Introduction:Real-world data on the effect of polyethylene glycol loxenatide (PEG-Loxe) in patients with Type 2 diabetes mellitus (T2DM) with normal body mass index (BMI) are lacking. Therefore, this study aims to observe the effect of PEG-Loxe on the weight of patients with T2DM with different BMIs. Methods:This single-center, retrospective real-world study included patients with T2DM, aged ≥ 18 years, and receiving PEG-Loxe/sodium-glucose cotransporter 2 inhibitor (SGLT2i). The primary endpoint was change in body weight after 24 weeks of treatment. Secondary endpoints included proportion of patients with body weight reduction < 5.0% and < 10%, changes in BMI, and glycosylated hemoglobin (HbA1c). Results:Overall, 487 patients treated with SGLT2i or PEG-Loxe were identified; after propensity score matching, 68 patients were included in each group. After 24 weeks, the mean change in body weight and BMI was -1.2 (-2.3, -0.1) and -0.4 (-0.8, -0.1) in the PEG-Loxe group and -2.4 (-3.5, -1.3) and -0.7 (-1.1, -0.4) in the SGLT2i group. A ≥ 5% and ≥ 10% weight loss was noted by 32.4% and 8.8% of patients in the PEG-Loxe group, with a mean change in HbA1c (%) of -1.48 (-1.98, -0.99). Weight loss (≥ 5%) in obese patients (BMI > 28 kg/m2) was greater (PEG-Loxe: 53.3%, SGLT2i: 57.1%) compared to patients with 24 ≤ BMI < 28 kg/m2 (PEG-Loxe: 25.7%, SGLT2i: 41.4%) and BMI < 24 kg/m2 (PEG-Loxe: 27.8%, SGLT2i: 28%). Conclusion:PEG-Loxe resulted in weight loss and glycemic control in patients with T2DM. The weight loss was negatively correlated with baseline BMI without excessive weight loss in normal BMI, supporting PEG-Loxe's use in this group. Trial Registration: Chinese Registry of Clinical Trials: ChiCTR2400087532.

Enterohepatic circulation is essential for maintaining a constant bile acid concentration. Diseases with enterohepatic circulation disturbances are usually difficult to diagnose definitively without the time-consuming and expensive genetic tests. This study analyzed and compared duodenal fluid in patients with biliary atresia (BA), familial intrahepatic cholestasis 2 (FIC2), and sodium taurocholate cotransporting polypeptide (NTCP) deficiency. This study aimed to assess the diagnostic value of duodenal fluid analysis in patients with enterohepatic circulation disturbance. This study retrospectively analyzed data from 18 patients with BA, 13 patients with FIC2, and 15 patients with NTCP deficiency. All patients completed the duodenal tube tests before receiving treatment for cholestasis. The patients were intubated through the right nasal cavity to the middle or lower duodenum, as confirmed by radiography. 3-5 mL of duodenal fluid was collected at last. Clinical presentations, laboratory data, genetic data, and so forth were collected for the analysis. Among the 3 types of diseases, levels of total bile acid (TBA), total bilirubin (TB), direct bilirubin (DB), and gamma-glutamyl transpeptidase (GGT) in duodenal fluid showed significant differences (P < .01). Compared with the same indications in duodenal fluid, levels of TBA and GGT in serum did not show significant differences between patients with FIC2 and NTCP deficiency (P > .05). Duodenal TBA/serum TBA ratio, duodenal TB/serum TB ratio, duodenal DB/serum DB ratio, and duodenal GGT/serum GGT ratio also showed significant differences between patients with BA and NTCP deficiency, between patients with FIC2 and NTCP deficiency (P < .01). For diagnosis of BA, increased GGT and absent TB, DB, and TBAs had a sensitivity of 100%, 100%, 100%, and 100%, a specificity of 86.1%, 100%, 97.2%, and 97.2%. Duodenal tube tests have been used for the diagnosis of BA for over 10 years. Our findings support the duodenal fluid analysis as a tool for prompt timely diagnosis of BA. This study also indicates that the test is a useful diagnostic method with high accuracy for other diseases with enterohepatic circulation disturbance.

