Early detection of multiple endocrine neoplasia type 1: A case report

BACKGROUND Multiple endocrine neoplasias(MENs)are a group of hereditary diseases invol-ving multiple endocrine glands,and their prevalence is low.MEN type 1(MEN1)has diverse clinical manifestations,mainly involving the parathyroid glands,gastrointestinal tract,pancreas and pituitary gland,making it easy to miss the clinical diagnosis.CASE SUMMARY We present the case of a patient in whom MEN1 was detected early.A middle-aged male with recurrent abdominal pain and diarrhea was admitted to the hos-pital.Blood tests at admission revealed hypercalcemia and hypophosphatemia,and emission computed tomography of the parathyroid glands revealed a hy-perfunctioning parathyroid lesion.Gastroscopy findings suggested a duodenal bulge and ulceration.Ultrasound endoscopy revealed a hypoechoic lesion in the duodenal bulb.Further blood tests revealed elevated levels of serum gastrin.Surgery was performed,and pathological analysis of the surgical specimens revealed a parathyroid adenoma after parathyroidectomy and a neuroendocrine tumor after duodenal bulbectomy.The time from onset to the definitive diagnosis of MEN1 was only approximately 1 year.CONCLUSION For patients who present with gastrointestinal symptoms accompanied by hyper-calcemia and hypophosphatemia,clinicians need to be alert to the possibility of MEN1.

C634Y mutation in RET-induced multiple endocrine neoplasia type 2A:A case report

BACKGROUND Multiple endocrine neoplasia type 2(MEN2)is a rare,autosomal dominant endocrine disease.Currently,the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis.Once an RET carrier is detected,family members should be screened to enable early detection of medullary thyroid carcinoma,pheochromocytoma,and hyperparatitity.Among these,medullary thyroid carcinoma is the main factor responsible for patient mortality.Accordingly,delineating strategies to inform clinical follow-up and treatment plans based on genes is paramount for clinical practitioners.CASE SUMMARY Herein,we present RET proto-oncogene mutations,clinical characteristics,and treatment strategies in a family with MEN2A.A family study was conducted on patients diagnosed with MEN2A.DNA was extracted from the peripheral blood of family members,and first-generation exon sequencing of the RET protooncogene was conducted.The C634Y mutation was identified in three family members spanning three generations.Two patients were sequentially diagnosed with pheochromocytomas and bilateral medullary thyroid carcinomas.A 9-yearold child harboring the gene mutation was diagnosed with medullary thyroid carcinoma.Surgical resection of the tumors was performed.All family members were advised to undergo complete genetic testing related to the C634Y mutation,and the corresponding treatments administered based on test results and associated clinical guidelines.CONCLUSION Advancements in MEN2A research are important for familial management,assessment of medullary thyroid cancer invasive risk,and deciding surgical timing.

Chinese herbal medicine for the treatment of endocrine therapyrelated osteoporosis among patients with breast cancer:A systematic review and meta-analysis

Objective:To assess the efficacy and safety of combining traditional Chinese medicine(TCM),specifically Chinese herbal medicine(CHM),with Western medicine(WM),compared to WM alone to treat breast cancer endocrine therapy-related osteoporosis(BCET-OP)by meta-analysis.Methods:Thirty-eight randomized controlled trials involving 2170 participants were analyzed.Eight databases were searched for articles published between inception and December 2023.Quality assessment was performed using the Risk of Bias 2 tool.Results:Significant increases were observed in the TCM-WM group in lumbar vertebrae bone mineral density(BMD)(P<.001,mean difference(MD)=0.07,95%confidence interval(CI):0.06 to 0.08),lumbar vertebrae T-score(P=.0005,MD=0.21,95%CI:0.09 to 0.33)and collum femoris BMD(P=.01,MD=0.10,95%CI:0.02 to 0.19).No significant difference was observed between the groups in the collum femoris T-score and estradiol levels.Bone gla-protein levels were significantly increased in the TCM-WM group(P=.0002,MD=0.52,95%CI:0.25 to 0.79).Beta-CrossLaps decreased significantly in the TCM-WM group(P=.0008,MD=−0.10,95%CI:−0.16 to−0.04).No significant difference was observed between the TCM-WM and WM groups in alkaline phosphatase,in procollagen type I N-terminal propeptide,and in the Kupperman index.The visual analog score(VAS)was decreased in the TCM-WM group compared to the WM group(P<.001,MD=−1.40,95%CI:−1.94 to−0.87).No significant difference in adverse events was observed between the two groups.Conclusion:Combining CHM with WM in patients with BCET-OP significantly improved BMD,T-score,and certain bone turnover markers and reduced the VAS score,indicating potential benefits for bone health and related pain.Adverse event analysis revealed no differences between the groups,supporting the feasibility of the combination therapy.However,further research,particularly in diverse populations,is required.

