BACKGROUND:Aberrant metabotropic glutamate receptor 2/3 (mGluR2/3) signaling has been implicated in the synaptic and cognitive deficits observed in Alzheimer's disease (AD), yet the underlying regulatory mechanisms remain unclear. This study investigated the therapeutic potential of LY341495, a selective mGluR2/3 antagonist, in APP/PS1 transgenic mice, a widely used AD model. METHODS:Male APP/PS1 mice were treated with the selective mGluR2/3 antagonist LY341495. Cognitive performance was evaluated using behavioral tests. Hippocampal dentate gyrus (DG) alterations were examined by immunohistochemistry and electrophysiology, including analyses of mGluR2/3 expression, excitatory synaptic activity, adult neurogenesis, calbindin expression, and amyloid-β plaque burden. RESULTS:APP/PS1 mice exhibited pathological upregulation of mGluR2/3 in the DG, accompanied by altered presynaptic glutamatergic transmission, reduced neurogenesis, decreased calbindin expression, and deficits in recognition and spatial memory. LY341495 treatment attenuated the aberrant mGluR2/3 upregulation, enhanced excitatory synaptic activity, and improved calbindin levels and neurogenesis in the DG. Importantly, these changes were associated with significant reductions in DG amyloid-β plaque burden and marked improvements in cognitive performance. CONCLUSIONS:This study highlights the novelty of linking mGluR2/3 inhibition to the restoration of calcium-buffering capacity, as reflected by calbindin expression and neurogenesis, processes critical for DG plasticity and resilience. These findings underscore the therapeutic potential of LY341495 as a novel intervention targeting mGluR2/3 signaling in AD.

Importance Few of the available therapies for type 2 diabetes (T2D) comprehensively address disease burden beyond glycemic control. Examining whether berberine ursodeoxycholate (HTD1801), a first-in-class gut-liver anti-inflammatory metabolic modulator, has the potential to treat the core aspects of metabolic disease is important. Objective To assess the safety and efficacy of HTD1801 in patients with T2D that is inadequately controlled with diet and exercise. Design, Setting, and Participants This phase 2 double-blind, placebo-controlled, 12-week randomized clinical trial, conducted in China between March 2022 and January 2023, included patients with T2D who underwent 8 or more weeks of diet and exercise, had a hemoglobin A1c (HbA1c) level of 7.0% to 10.5%, and had a fasting plasma glucose (FPG) level less than 250.5 mg/dL. Interventions Patients were randomized 1:1:1 to placebo (n = 38), HTD1801 500 mg twice daily (n = 37), and HTD1801 1000 mg twice daily (n = 38). Main Outcomes and MeasuresThe primary end point was the HbA1c level change from baseline to week 12. Secondary end points included glycemic, hepatic, and cardiometabolic parameters. The primary end point was analyzed using a mixed-effects model for repeated measures, with the HbA1c level change from baseline as the dependent variable. Treatment group, measurement time point, and interaction between treatment group and measurement time point were independent variables. Results The study included 113 patients with T2D (mean [SD] age, 54.3 [10.6] years; 72 male [63.7%]) who were randomized. Among these patients, the mean (SD) HbA1c level was 8.2% (0.8%); body mass index, 25.5 (3.7), calculated as weight in kilograms divided by height in meters squared; and FPG level, 160.7 (38.3) mg/dL. Baseline disease severity was balanced across treatment groups. The primary end point was achieved with significant dose-dependent reductions in the HbA1c level in both HTD1801 groups compared with the placebo group. The least-squares mean difference in the HbA1c level at week 12 was -0.4% (95% CI, -0.79% to -0.03%; P = .04) for the 500-mg group and -0.7% (95% CI, -1.10% to -0.35%; P < .001) for the 1000-mg group compared with the placebo group. HbA1c level reductions were paralleled with mean (SD) improvements in the FPG level in both the 500-mg group (-13.0 [38.2] mg/dL) and the 1000-mg group (-18.4 [21.8] mg/dL) groups. Reductions were observed in lipids and markers of liver injury in the 1000-mg group. HTD1801 was safe and well tolerated, with 110 patients (97.3%) completing the study. Treatment-emergent adverse events, generally mild, occurred in 59 patients (52.2%) overall. One patient (in the 500-mg group) experienced a serious adverse event of retinal hemorrhage, which was unlikely related to treatment. No patients discontinued due to an adverse event. Conclusions and Relevance In this placebo-controlled randomized clinical trial, treatment with HTD1801 resulted in significant reductions in the HbA1c level and improvements in key cardiometabolic and liver parameters. HTD1801 was safe and well tolerated. These findings are being confirmed in ongoing phase 3 studies. The effects demonstrated by HTD1801 support an oral treatment option for T2D and its comorbidities.

