious and could be a further supplement of GnRHa trigger with or without applying freeze-all strategy to completely prevent early-onset moderate to severe OHSS,especially for the patients characterized by≥30 follicles measuring≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL.Further studies should be performed to compare this regimen with conventional methods of OHSS prevention.展开更多
Background: This study aimed to determine if the gonadotropin releasing hormone (GnRH) antagonist protocol is optimal for expected poor ovarian responders with tubal factor undergoing in vitro fertilization-embryo tra...Background: This study aimed to determine if the gonadotropin releasing hormone (GnRH) antagonist protocol is optimal for expected poor ovarian responders with tubal factor undergoing in vitro fertilization-embryo transfer (IVF-ET). Methods: A total of 341 IVF-ET cycles were retrospectively identified. The following inclusion criteria were applied: age ≥ 40 years and patients with tubal factors. The cycles were divided into two groups: a GnRH antagonist group (157 cycles) and a GnRH agonist group (184 cycles). Results: The duration of stimulation and the total doses of gonadotropin in the GnRH agonist group were significantly more than those in the GnRH antagonist group (P < 0.05). There were significant differences in LH and P values on the hCG measurement days between the two groups (0.91 ± 1.17 vs. 4.82 ± 4.69 U/L and 0.69 ± 0.42 vs. 1.03 ± 0.50 ng/mL, P < 0.05). The implantation rate of the GnRH antagonist group was 12.24%, which was slightly higher than that of the GnRH agonist group (10.10%, P = 0.437). The clinical pregnancy rate of the two groups showed no statistical differences (23.36% vs. 23.03%, P = 1.000). Conclusion: For expected poor ovarian responders, the GnRH antagonist protocol was, to some extent, superior to the GnRH agonist protocol in terms of the implantation and clinical pregnancy rates.展开更多
Background: To assess the effect of these two protocols in patients of different ages. Methods: 1923 in vitro fertilization and embryo transfer (IVF-ET) cycles were divided into two groups: a GnRH-ant protocol group a...Background: To assess the effect of these two protocols in patients of different ages. Methods: 1923 in vitro fertilization and embryo transfer (IVF-ET) cycles were divided into two groups: a GnRH-ant protocol group and GnRH-a long protocol group, and then every group were subdivided into four age ranges. The general materials and IVF outcomes were compared. Results: The incidence of OHSS fluctuated from 0% to 2.37% with GnRH-ant protocol, which was significantly lower than another (P P Conclusion: The antagonist protocol should be considered in patients with a high ovarian response (e.g., PCOS patients) to avoid OHSS. Older patients (>35 years) could be treated with the antagonist protocol.展开更多
Glucagon-like peptide1(GLP-1)is secreted from Langerhans cells in response to oral nutrient intake.Glucagon-like peptide-1 receptor agonists(GLP-1RAs)are a new class of incretin-based anti-diabetic drugs.They function...Glucagon-like peptide1(GLP-1)is secreted from Langerhans cells in response to oral nutrient intake.Glucagon-like peptide-1 receptor agonists(GLP-1RAs)are a new class of incretin-based anti-diabetic drugs.They function to stimulate insulin secretion while suppressing glucagon secretion.GLP-1-based therapies are now well established in the management of type 2 diabetes mellitus(T2DM),and recent literature has suggested potential applications of these drugs in the treatment of obesity and for protection against cardiovascular and neurological diseases.As we know,along with change in lifestyles,the prevalence of non-alcoholic fatty liver disease(NAFLD)in China is rising more than that of viral hepatitis and alcoholic fatty liver disease,and NAFLD has become the most common chronic liver disease in recent years.Recent studies further suggest that GLP-1RAs can reduce transaminase levels to improve NAFLD by improving blood lipid levels,cutting down the fatcontent to promote fat redistribution,directly decreasing fatty degeneration of the liver,reducing the degree of liver fibrosis and improving inflammation.This review shows the NAFLD-associated effects of GLP-1RAs in animal models and in patients with T2DM or obesity who are participants in clinical trials.展开更多
Glucagon-like peptide-1(GLP-1)receptor agonists result in greater improvements in glycemic control than placebo and promote weight loss with minimal hypoglycemia in patients with type 2 diabetes mellitus.A number of c...Glucagon-like peptide-1(GLP-1)receptor agonists result in greater improvements in glycemic control than placebo and promote weight loss with minimal hypoglycemia in patients with type 2 diabetes mellitus.A number of case reports show an association of GLP-1receptor agonists,mainly exenatide,with the development of acute kidney injury.The present review aims to present the available data regarding the effects of GLP-1 receptor agonists on renal function,their use in subjects with chronic renal failure and their possible association with acute kidney injury.Based on the current evidence,exenatide is eliminated by renal mechanisms and should not be given in patients with severe renal impairment or end stage renal disease.Liraglutide is not eliminated by renal or hepatic mechanisms,but it should be used with caution since there are only limited data in patients with renal or hepatic impairment.There is evidence from animal studies that GLP-1 receptor agonists exert protective role in diabetic nephropathy with mechanisms that seem to be independent of their glucose-lowering effect.Additionally,there is evidence that GLP-1 receptor agonists influence water and electrolyte balance.These effects may represent new ways to improve or even prevent diabetic nephropathy.展开更多
