Pregnancy in women with monogenic diabetes is potentially complex,with significant implications for both maternal and fetal health.Among these,maturity-onset diabetes of the young(MODY)stands out as a prevalent monoge...Pregnancy in women with monogenic diabetes is potentially complex,with significant implications for both maternal and fetal health.Among these,maturity-onset diabetes of the young(MODY)stands out as a prevalent monogenic diabetes subtype frequently encountered in clinical practice.Each subtype of MODY requires a distinct approach tailored to the pregnancy,diverging from management strategies in non-pregnant individuals.Glucokinase MODY(GCK-MODY)typically does not require treatment outside of pregnancy,but special considerations arise when a woman with GCK-MODY becomes pregnant.The glycemic targets in GCK-MODY pregnancies are not exclusively dictated by the maternal/paternal MODY genotype but are also influenced by the genotype of the developing fetus.During pregnancy,the choice between sulfonylurea or insulin for treating hepatocyte nuclear factor 1-alpha(HNF1A)-MODY and HNF4A-MODY depends on the mother’s specific circumstances and the available expertise.Management of other rarer MODY subtypes is individu-alized,with decisions made on a case-by-case basis.Therefore,a collaborative approach involving expert diabetes and obstetric teams is crucial for the compre-hensive management of MODY pregnancies.展开更多
Cell transplantation has come to the forefront of regenerative medicine alongside the discovery and application of stem cells in both research and clinical settings.There are several types of stem cells currently bein...Cell transplantation has come to the forefront of regenerative medicine alongside the discovery and application of stem cells in both research and clinical settings.There are several types of stem cells currently being used for pre-clinical regenerative therapies,each with unique characteristics,benefits and limitations.This brief review will focus on recent basic science advancements made with embryonic stem cells and induced pluripotent stem cells.Both embryonic stem cells and induced pluripotent stem cells provide platforms for new neurons to replace dead and/or dying cells following injury.Due to their capacity for reprogramming and differentiation into any neuronal type,research in preclinical rodent models has shown that embryonic stem cells and induced pluripotent stem cells can integrate,survive and form connections in the nervous system similar to de novo cells.Going forward however,there are some limitations to consider with the use of either stem cell type.Ethically,embryonic stem cells are not an ideal source of cells,genetically,induced pluripotent stem cells are not ideal in terms of personalized treatment for those with certain genetic diseases the latter of which may guide regenerative medicine away from personalized stem cell based therapies and into optimized stem cell banks.Nonetheless,the potential of these stem cells in central nervous system regenerative therapy is only beginning to be appreciated.For example,through genetic modification,stem cells serve as ideal platforms to reintroduce missing or downregulated molecules into the nervous system to further induce regenerative growth.In this review,we highlight the limitations of stem cell based therapies whilst discussing some of the means of overcoming these limitations.展开更多
Inhibitions or blockages of ligand-receptor interactions on cancer cell surfaces by exogenous competetors or antibodies often result in apoptosis or “programmed cell death.” The underlying mechanisms of action for c...Inhibitions or blockages of ligand-receptor interactions on cancer cell surfaces by exogenous competetors or antibodies often result in apoptosis or “programmed cell death.” The underlying mechanisms of action for cellular apoptosis depend greatly on the molecular nature of specific ligand-receptor interactions and the signal transduction pathways involved. Two such unrelated systems which are potentially involved in apoptosis of cancer cells are described in this review. They are, respectively, gonadotropinreleasing hormone (GnRH) receptor and cancerous immunoglobulins, or CA215, both of which are widely expressed on the surface of cancer cells from diversified tissue origins. Bindings of GnRH or its