Background:This study aimed to preliminarily explore the efficacy and safety of narlumosbart, an anti-RANKL monoclonal antibody, in treating postmenopausal women with osteoporosis. Methods:This multi-center, randomized, double -blind, placebo- and active-controlled study was conducted at 23 clinics across China between April 21, 2022 and April 19, 2023. Eligible patients were randomly assigned (1:1:1:1:1) to receive either 45 mg. 60 mg, 90 mg of narlumosbart, 60 mg of denosumab, or placebo, administered once every 6 months over a 12-month period, with the treatment allocation masked for participants, sponsors, and clinical investigators. The primary efficacy endpoint was the percentage change in lumbar spine bone mineral density (BMD) from baseline to 12 months. The secondary measures were percentage changes in lumbar spine, total hip, and femoral neck BMD, height changes, bone turnover markers, safety, and immunogenicity. Study registration: www.clinicaltrials.gov (NCT05278338). Findings:207 postmenopausal women with osteoporosis were enrolled and randomly assigned to received narlumosbart 45-90 mg (n = 41 in each group), denosumab (n = 42), or placebo (n = 42). At month 12, patients receiving narlumosbart 45 mg, 60 mg, and 90 mg had the percentage change in lumbar spine BMD from baseline (least-squares [LS] mean [standard error]) of 4.83% (0.65), 6.52% (0.62), and 5.74% (0.64), respectively, and all showed significant increases compared with the placebo group (0.63% [0.67]), with LS mean differences (99% confidence interval [CI]) of 4.20% (1.92∼6.48), 5.90% (3.63∼8.16), and 5.11% (2.84∼7.39), respectively (all P < 0.001). Treatment-emergent adverse events (TEAEs) were observed in 91.9% of patients in the pooled narlumosbart groups, and 92.9% in both the placebo and the denosumab groups. Most common TEAEs were decreased vitamin D levels (34.1% [pooled narlumosbart] vs. 35.7% [placebo] vs. 33.3% [denosumab]), COVID-19 (38.2% vs. 40.5% vs. 35.7%), and increased serum parathyroid hormone (22.8% vs. 14.3% vs. 19.0%). Interpretation:In this phase II trial of postmenopausal women with osteoporosis, narlumosbart demonstrated superiority over placebo in increasing BMD at 12 months following administration at 6-month intervals, with a tolerable safety profile in the short term, consistent with that of anti-RANKL monoclonal antibodies. Funding:This study was supported by Shanghai JMT-Bio Technology Co., Ltd.; National Key R&D Program of China [2021YFC2501700]; CAMS Innovation Fund for Medical Sciences (CIFMS) [2021-I2M-1-002]; National High Level Hospital Clinical Research Funding [2022-PUMCH-D-006]; the National Natural Science Foundation of China [No. 82270938, No. 81970757]; and the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2023-PT320-10].