This study aimed to investigate the effect of different gonadotropin-releasing hormone agonist (GnRH-a) administration methods on pregnancy outcomes of patients undergoing in-vitro fertilization-embryo transfer (IVF-E...This study aimed to investigate the effect of different gonadotropin-releasing hormone agonist (GnRH-a) administration methods on pregnancy outcomes of patients undergoing in-vitro fertilization-embryo transfer (IVF-ET). Clinical data of 5217 patients who underwent IVF-ET were retrospectively analyzed. Patients were divided into the long-acting GnRH-a group (n=1330) and the short-acting GnRH-a group (w=3887) based on their various treatment plans. The clinical and laboratory embryo data and clinical pregnancy outcomes were compared between the two groups. The results showed that there were no significant differences in the age, infertility, primary/secondary infertility rate, IVF rate, body mass index (BMI), antral follicle counting (AFC), folliclestimulating hormone (FSH) level, and the number of transplanted embryos between the two groups (P>0.05). There were no significant differences in the oocyte numbers, M II rate, fertilization rate, cleavage rate and blastocyst formation rate (P>0.05) between the two groups. The gonadotropin (Gn) using days, Gn dose and endometrial thickness were significantly greater in the long-acting GnRH-a group than those in the short-acting GnRH-a group (P<0.01). Additionally, the estradiol (E2) levels, blastocyst freezing rate, embryo utilization rate, transplant cancellation rate and abortion rate were significantly lower in the long-acting GnRH-a group than those in the shortacting GnRH-a group (P<0.01). The clinical pregnancy rate and embryo implantation rate were significantly higher in the long-acting GnRH-a group than in the short-acting GnRH-a group (P<O.Ol). It was concluded that use of long-acting GnRH-a can effectively reduce the transplant cancellation rate and improve the clinical pregnancy rate of the fresh cycle.展开更多
AIM: To investigate the effects of 17β-estradiol via estrogen receptors(ER) or direct administration of ER agonists on human colorectal cancer. METHODS: Lo Vo cells were established from the Bioresource Collection an...AIM: To investigate the effects of 17β-estradiol via estrogen receptors(ER) or direct administration of ER agonists on human colorectal cancer. METHODS: Lo Vo cells were established from the Bioresource Collection and Research Center and cultured in phenol red-free DMEM(Sigma, United States). To investigate the effects of E2 and/or ER selective agonists on cellular proliferation, Lo Vo colorectal cells were treated with E2 or ER-selective agonists for 24 h and 48 h and subjected to the MTT(Sigma) assay to find the concentration. And investigate the effects of E2 and/or ER selective agonists on cell used western immunoblotting to find out the diversification of signaling pathways. In order to observe motility and migration the wound healing assay and a transwell chamber(Neuro Probe) plate were tased. For a quantitative measure, we counted the number of migrating cells to the wound area post-wounding for 24 h. We further examined the cellular migration-regulating factors urokinase-type plasminogen activator(u-PA), tissue-type plasminogen activator(t-PA) and matrix metalloproteinase(MMP)-9 in human Lo Vo cells so gelatin zymography that we used and gelatinolytic activity was visualized by Coomassie blue staining. And these results are presented as means ± SE, and statistical comparisons were made using Student's t-test.RESULTS: The structure was first compared with E2 and ER agonists. We then treated the Lo Vo cells with E2 and ER agonists(10-8 mol/L) for 24 h and 48 h and subsequently measured the cell viability using MTT assay. Our results showed that treatment with 17β-estradiol and/or ER agonists in human Lo Vo colorectal cancer cells activated p53 and then up-regulated p21 and p27 protein levels, subsequently inhibiting the downstream target gene, cyclin D1, which regulates cell proliferation. Taken together, our findings demonstrate the anti-tumorigenesis effects of 17β-estradiol and/or ER agonists and suggest that these compounds may prove to be a potential alternative therapy in the treatment of human colorectal cancer. These results demonstrate that 17β-estradiol and/or ER agonists downregulate migration-related proteins through the p53 signaling pathway in human Lo Vo colorectal cancer cells. These findings suggest that p53 plays a critical role in the 17β-estradiol and/or ER agonist-mediated protective activity against colorectal cancer progression. In addition, 17β-estradiol and/or ER agonists dramatically inhibited cell migration and reduced the expression of u-PA, t-PA and MMP-9 as well as MMP-2/9 activity in Lo Vo cells, which regulate cell metastasis. Moreover, we observed that pretreatment with a p53 inhibitor significantly blocked the anti-migration effects of E2 and/or ER agonists on Lo Vo cells. That E2 and/or ER agonists may impair Lo Vo cell migration by modulating migration-related factors via the p53 tumor suppressor gene.CONCLUSION: Direct ER treatment may prove to be an attractive alternative therapy in the treatment of human colorectal tumors in the future.展开更多
文摘Practical guide:Glucagon-like peptide-1 and dual glucosedependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists in diabetes mellitus common second-line choice after metformin for treating T2DM.Various considerations can make selecting and switching between different GLP-1 RAs challenging.Our study aims to provide a comprehensive guide for the usage of GLP-1 RAs and dual GIP and GLP-1 RAs for the management of T2DM.
