Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

The breakage pattern of unit particles during the production of oral solid dosage forms (OSD) is closely related to the quality of intermediate or final products. To accurately characterize the particles and study the evolution law of particle breakage, the Bonding model of the discrete element method (DEM) was used to investigate the breakage patterns of model parameters, particle shape and process conditions (loading mode and loading rate) on the dynamic breakage, force-time curve, breakage rate, maximum breakage size ratio and fracture strength of particles. The results showed that the particle breakage force was positively correlated with normal strength and bonded disk scale, negatively correlated with normal stiffness per unit area and tangential stiffness per unit area, and weakly correlated with tangential strength. The particle breakage rate was negatively correlated with the aspect ratio of the particles, and the maximum breakage size ratio was positively correlated with the aspect ratio of the particles; among the three loading modes, the breakage rate of compression breakage model was the largest, the breakage rate of shear breakage model was the second largest, and the breakage rate of wear breakage model was the smallest; the maximum breakage size ratio was positively correlated with the loading rate, the loading mode and the loading rate had no mutual influence on particle breakage rate, but had mutual influence on the maximum breakage size ratio. The research results will provide a theoretical basis for the shift of OSD from batch manufacturing to advanced manufacturing.

Objective:The study aimed to investigate the factors of pregnancy failures in patients with low ser-um anti-Müllerian hormone(AMH)level after in vitro fertilization(IVF)or intracytoplasmic sperm injection(ICSI).Method:The clinical outcome of 1184 cycles in 931 patients with serum AMH＜1.1 ng/ml undergoing IVF/ICSI at the Department of Reproductive Medicine of West China Second Hospital,Sichuan University between January 1,2020 and December 31,2020,was retrospectively studied.In total,503 patients(525 cycles)underwent embryo transfer,including clinical pregnant group in 193 patients(193 cycles)and clinical non-pregnant group in 310 pa-tients(332 cycles).All of the patients were divided into three different groups according to their chronological age(＜35,35-＜40,40-51 years old)and five different serum AMH levels(＜0.06 ng/ml,0.06-＜0.20 ng/ml,0.20-＜0.50 ng/ml,0.50-＜0.80 ng/ml,0.80-＜1.10 ng/ml),to explore the relationship with IVF pregnancy outcomes.Multivariate Logistic regression analysis was carried out to explore factors affecting pregnancy out-comes afer IVF/ICSI.Results:①Compared with the clinical pregnancy group,the clinical non-pregnant patients were older,AMH level and antral follicle count(AFC)were lower,the number of MII,2PN,available embryos and top quality embryos were also lower,and endometrial thickness at oocyte pickup(OPU)was thinner,and differ-ences above were statistically significant(P＜0.05).②AMH level,AFC,BMI,total Gn and MII number were signifi-cantly different among different age groups(P＜0.05).The clinical pregnancy rate per transplantation cycle,per oocyte pickup cycle and per ovulation induction cycle also had statistically significant differences(P＜0.001),and the pregnancy rate showed a decreasing trend with the increase of age.③There were significant differences in clinical pregnancy rate per transplantation cycle,per oocyte pickup cycle and per ovulation induction cycle among different ranges of low level AMH(P＜0.05).④Multivariable Logistic regression analysis confirmed that the prob-ability of pregnancy in patients with low AMH level after transfering embryo was significantly affected by patients'age(P=0.002).Receiver operating characteristic(ROC)curve showed that the best cut-off value for predicting clinical pregnancy was 35.5 years,the area under the curve(AUC)was 0.634(95%CI 0.586-0.682,P＜0.001).Conclusions:Patients with low AMH level(＜1.1 ng/ml)still have a good chance of pregnancy after IVF/ICSI treatment,and the most notable influencing factor is the patient's chronological age,rather than AMH.When the actual age of patients is less than 35.5 years,the clinical pregnancy outcome after transferring embryo is better e-ven with low AMH level.