decapeptide analogs as ligands to GnRH receptor were known to induce apoptosis of several extrapituitary cell types in gonadal tissues, as well as different cancer cells. Monoclonal antibodies against the GnRH receptor of cancer cells were shown to induce apoptosis, similar to the action of GnRH analogs. In contrast, RP215 monoclonal antibody reacts specifically with the carbohydrate-associated epitope of cancerous immunoglobulins and is known to induce apoptosis of cancer cells in vitro. It also causes growth inhibition of tumor cells in nude mouse experimental models. Elucidations of the specific mechanisms of apoptosis in cancer cells of these two molecular interaction systems will not only lead to a better understanding of cancer biology but also benefit patients in cancer monitoring and therapy.展开更多
Overnutrition causes hyperactivation of mTORC1-dependent negative feedback loops leading to the downregulation of insulin signaling and development of insulin resistance.In osteoblasts(OBs),insulin signaling plays a c...Overnutrition causes hyperactivation of mTORC1-dependent negative feedback loops leading to the downregulation of insulin signaling and development of insulin resistance.In osteoblasts(OBs),insulin signaling plays a crucial role in the control of systemic glucose homeostasis.We utilized mice with conditional deletion of Rptor to investigate how the loss of mTORC1 function in OB affects glucose metabolism under normal and overnutrition dietary states.Compared to the controls,chow-fed Rptorob−/−mice had substantially less fat mass and exhibited adipocyte hyperplasia.Remarkably,upon feeding with high-fat diet,mice with pre-and post-natal deletion of Rptor in OBs were protected from diet-induced obesity and exhibited improved glucose metabolism with lower fasting glucose and insulin levels,increased glucose tolerance and insulin sensitivity.This leanness and resistance to weight gain was not attributable to changes in food intake,physical activity or lipid absorption but instead was due to increased energy expenditure and greater whole-body substrate flexibility.RNA-seq revealed an increase in glycolysis and skeletal insulin signaling pathways,which correlated with the potentiation of insulin signaling and increased insulin-dependent glucose uptake in Rptorknockout osteoblasts.Collectively,these findings point to a critical role for the mTORC1 complex in the skeletal regulation of wholebody glucose metabolism and the skeletal development of insulin resistance.展开更多
Objective To compare the efficacy and safety of medical abortion of different regimens for termination of pregnancy at 8-16 weeks of gestation. Methods Healthy pregnant women requesting medical abortion at 8-16 weeks...Objective To compare the efficacy and safety of medical abortion of different regimens for termination of pregnancy at 8-16 weeks of gestation. Methods Healthy pregnant women requesting medical abortion at 8-16 weeks＇ gestation within 12 hospitals in Shanghai were randomly allocated to four treatment groups. Three intervention groups were given mifepristone 200 mg as a single dose then 24 h later misoprostol 600 #g at 3 h intervals vaginally, orally or vaginally followed by orally, respectively. Control group was given mifepristone 100 mg for 2 d, followed at 48 h by initiation of misoprostol 600 μg vaginally every 12 h. The primary outcome measures were the successful abortion rate, the induction-to-abortion interval, vaginal bleeding and side effects. Results Efficacy outcomes were analyzed for 1 112 women （92.67%）, excluding 88 protocol violations. Termination successful rates were similar among the four groups from 97.1% to 97.8%. The average dose of misoprostol and the incidence of side effects in control group were lower than those in three intervention groups. Stratified analysis showed that the interval of induction-to-abortion at gestation of 1116 weeks was decreased in control group. Conclusion The four regimens have the similar termination successful rates in spite of different administration intervals or routes. Control group was recommended for the advantages of reduced dose of misoprostol and fewer side effects.展开更多
Alow-calorie diet in a group of overweight or obese patients for a short period before and during IVF results in variable tolerance to the dietary regime and an unsatisfactory IVF outcome.