Improving early diagnosis of multiple endocrine neoplasia type 1 by assessing the gastrointestinal symptoms,hypercalcemia,and elevated serum gastrin

Despite advancements in the field,early diagnosis of multiple endocrine neoplasia type 1(MEN1)remains unachievable.This letter to the editor highlighted the importance of carefully assessing gastrointestinal symptoms,hypercalcemia,and elevated serum gastrin levels,as suggested by Yuan et al in their paper.They focused on a patient with recurrent abdominal pain and diarrhea whose diagnostic path led to establishing a MEN1 diagnosis within a year.This emphasized the need for clinicians to consider MEN1 in patients with similar presentations,particularly when gastrointestinal symptoms persist or recur after discontinuation of proton pump inhibitors,especially knowing that early recognition and intervention are crucial for improving patient outcomes.

Impacts of different pancreatic resection ranges on endocrine function in Suncus murinus

BACKGROUND Surgical intervention involving the pancreas can lead to impaired glucose tolerance and other types of endocrine dysfunction.The scope of pancreatectomy and whether it includes the ventral pancreas are the key factors in the development of postoperative diabetes.The ventral and dorsal pancreases are almost separated in Suncus murinus(S.murinus).AIM To investigate the effects of different extents of pancreatic resection on endocrine function in S.murinus.METHODS Eight-week-old male S.murinus shrews were randomly divided into three experimental groups according to different pancreatic resection ranges as follows:ventral pancreatectomy(VPx)group;partial pancreatectomy(PPx)group;subtotal pancreatectomy(SPx)group;and a sham-operated group.Postprandial serum insulin,glucagon-like peptide-1(GLP-1),pancreatic polypeptide(PP),and somatostatin(SST)levels,as well as food intake,weight,blood glucose,and glucose tolerance were regularly measured for each animal.RESULTS S.murinus treated with PPx and SPx suffered from varying degrees of impaired glucose tolerance,but only a small proportion of the SPx group developed diabetes.Only S.murinus in the SPx group showed a significant decrease in food intake accompanied by severe weight loss,as well as a significant increase in postprandial serum GLP-1 levels.Postprandial serum PP levels decreased in both the VPx and PPx groups,but not in the SPx group.Postprandial serum SST levels decreased in both VPx and PPx groups,but the decrease was marginal.CONCLUSION Severe weight loss after pancreatectomy may be related to loss of appetite caused by compensatory elevation of GLP-1.PP and GLP-1 may play a role in resisting blood glucose imbalance.

Periampullary duodenal neuroendocrine tumor in a patient with neurofibromatosis-1:A case report

BACKGROUND Patients with neurofibromatosis type 1(NF1)are exposed to a higher risk of developing neuroendocrine tumors(NETs).Periampullary neuroendocrine neoplasms(NENs)in NF1 patients primarily affect the duodenum and periampullary region.CASE SUMMARY A 50-year-old male patient was admitted to our hospital due to progressive skin and scleral yellowing for over 6 months.An abdominal contrast-enhanced computed tomography scan revealed a tumor in the periampullary region,which measured 1.2 cm×1.4 cm in size and showed a progressive enhancement.Magnetic resonance cholangiopancreatography indicated the dilation of intrahepatic and extrahepatic bile ducts.The patient was diagnosed with an ampullary tumor with the possibility of malignancy.A Whipple procedure was performed.Microscopically,the duodenum tumor was found to invade the mucosa,sphincter,and muscular layer of the duodenal papilla.Histologic hematoxylin and eosin staining confirmed the presence of duodenal G1 NET.Subsequently,a bibliometric analysis was performed to evaluate the state of NEN research.Publications about periampullary NENs showed an annual increase,with most of them focusing on the treatment and diagnosis of NENs.CONCLUSION This article reported a case of periampullary duodenal NET in a patient with NF1,and a bibliometric analysis was conducted.