Objective:The study aimed to investigate the factors of pregnancy failures in patients with low ser-um anti-Müllerian hormone(AMH)level after in vitro fertilization(IVF)or intracytoplasmic sperm injection(ICSI).Method:The clinical outcome of 1184 cycles in 931 patients with serum AMH＜1.1 ng/ml undergoing IVF/ICSI at the Department of Reproductive Medicine of West China Second Hospital,Sichuan University between January 1,2020 and December 31,2020,was retrospectively studied.In total,503 patients(525 cycles)underwent embryo transfer,including clinical pregnant group in 193 patients(193 cycles)and clinical non-pregnant group in 310 pa-tients(332 cycles).All of the patients were divided into three different groups according to their chronological age(＜35,35-＜40,40-51 years old)and five different serum AMH levels(＜0.06 ng/ml,0.06-＜0.20 ng/ml,0.20-＜0.50 ng/ml,0.50-＜0.80 ng/ml,0.80-＜1.10 ng/ml),to explore the relationship with IVF pregnancy outcomes.Multivariate Logistic regression analysis was carried out to explore factors affecting pregnancy out-comes afer IVF/ICSI.Results:①Compared with the clinical pregnancy group,the clinical non-pregnant patients were older,AMH level and antral follicle count(AFC)were lower,the number of MII,2PN,available embryos and top quality embryos were also lower,and endometrial thickness at oocyte pickup(OPU)was thinner,and differ-ences above were statistically significant(P＜0.05).②AMH level,AFC,BMI,total Gn and MII number were signifi-cantly different among different age groups(P＜0.05).The clinical pregnancy rate per transplantation cycle,per oocyte pickup cycle and per ovulation induction cycle also had statistically significant differences(P＜0.001),and the pregnancy rate showed a decreasing trend with the increase of age.③There were significant differences in clinical pregnancy rate per transplantation cycle,per oocyte pickup cycle and per ovulation induction cycle among different ranges of low level AMH(P＜0.05).④Multivariable Logistic regression analysis confirmed that the prob-ability of pregnancy in patients with low AMH level after transfering embryo was significantly affected by patients'age(P=0.002).Receiver operating characteristic(ROC)curve showed that the best cut-off value for predicting clinical pregnancy was 35.5 years,the area under the curve(AUC)was 0.634(95%CI 0.586-0.682,P＜0.001).Conclusions:Patients with low AMH level(＜1.1 ng/ml)still have a good chance of pregnancy after IVF/ICSI treatment,and the most notable influencing factor is the patient's chronological age,rather than AMH.When the actual age of patients is less than 35.5 years,the clinical pregnancy outcome after transferring embryo is better e-ven with low AMH level.

Objective:The study aimed to investigate the factors of pregnancy failures in patients with low ser-um anti-Müllerian hormone(AMH)level after in vitro fertilization(IVF)or intracytoplasmic sperm injection(ICSI).Method:The clinical outcome of 1184 cycles in 931 patients with serum AMH＜1.1 ng/ml undergoing IVF/ICSI at the Department of Reproductive Medicine of West China Second Hospital,Sichuan University between January 1,2020 and December 31,2020,was retrospectively studied.In total,503 patients(525 cycles)underwent embryo transfer,including clinical pregnant group in 193 patients(193 cycles)and clinical non-pregnant group in 310 pa-tients(332 cycles).All of the patients were divided into three different groups according to their chronological age(＜35,35-＜40,40-51 years old)and five different serum AMH levels(＜0.06 ng/ml,0.06-＜0.20 ng/ml,0.20-＜0.50 ng/ml,0.50-＜0.80 ng/ml,0.80-＜1.10 ng/ml),to explore the relationship with IVF pregnancy outcomes.Multivariate Logistic regression analysis was carried out to explore factors affecting pregnancy out-comes afer IVF/ICSI.Results:①Compared with the clinical pregnancy group,the clinical non-pregnant patients were older,AMH level and antral follicle count(AFC)were lower,the number of MII,2PN,available embryos and top quality embryos were also lower,and endometrial thickness at oocyte pickup(OPU)was thinner,and differ-ences above were statistically significant(P＜0.05).②AMH level,AFC,BMI,total Gn and MII number were signifi-cantly different among different age groups(P＜0.05).The clinical pregnancy rate per transplantation cycle,per oocyte pickup cycle and per ovulation induction cycle also had statistically significant differences(P＜0.001),and the pregnancy rate showed a decreasing trend with the increase of age.③There were significant differences in clinical pregnancy rate per transplantation cycle,per oocyte pickup cycle and per ovulation induction cycle among different ranges of low level AMH(P＜0.05).④Multivariable Logistic regression analysis confirmed that the prob-ability of pregnancy in patients with low AMH level after transfering embryo was significantly affected by patients'age(P=0.002).Receiver operating characteristic(ROC)curve showed that the best cut-off value for predicting clinical pregnancy was 35.5 years,the area under the curve(AUC)was 0.634(95%CI 0.586-0.682,P＜0.001).Conclusions:Patients with low AMH level(＜1.1 ng/ml)still have a good chance of pregnancy after IVF/ICSI treatment,and the most notable influencing factor is the patient's chronological age,rather than AMH.When the actual age of patients is less than 35.5 years,the clinical pregnancy outcome after transferring embryo is better e-ven with low AMH level.