To assess the side effects and the continuation rate of combined oral contraceptive （COC） containing desogestrel （Marvelon） during 12 months. Methods This was a post-marketing surveillance study on Marvelon COC am...To assess the side effects and the continuation rate of combined oral contraceptive （COC） containing desogestrel （Marvelon） during 12 months. Methods This was a post-marketing surveillance study on Marvelon COC among 870 healthy rural women in 5 different counties of Jiangsu Province during 12 months. Results About 24.02% of the women who used Marvelon COC experienced side effects during 12 months. Gastrointestinal disorder, bleeding/spotting and chloasma were ranked the first three in the side effects. The rate of side effects of Marvelon COC users during the first 3 months in southern area of Jiangsu was significantly higher than that of users in northern area of Jiangsu. Most of the users did not experience obvious weight changes i.e., loss or increase in weight of more than 5 kg during 12 months. Blood pressure and biochemical indicators of almost 99% among users were within the normal range. The gross cumulative continuation rate for 12 months was 83.14%; the most common medical reason for discontinuation was gastrointestinal disorder. There was an increased risk of discontinuation use among women with lower educational level. Conclusion Marvelon COC brought fewer side effects and was well accepted when applied in Chinese rural women.展开更多
In Europe,population ageing poses a challenge.Given accelerating population ageing in Europe,longterm care(LTC)is a growing concern.Unmet healthcare needs varied among European countries during the coronavirus disease...In Europe,population ageing poses a challenge.Given accelerating population ageing in Europe,longterm care(LTC)is a growing concern.Unmet healthcare needs varied among European countries during the coronavirus disease 2019(COVID-19)pandemic,and greater attention should be paid to ensuring that the healthcare needs of vulnerable populations are met.Notably,developing common and comparable indicators is useful for monitoring the LTC and healthcare of older adults at the national and international levels,and understanding the reasons for the differences in indicators between European countries could shed light on how to improve the health of older adults.展开更多
Acute epididymitis represents a common medical condition in the urological outpatient clinic. Mostly, epididymitis is caused by bacterial ascent through the urogenital tract, with pathogens originating either from sex...Acute epididymitis represents a common medical condition in the urological outpatient clinic. Mostly, epididymitis is caused by bacterial ascent through the urogenital tract, with pathogens originating either from sexually transmitted diseases or urinary tract infections. Although conservative antimicrobial therapy is possible in the majority of patients and is usually sufficient to eradicate the pathogen, studies have shown persistent oligozoospermia and azoospermia in up to 40% of these patients. Animal models of epididymitis are created to delineate the underlying reasons for this observation and the additional impairment of sperm function that is often associated with the disease. Accumulated data provide evidence of a differential expression of immune cells, immunoregulatory genes and pathogen-sensing molecules along the length of the epididymal duct. The evidence suggests that a tolerogenic environment exists in the caput epididymidis, but that inflammatory responses are most intense toward the cauda epididymidis. This is consistent with the need to provide protection for the neo-antigens of spermatozoa emerging from the testis, without compromising the ability to respond to ascending infections. However, severe inflammatory responses, particularly in the cauda, may lead to collateral damage to the structure and function of the epididymis. Convergence of the clinical observations with appropriate animal studies should lead to better understanding of the immunological environment throughout the epididymis, the parameters underlying susceptibility to epididymitis, and to therapeutic approaches that can mitigate epididymal damage and subsequent fertility problems.展开更多
文摘Pregnancy in women with monogenic diabetes is potentially complex,with significant implications for both maternal and fetal health.Among these,maturity-onset diabetes of the young(MODY)stands out as a prevalent monogenic diabetes subtype frequently encountered in clinical practice.Each subtype of MODY requires a distinct approach tailored to the pregnancy,diverging from management strategies in non-pregnant individuals.Glucokinase MODY(GCK-MODY)typically does not require treatment outside of pregnancy,but special considerations arise when a woman with GCK-MODY becomes pregnant.The glycemic targets in GCK-MODY pregnancies are not exclusively dictated by the maternal/paternal MODY genotype but are also influenced by the genotype of the developing fetus.During pregnancy,the choice between sulfonylurea or insulin for treating hepatocyte nuclear factor 1-alpha(HNF1A)-MODY and HNF4A-MODY depends on the mother’s specific circumstances and the available expertise.Management of other rarer MODY subtypes is individu-alized,with decisions made on a case-by-case basis.Therefore,a collaborative approach involving expert diabetes and obstetric teams is crucial for the compre-hensive management of MODY pregnancies.
基金This work was supported by the Wessex Medical Research Trust and the Biotechnology and Biological Research Council(both to MRA).