Molecular diagnostic approaches in detecting rearranged during transfection oncogene mutations in multiple endocrine neoplasia type 2

Different types of neuroendocrine cancer,including medullary thyroid cancer(MTC)and thyroid C-cell hyperplasia,are part of multiple endocrine neoplasia type 2(MEN2).A proto-oncogene mutation of the rearranged during transfection(RET)gene changes the way that receptor tyrosine kinases work.Multiple endocrine neoplasia,a pathological condition,involves these kinases.When the RET protooncogene changes,it can cause endocrine adenomas and hyperplasia to happen at the same time or one after the other.Pheochromocytoma,medullary thyroid carcinoma,and hyperparathyroidism,alone or in combination,are present in MEN2A patients.Some patients may also have skin lichen amyloidosis or Hirschsprung's disease.Patients with MEN2A often present with MTC.MTC is aggressive and has the worst prognosis,as most patients exhibit lymph node metastasis.MTC is one of the important causes of death in patients with MEN2A.RET mutation analysis aids in identifying MEN2A symptoms and monitoring levels of calcium,thyroid hormones,calcitonin,normetanephrine,fractionated metanephrines,and parathyroid hormone.The earlier diagnosis of MTC significantly improves survival and prompts better management of MEN2A.In this editorial,we will discuss the significance of molecular diagnostic approaches in detecting RET oncogene mutations in MEN2A.

Research progress of traditional Chinese medicine in the treatment of endocrine metabolic diseases in 2023

This study aimed to provide a comprehensive review of the research progress in Chinese medicine in the treatment of endocrine metabolic diseases in 2023,covering traditional Chinese medicine(TCM)monomers,TCM extracts,and TCM combinations,including non-alcoholic fatty liver disease,type 2 diabetes mellitus and its complications,obesity,hyperuricaemia,and thyroid disorders.After systematic sorting and summary,we found that in 2023,the research focusing on the application of TCM for endocrine metabolic diseases was still on the mechanism of action at the cellular and molecular levels,which not only influenced the classical pathways of lipid metabolism,but also delved into the key mechanisms of anti-inflammation,anti-oxidation,anti-insulin resistance,and so on.Additionally,TCM has shown remarkable results in the treatment of endocrine metabolic diseases by improving intestinal flora disorders and abnormal cellular iron death.These research results provide valuable ideas,methods,and tools for TCM in the prevention and treatment of endocrine metabolic diseases,and provide important references and guidance for future research and practice.

Circadian rhythm disruption and endocrine-related tumors

This review delved into the intricate relationship between circadian clocks and physiological processes,emphasizing their critical role in maintaining homeo-stasis.Orchestrated by interlocked clock genes,the circadian timekeeping system regulates fundamental processes like the sleep-wake cycle,energy metabolism,immune function,and cell proliferation.The central oscillator in the hypothalamic suprachiasmatic nucleus synchronizes with light-dark cycles,while peripheral tissue clocks are influenced by cues such as feeding times.Circadian disruption,linked to modern lifestyle factors like night shift work,correlates with adverse health outcomes,including metabolic syndrome,cardiovascular diseases,infec-tions,and cancer.We explored the molecular mechanisms of circadian clock genes and their impact on metabolic disorders and cancer pathogenesis.Specific associ-ations between circadian disruption and endocrine tumors,spanning breast,ovarian,testicular,prostate,thyroid,pituitary,and adrenal gland cancers,are highlighted.Shift work is associated with increased breast cancer risk,with PER genes influencing tumor progression and drug resistance.CLOCK gene expression correlates with cisplatin resistance in ovarian cancer,while factors like aging and intermittent fasting affect prostate cancer.Our review underscored the intricate interplay between circadian rhythms and cancer,involving the regulation of the cell cycle,DNA repair,metabolism,immune function,and the tumor microenvir-onment.We advocated for integrating biological timing into clinical consider-ations for personalized healthcare,proposing that understanding these connec-tions could lead to novel therapeutic approaches.Evidence supports circadian rhythm-focused therapies,particularly chronotherapy,for treating endocrine tumors.Our review called for further research to uncover detailed connections between circadian clocks and cancer,providing essential insights for targeted treatments.We emphasized the importance of public health interventions to mitigate lifestyle-related circadian disruptions and underscored the critical role of circadian rhythms in disease mechanisms and therapeutic interventions.