文摘Type 1 diabetes(T1D)is a chronic autoimmune condition that destroys insulinproducing beta cells in the pancreas,leading to insulin deficiency and hyperglycemia.The management of T1D primarily focuses on exogenous insulin replacement to control blood glucose levels.However,this approach does not address the underlying autoimmune process or prevent the progressive loss of beta cells.Recent research has explored the potential of glucagon-like peptide-1 receptor agonists(GLP-1RAs)as a novel intervention to modify the disease course and delay the onset of T1D.GLP-1RAs are medications initially developed for treating type 2 diabetes.They exert their effects by enhancing glucose-dependent insulin secretion,suppressing glucagon secretion,and slowing gastric emptying.Emerging evidence suggests that GLP-1RAs may also benefit the treatment of newly diagnosed patients with T1D.This article aims to highlight the potential of GLP-1RAs as an intervention to delay the onset of T1D,possibly through their potential immunomodulatory and anti-inflammatory effects and preservation of beta-cells.This article aims to explore the potential of shifting the paradigm of T1D management from reactive insulin replacement to proactive disease modification,which should open new avenues for preventing and treating T1D,improving the quality of life and long-term outcomes for individuals at risk of T1D.
文摘Background: The objective of this study was to compare and analyze the variations in clinical indices before and after treatment of type 2 mellitus (T2DM) combined with nonalcoholic fatty liver disease (NAFLD) that were treated with glucagon-like peptide 1 receptor agonists (GLP-1RAs). Methods: The electronic medical record system was utilized to search for a total of 16 patients with type 2 diabetes complicated by NAFLD who were hospitalized at the First Affiliated Hospital of Yangtze University from October 2022 to April 2023 and treated with GLP-1RA for the first time. The clinical indices were compared before and after 12 weeks of treatment with GLP-1RA. Results: The liver-spleen CT ratio (L/S), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) in all patients treated with GLP-1RA after 12 weeks were significantly different (P 0.05). The patients were categorized into two groups based on the types of GLP-1RAs. The changes in L/S, TC, TG, and LDL-C in the long-acting group after treatment were statistically significant (P Conclusions: GLP-1RAs can improve liver function, regulate lipid metabolism, and reduce the severity of fatty liver in patients with T2DM complicated by NAFLD, which demonstrates the importance of clinical applications.
基金Supported by Scientific Research Project of Dalian Customs(2022DK09).
文摘[Objectives]The paper was to establish an ultra high performance liquid chromatography-quadrupole/linear ion trap complex mass spectrometry for the determination of 10 kinds ofα2-receptor agonists in animal derived food.[Methods]The samples were extracted with sodium carbonate buffer solution and ethyl acetate,and analyzed by mass spectrometry after solid phase extraction and high performance liquid chromatography separation.[Results]Ten kinds ofα2-receptor agonists showed a good linear relationship in the range of 1-100μg/mL,with the average recovery of over 69%and the relative standard deviation less than 8.32%.The detection limit of 10 kinds of α_(2)-receptor agonists was up to 1μg/kg.[Conclusions]The method has good selectivity and strong anti-interference ability,and can meet the requirements of 10 kinds ofα2-receptor agonists residues in animal derived food.