文摘Cell transplantation has come to the forefront of regenerative medicine alongside the discovery and application of stem cells in both research and clinical settings.There are several types of stem cells currently being used for pre-clinical regenerative therapies,each with unique characteristics,benefits and limitations.This brief review will focus on recent basic science advancements made with embryonic stem cells and induced pluripotent stem cells.Both embryonic stem cells and induced pluripotent stem cells provide platforms for new neurons to replace dead and/or dying cells following injury.Due to their capacity for reprogramming and differentiation into any neuronal type,research in preclinical rodent models has shown that embryonic stem cells and induced pluripotent stem cells can integrate,survive and form connections in the nervous system similar to de novo cells.Going forward however,there are some limitations to consider with the use of either stem cell type.Ethically,embryonic stem cells are not an ideal source of cells,genetically,induced pluripotent stem cells are not ideal in terms of personalized treatment for those with certain genetic diseases the latter of which may guide regenerative medicine away from personalized stem cell based therapies and into optimized stem cell banks.Nonetheless,the potential of these stem cells in central nervous system regenerative therapy is only beginning to be appreciated.For example,through genetic modification,stem cells serve as ideal platforms to reintroduce missing or downregulated molecules into the nervous system to further induce regenerative growth.In this review,we highlight the limitations of stem cell based therapies whilst discussing some of the means of overcoming these limitations.
文摘Inhibitions or blockages of ligand-receptor interactions on cancer cell surfaces by exogenous competetors or antibodies often result in apoptosis or “programmed cell death.” The underlying mechanisms of action for cellular apoptosis depend greatly on the molecular nature of specific ligand-receptor interactions and the signal transduction pathways involved. Two such unrelated systems which are potentially involved in apoptosis of cancer cells are described in this review. They are, respectively, gonadotropinreleasing hormone (GnRH) receptor and cancerous immunoglobulins, or CA215, both of which are widely expressed on the surface of cancer cells from diversified tissue origins. Bindings of GnRH or its decapeptide analogs as ligands to GnRH receptor were known to induce apoptosis of several extrapituitary cell types in gonadal tissues, as well as different cancer cells. Monoclonal antibodies against the GnRH receptor of cancer cells were shown to induce apoptosis, similar to the action of GnRH analogs. In contrast, RP215 monoclonal antibody reacts specifically with the carbohydrate-associated epitope of cancerous immunoglobulins and is known to induce apoptosis of cancer cells in vitro. It also causes growth inhibition of tumor cells in nude mouse experimental models. Elucidations of the specific mechanisms of apoptosis in cancer cells of these two molecular interaction systems will not only lead to a better understanding of cancer biology but also benefit patients in cancer monitoring and therapy.
基金the National Health and Medical Research Council of Australia(APP1109207,awarded to ACWZ,PMB,and CGP)Australian Research Council(DP160100454,awarded to ACWZ and PMB)+1 种基金Diabetes Australia Research Program(awarded to ACWZ,SF and SM)an Australia Postgraduate Award(PT).
文摘Overnutrition causes hyperactivation of mTORC1-dependent negative feedback loops leading to the downregulation of insulin signaling and development of insulin resistance.In osteoblasts(OBs),insulin signaling plays a crucial role in the control of systemic glucose homeostasis.We utilized mice with conditional deletion of Rptor to investigate how the loss of mTORC1 function in OB affects glucose metabolism under normal and overnutrition dietary states.Compared to the controls,chow-fed Rptorob−/−mice had substantially less fat mass and exhibited adipocyte hyperplasia.Remarkably,upon feeding with high-fat diet,mice with pre-and post-natal deletion of Rptor in OBs were protected from diet-induced obesity and exhibited improved glucose metabolism with lower fasting glucose and insulin levels,increased glucose tolerance and insulin sensitivity.This leanness and resistance to weight gain was not attributable to changes in food intake,physical activity or lipid absorption but instead was due to increased energy expenditure and greater whole-body substrate flexibility.RNA-seq revealed an increase in glycolysis and skeletal insulin signaling pathways,which correlated with the potentiation of insulin signaling and increased insulin-dependent glucose uptake in Rptorknockout osteoblasts.Collectively,these findings point to a critical role for the mTORC1 complex in the skeletal regulation of wholebody glucose metabolism and the skeletal development of insulin resistance.