Detection of Endocrine Disruptors in Water around Landfills

[Objectives]This study was conducted to explore the occurrence levels of endocrine disruptors(EDCs)in rural areas around a county landfill in Tongren City.[Methods]The water around the landfill was sampled and analyzed.A solid-phase extraction and high performance liquid chromatography-tandem mass spectrometry(SPE-UPLC-MS/MS)method was established for the determination of 27 EDCs.After the HLB solid-phase extraction column was activated,a water sample,which was adjusted with phosphoric acid to a pH of 2(±0.5)and added with 500 mg of disodium EDTA,was loaded,and 5 ml of water and 20%methanol water was added for washing.Next,10 ml of elution solution was added for elution,and the collected eluate was evaporated under reduced pressure at 40℃to near dryness,and 1 ml of reconstitution solution was added to a constant volume.An ACQUITY UPLC BEH C18(100×2.1 mm,2.6μm)chromatographic column was adopted for LC separation by gradient elution with pure water solution-acetonitrile as the mobile phase.For MS detection,the MRM mode was adopted for collection,and the positive and negative ion modes were switched for simultaneous determination,and the internal standard method was used for quantification.[Results]The correlation coefficient R2 was greater than 0.99 in the linear range of each target substance.The limits of quantitation in the method were between 0.05 and 2.00 ng/L,and the recoveries ranged from 75.3%to 105.7%.[Conclusions]The method has high sensitivity,good accuracy and strong practical value.

Myo-inositol versus metformin effects on clinical features, endocrine and metabolic profiles in infertile women with polycystic ovary syndrome: A randomized controlled trial

Objective:To compare the effectiveness of inositol and metformin on the clinical characteristics,and endocrine and metabolic profiles of infertile polycystic ovarian syndrome(PCOS)women from Vietnam.Methods:From June 2018 to August 2022,a randomized trial was undertaken at the Hue Center for Endocrinology and Reproduction on infertile women aged 18 to 40 years with polycystic ovarian syndrome.The clinical,endocrine,and metabolic features of these individuals were assessed before and after 3 months of treatment with 2 g of inositol or 1700 mg of metformin per day.Natural pregnancy rates,adverse effects,and tolerance of inositol were recorded.Results:The study included 171 infertile PCOS women who were eligible to participate and took part in the baseline assessment,of whom 132 women participated in data analysis after 3 months.After metformin treatment,42.1%of women with oligomenorrhea experienced regular menstruation.Metformin significantly lowered body mass index(BMI),waist circumference and testosterone levels,but had no effect on other clinical characteristics,endocrine profiles,or metabolic profiles.29.2%Of women reported experiencing side effects.21%Of them attained pregnancy,which resulted in 17.1%of live births.In the inositol group,the rate of regular cycle increased by 18.2%and the total testosterone concentration significantly decreased.In overweight/obese women with PCOS,inositol significantly decreased weight,BMI,waist and hip circumferences(P<0.05).100%Of women tolerated inositol and continued treatment.18.9%Of them became pregnant,leading to 17%of live births.Conclusions:Metformin and inositol can improve weight and waist circumference in overweight/obese infertile women with PCOS.Metformin is associated with a higher rate of regular menstruation,whereas inositol is associated with a lower rate of adverse effects.The spontaneous conception,clinical pregnancy,and live birth rates between two groups are comparable.

Systematic review and meta-analysis of endometrial thickening during endocrine therapy combined with Chinese herbal medicine intervention after breast cancer surgery