文摘Objective:To determine whether a single dose of gonadotropin-releasing hormone(GnRH)agonist administered subcutaneously in addition to the regular progesterone supplementation could provide a better luteal support in antagonist protocol fresh embryo transfer cycles.Methods:This prospective,multicentric,cohort study included total 140 women,70 in each group.Controlled ovarian stimulation was carried out as per fixed GnRH antagonist protocol.The trigger was given with hCG.In vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI)was performed and day-3 embryos were transferred.Patients were divided into groups 1 and 2 based on computer generated randomization sheet.Six days following oocyte retrieval,group 1 received 0.2 mg decapeptyl subcutaneously in addition to regular progesterone support while group 2 received progesterone only.Luteal support was given for 14 days to both groups;if pregnancy was confirmed luteal support was continued till 12 weeks of gestation.The clinical pregnancy rate was the primary outcome.The implantation rate,miscarriage rate,live birth delivery rate,and multiple pregnancy rates were the secondary outcomes.Results:A total of 140 patients were analysed,70 in each group.Clinical pregnancy rates(47.1%vs.35.7%;P=0.17),implantation rates(23.4%vs.18.1%,P=0.24),live birth delivery rates(41.4%vs.27.1%,P=0.08),and multiple pregnancy rates(21.2%vs.16.0%,P=0.74)were higher in group 1 than in group 2.Group 1 had a lower miscarriage rate than group 2(5.7%vs.8.6%;P=0.75).However,these differences were not statistically significant between the two groups.Conclusions:Administration of a single dose of GnRH agonist in addition to regular natural micronized vaginal progesterone as luteal support in GnRH antagonist protocol cycles marginally improves implantation rates,clinical pregnancy rates,and live birth delivery rates.However,more studies with higher sample sizes are needed before any conclusive statements about GnRH agonist as luteal phase support can be made.
基金supported by the Technology Innovation and Application Developnent Key Program of Chongqing(Grant No.CSTC2021jscx-gksb-N0026)the National Natural Science Foundation of China(Grant No.31540016)+1 种基金the Basic Research and Frontier Exploration Projects of Chongqing(Grant No.cstc2018jcyjAX0075)the Subsidy Fund for the Development of National Silk in Chongqing(Grant No.CQ2018JSCE05).
文摘Objective:CAR-T/NK cells have had limited success in the treatment of solid tumors,such as colorectal cancer(CRC),in part because of the heterogeneous nature of tumor-associated antigens that lead to antigen-negative relapse after the initial response.This barrier might be overcome by enhancing the recruitment and durability of endogenous immune cells.Methods:Immunohistochemistry and flow cytometry were used to assess the expression of CD133 antigen in tissue microarrays and cell lines,respectively.Retroviral vector transduction was used to generate CBLB502-secreting CAR133-NK92 cells(CAR133-i502-NK92).The tumor killing capacity of CAR133-NK92 cells in vitro and in vivo were quantified via LDH release,the RTCA assay,and the degranulation test,as well as measuring tumor bioluminescence signal intensity in mice xenografts.Results:We engineered CAR133-i502-NK92 cells and demonstrated that those cells displayed enhanced proliferation(9.0×10^(4)cells vs.7.0×10^(4)cells)and specific anti-tumor activities in vitro and in a xenogeneic mouse model,and were well-tolerated.Notably,CBLB502 secreted by CAR133-i502-NK92 cells effectively activated endogenous immune cells.Furthermore,in hCD133+/hCD133−mixed cancer xenograft models,CAR133-i502-NK92 cells suppressed cancer growth better than the counterparts(n=5,P=0.0297).Greater T-cell infiltration was associated with greater anti-tumor potency(P<0.0001).Conclusions:Armed with a CBLB502 TLR5 agonist,CAR133-NK92 cells were shown to be capable of specifically eliminating CD133-positive colon cancer cells in a CAR133-dependent manner and indirectly eradicating CD133-negative colon cancer cells in a CBLB502-specific endogenous immune response manner.This study describes a novel technique for optimizing CAR-T/NK cells for the treatment of antigenically-diverse solid tumors.
基金supported by the National Key Research and Development Program (grant no. 2021YFA1101301)the National Natural Science Foundation of China (grant no. 82225027, 82271419, 81820108013, 62127810, 81901902)+1 种基金Shanghai Rising-Star Program (grant no. 22QA1408200)the Fundamental Research Funds for the Central Universities(no. 22120220555, no. 22120230292, no. 22120230138)
文摘Alzheimer’s disease(AD)is a typical neurodegenerative disease that leads to irreversible neuronal degeneration,and effective treatment remains elusive due to the unclear mechanism.We utilized biocompatible mesenchymal stem cell-derived extracellular vesicles as carriers loaded with the CB2 target medicine AM1241(EVs-AM1241)to protect against neurodegenerative progression and neuronal function in AD model mice.According to the results,EVs-AM1241 were successfully constructed and exhibited better bioavailability and therapeutic effects than bare AM1241.The Morris water maze(MWM)and fear conditioning tests revealed that the learning and memory of EVs-AM1241-treated model mice were significantly improved.In vivo electrophysiological recording of CA1 neurons indicated enhanced response to an auditory conditioned stimulus following fear learning.Immunostaining and Western blot analysis showed that amyloid plaque deposition and amyloidβ(Aβ)-induced neuronal apoptosis were significantly suppressed by EVs-AM1241.Moreover,EVs-AM1241 increased the number of neurons and restored the neuronal cytoskeleton,indicating that they enhanced neuronal regeneration.RNA sequencing revealed that EVs-AM1241 facilitated Aβphagocytosis,promoted neurogenesis and ultimately improved learning and memory through the calcium-Erk signaling pathway.Our study showed that EVs-AM1241 efficiently reversed neurodegenerative pathology and enhanced neurogenesis in modelmice,indicating that they are very promising particles for treating AD.