Few of the available therapies for type 2 diabetes (T2D) comprehensively address disease burden beyond glycemic control. Examining whether berberine ursodeoxycholate (HTD1801), a first-in-class gut-liver anti-inflammatory metabolic modulator, has the potential to treat the core aspects of metabolic disease is important. To assess the safety and efficacy of HTD1801 in patients with T2D that is inadequately controlled with diet and exercise. This phase 2 double-blind, placebo-controlled, 12-week randomized clinical trial, conducted in China between March 2022 and January 2023, included patients with T2D who underwent 8 or more weeks of diet and exercise, had a hemoglobin A1c (HbA1c) level of 7.0% to 10.5%, and had a fasting plasma glucose (FPG) level less than 250.5 mg/dL. Patients were randomized 1:1:1 to placebo (n = 38), HTD1801 500 mg twice daily (n = 37), and HTD1801 1000 mg twice daily (n = 38). The primary end point was the HbA1c level change from baseline to week 12. Secondary end points included glycemic, hepatic, and cardiometabolic parameters. The primary end point was analyzed using a mixed-effects model for repeated measures, with the HbA1c level change from baseline as the dependent variable. Treatment group, measurement time point, and interaction between treatment group and measurement time point were independent variables. The study included 113 patients with T2D (mean [SD] age, 54.3 [10.6] years; 72 male [63.7%]) who were randomized. Among these patients, the mean (SD) HbA1c level was 8.2% (0.8%); body mass index, 25.5 (3.7), calculated as weight in kilograms divided by height in meters squared; and FPG level, 160.7 (38.3) mg/dL. Baseline disease severity was balanced across treatment groups. The primary end point was achieved with significant dose-dependent reductions in the HbA1c level in both HTD1801 groups compared with the placebo group. The least-squares mean difference in the HbA1c level at week 12 was −0.4% (95% CI, −0.79% to −0.03%; P = .04) for the 500-mg group and −0.7% (95% CI, −1.10% to −0.35%; P < .001) for the 1000-mg group compared with the placebo group. HbA1c level reductions were paralleled with mean (SD) improvements in the FPG level in both the 500-mg group (−13.0 [38.2] mg/dL) and the 1000-mg group (−18.4 [21.8] mg/dL) groups. Reductions were observed in lipids and markers of liver injury in the 1000-mg group. HTD1801 was safe and well tolerated, with 110 patients (97.3%) completing the study. Treatment-emergent adverse events, generally mild, occurred in 59 patients (52.2%) overall. One patient (in the 500-mg group) experienced a serious adverse event of retinal hemorrhage, which was unlikely related to treatment. No patients discontinued due to an adverse event. In this placebo-controlled randomized clinical trial, treatment with HTD1801 resulted in significant reductions in the HbA1c level and improvements in key cardiometabolic and liver parameters. HTD1801 was safe and well tolerated. These findings are being confirmed in ongoing phase 3 studies. The effects demonstrated by HTD1801 support an oral treatment option for T2D and its comorbidities. ClinicalTrials.gov Identifier: NCT06411275

Although current guidelines for type 2 diabetes (T2D) underscored the importance of attaining glycemic control and weight management goals, the patient perspectives on achieving these goals remained unclear in China. This study aimed to understand Chinese patients’ perspectives on stringent glycemic control (hemoglobin A1c [HbA1c] ≤ 6.5

A large number of clinical and animal studies have demonstrated that osteocalcin (OC) secreted by osteoblasts plays an important role in glucose metabolism. The purpose of this study was to further investigate the correlation between OC and different blood glucose markers in patients with type 2 diabetes.A total of 480 patients were divided into male group(n = 258) and postmenopausal female group(n = 258). OC, Glycated hemoglobin (HbA1c), Glycated albumin (GA) and 1,5-anhydroglucitol (1,5-AG) were measured. The correlation between serum osteocalcin level and different blood glucose markers were analyzed by Spearman correlation analysis and multiple linear regression. Spearman correlation analysis showed that in the male group, the OC level was negatively correlated with HbA1c (r=-0.252, p < 0.001) and GA (r = 0.158, p = 0.011), but positively correlated with 1, 5-AG (r = 0.204, p < 0.001). Similarly, in the postmenopausal female group, the OC level was found to have a negative relation with HbA1c (r=-0.286, p < 0.001) and GA (r=-0.160, p = 0.017), and a positive relation with 1, 5-AG (r = 0.329, p < 0.001). Different models were used to adjust for confounding factors. According to multiple stepwise regression analysis results, OC was an independent factor affecting the HbA1c and 1, 5-AG levels in both the male group and the postmenopausal female group. Serum osteocalcin was correlated with glycemic function in type 2 diabetes mellitus, and could be taken as an independent factor affecting not only long-term blood glucose but also short-term blood glucose, especially the postprandial hyperglycemia state.

All eight pangolin species, especially captive Manis pentadactyla, are critically endangered and susceptible to various pathogenic microorganisms, causing mass mortality. They are involved in the complement system, iron transport system, and inflammatory factors. M. pentadactyla exhibited a higher abundance of opportunistic pathogens, Moraxella, which potentially evaded complement-mediated immune response by reducing C5 levels and counteracting detrimental effects through transferrin neutralization. In addition, we found that the major structure of C5a, an important inflammatory factor, was lacking in M. javanica. In brief, this study revealed the differences in immune factors and microbiome between M. javanica and M. pentadactyla, thus providing a theoretical basis for subsequent immunotherapy.

