BACKGROUND:In recent years,studies have shown that obesity is closely related to chronic inflammation.Due to excessive energy intake,inflammatory macrophage infiltration and inflammatory response occur in visceral adipose tissue,which is crucial for the regulation of adipose tissue fibrosis. OBJECTIVE:To summarize the molecular mechanism of inflammation-related signals involved in the regulation of adipose tissue fibrosis and to provide reference for the treatment of adipose tissue fibrosis and related metabolic diseases through anti-inflammatory pathways. METHODS:Relevant documents were retrieved from CNKI and PubMed,and the Chinese and English search words were"inflammation,inflammatory factors,inflammatory signals,lip fibrosis,adipose fibrosis,adipose tissue fibrosis"respectively.The search period was from January 2003 to December 2022.Finally,52 documents meeting the criteria were included for review. RESULTS AND CONCLUSION:During obesity,visceral adipose tissue expands through adipocyte proliferation and hypertrophy to store excess energy,and defects caused by remodeling or functional changes mainly include impaired angiogenesis,adipocyte apoptosis promoted by white adipose tissue hypoxia,macrophage infiltration,and adipocyte fibrosis.Adipose tissue fibrosis has adverse effects on the natural growth of adipose cells.The factors that trigger chronic inflammation of adipose tissue include a variety of signal stimuli,such as adipocyte death caused by hypoxia,mechanical signal transduction caused by extracellular matrix remodeling and lipogenic factor imbalance.Inflammatory factors such as interleukin-1β,tumor necrosis factor-α,C-type lectins and adiponectin secreted by adipocytes and other inflammatory signaling pathways such as nuclear factor-κB,transforming growth factor-β/Smad and MAPK jointly regulate the process of adipose tissue fibrosis.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To investigate the clinical profile of primary bilateral macronodular adrenal hyperplasia(PBMAH) and sex difference.Methods:One hundred and forty cases of PBMAH were recruited in our center from 2014, and all patients were evaluated for hormone secretion, adrenal imaging, and metabolic parameters.Results:Overt Cushing′s syndrome accounted for 76.4% of PBMAH cohort and 47.9% were female. The overt group had higher serum cortisol and 24 h urinary free cortisol levels, lower adrenocorticotropic hormone, higher serum cortisol after low-dose dexamethasone suppression tests, larger total adrenal size, and a higher percentage of obesity, hypertension, diabetes mellitus, and hypokalemia than the subclinical group(all P<0.05). When compared with the male group, the female group had smaller adrenal size( P<0.001), lower HbA 1C( P=0.003), higher total cholesterol( P=0.005), and lower density lipoprotein-cholesterol levels( P=0.035). Further, 24 h urinary free cortisol in the male group was found to be positively correlated with diastolic blood pressure, fasting glucose, 2 h postprandial glucose after oral glucose tolerance test(OGTT), and HbA 1C after adjusted for age, body mass index, and onset duration, and was negatively correlated with body mass index and potassium levels. While 24 h urinary free cortisol in the female group was positively correlated only with diastolic blood pressure, fasting glucose, and 2 h postprandial glucose after OGTT(all P<0.05). During follow-up, 80.0% of patients achieved remission after unilateral adrenalectomy, with a recurrence rate of 17.9%. Conclusion:PBMAH related metabolic disorder is more pronounced in overt Cushing′s syndrome and males. Unilateral adrenalectomy as an effective treatment can benefit the majority of patients.

The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Objective:To investigate the effect of growth hormone replacement therapy(GHRT) on glucose and lipid metabolism in patients with hypopituitarism.Methods:Clinical data of patients with hypopituitarism who received GHRT in Department of Endocrine and Metabolic Diseases, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from December 2016 to February 2020 were retrospectively analyzed. The patients were divided into normal glucose regulation(NGR) group and impaired glucose regulation(IGR) group according to their glucose metabolism status before GHRT. The changes of the characteristics of glucose metabolism before and after GHRT were analyzed.Results:A total of 30 patients aged(23.0±5.2) years were included, 23 patients in NGR group and 7 patients in IGR group. After 12 months of GHRT, there were no significant changes in fasting plasma glucose(FPG), 2-hour postprandial plasma glucose(2hPG), and insulin sensitivity index(ISI) in both groups(all P>0.05), while homeostasis model assessment insulin resistance(HOMA-IR) in IGR group was significantly decreased compared with that before GHRT( P<0.05). None of the patients in NGR group progressed to IGR or diabetes mellitus, and none of the 7 patients in the IGR group progressed to diabetes mellitus, while 4 of them recovered from impaired glucose tolerance(IGT) to NGR. Triglyceride, total cholesterol, and low density lipoprotein-cholesterol levels were all significantly decreased in two groups(all P<0.05). Multivariate linear regression analysis showed that the increase of body mass index was an independent risk factor for the increase of FPG and 2hPG( P<0.05). Conclusion:12-month GHRT significantly improved their blood lipid profiles in patients with hypopituitarism without adversely affecting glucose homeostasis.

Congenital generalized lipodystrophy type 1 (CGL1) is an autosomal recessive genetic disease caused by mutations in AGPAT2 gene. The main clinical mainifestations include body subcutaneous fat loss, muscle hypertrophy, obvious subcutaneous veins, pseudoacromegaly, hirsutism, and acanthosis nigricans. What′s more, CGL1 is always accompanied by metabolic diseases. Therefore, it is easily misdiagnosed as metabolic syndrome, type 2 diabetes, polycystic ovary syndrome, acromegaly, or Cushing′s syndrome. Meanwhile, it is difficult to distinguish it from partial lipoatrophy syndrome. In this article, we present clinical and molecular characteristics of a patient with CGL1 and review mutations reported in literature to replenish current knowledge about this orphan disease.