Objective:The study aimed to investigate the factors of pregnancy failures in patients with low ser-um anti-Müllerian hormone(AMH)level after in vitro fertilization(IVF)or intracytoplasmic sperm injection(ICSI).Method:The clinical outcome of 1184 cycles in 931 patients with serum AMH＜1.1 ng/ml undergoing IVF/ICSI at the Department of Reproductive Medicine of West China Second Hospital,Sichuan University between January 1,2020 and December 31,2020,was retrospectively studied.In total,503 patients(525 cycles)underwent embryo transfer,including clinical pregnant group in 193 patients(193 cycles)and clinical non-pregnant group in 310 pa-tients(332 cycles).All of the patients were divided into three different groups according to their chronological age(＜35,35-＜40,40-51 years old)and five different serum AMH levels(＜0.06 ng/ml,0.06-＜0.20 ng/ml,0.20-＜0.50 ng/ml,0.50-＜0.80 ng/ml,0.80-＜1.10 ng/ml),to explore the relationship with IVF pregnancy outcomes.Multivariate Logistic regression analysis was carried out to explore factors affecting pregnancy out-comes afer IVF/ICSI.Results:①Compared with the clinical pregnancy group,the clinical non-pregnant patients were older,AMH level and antral follicle count(AFC)were lower,the number of MII,2PN,available embryos and top quality embryos were also lower,and endometrial thickness at oocyte pickup(OPU)was thinner,and differ-ences above were statistically significant(P＜0.05).②AMH level,AFC,BMI,total Gn and MII number were signifi-cantly different among different age groups(P＜0.05).The clinical pregnancy rate per transplantation cycle,per oocyte pickup cycle and per ovulation induction cycle also had statistically significant differences(P＜0.001),and the pregnancy rate showed a decreasing trend with the increase of age.③There were significant differences in clinical pregnancy rate per transplantation cycle,per oocyte pickup cycle and per ovulation induction cycle among different ranges of low level AMH(P＜0.05).④Multivariable Logistic regression analysis confirmed that the prob-ability of pregnancy in patients with low AMH level after transfering embryo was significantly affected by patients'age(P=0.002).Receiver operating characteristic(ROC)curve showed that the best cut-off value for predicting clinical pregnancy was 35.5 years,the area under the curve(AUC)was 0.634(95%CI 0.586-0.682,P＜0.001).Conclusions:Patients with low AMH level(＜1.1 ng/ml)still have a good chance of pregnancy after IVF/ICSI treatment,and the most notable influencing factor is the patient's chronological age,rather than AMH.When the actual age of patients is less than 35.5 years,the clinical pregnancy outcome after transferring embryo is better e-ven with low AMH level.

Objective:The study aimed to investigate the factors of pregnancy failures in patients with low ser-um anti-Müllerian hormone(AMH)level after in vitro fertilization(IVF)or intracytoplasmic sperm injection(ICSI).Method:The clinical outcome of 1184 cycles in 931 patients with serum AMH＜1.1 ng/ml undergoing IVF/ICSI at the Department of Reproductive Medicine of West China Second Hospital,Sichuan University between January 1,2020 and December 31,2020,was retrospectively studied.In total,503 patients(525 cycles)underwent embryo transfer,including clinical pregnant group in 193 patients(193 cycles)and clinical non-pregnant group in 310 pa-tients(332 cycles).All of the patients were divided into three different groups according to their chronological age(＜35,35-＜40,40-51 years old)and five different serum AMH levels(＜0.06 ng/ml,0.06-＜0.20 ng/ml,0.20-＜0.50 ng/ml,0.50-＜0.80 ng/ml,0.80-＜1.10 ng/ml),to explore the relationship with IVF pregnancy outcomes.Multivariate Logistic regression analysis was carried out to explore factors affecting pregnancy out-comes afer IVF/ICSI.Results:①Compared with the clinical pregnancy group,the clinical non-pregnant patients were older,AMH level and antral follicle count(AFC)were lower,the number of MII,2PN,available embryos and top quality embryos were also lower,and endometrial thickness at oocyte pickup(OPU)was thinner,and differ-ences above were statistically significant(P＜0.05).②AMH level,AFC,BMI,total Gn and MII number were signifi-cantly different among different age groups(P＜0.05).The clinical pregnancy rate per transplantation cycle,per oocyte pickup cycle and per ovulation induction cycle also had statistically significant differences(P＜0.001),and the pregnancy rate showed a decreasing trend with the increase of age.③There were significant differences in clinical pregnancy rate per transplantation cycle,per oocyte pickup cycle and per ovulation induction cycle among different ranges of low level AMH(P＜0.05).④Multivariable Logistic regression analysis confirmed that the prob-ability of pregnancy in patients with low AMH level after transfering embryo was significantly affected by patients'age(P=0.002).Receiver operating characteristic(ROC)curve showed that the best cut-off value for predicting clinical pregnancy was 35.5 years,the area under the curve(AUC)was 0.634(95%CI 0.586-0.682,P＜0.001).Conclusions:Patients with low AMH level(＜1.1 ng/ml)still have a good chance of pregnancy after IVF/ICSI treatment,and the most notable influencing factor is the patient's chronological age,rather than AMH.When the actual age of patients is less than 35.5 years,the clinical pregnancy outcome after transferring embryo is better e-ven with low AMH level.