Introduction: HTD1801 is a gut-liver anti-inflammatory metabolic modulator shown to improve key glycemic and cardiometabolic parameters. The aim of this study was to evaluate the effectiveness of HTD1801 across the T2DM disease spectrum. Method: In a Ph2 study of treatment-naïve patients with T2DM 113 patients were randomized 1:1:1 to placebo (n=38), HTD1801 500 mg BID (n=37), and 1000 mg BID (n=38) for 12 weeks. Key inclusion criteria included T2DM (WHO criteria), HbA1c 7%-10.5% and FPG <13.9 mmol/L. The primary endpoint was change from baseline (BL) in HbA1c at Week 12. For this analysis, patients were assigned to high/low risk groups by BL HbA1c above/below 8.5%. Result: At BL, 35% of patients had HbA1c ≥8.5%. BL characteristics were balanced between treatment groups and subgroups. Patients with elevated HbA1c had elevated glycemic and cardiometabolic parameters at BL. Treatment with HTD1801 for 12 weeks resulted in a dose dependent reduction across both subgroups (Table). Improvements with 1000 mg BID were significant vs placebo at Week 12. HTD1801 patients with higher HbA1c had more substantial reductions across all parameters compared to patients with lower HbA1c. Conclusion: Regardless of BL disease severity, HTD1801 treatment resulted in significant improvements in key glycemic and cardiometabolic parameters. HTD1801 continues to be evaluated for T2DM in Ph3 studies. Disclosure L. Ji: None. J. Ma: None. Y. Ma: None. Z. Cheng: None. S. Gan: None. G. Yuan: None. D. Liu: None. S. Li: None. Y. Liu: None. X. Xue: None. J. Bai: None. K. Wang: None. H. Cai: None. S. Li: None. K. Liu: Employee; Shenzhen HighTide Biopharmaceutical Ltd. Stock/Shareholder; Shenzhen HighTide Biopharmaceutical Ltd. M. Yu: Employee; Shenzhen HighTide Biopharmaceutical Ltd. Stock/Shareholder; Shenzhen HighTide Biopharmaceutical Ltd. L. Liu: Employee; Shenzhen HighTide Biopharmaceutical Ltd. Stock/Shareholder; Shenzhen HighTide Biopharmaceutical Ltd.

PURPOSE:Human evidence on the association between oxidative stress and osteoporosis is inconsistent. Fluorescent Oxidation Products (FlOPs) are global biomarkers of oxidative stress. We examined the associations of FlOPs (excitation/emission wavelengths 320/420 nm for FlOP_320, 360/420 nm for FlOP_360, and 400/475 nm for FlOP_400) with osteoporosis, bone microstructure, and bone turnover markers in humans and rats. METHODS:In humans, we conducted a 1:2 age, sex, hospital, and specimen-matched case-control study to test the association between FlOPs and osteoporosis diagnosed from dual-energy X-ray absorptiometry. In eight-week-old male Wistar rats, we administrated D-galactose and 0.9 % saline for 90 days in treatment and control groups (n = 8/group); micro-CT was used to determine bone microstructure. RESULTS:In humans, higher levels of FlOP_320 (OR for per 1 SD increase = 1.49, 95 % CI: 1.01-2.20) and FlOP_360 (OR for per 1 SD increase = 1.59, 95 % CI: 1.07-2.37) were associated with increased odds of osteoporosis. FlOP_400 were not associated with osteoporosis. D-galactose treated rats, as compared with control rats, showed higher levels of FlOP_320 and MDA, and lower P1NP levels during 90 days of experiment (all P < 0.05). The D-galactose group had lower trabecular bone volume fraction (0.07 ± 0.03 vs. 0.13 ± 0.05; P = 0.008) and volumetric BMD (225.4 ± 13.8 vs. 279.1 ± 33.2 mg HA/cm3; P = 0.001) than the control group. CONCLUSION:In conclusion, higher FlOP_320 levels were associated with increased odds of osteoporosis, impaired bone microstructure and decreased bone formation.