AimsTo map transcriptome-wide N6-methyladenosine (m6A) profile at different stages of type 1 diabetes (T1D).Materials & MethodsRNA extracted from islet tissues of non-obese diabetic mice at different ages (4-week-old control group, 8-week-old pre-diabetes group, and 14-week-old diabetes group) was analyzed by MeRIP-seq and mRNA-seq. Bioinformatics analyses, including m6A motif enrichment, differential methylation, gene ontology and pathway analysis.ResultsBioinformatic analysis revealed a progressive increase in m6A methylation sites and unique peaks throughout diabetes progression. The predominant m6A motif was "GGACU" in the control and pre-diabetes stages, shifting to "GGACU/A" in the diabetes stage. m6A modifications were primarily enriched at the start codon, coding region, and stop codon. Integrated analysis found pre-diabetes, diabetes groups showed distinct m6A and mRNA changes versus control. Pathway analysis indicated that differentially expressed mRNAs with m6A methylation were predominantly enriched in insulin/IGF-MAPKK/MAPK cascades, apoptosis, T-cell activation, interleukins, CCKR, and inflammation-related pathways in the pre-diabetes stage. As diabetes progressed, additional pathways, including Wnt, EGF receptor, PDGF, GnRH receptor, and angiogenesis, became involved in disease development. In vitro, cytokine stimulation of INS-1 cells increased m6A methylation, upregulated METTL3, downregulated ALKBH5.Conclusionsm6A methyl group dynamics in T1D disease progression, potentially influencing mRNA expression and signal transduction pathways.

BACKGROUND:The Notch signaling pathway plays a crucial role in intrahepatic bile duct development. Here, we aimed to investigate the effect of the Notch receptor, NOTCH2, on intrahepatic bile duct development to better understand congenital intrahepatic bile duct dysplasia. RESULTS:Estradiol increased NOTCH2 and its downstream proteins expression, which promoted the differentiation of hepatoblasts into intrahepatic cholangiocytes and the development of intrahepatic bile ducts by upregulating the Notch signaling pathway. NOTCH2 siRNA inhibited the above processes (P < 0.05). There was no significant difference between estradiol and estradiol + non-targeting siRNA groups (P > 0.1). CONCLUSIONS:In conclusion, the activation of the Notch signaling pathway leads to increased NOTCH2 expression, which promotes the differentiation of hepatoblasts into intrahepatic cholangiocytes and the development of intrahepatic bile ducts during embryonic stages in C57BL/6CrSlc mice. The results of this study may provide a theoretical basis for infantile intrahepatic cholestasis treatment.

To investigate the potential mediating effect of remnant cholesterol (RC) in the associations between angiopoietin-like 8 (ANGPTL8) and the risk of all-cause, cardiovascular disease (CVD), and cancer death. This prospective observational study included 3278 individuals from China. Binary logistic regression and mediation analyses were conducted to investigate the mediating effect of RC in the associations between ANGPTL8 and all-cause, CVD, and cancer death. During up to 5-year follow-up, a total of 265 deaths (8.08

Previous studies have been limited by their inability to differentiate between the effects of insulin sensitivity and β-cell function on the risk of kidney function decline, cardiovascular disease (CVD), and all-cause mortality. To address this knowledge gap, we aimed to investigate whether the physiological subtypes based on homeostasis model assessment-2 (HOMA2) indices of β-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) could be used to identify individuals with subsequently high or low of clinical outcome risk. This retrospective cohort study included 7,317 participants with a follow-up of up to 5 years. Based on HOMA2 indices, participants were categorized into four physiologic subtypes: the normal phenotype (high insulin sensitivity and high β-cell function), the insulinopenic phenotype (high insulin sensitivity and low β-cell function), the hyperinsulinaemic phenotype (low insulin sensitivity and high β-cell function), and the classical phenotype (low insulin sensitivity and low β-cell function). The outcomes included kidney function decline, CVD events (fatal and nonfatal), and all-cause mortality. Cox regression models were used to calculate hazard ratios (HRs) for outcomes, and spline models were used to examine the dose-dependent associations of HOMA2-B and HOMA2-S with outcomes. A total of 1,488 (20.3