基金supported by the Science and Technology Commission of Shanghai Municipality (No. 09DZ 1905700)the EBM-CONNECT Collaboration (Proposal No.: 101377 Grant Agreement No.: 247613)
文摘Objective To compare the efficacy and safety of medical abortion of different regimens for termination of pregnancy at 8-16 weeks of gestation. Methods Healthy pregnant women requesting medical abortion at 8-16 weeks＇ gestation within 12 hospitals in Shanghai were randomly allocated to four treatment groups. Three intervention groups were given mifepristone 200 mg as a single dose then 24 h later misoprostol 600 #g at 3 h intervals vaginally, orally or vaginally followed by orally, respectively. Control group was given mifepristone 100 mg for 2 d, followed at 48 h by initiation of misoprostol 600 μg vaginally every 12 h. The primary outcome measures were the successful abortion rate, the induction-to-abortion interval, vaginal bleeding and side effects. Results Efficacy outcomes were analyzed for 1 112 women （92.67%）, excluding 88 protocol violations. Termination successful rates were similar among the four groups from 97.1% to 97.8%. The average dose of misoprostol and the incidence of side effects in control group were lower than those in three intervention groups. Stratified analysis showed that the interval of induction-to-abortion at gestation of 1116 weeks was decreased in control group. Conclusion The four regimens have the similar termination successful rates in spite of different administration intervals or routes. Control group was recommended for the advantages of reduced dose of misoprostol and fewer side effects.
文摘Alow-calorie diet in a group of overweight or obese patients for a short period before and during IVF results in variable tolerance to the dietary regime and an unsatisfactory IVF outcome.
基金funded by the National Tenth Five-year Key Project (2002BA709B06)
文摘To assess the side effects and the continuation rate of combined oral contraceptive （COC） containing desogestrel （Marvelon） during 12 months. Methods This was a post-marketing surveillance study on Marvelon COC among 870 healthy rural women in 5 different counties of Jiangsu Province during 12 months. Results About 24.02% of the women who used Marvelon COC experienced side effects during 12 months. Gastrointestinal disorder, bleeding/spotting and chloasma were ranked the first three in the side effects. The rate of side effects of Marvelon COC users during the first 3 months in southern area of Jiangsu was significantly higher than that of users in northern area of Jiangsu. Most of the users did not experience obvious weight changes i.e., loss or increase in weight of more than 5 kg during 12 months. Blood pressure and biochemical indicators of almost 99% among users were within the normal range. The gross cumulative continuation rate for 12 months was 83.14%; the most common medical reason for discontinuation was gastrointestinal disorder. There was an increased risk of discontinuation use among women with lower educational level. Conclusion Marvelon COC brought fewer side effects and was well accepted when applied in Chinese rural women.
文摘In Europe,population ageing poses a challenge.Given accelerating population ageing in Europe,longterm care(LTC)is a growing concern.Unmet healthcare needs varied among European countries during the coronavirus disease 2019(COVID-19)pandemic,and greater attention should be paid to ensuring that the healthcare needs of vulnerable populations are met.Notably,developing common and comparable indicators is useful for monitoring the LTC and healthcare of older adults at the national and international levels,and understanding the reasons for the differences in indicators between European countries could shed light on how to improve the health of older adults.
文摘Acute epididymitis represents a common medical condition in the urological outpatient clinic. Mostly, epididymitis is caused by bacterial ascent through the urogenital tract, with pathogens originating either from sexually transmitted diseases or urinary tract infections. Although conservative antimicrobial therapy is possible in the majority of patients and is usually sufficient to eradicate the pathogen, studies have shown persistent oligozoospermia and azoospermia in up to 40% of these patients. Animal models of epididymitis are created to delineate the underlying reasons for this observation and the additional impairment of sperm function that is often associated with the disease. Accumulated data provide evidence of a differential expression of immune cells, immunoregulatory genes and pathogen-sensing molecules along the length of the epididymal duct. The evidence suggests that a tolerogenic environment exists in the caput epididymidis, but that inflammatory responses are most intense toward the cauda epididymidis. This is consistent with the need to provide protection for the neo-antigens of spermatozoa emerging from the testis, without compromising the ability to respond to ascending infections. However, severe inflammatory responses, particularly in the cauda, may lead to collateral damage to the structure and function of the epididymis. Convergence of the clinical observations with appropriate animal studies should lead to better understanding of the immunological environment throughout the epididymis, the parameters underlying susceptibility to epididymitis, and to therapeutic approaches that can mitigate epididymal damage and subsequent fertility problems.
基金supported by funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development(NICHD)is carried out at the MRC Centre for Reproductive Health,which is funded by MRC Centre(grant MR/N022556/1).