报道2例在吉林大学白求恩第二医院内分泌科就诊的2型糖尿病（T2DM）患者，由基础胰岛素联合口服降糖药物治疗调整为德谷胰岛素利拉鲁肽注射液取得了良好的效果。2例患者均为应用基础胰岛素联合口服降糖药血糖控制不佳（糖化血红蛋白分别为8.9%、9.5%）的成人T2DM患者，病程均约10年，胰岛功能欠佳，合并高脂血症、超重或腹型肥胖。结合患者个人意愿，转换为德谷胰岛素利拉鲁肽注射液联合口服药物降糖治疗后，血糖短期内改善并持续达标（<7 mmol/L），体重及腰围有不同程度下降，无胃肠道不良反应及低血糖事件，耐受程度及安全性良好。

Farnesyl diphosphate synthase (FDPS), an essential enzyme involved in the mevalonate pathway, is implicated in various diseases, including multiple types of cancer. As an RNA-binding protein (RBP), FDPS is also involved in transcriptional and post-transcriptional regulation. However, to the best of our knowledge, transcriptome-wide targets of FDPS still remain unknown. In the present study, FDPS expression patterns in pan-cancer were analyzed. In addition, it was investigated how FDPS overexpression (FDPS-OE) regulates the transcriptome in HeLa cells. FDPS-OE increased the proliferation rate in HeLa cells by MTT assay. Using transcriptome-wide high throughput sequencing and bioinformatics analysis, it was found that FDPS upregulated the expression levels of genes enriched in cell proliferation and extracellular matrix organization, including the laminin subunit γ2, interferon-induced proteins with tetratricopeptide repeats 2 and matrix metallopeptidase 19 genes. According to alternative splicing (AS) analysis, FDPS modulated the splicing patterns of the bone morphogenic protein 1, semaphorin 4D, annexin A2 and sirtuin 2 genes, which are enriched in the cell cycle and DNA repair, and are related to cell proliferation. To corroborate the FDPS-regulated transcriptome findings, FDPS was overexpressed in human osteosarcoma cells. Differentially expressed genes and regulated AS genes in the cells were both validated by reverse transcription-quantitative PCR. The results suggested that, as an emerging RBP, FDPS may serve an important role in transcriptome profiles by altering gene expression and regulating AS. FDPS also affected the cell proliferation rate. These findings broaden the understanding of the molecular functions of FDPS, and the potential of FDPS as a target in therapy should be investigated.

Abstract Diabetic nephropathy (DN) is a common chronic complication of diabetes mellitus (DM), and dapagliflozin, a representative drug of sodium-glucose co-transport protein 2 inhibitors (SGLT2i), is a novel hypoglycemic agent for the treatment of type 2 diabetes mellitus (T2DM), which has been shown to reverse microalbuminuria in early type 2 diabetic nephropathy (T2DN), but the mechanism of action remains to be elucidated. In this study, five patients with early T2DN treated in our hospital from October 2020 to May 2021 were selected for the study and were treated with insulin combined with dapagliflozin to lower glucose, and the initial insulin treatment was named as DN group, and the addition of dapagliflozin was named as DN-DAPA group, and another five patients with a healthy physical examination at the same period were selected as the blank control group (NC group). Patients' morning urine samples were collected and processed using iTRAQ unlabeled quantitative proteomics technology. Bioinformatics analysis was performed to obtain 193 differentially expressed proteins. 91 expressions were up-regulated and 72 expressions were down-regulated in the DN group compared with the NC group, and 11 expressions were up-regulated and 26 expressions were down-regulated in the DN-DAPA group compared with the DN group. Five significantly co-expressed protein molecules were screened at P < 0.05 and [logFC] >1.5: SOD1, SLC25A6, S100A13, PPP2R2A, CXCL12. Therefore, these differential proteins are associated with early T2DN injury. Molecularly, dapagliflozin improves mitochondrial oxidative stress and reduces urinary microalbumin excretion in early T2DN patients by inhibiting PPP2R2A and CXCL12/ S100A13 pathways to reverse early T2DN.