Objective:The study aimed to investigate the factors of pregnancy failures in patients with low ser-um anti-Müllerian hormone(AMH)level after in vitro fertilization(IVF)or intracytoplasmic sperm injection(ICSI).Method:The clinical outcome of 1184 cycles in 931 patients with serum AMH＜1.1 ng/ml undergoing IVF/ICSI at the Department of Reproductive Medicine of West China Second Hospital,Sichuan University between January 1,2020 and December 31,2020,was retrospectively studied.In total,503 patients(525 cycles)underwent embryo transfer,including clinical pregnant group in 193 patients(193 cycles)and clinical non-pregnant group in 310 pa-tients(332 cycles).All of the patients were divided into three different groups according to their chronological age(＜35,35-＜40,40-51 years old)and five different serum AMH levels(＜0.06 ng/ml,0.06-＜0.20 ng/ml,0.20-＜0.50 ng/ml,0.50-＜0.80 ng/ml,0.80-＜1.10 ng/ml),to explore the relationship with IVF pregnancy outcomes.Multivariate Logistic regression analysis was carried out to explore factors affecting pregnancy out-comes afer IVF/ICSI.Results:①Compared with the clinical pregnancy group,the clinical non-pregnant patients were older,AMH level and antral follicle count(AFC)were lower,the number of MII,2PN,available embryos and top quality embryos were also lower,and endometrial thickness at oocyte pickup(OPU)was thinner,and differ-ences above were statistically significant(P＜0.05).②AMH level,AFC,BMI,total Gn and MII number were signifi-cantly different among different age groups(P＜0.05).The clinical pregnancy rate per transplantation cycle,per oocyte pickup cycle and per ovulation induction cycle also had statistically significant differences(P＜0.001),and the pregnancy rate showed a decreasing trend with the increase of age.③There were significant differences in clinical pregnancy rate per transplantation cycle,per oocyte pickup cycle and per ovulation induction cycle among different ranges of low level AMH(P＜0.05).④Multivariable Logistic regression analysis confirmed that the prob-ability of pregnancy in patients with low AMH level after transfering embryo was significantly affected by patients'age(P=0.002).Receiver operating characteristic(ROC)curve showed that the best cut-off value for predicting clinical pregnancy was 35.5 years,the area under the curve(AUC)was 0.634(95%CI 0.586-0.682,P＜0.001).Conclusions:Patients with low AMH level(＜1.1 ng/ml)still have a good chance of pregnancy after IVF/ICSI treatment,and the most notable influencing factor is the patient's chronological age,rather than AMH.When the actual age of patients is less than 35.5 years,the clinical pregnancy outcome after transferring embryo is better e-ven with low AMH level.