Inhibition of immunocyte infiltration and activation has been suggested to effectively ameliorate nonalcoholic steatohepatitis (NASH). Paired immunoglobulin-like receptor B (PirB) and its human ortholog receptor, leukocyte immunoglobulin-like receptor B (LILRB2), are immune-inhibitory receptors. However, their role in NASH pathogenesis is still unclear. Here, we demonstrate that PirB/LILRB2 regulates the migration of macrophages during NASH by binding with its ligand angiopoietin-like protein 8 (ANGPTL8). Hepatocyte-specific ANGPTL8 knockout reduces MDM infiltration and resolves lipid accumulation and fibrosis progression in the livers of NASH mice. In addition, PirB −/− bone marrow (BM) chimeras abrogate ANGPTL8-induced MDM migration to the liver. And yet, PirB ectodomain protein could ameliorate NASH by sequestering ANGPTL8. Furthermore, LILRB2-ANGPTL8 binding-promoted MDM migration and inflammatory activation are also observed in human peripheral blood monocytes. Taken together, our findings reveal the role of PirB/LILRB2 in NASH pathogenesis and identify PirB/LILRB2-ANGPTL8 signaling as a potential target for the management or treatment of NASH.

Aims: To investigate the associations between metabolic score for visceral fat (METS-VF) and clinical outcomes among populations with different glucose tolerance statuses.Methods: We analysed 6827 participants aged & GE; 40 years with different glucose tolerance statuses from a cohort study. The associations between METS-VF and cardiovascular disease (CVD) events and all-cause mortality were assessed using Cox regression, restricted cubic spline and receiver operating characteristic curves. Results: During a follow-up of 5.00 years, there were 338 CVD events and 307 subjects experienced all-cause death. The METS-VF quartile (Quartile 4 versus 1) was significantly related to CVD events [adjusted HRs and 95% CIs: 5.75 (2.67-12.42), 2.80 (1.76-4.48), and 3.31 (1.28-8.54) for subjects with normal glucose tolerance, prediabetes and diabetes, respectively] and all-cause mortality [adjusted HRs and 95% CIs: 2.80 (1.43-5.49), 4.15 (2.45-7.01), and 4.03 (1.72-9.42), respectively]. Restricted cubic spline suggested a dose-response asso-ciation of METS-VF with the risk of CVD events and all-cause mortality. The area under curve for CVD events and all-cause mortality was higher for METS-VF than for the other obesity and IR indexes in subjects with different glucose tolerance statuses. Conclusions: The METS-VF was associated with an increased risk of CVD events and all-cause mortality and could be used as a predictive index of the risk of CVD events and all-cause mortality among populations with different glucose tolerance statuses.

患者,42岁,社会性别男,已婚,未育,因"体检发现肾上腺肿物1周余"于2020年11月2日就诊于我院.患者2022年10月22日于当地医院体检,行腹部超声检查发现肾上腺肿块,CT检查提示双侧肾上腺结节灶,无明显不适症状,为求进一步诊治,来我院就诊,以"肾上腺肿物"收入院.患者30年前行尿道下裂手术,父母为近亲结婚,母亲孕期无特殊药物接触史.