Improvement of glucose and insulin sensitivity remains an unmet medical need in diabetes management, in which the underlying cause of type 2 diabetes(T2D) was not well addressed by current treatment. We report the findings of a randomized, double-blind, placebo-controlled, phase 3 clinical trial (NCT03173391) to evaluate the efficacy and safety of dorzagliatin, a dual-acting glucokinase (GK) allosteric modulator, which enhances the GK activity in T2D patients in a glucose dependent manner, and has demonstrated its effects in blood glucose control through improvement of glucose sensitivity in T2D patients. Eligible drug-naïve T2D patients (n=463) were randomly assigned to dorzagliatin group or placebo group in a 2:1 ratio for a 24-week double-blind treatment, then followed by a 28-week open-label treatment with dorzagliatin in all patients. The primary efficacy endpoint was the change from baseline in the glycated hemoglobin (HbA1c) level at week 24. Safety was assessed throughout the trial. At week 24, the change from baseline in HbA1c was -1.07% in the dorzagliatin group and -0.50% with placebo (ETD, -0.57%; 95%CI, -0.79 to -0.36; P<0.001), and the effects sustained through 52 weeks. Improvement of β-cell function was demonstrated by an increase of HOMA2-β in dorzagliatin group over placebo group (2.56 vs -0.72; 95% CI, 0.44 to 6.11; P<0.05) at week 24. The incidence of adverse events(AEs) was similar between the two groups during the 24 weeks and most AEs were mild during 52 weeks. There were no severe hypoglycemia events and drug related serious adverse events. The incidence of hypoglycemia was 1 of 310 patients (0.3%) in the dorzagliatin group during the 24 weeks. There was no body weight gain during the study period. In drug-naïve T2D patients, dorzagliatin demonstrated fast onset and sustained glycemic control with a good safety and tolerability profile for 52 weeks.

In vitro and vivo studies indicate that oxidative stress contributes to bone loss. Fluorescent oxidation products (FlOPs) are novel biomarkers of oxidative stress; they reflect global oxidative damage of lipids, proteins, carbohydrates, and DNA. However, whether FlOPs are associated with bone mineral density (BMD) is still unclear. In the present study, we examined the association between FlOPs and BMD among male veterans. This cross-sectional study was conducted among participants recruited from the Department of Medical Examination, The Second Hospital of Jilin University in Jilin, China. We identified male veterans who were at least 50 y old between June and October of 2019. Plasma FlOPs were measured with a fluorescent microplate reader (excitation/emission wavelength: 320/420 nm). BMD were measured by dual-energy X-ray absorptiometry (DXA). The association between FlOPs and BMD was tested by multivariable linear regression models. A total of 164 male veterans were enrolled in the study, the average age was 56.6 y. After adjusting for covariates, veterans who had FlOP levels in the highest tertile had a statistically significant lower femoral neck (β = -0.044; p = 0.007) and total hip BMD (β = -0.045; p = 0.020) as compared to those with FlOP levels in the lowest tertile. Similar results were found when FlOPs were treated as a continuous variable (per 1-SD increase, β = -0.014 and p = 0.033 for femoral neck BMD; β = -0.016 and p = 0.047 for total hip BMD). Higher FlOP levels were associated with lower BMD among male veterans.

Objective: Expression of circular RNAs (circRNAs) in the peripheral blood of individuals with latent autoimmune diabetes in adults (LADA) and type 2 diabetes mellitus (T2DM) were quantified to identify dysregulated circRNAs compared with control individuals.Methods: circRNAs were obtained from the peripheral blood serum of 12 healthy adults and 12 individuals with LADA and 12 type 2 diabetics. The circRNA expression profiles were analyzed by high-throughput RNA sequencing. The most highly dysregulated circular RNAs were validated by quantitative real-time polymerase chain reaction. A circular RNA-microRNA (miRNA) network diagram predicted the interactions of circular RNAs, miRNAs, and coding genes.Results: A total of 2334 differentially expressed circRNAs were detected among the three groups, with 277 circRNAs in the Group DM versus Group NG; 992 circRNAs in the Group LADA versus Group NG and 1065 circRNAs in the Group DM versus Group LADA. Six circRNAs were identified as the most distinctive differentially expressed targets (p < 0.05). The proposed molecular functions of these differentially expressed circRNAS included the tumor necrosis factor signaling pathway, the FoxO signaling pathway, cellular senescence, and long-term potentiation (all false discovery rate p < 0.05) which may contribute to T2DM and LADA.Conclusion: circRNAs are aberrantly expressed in the peripheral blood of patients with T2DM and LADA and may interact with miRNA and circRNA-derived peptides in the development of diabetes. Further investigations may illustrate the partial pathogenesis of diabetes mellitus.Clinical Trial Registration number: ChiCTR1900020644.