Objective:The study aimed to investigate the factors of pregnancy failures in patients with low ser-um anti-Müllerian hormone(AMH)level after in vitro fertilization(IVF)or intracytoplasmic sperm injection(ICSI).Method:The clinical outcome of 1184 cycles in 931 patients with serum AMH＜1.1 ng/ml undergoing IVF/ICSI at the Department of Reproductive Medicine of West China Second Hospital,Sichuan University between January 1,2020 and December 31,2020,was retrospectively studied.In total,503 patients(525 cycles)underwent embryo transfer,including clinical pregnant group in 193 patients(193 cycles)and clinical non-pregnant group in 310 pa-tients(332 cycles).All of the patients were divided into three different groups according to their chronological age(＜35,35-＜40,40-51 years old)and five different serum AMH levels(＜0.06 ng/ml,0.06-＜0.20 ng/ml,0.20-＜0.50 ng/ml,0.50-＜0.80 ng/ml,0.80-＜1.10 ng/ml),to explore the relationship with IVF pregnancy outcomes.Multivariate Logistic regression analysis was carried out to explore factors affecting pregnancy out-comes afer IVF/ICSI.Results:①Compared with the clinical pregnancy group,the clinical non-pregnant patients were older,AMH level and antral follicle count(AFC)were lower,the number of MII,2PN,available embryos and top quality embryos were also lower,and endometrial thickness at oocyte pickup(OPU)was thinner,and differ-ences above were statistically significant(P＜0.05).②AMH level,AFC,BMI,total Gn and MII number were signifi-cantly different among different age groups(P＜0.05).The clinical pregnancy rate per transplantation cycle,per oocyte pickup cycle and per ovulation induction cycle also had statistically significant differences(P＜0.001),and the pregnancy rate showed a decreasing trend with the increase of age.③There were significant differences in clinical pregnancy rate per transplantation cycle,per oocyte pickup cycle and per ovulation induction cycle among different ranges of low level AMH(P＜0.05).④Multivariable Logistic regression analysis confirmed that the prob-ability of pregnancy in patients with low AMH level after transfering embryo was significantly affected by patients'age(P=0.002).Receiver operating characteristic(ROC)curve showed that the best cut-off value for predicting clinical pregnancy was 35.5 years,the area under the curve(AUC)was 0.634(95%CI 0.586-0.682,P＜0.001).Conclusions:Patients with low AMH level(＜1.1 ng/ml)still have a good chance of pregnancy after IVF/ICSI treatment,and the most notable influencing factor is the patient's chronological age,rather than AMH.When the actual age of patients is less than 35.5 years,the clinical pregnancy outcome after transferring embryo is better e-ven with low AMH level.

Objective:The study aimed to investigate the factors of pregnancy failures in patients with low ser-um anti-Müllerian hormone(AMH)level after in vitro fertilization(IVF)or intracytoplasmic sperm injection(ICSI).Method:The clinical outcome of 1184 cycles in 931 patients with serum AMH＜1.1 ng/ml undergoing IVF/ICSI at the Department of Reproductive Medicine of West China Second Hospital,Sichuan University between January 1,2020 and December 31,2020,was retrospectively studied.In total,503 patients(525 cycles)underwent embryo transfer,including clinical pregnant group in 193 patients(193 cycles)and clinical non-pregnant group in 310 pa-tients(332 cycles).All of the patients were divided into three different groups according to their chronological age(＜35,35-＜40,40-51 years old)and five different serum AMH levels(＜0.06 ng/ml,0.06-＜0.20 ng/ml,0.20-＜0.50 ng/ml,0.50-＜0.80 ng/ml,0.80-＜1.10 ng/ml),to explore the relationship with IVF pregnancy outcomes.Multivariate Logistic regression analysis was carried out to explore factors affecting pregnancy out-comes afer IVF/ICSI.Results:①Compared with the clinical pregnancy group,the clinical non-pregnant patients were older,AMH level and antral follicle count(AFC)were lower,the number of MII,2PN,available embryos and top quality embryos were also lower,and endometrial thickness at oocyte pickup(OPU)was thinner,and differ-ences above were statistically significant(P＜0.05).②AMH level,AFC,BMI,total Gn and MII number were signifi-cantly different among different age groups(P＜0.05).The clinical pregnancy rate per transplantation cycle,per oocyte pickup cycle and per ovulation induction cycle also had statistically significant differences(P＜0.001),and the pregnancy rate showed a decreasing trend with the increase of age.③There were significant differences in clinical pregnancy rate per transplantation cycle,per oocyte pickup cycle and per ovulation induction cycle among different ranges of low level AMH(P＜0.05).④Multivariable Logistic regression analysis confirmed that the prob-ability of pregnancy in patients with low AMH level after transfering embryo was significantly affected by patients'age(P=0.002).Receiver operating characteristic(ROC)curve showed that the best cut-off value for predicting clinical pregnancy was 35.5 years,the area under the curve(AUC)was 0.634(95%CI 0.586-0.682,P＜0.001).Conclusions:Patients with low AMH level(＜1.1 ng/ml)still have a good chance of pregnancy after IVF/ICSI treatment,and the most notable influencing factor is the patient's chronological age,rather than AMH.When the actual age of patients is less than 35.5 years,the clinical pregnancy outcome after transferring embryo is better e-ven with low AMH level.