Objective:To systematically evaluate the endometrial thickening and Chinese herbal medicine intervention effects during endocrine therapy following breast cancer surgery.Methods:Computerized searches were performed on CNKI,CBM,Wanfang,VIP,Pub Med,Embase,and Cochrane to gather randomized controlled trials(RCTs)of endometrial thickening combined with Chinese herbal medicine intervention during endocrine therapy after breast cancer surgery.The meta analysis is done using Rev Man 5.4,and the retrieval range is from the database's creation to January 2023.Results:There were 710 patients enrolled in a total of 12 RCTs.The results of Meta-analysis were as follows:combined with Chinese herbal medicine treatment for 3 months of endometrial thickness(MD=-1.12,95%CI[-1.47,0.77],P<0.00001);6 months endometrial thickness(MD=-1.90,95%CI[-2.38,-1.42],P<0.00001);endometrial thickness at 12 months(MD=-2.24,95%CI[-2.96,-1.52],P<0.00001);modified Kupperman score(MD=-10.45,95%CI[-19.10,-1.80],P=0.02);TCM syndrome score(SMD=-1.53,95%CI[-1.84,-1.22],P<0.00001);KPS score(MD=3.75,95%CI[2.81,4.68],P<0.00001);there was no significant difference in CA153,CEA,FSH and E2 between the two groups.Conclusion:After breast cancer surgery,endocrine therapy combined with Chinese herbal medicine can significantly lessen endometrial thickening and enhance patient quality of life.

Endocrine-Disrupting Chemicals: Possible Genesis of Ovarian Tumors

Background: Prolonged exposure to environmental toxicants like endocrine-disrupting chemicals has been linked to several ovarian pathologies. Exposure to endocrine-disrupting chemicals may start at any time of life from the fetal stage to adulthood resulting in various health complications The purpose of our study is to compare the concentration levels and association of benzopyrene, bisphenol A and genistein in patients with ovarian tumors and normal control group. We also sort to evaluate the predictive performance of benzopyrene, bisphenol A and genistein in patients with ovarian tumors. Methods: A case-control study was conducted for randomly selected participants involving 30 patients and 30 controls. 30 patients with radiologically diagnosed and histopathological confirmed ovarian tumors were included in the study between January 2022 and December 2022. Urine samples from each group were analyzed using liquid chromatography-mass spectrometry. Descriptive analysis for normally distributed continuous variables was done accordingly. Concentration levels of endocrine-disrupting chemicals were assessed using the Mann-Whitney test. The association of endocrine-disrupting chemicals with pathological ovarian tumors was analyzed using binary logistic regression. Evaluation of the diagnostic performance of endocrine-disrupting chemicals was analyzed using the ROC curve. Results: Overall, patients were significantly (P = 0.000) older than the healthy controls. Mean years (SD) were 36.7 (7.90) and 28.8 years (4.89) for patients and normal women respectively. Endometriomas had the highest incidence of 50%. The level of benzopyrene and bisphenol A in patients was significantly higher than those in the control group, while the level of genistein was significantly higher in normal controls. Benzopyrene and bisphenol A were significantly associated with ovarian cysts, and the incidence of pathological ovarian cysts was positively correlated to these EDCs, with OR value 64.79 (P = 0.005) for benzopyrene and 9.609 (P = 0.001) for bisphenol A. Genistein was significantly negatively correlated with the incidence of pathological ovarian tumors, with OR value of 0.153 (P = 0.007). Diagnostic performance on the AUC for benzopyrene, bisphenol A and genistein&l.

Immunohistochemical Location of Six Kinds of Endocrine Cell from Digestive Tract of Misgurnus anguillicaudatus

[Objective] The study was to immunohistochemical localize the endocrine cells from digestive tract of Misgurnus [ Method ] Using six gastrointestinal hormone antisera, the endocrine cells from digestive tract of M. anguillicaudatus was localized. [ Result ]The 5-hydroxytryptamine immunoreactive（5-HT-IR） cells distribute in oesophagus, foregut and midgut; the distribution density was determined to be forepart of foregut 〉 oesophagus and hindpart of foregut 〉 gut, and the differences in the three density gradients reached significant level. Like PP-IR, SS-IR cells were observed mostly in oesophagus, followed by hindpart of foregut, least in forepart of foregut, but never found in gut and hindgut. The three kinds of immunocompetent cells Gas-IR, Glu-IR and SP-IR were not detected in each part of digestive tract. [ Conctusion] This study may provide basic data for studying the nutritional and digestive physiology, as well as the preparation of meridic diets for M. anguillicaudatus.