BACKGROUND Lymphocytic hypophysitis（LYH） is an important condition to consider in the differential diagnosis of patients with a pituitary mass. The main clinical manifestations of LYH include headache, symptoms related to sellar compression, hypopituitarism, diabetes insipidus and hyperprolactinemia. Headache, which is a frequent complaint of patients with LYH, is thought to be related to the occupying effect of the pituitary mass and is rapidly resolved with a good outcome after timely and adequate glucocorticoid treatment or surgery.CASE SUMMARY Here, we report a patient with LYH whose initial symptom was headache and whose pituitary function assessment showed the presence of secondary hypoadrenalism, central hypothyroidism and hypogonadotropic hypogonadism. Pituitary magnetic resonance imaging showed symmetrical enlargement of the pituitary gland with suprasellar extension in a dumbbell shape with significant homogeneous enhancement after gadolinium enhancement. The size of the gland was approximately 17.7 mm × 14.3 mm × 13.8 mm. The pituitary stalk was thickened without deviation, and there was an elevation of the optimal crossing. The lesion grew bilaterally toward the cavernous sinuses, and the parasternal dural caudal sign was visible. The patient presented with repeatedly worsening and prolonged headaches three times even though the hypopituitarism had fully resolved after glucocorticoid treatment during this course.CONCLUSION This rare headache regression suggests that patients with chronic headaches should also be alerted to the possibility of LYH.

维生素D对机体钙磷代谢、细胞生长和分化方面具有十分重要的作用.近几十年来研究证实糖脂代谢、炎症反应及免疫调节等生物过程均有维生素D的参与.机体几乎所有细胞均具有维生素 D 受体(Vitamin D receptor,VDR),如:心肌细胞、胰腺细胞、脂肪细胞等,维生素 D通过与 VDR结合,在机体中发挥调节作用.维生素 D介导了多种疾病的发病.大量研究证实,维生素 D在糖代谢疾病的发病中具有重要作用.维生素 D 对胰岛β细胞还有保护作用,是胰岛β细胞的保护因子之一,对机体血糖平衡和胰岛素的合成分泌过程具有重要作用.

An 82-year-old female patient received monotherapy with nivolumab (240 mg by an IV infusion on the firsr day, 14 days as a cycle) because of multiple metastases of central adenocarcinoma in the right upper lobe of the lung. After 8 cycles of immunotherapy (about 4 months), the patient developed severe nausea and vomiting. Laboratory tests showed random blood glucose 43.2 mmol/L and β-hydroxybutyric acid 5.3 mmol/L. Blood gas analysis showed pH 7.01, bicarbonate root 4.0 mmol/L, alkali residual -22.4 mmol/L, serum potassium 6.1 mmol/L, and lactic acid 2.9 mmol/L. The patient had no previous history of diabetes mellitus. Fulminant type 1 diabetes mellitus due to nivolimab was considered. Nivolumab was stopped and rehydration, hypoglycemia, acidosis correction, and other symptomatic treatments were given. Two days later, her symptoms were improved obviously. Laboratory tests showed fasting plasma glucose 15.8 mmol/L and β-hydroxybutyric acid 0.2 mmol/L. Blood gas analysis showed pH 7.39, bicarbonate root 21.2 mmol/L, alkali residual -3.8 mmol/L, serum potassium 4.3 mmol/L, and lactic acid 1.0 mmol/L.

Abstract Background Osteoporosis and cardiovascular diseases (CVDs) are 2 major public health problems. Osteoporosis and CVDs may be linked but the association between lipid profile and osteoporosis is still controversial. The purpose of this study was to examine the associations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) with osteoporosis. Methods Using inpatients’ and outpatients’ electronic medical records (EMR) and dual X-ray absorptiometry (DXA) database stored at The Second Hospital of Jilin University, we included 481 individuals with complete and valid lipid and bone mineral density (BMD) data in 2017. Serum samples were used to measure TC, LDL-C, HDL-C and TG. Femoral neck and total hip BMD were measured by DXA; osteoporosis was defined as femoral neck or total hip T-score ≤ -2.5. Multivariable logistic regression models were used to test the associations of TC, LDL-C, HDL-C and TG with osteoporosis. Results The mean age for included individuals was 62.7 years (SD = 8.6 years); 60.1 % of them were female. Each standard deviation (SD) increase in TC (Odds Ratio [OR]: 1.48; 95 % Confidence Interval [CI]: 1.06–2.07) and TG (OR: 1.67; 95 % CI: 1.16–2.39) were associated with increased risk of osteoporosis; LDL-C and HDL-C levels were not associated with osteoporosis. Age, sex and body mass index (BMI) did not interact with the relationships of TC and TG with osteoporosis (all P > 0.10). Conclusions Higher TC and TG levels were associated with greater risk of osteoporosis in this cross-sectional study.