文摘BACKGROUND The prevalence of female infertility between the ages of 25 and 44 is 3.5%to 16.7%in developed countries and 6.9%to 9.3%in developing countries.This means that infertility affects one in six couples and is recognized by the World Health Organization as the fifth most serious global disability.The International Committee for Monitoring Assisted Reproductive Technology reported that the global total of babies born as a result of assisted reproductive technology procedures and other advanced fertility treatments is more than 8 million.Advancements in controlled ovarian hyperstimulation procedures led to crucial accomplishments in human fertility treatments.The European Society for Human Reproduction and Embryology guideline on ovarian stimulation gave us valuable evidence-based recommendations to optimize ovarian stimulation in assisted reproductive technology.Conventional ovarian stimulation protocols for in vitro fertilization(IVF)–embryo transfer are based upon the administration of gonadotropins combined with gonadotropin-releasing hormone(GnRH)analogues,either GnRH agonists(GnRHa)or antagonists.The development of ovarian cysts requires the combination of GnRHa and gonadotropins for controlled ovarian hyperstimulation.However,in rare cases patients may develop an ovarian hyper response after administration of GnRHa alone.CASE SUMMARY Here,two case studies were conducted.In the first case,a 33-year-old female diagnosed with polycystic ovary syndrome presented for her first IVF cycle at our reproductive center.Fourteen days after triptorelin acetate was administrated(day 18 of her menstrual cycle),bilateral ovaries presented polycystic manifestations.The patient was given 5000 IU of human chorionic gonadotropin.Twenty-two oocytes were obtained,and eight embryos formed.Two blastospheres were transferred in the frozen-thawed embryo transfer cycle,and the patient was impregnated.In the second case,a 37-year-old woman presented to the reproductive center for her first donor IVF cycle.Fourteen days after GnRHa administration,the transvaginal ultrasound revealed six follicles measuring 17-26 mm in the bilateral ovaries.The patient was given 10000 IU of human chorionic gonadotropin.Three oocytes were obtained,and three embryos formed.Two high-grade embryos were transferred in the frozen-thawed embryo transfer cycle,and the patient was impregnated.CONCLUSION These two special cases provide valuable knowledge through our experience.We hypothesize that oocyte retrieval can be an alternative to cycle cancellation in these conditions.Considering the high progesterone level in most cases of this situation,we advocate freezing embryos after oocyte retrieval rather than fresh embryo transfer.
文摘Acute Kidney Injury (AKI) is a condition that causes nephrotoxicity in kidney tissues due to cisplatin-induced cancer treatments. Hence, it is proposed in this review that AVE0991 (a MAS-receptor Angiotensin II (1-7) agonist) may reduce cisplatin-induced acute kidney injury by promoting nitric oxide production.
基金the Clinical Research and Cultivation Plan Project of the Second Affiliated Hospital of Anhui Medical University,No.2021LCYB17.
文摘BACKGROUND Currently,the lack of comparative studies between weekly and daily formulations of glucagon-like peptide-1 receptor agonists(GLP-1RAs)for glucose excursion is worth investigation.AIM To investigate the effects of weekly and daily formulations of GLP-1RA on glucose excursion and inflammation in overweight and obese patients with type 2 diabetes.METHODS Seventy patients with type 2 diabetes mellitus who were treated at our hospital between January 2019 and January 2022 were enrolled in this retrospective analysis.All patients were treated with metformin.We evaluated changes in blood glucose levels and a series of important indicators in patients before and after treatment with either a weekly or daily preparation of GLP-1RA(group A;n=33 and group B;n=37).RESULTS The degree of decrease in the levels of fasting blood glucose,mean blood glucose,mean amplitude of glycemic excursions,total cholesterol,triglycerides,tumor necrosis factor-α,interleukin-6,and high-sensitivity C-reactive protein after treatment in group A was higher than that in group B(P<0.05),whereas the 2-h postprandial blood glucose levels decreased more so in group B than in group A(P<0.001).However,there were no statistically significant differences in the levels of glycated hemoglobin,standard deviation of blood glucose,coefficient of variation,absolute mean of daily differences,percentage of time with 3.9 mmol/L<glucose<10 mmol/L,and high-and low-density lipoproteins between the two groups(P>0.05).The incidence of adverse reactions was significantly lower in group A than in group B(P<0.05).CONCLUSION The effect of the weekly preparation of GLP-1RA in controlling blood glucose levels in the patients,suppressing inflammation,and reducing adverse reactions was significantly higher than that of the daily preparations,which is worthy of clinical promotion.