Oestradiol (E2) is a critical factor for multiple systems' development during the embryonic period. Here, we aimed to investigate the effects of oestradiol on intrahepatic bile duct development, which may allow a better understanding of congenital bile duct dysplasia. DLK+ hepatoblasts were extracted from the C57BL/6CrSlc foetal mice and randomly divided into control group, oestradiol groups (1, 10, 100 nM) and oestradiol (10 nM) + DAPT (inhibitor of Notch signalling; 40 µM) group for in vitro experiments. For in vivo analysis, pregnant mice were divided into control group, oestradiol (intraperitoneal injection of 0.6 mg/kg/day) ± DAPT (subcutaneous injection of 10 mg/kg/day) groups and tamoxifen (gavage administration of 0.4 mg/kg/day) group. The results showed that oestradiol promoted hepatoblast differentiation into cholangiocytes and intrahepatic bile duct development during the embryonic period. Tamoxifen, an antioestrogenic drug, inhibited the above processes. Moreover, oestradiol promoted the expression of Notch signalling pathway-associated proteins and genes both in vitro and in vivo. Notably, DAPT addition inhibited the oestradiol-mediated effects. In conclusion, oestradiol can promote hepatoblast differentiation into cholangiocytes and intrahepatic bile duct development of C57BL/6CrSlc mice during embryonic period via the Notch signalling pathway.

ABSTRACT:Coronavirus disease 2019 (COVID-19) has been a rampant worldwide health threat and we aimed to develop a model for early prediction of disease progression.This retrospective study included 124 adult inpatients with COVID-19 who presented with severe illness at admission and had a definite outcome (recovered or progressed to critical illness) during February 2020. Eighty-four patients were used as training cohort and 40 patients as validation cohort. Logistic regression analysis and receiver operating characteristic curve (ROC) analysis were used to develop and evaluate the prognostic prediction model.In the training cohort, the mean age was 63.4 ± 1.5 years, and male patients (48, 57%) were predominant. Forty-three (52%) recovered, and 41 (49%) progressed to critical. Decreased lymphocyte count (LC, odds ratio [OR] = 4.40, P = .026), elevated lactate dehydrogenase levels (LDH, OR = 4.24, P = .030), and high-sensitivity C-reactive protein (hsCRP, OR = 1.01, P = .025) at admission were independently associated with higher odds of deteriorated outcome. Accordingly, we developed a predictive model for disease progression based on the levels of the 3 risk factors (LC, LDH, and hsCRP) with a satisfactory performance in ROC analysis (area under the ROC curve [AUC] = 0.88, P < .001) and the best cut-off value was 0.526 with the sensitivity and specificity of 75.0% and 90.7%, respectively. Then, the model was internally validated by leave-one-out cross-validation with value of AUC 0.85 (P < .001) and externally validated in another validation cohort (26 recovered patients and 14 progressed patients) with AUC 0.84 (P < .001).We identified 3 clinical indicators of risk of progression and developed a severe COVID-19 prognostic prediction model, allowing early identification and intervention of high-risk patients being critically illness.

Background While orbital decompression can alleviate optic nerve compression and prevent further vision loss in dysthyroid optic neuropathy (DON), it cannot relieve inflammatory symptoms. Very high doses of intravenous glucocorticoids (GCs) are the first-line therapy for DON; however, the effective rate is only 40% and might be much lower in patients who fail high-dose GC pulse therapy and progressed to DON. The results of two case series studies indicated that rituximab treatment had a much better curative effect compared to very high doses of intravenous GCs, but some patients required urgent orbital decompression after rituximab injection because rituximab might lead to the release of cytokines, aggravated intraorbital edema, and further vision loss. Methods We retrospectively studied the therapeutic process of two Grave’s ophthalmopathy (GO) patients complicated with DON who failed high-dose GC pulse therapy and underwent orbital decompression. Both patients received single-dose (500 mg) rituximab treatment. Results During more than 2 years of follow-up, rituximab treatment exhibited significant improvement in inflammatory symptoms, as manifested by a substantial decrease in Clinical Activity Score (CAS); meanwhile, the vision of both patients improved significantly and their diplopia was relieved. Conclusions The results of this study were consistent with those of two previous case series studies indicating the significant and lasting effect of rituximab treatment on DON, especially for patients with GC resistance or recurrence after GC therapy. Orbital decompression before rituximab treatment might reduce the incidence of rapid vision loss and urgent orbital decompression surgery caused by aggravated orbital edema after rituximab injection; however, the necessity for preventive decompression surgery requires further study.