Pollution of Environmental Endocrine Disrupting Chemicals(EDCs) in Water and Its Adverse Reproductive Effect on Fish

Environmental endocrine disrupting chemicals （EDCs）, commonly found in the environment, come from industry and agriculture, including pesticides, fungicides, insecticides, herbicides, and other chemicals. Nowadays, more and more EDCs were released into the environment. EDCs go into water body via atmosphere sedi-mentation, surface runoff, soil eluviation, etc., so water body becomes the main place for existing. In order to attract scientific and public attention worldwide and to prevent EDCs pol ution, in this study we reviewed the classification of EDCs and their concentrations in natural water bodies, drinking water sources and water plants, and the reproductive toxicity of EDCs to fish were reviewed. EDCs could disturb the endocrine system and make reproductive organs and reproduction abnor-mal, resulting in fertility descending, reproduction function damage, community quan-tity decrease and even species extinction. In addition, EDCs could disrupt the homeostasis maintained by hormones, which would result in defects of neural de-velopment and abnormalities of the endocrine and reproductive systems. The exact molecular mechanisms have not been completely reported, but researches have suggested that multiple mechanisms were involved in the action of EDCs. Although there have been researches on the biohazard of EDCs, there stil exist problems of weakness in fundamental researches, difficulties in recognizing and identifying EDCs and high cost, which restraint the knowledge on them.

关于Endocrine Disruptors的译名

当今环境科学的发展十分迅速 ,新的名词术语大量涌现 ,但由于对这些名词翻译和使用上的不统一 ,给广大的科技工作者和关心环境问题的普通百姓造成了工作中或认识上的麻烦和混乱。例如 ,“一类来源于环境中的、能干扰生物体内分泌功能的物质” ,就有“环境内分泌干扰物”、“内分泌干扰物”、“内分泌紊乱剂”、“环境激素”、“环境荷尔蒙”等多种中文名称 ,其英文名称也有“endocrinedisruptors”、“environ mentalendocrinedisruptors”、“endocrinedisruptingchemicals”、“environmentalhormones”等多种表述 ,并且对这类物质的定义 ,在国际上还没有达到完全一致 ,亟待统一和规范。为了尽快统一和规范环境科学的名词术语 ,我们邀请有关专家在本刊对一些新近出现的影响较大、分歧较多的环境科学名词术语进行研究和讨论 ,以期为将来名词的最终审定奠定基础。我们欢迎广大读者来稿发表意见 ,以使审定的名词更科学、更准确、更有利于普及利用。

Mechanisms and therapeutic advances in the management of endocrine-resistant breast cancer

The estrogen receptor(ER) pathway plays a critical role in breast cancer development and progression. Endocrine therapy targeting estrogen action is the most important systemic therapy for ER positive breast cancer. However its efficacy is limited by intrinsic and acquired resistance. Mechanisms responsible for endocrine resistance include deregulation of the ER pathway itself, including loss of ER expression, posttranslational modification of ER, deregulation of ER coactivators; increased receptor tyrosine kinase signaling leading to activation of various intracellular pathways involved in signal transduction, proliferation and cell survival, including growth factor receptor tyrosine kinases human epidermal growth factor receptor-2, epidermal growth factor receptor, PI3K/AKT/mammalian target of rapamycin(m TOR), Mitogen activated kinase(MAPK)/ERK, fibroblast growth factor receptor, insulin-like growth factor-1 receptor; alterations in cell cycle and apoptotic machinery; Epigenetic modificationincluding dysregulation of DNA methylation, histone modification, and nucleosome remodeling; and altered expression of specific micro RNAs. Functional genomics has helped us identify a catalog of genetic and epigenetic alterations that may be exploited as potential therapeutic targets and biomarkers of response. New treatment combinations targeting ER and such oncogenic signaling pathways which block the crosstalk between these pathways have been proven effective in preclinical models. Results of recent clinical studies suggest that subsets of patients benefit from the combination of inhibitor targeting certain oncogenic signaling pathway with endocrine therapy. Especially, inhibition of the m TOR signaling pathway, a key component implicated in mediating multiple signaling cascades, offers a promising approach to restore sensitivity to endocrine therapy in breast cancer. We systematically reviewed important publications cited in Pub Med, recent abstracts from ASCO annual meetings and San Antonio Breast Cancer Symposium, and relevant trials registered at Clinical Trials.gov. We present the molecular mechanisms contributing to endocrine resistance, in particular focusing on the biological rationale for the clinical development of novel targeted agents in endocrine resistant breast cancer. We summarize clinical trials utilizing novel strategies to overcome therapeutic resistance, highlighting the need to better identify the appropriate patients whose diseases are most likely to benefit from these specific strategies.