文摘BACKGROUND Breast cancer in young women has been shown to have an aggressive behavior and poor prognosis.AIM To evaluate the outcomes of young hormone receptor(HR)-positive patients with breast cancer treated with neoadjuvant chemotherapy(NAC),and the oncologic efficacy of gonadotropin-releasing hormone(GnRH)agonists.METHODS This retrospective study involved a prospectively enrolled cohort.We included patients diagnosed with invasive breast cancer who were treated with NAC followed by curative surgery at the Samsung Medical Center and Samsung Changwon Hospital between January 2006 and December 2017.Among patients with HR-positive and human epidermal grow factor 2(HER2)-negative breast cancer,we analyzed the characteristics and oncology outcomes between the patients equal to or younger than 35 years and the patients older than 35 years.RESULTS Among 431 patients with NAC and HR-positive/HER2-negative breast cancer,78 were 35 years old or younger,and 353 patients were older than 35 years.The median follow-up was 71.0 months.There was no statistically significant difference in disease free survival(DFS,P=0.565)and overall survival(P=0.820)between the patients equal to or younger than 35 years and the patients older than 35 years.The two groups differed in that the GnRH agonist was used more frequently in the group of patients equal to or younger than 35 years than in the other group(52.4%vs 11.2%,P<0.001).Interestingly,for the DFS according to the GnRH agonist in the group of patients equal to or younger than 35 years,patients treated with the GnRH agonist had better DFS(P=0.037).CONCLUSION Administration of GnRH agonists might improve the DFS rate of HR-positive/HER2-negative breast cancer in the equal to or younger than 35 years group of patients with NAC.
基金Supported by The Fourth Batch of High-end Talent Project in Hebei ProvinceTangshan Science and Technology Entrepreneurship and Innovation Leading Talent Project(21130243A).
文摘[Objectives]A high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method was established for the determination of 14β-receptor agonist residues in mutton.[Methods]Samples were hydrolyzed byβ-glucuronidase and extracted with 5%acetic acid-acetonitrile(1:99,V/V)solution.An Eclipse plus C 18 column was used for separation,and the MRM mode was used for qualitative analysis,and the external standard method was used for quantitative analysis of matrix standard solutions.[Results]Under the optimal conditions,the retention time of the 14 kinds ofβ-receptor agonists ranged from 1.0 to 9.5 min.When the mass concentration was in the range of 0.05-0.50μg/ml,the linear relationship ofβ-receptor agonists was good,with correlation coefficients(r)≥0.9992.The detection limits of the method were in the range of 0.04-0.87μg/kg,and the quantitative limits were in the range of 0.35-1.86μg/kg.The average recovery values were in the range of 82.8%-108.9%,with RSDs(n=6)in the range of 1.9%-6.7%.[Conclusions]The method is simple,sensitive,reproducible,accurate,and can be used for simultaneous determination of the 14 kinds ofβ-receptor agonist residues in mutton.
文摘An agonistic display by a white shark was observed and photographed during a cage dive at Guadalupe Island in November 2015. Exhibiting exaggerated pectoral fin depression, agonistic behaviors have been previously observed and described in several shark species. This account may be the first record of a white shark in close proximity to a caged diver, exhibiting strong pectoral fin depression significantly dipped, in the mid-agonistic display. Such displays should be considered as aggressive and potentially life-threatening by those using the ocean for recreational or professional purposes.
基金the National Natural Science Foundation of China(No.81401177)Guangdong Province Natural Science Foundation(No.2015A030313286)Milstein Medical Asian American Partnership Foundation Fellowship Award in Reproductive Medicine,Nanfang Hospital High-level Project Matching Funds(No.G2014005).