Acromegaly is a commonly functional pituitary tumor. Standardized managements are crucial for the patients. Chinese Expert Consensus on the Diagnosis and Treatment of Acromegaly(2020) has been updated in 2020 based upon latest advance. This essential introduction about genetic causes would further guide and standardize the management of acromegaly.

Objective:To explore the selection and effects of flap/myocutaneous flap repair methods for the defect after perineum tumor resection.Methods:From January 2011 to February 2017, 31 patients with vulvar tumor who were admitted to Hunan Cancer Hospital underwent repair of wound after tumor resection with various flaps/myocutaneous flaps. The patients were composed of 5 males and 26 females, aged 39-76 years, with 27 vulvar cancer and 4 Paget′s disease in primary diseases. The size of defects after vulvar tumor radical resection ranged from 8.0 cm×4.5 cm to 27.5 cm×24.0 cm. According to the theory of perforasome, the defects were repaired by the external pudendal artery perforator flap, deep inferior epigastric artery perforator flap, rectus abdominis myocutaneous flap, anterolateral thigh flap, internal pudendal artery perforator flap, gracilis myocutaneous flap, and profunda artery perforator flap based on the specific size and location of perineum and groin where the defect was located. According to the blood supply zone of flap, totally 17 local translocation flaps, 18 axial flaps/myocutaneous flaps, and 7 V-Y advancement flaps were resected, with an area of 7.0 cm×4.0 cm to 21.0 cm×13.0 cm. All the flaps/myocutaneous flaps were transferred in pedicled fashion, and the donor sites were closed without tension. The number of flaps/myocutaneous flaps, wound closure, flaps/myocutaneous flaps survival, and follow-up were observed and recorded.Results:Altogether 42 flaps/myocutaneous flaps were harvested in 31 patients. Two flaps/myocutaneous flaps were used in 11 cases for large circular defect repair. All the defects achieved tension-free primary closure. The blood supply of 32 flaps/myocutaneous flaps was good, while insufficient blood supply was noted in the other 10 flaps/myocutaneous flaps. Seventeen flaps/myocutaneous flaps survived smoothly. Wound dehiscence occurred in 5 flaps/myocutaneous flaps 8 to 14 days postoperatively, which was healed with dressing change. Temporary congestion was noted in 7 flaps/myocutaneous flaps 2 to 5 days postoperatively, which recovered without special treatment. Three flaps/myocutaneous flaps had infection 7 to 15 days postoperatively, two of which recovered after dressing change, while the other one had partial necrosis and received debridement and direct closure. Two flaps/myocutaneous flaps were totally necrotic 8 to 15 days postoperatively, which were repaired with pedicled rectus abdominis myocutaneous flap after debridement. Seven flaps/myocutaneous flaps had partial necrosis 7 to 20 days postoperatively and were healed after dressing change. Twenty-four patients were followed up for 9-38 months. The color of flaps/myocutaneous flaps was similar to that of the surrounding skin, the shape of vulva was natural, the movement of hip joint was not limited, the function of micturition and defecation was not affected, and tumor recurrence was noted in 3 patients.Conclusions:For the complicated large defect after perineum tumor resection, the flexible application of different forms of flaps/myocutaneous flaps to repair according to different areas regains the appearance and function. However, there are many complications, so it is necessary to further strengthen the postoperative care.

Objective To explore the effects of arsenic exposure on learning and memory and its potential mechanism in rats.Methods Water-based arsenic-exposed rat models were established on 4-l0 postnatal days.The experimental animals were divided into 4 groups (10-12 cases in each group):the control group,the 15 μg/L As2O3 water group,the 30 μg/L As2O3 water group,and the 45 μg/L As2O3 water group.Cognitive functions were examined with the Morris water maze,exploratory behavior was detected by the exploratory behavior test.The hippocampus of pups from each experimental group was sectioned at various time points after arsenic exposure.The morphologies and neurogenesis of the neurons in the hippocampus CA1-CA3 region and dentate gyrus (DG) were observed by hematoxylin-eosin staining,Nissl staining,and doublecortin (DCX) immunostaining at different time points after arsenic exposure.Results Compared with the normal control group,the escape latency of the rats in the arsenic-exposed group was prolonged.The average escape latency of the rats in the normal control group,15 μg/L As2O3 group,30 μg/L As2O3 group and45 μg/L As2O3 group were (17.00±9.53) s,(35.89 ±19.81) s,(26.60 ±18.84) s,and (33.79 ±18.08) s,respectively,and the difference among 4 groups was statistically significant (F =3.591,P ＜ 0.05),and the residence time in the original target quadrant was shortened,respectively,(38.93 ± 8.33) s,(36.03 ± 16.25) s,(29.85 ± 9.27) s,and (29.84 ± 10.16) s,respectively,and there was no significant difference among 4 groups (F =1.681,P =0.187).HE staining and Nissl staining showed that pathological changes such as edema,degeneration and necrosis were observed in the hippocampal CA1 area and CA2 area as well as dentate gyrus cells in rats exposed to arsenic in the acute phase.The higher the concentration of arsenic exposure,the more obvious the cell structure disorder was.However,5 weeks after exposure,the pathological changes in hippocampal neurons in the arsenic-exposed group gradually returned to normal.Immunohistochemistry showed that the expressions of DCX in the CA1,CA2 and dentate gyrus of rats exposed to arsenic decreased significantly 24 h after arsenic exposure,especially in the 45 μg/L group.Five weeks after arsenic exposure,there was no expression in the hippocampal CA1-CA3 area,and there was still a small amount of expression in the dentate gyrus.Conclusions Postnatal low-concentration arsenic exposure may impair learning and abnormal germination of neurons in the hippocampal dentate gyrus may be the underlying mechanism.