Paracrine and endocrine actions of bone——the functions of secretory proteins from osteoblasts, osteocytes, and osteoclasts

The skeleton is a dynamic organ that is constantly remodeled. Proteins secreted from bone cells, namely osteoblasts, osteocytes,and osteoclasts exert regulation on osteoblastogenesis, osteclastogenesis, and angiogenesis in a paracrine manner. Osteoblasts secrete a range of different molecules including RANKL/OPG, M-CSF, SEMA3A, WNT5A, and WNT16 that regulate osteoclastogenesis. Osteoblasts also produce VEGFA that stimulates osteoblastogenesis and angiogenesis. Osteocytes produce sclerostin（SOST） that inhibits osteoblast differentiation and promotes osteoclast differentiation. Osteoclasts secrete factors including BMP6, CTHRC1, EFNB2, S1P, WNT10B, SEMA4D, and CT-1 that act on osteoblasts and osteocytes, and thereby influencea A osteogenesis. Osteoclast precursors produce the angiogenic factor PDGF-BB to promote the formation of Type H vessels, which then stimulate osteoblastogenesis. Besides, the evidences over the past decades show that at least three hormones or ＂osteokines＂from bone cells have endocrine functions. FGF23 is produced by osteoblasts and osteocytes and can regulate phosphate metabolism. Osteocalcin（OCN） secreted by osteoblasts regulates systemic glucose and energy metabolism, reproduction, and cognition. Lipocalin-2（LCN2） is secreted by osteoblasts and can influence energy metabolism by suppressing appetite in the brain.We review the recent progresses in the paracrine and endocrine functions of the secretory proteins of osteoblasts, osteocytes, and osteoclasts, revealing connections of the skeleton with other tissues and providing added insights into the pathogenesis of degenerative diseases affecting multiple organs and the drug discovery process.

Endocrine disruptors and estrogenic effects on male reproductive axis

Endocrine disruptors （e.g., polychlorinated biphenyls [PCBs], dichlorodiphenyl-trichloroethane [DDT], dioxin, and some pesticides） are estrogen-like and anti-androgenic chemicals in the environment. They mimic natural hormones, inhibit the action of hormones, or alter the normal regulatory function of the endocrine system and have potential hazardous effects on male reproductive axis causing infertility. Although testicular and prostate cancers, abnormal sexual development, undescended testis, chronic inflammation, Sertoli-cell-only pattern, hypospadias, altered pituitary and thyroid gland functions are also observed, the available data are insufficient to deduce worldwide conclusions. The development of intra-cytoplasmic sperm injection （ICSI） is beyond doubt the most important recent breakthrough in the treatment of male infertility, but it does not necessarily treat the cause and may inadvertently pass on adverse genetic consequences. Many well-controlled clinical studies and basic scientific discoveries in the physiology, biochemistry, and molecular and cellular biology of the male reproductive system have helped in the identification of greater numbers of men with male factor problems. Newer tools for the detection of Y-chromosome deletions have further strengthened the hypothesis that the decline in male reproductive health and fertility may be related to the presence of certain toxic chemicals in the environment. Thus the etiology, diagnosis, and treatment of male factor infertility remain a real challenge. Clinicians should always attempt to identify the etiology of a possible testicular toxicity, assess the degree of risk to the patient being evaluated for infertility, and initiate a plan to control and prevent exposure to others once an association between occupation/toxicant and infertility has been established.

Autonomic and endocrine control of cardiovascular function

The function of the heart is to contract and pump oxygenated blood to the body and deoxygenated blood to the lungs.To achieve this goal,a normal human heart must beat regularly and continuously for one's entire life.Heartbeats originate from the rhythmic pacing discharge from the sinoatrial(SA) node within the heart itself.In the absence of extrinsic neural or hormonal influences,the SA node pacing rate would be about 100 beats per minute.Heart rate and cardiac output,however,must vary in response to the needs of the body's cells for oxygen and nutrients under varying conditions.In order to respond rapidly to the changing requirements of the body's tissues,the heart rate and contractility are regulated by the nervous system,hormones,and other factors.Here we review how the cardiovascular system is controlled and influenced by not only a unique intrinsic system,but is also heavily influenced by the autonomic nervous system as well as the endocrine system.