文摘This observational study included 21 patients at remarkably high risk of ovarian hyperstimulation syndrome(OHSS),characterized by more than 30 follicles measuring≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL.which was also the feature of women with established severe early OHSS followed by gonadotrophin-releasing hormone agonist(GnRHa)trigger and freeze-all policy that previously have been reported.All patients received a second dose of GnRHa 12 h after the first GnRHa trigger combined with administration of GnRH antagonist at 0.25 mg/day for a period of 3 days from the day of oocyte retrieval onwards.The in vitro fertilization(IVF)outcomes may be preferable compared with a bolus of GnRHa trigger and none of the included patients developed moderate-to-severe OHSS.Moreover,patients'symptoms,reproductive honnone levels and ultrasound findings were improved significantly.This new strategy seems to be efficacious and could be a further supplement of GnRHa trigger with or without applying freeze-all strategy to completely prevent early-onset moderate to severe OHSS,especially for the patients characterized by≥30 follicles measuring≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL.Further studies should be performed to compare this regimen with conventional methods of OHSS prevention.
文摘Background: This study aimed to determine if the gonadotropin releasing hormone (GnRH) antagonist protocol is optimal for expected poor ovarian responders with tubal factor undergoing in vitro fertilization-embryo transfer (IVF-ET). Methods: A total of 341 IVF-ET cycles were retrospectively identified. The following inclusion criteria were applied: age ≥ 40 years and patients with tubal factors. The cycles were divided into two groups: a GnRH antagonist group (157 cycles) and a GnRH agonist group (184 cycles). Results: The duration of stimulation and the total doses of gonadotropin in the GnRH agonist group were significantly more than those in the GnRH antagonist group (P < 0.05). There were significant differences in LH and P values on the hCG measurement days between the two groups (0.91 ± 1.17 vs. 4.82 ± 4.69 U/L and 0.69 ± 0.42 vs. 1.03 ± 0.50 ng/mL, P < 0.05). The implantation rate of the GnRH antagonist group was 12.24%, which was slightly higher than that of the GnRH agonist group (10.10%, P = 0.437). The clinical pregnancy rate of the two groups showed no statistical differences (23.36% vs. 23.03%, P = 1.000). Conclusion: For expected poor ovarian responders, the GnRH antagonist protocol was, to some extent, superior to the GnRH agonist protocol in terms of the implantation and clinical pregnancy rates.
文摘Background: To assess the effect of these two protocols in patients of different ages. Methods: 1923 in vitro fertilization and embryo transfer (IVF-ET) cycles were divided into two groups: a GnRH-ant protocol group and GnRH-a long protocol group, and then every group were subdivided into four age ranges. The general materials and IVF outcomes were compared. Results: The incidence of OHSS fluctuated from 0% to 2.37% with GnRH-ant protocol, which was significantly lower than another (P P Conclusion: The antagonist protocol should be considered in patients with a high ovarian response (e.g., PCOS patients) to avoid OHSS. Older patients (>35 years) could be treated with the antagonist protocol.
文摘Glucagon-like peptide1(GLP-1)is secreted from Langerhans cells in response to oral nutrient intake.Glucagon-like peptide-1 receptor agonists(GLP-1RAs)are a new class of incretin-based anti-diabetic drugs.They function to stimulate insulin secretion while suppressing glucagon secretion.GLP-1-based therapies are now well established in the management of type 2 diabetes mellitus(T2DM),and recent literature has suggested potential applications of these drugs in the treatment of obesity and for protection against cardiovascular and neurological diseases.As we know,along with change in lifestyles,the prevalence of non-alcoholic fatty liver disease(NAFLD)in China is rising more than that of viral hepatitis and alcoholic fatty liver disease,and NAFLD has become the most common chronic liver disease in recent years.Recent studies further suggest that GLP-1RAs can reduce transaminase levels to improve NAFLD by improving blood lipid levels,cutting down the fatcontent to promote fat redistribution,directly decreasing fatty degeneration of the liver,reducing the degree of liver fibrosis and improving inflammation.This review shows the NAFLD-associated effects of GLP-1RAs in animal models and in patients with T2DM or obesity who are participants in clinical trials.
文摘Glucagon-like peptide-1(GLP-1)receptor agonists result in greater improvements in glycemic control than placebo and promote weight loss with minimal hypoglycemia in patients with type 2 diabetes mellitus.A number of case reports show an association of GLP-1receptor agonists,mainly exenatide,with the development of acute kidney injury.The present review aims to present the available data regarding the effects of GLP-1 receptor agonists on renal function,their use in subjects with chronic renal failure and their possible association with acute kidney injury.Based on the current evidence,exenatide is eliminated by renal mechanisms and should not be given in patients with severe renal impairment or end stage renal disease.Liraglutide is not eliminated by renal or hepatic mechanisms,but it should be used with caution since there are only limited data in patients with renal or hepatic impairment.There is evidence from animal studies that GLP-1 receptor agonists exert protective role in diabetic nephropathy with mechanisms that seem to be independent of their glucose-lowering effect.Additionally,there is evidence that GLP-1 receptor agonists influence water and electrolyte balance.These effects may represent new ways to improve or even prevent diabetic nephropathy.
基金This work was supported by the Natural Science Foundation of Hubei Province (No.2017CFB262).
文摘This study aimed to investigate the effect of different gonadotropin-releasing hormone agonist (GnRH-a) administration methods on pregnancy outcomes of patients undergoing in-vitro fertilization-embryo transfer (IVF-ET). Clinical data of 5217 patients who underwent IVF-ET were retrospectively analyzed. Patients were divided into the long-acting GnRH-a group (n=1330) and the short-acting GnRH-a group (w=3887) based on their various treatment plans. The clinical and laboratory embryo data and clinical pregnancy outcomes were compared between the two groups. The results showed that there were no significant differences in the age, infertility, primary/secondary infertility rate, IVF rate, body mass index (BMI), antral follicle counting (AFC), folliclestimulating hormone (FSH) level, and the number of transplanted embryos between the two groups (P>0.05). There were no significant differences in the oocyte numbers, M II rate, fertilization rate, cleavage rate and blastocyst formation rate (P>0.05) between the two groups. The gonadotropin (Gn) using days, Gn dose and endometrial thickness were significantly greater in the long-acting GnRH-a group than those in the short-acting GnRH-a group (P<0.01). Additionally, the estradiol (E2) levels, blastocyst freezing rate, embryo utilization rate, transplant cancellation rate and abortion rate were significantly lower in the long-acting GnRH-a group than those in the shortacting GnRH-a group (P<0.01). The clinical pregnancy rate and embryo implantation rate were significantly higher in the long-acting GnRH-a group than in the short-acting GnRH-a group (P<O.Ol). It was concluded that use of long-acting GnRH-a can effectively reduce the transplant cancellation rate and improve the clinical pregnancy rate of the fresh cycle.
基金Supported by Taiwan Department of Health Clinical Trial and Re-search Center of Excellence No.MOHW103-TDU-B-212-113002
文摘AIM: To investigate the effects of 17β-estradiol via estrogen receptors(ER) or direct administration of ER agonists on human colorectal cancer. METHODS: Lo Vo cells were established from the Bioresource Collection and Research Center and cultured in phenol red-free DMEM(Sigma, United States). To investigate the effects of E2 and/or ER selective agonists on cellular proliferation, Lo Vo colorectal cells were treated with E2 or ER-selective agonists for 24 h and 48 h and subjected to the MTT(Sigma) assay to find the concentration. And investigate the effects of E2 and/or ER selective agonists on cell used western immunoblotting to find out the diversification of signaling pathways. In order to observe motility and migration the wound healing assay and a transwell chamber(Neuro Probe) plate were tased. For a quantitative measure, we counted the number of migrating cells to the wound area post-wounding for 24 h. We further examined the cellular migration-regulating factors urokinase-type plasminogen activator(u-PA), tissue-type plasminogen activator(t-PA) and matrix metalloproteinase(MMP)-9 in human Lo Vo cells so gelatin zymography that we used and gelatinolytic activity was visualized by Coomassie blue staining. And these results are presented as means ± SE, and statistical comparisons were made using Student's t-test.RESULTS: The structure was first compared with E2 and ER agonists. We then treated the Lo Vo cells with E2 and ER agonists(10-8 mol/L) for 24 h and 48 h and subsequently measured the cell viability using MTT assay. Our results showed that treatment with 17β-estradiol and/or ER agonists in human Lo Vo colorectal cancer cells activated p53 and then up-regulated p21 and p27 protein levels, subsequently inhibiting the downstream target gene, cyclin D1, which regulates cell proliferation. Taken together, our findings demonstrate the anti-tumorigenesis effects of 17β-estradiol and/or ER agonists and suggest that these compounds may prove to be a potential alternative therapy in the treatment of human colorectal cancer. These results demonstrate that 17β-estradiol and/or ER agonists downregulate migration-related proteins through the p53 signaling pathway in human Lo Vo colorectal cancer cells. These findings suggest that p53 plays a critical role in the 17β-estradiol and/or ER agonist-mediated protective activity against colorectal cancer progression. In addition, 17β-estradiol and/or ER agonists dramatically inhibited cell migration and reduced the expression of u-PA, t-PA and MMP-9 as well as MMP-2/9 activity in Lo Vo cells, which regulate cell metastasis. Moreover, we observed that pretreatment with a p53 inhibitor significantly blocked the anti-migration effects of E2 and/or ER agonists on Lo Vo cells. That E2 and/or ER agonists may impair Lo Vo cell migration by modulating migration-related factors via the p53 tumor suppressor gene.CONCLUSION: Direct ER treatment may prove to be an attractive alternative therapy in the treatment of human colorectal tumors in the future.