AIMS/INTRODUCTION:The triglyceride-glucose (TyG) index has been proposed as a reliable and simple marker of insulin resistance. We investigated the association between TyG index and diabetic nephropathy (DN) in patients with type 2 diabetes. MATERIALS AND METHODS:A consecutive case series of 682 adult patients with type 2 diabetes hospitalized in the Department of Endocrinology at the Tongji Hospital (Wuhan, Hubei, China) from January 2007 to December 2009 was included in this cross-sectional analysis. Receiver operating characteristics curve analysis, correlation analysis and multiple logistic regression analysis were carried out. RESULTS:A total of 232 (34.0%) participants were identified with DN. Compared with the non-DN group, the DN group had longer disease duration, and higher bodyweight, systolic blood pressure, diastolic blood pressure, glycated hemoglobin, triglycerides, total cholesterol, serum uric acid, 24 h-urinary albumin, TyG index and homeostasis model assessment 2 estimates for insulin resistance (HOMA2-IR; P < 0.05 for each). The TyG index with an optimal cut-off point >9.66 showed a higher area under the receiver operating characteristic curve of 0.67 (P = 0.002) than HOMA2-IR (area under the curve 0.61, P = 0.029) on receiver operating characteristic curve analysis for DN identification. Additionally, the TyG index positively correlated with the levels of metabolic indicators (bodyweight, glycated hemoglobin, triglycerides, total cholesterol, serum uric acid, fasting glucose and HOMA2-IR) and natural logarithmic 24 h-urinary albumin (P < 0.05 for each), but not natural logarithm of estimated glomerular filtration rate. On multiple regression analysis, an increased TyG index was shown to be an independent risk factor (odds ratio 1.91, P = 0.001) for DN. CONCLUSIONS:The TyG index was independently associated with DN in patients with type 2 diabetes, and was a better marker than HOMA2-IR for identification of DN in type 2 diabetes patients.

Background Acute myocardial injury and heart failure characterized by elevated cardiac troponin and decreased heart pump function are significant clinical features and prognostic factors of coronavirus disease-19 (COVID-19). Triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio is an indicator of insulin resistance. This study aimed to explore the association of the TG/HDL-C ratio with cardiovascular risk and prognosis in COVID-19. Methods Ninety-eight laboratory-confirmed patients with COVID-19 admitted in a tertiary teaching hospital in Wuhan, China, were enrolled in this retrospective study. Regression models were used to investigate the association between TG/HDL-C ratio with myocardial injury, heart failure, severity, and mortality in COVID-19. Results Among the 98 patients, the mean age was 63.9±1.4 years, and male sex (58, 59%) was predominant. Forty-six patients (47%) were admitted to the intensive care unit (ICU), 32 (33%) and 46 (47%) patients suffered from myocardial injury and heart failure, respectively, and 36 (37%) patients died. The TG/HDL-C ratio was increased in patients with myocardial injury, heart failure, severe illness, and fatal outcome (P<0.05 for each). Baseline TG/HDL-C ratio significantly correlated with log transformed levels of plasma high-sensitivity cardiac troponin I (r=0.251, P=0.018), N-terminal brain natriuretic propeptide (r=0.274, P=0.008), glycated hemoglobin (r=0.239, P=0.038), and interleukin-6 (r=0.218, P=0.042). Multivariate logistic regression analysis showed that an increased TG/HDL-C ratio was independently associated with the risk of myocardial injury [odds ratio (OR)=2.73; P=0.013], heart failure (OR=2.64; P=0.019), disease severity (OR=3.01; P=0.032), and fatal outcome (OR=2.97; P=0.014). Conclusion Increased TG/HDL-C ratio was independently associated with myocardial injury, heart failure, disease severity, and mortality in patients with COVID-19, and it may be a useful marker for early identification of patients with high risk and poor outcome.

Abstract Aims/Introduction This study aimed to explore the association between glycemic control before admission with severity and mortality of coronavirus disease 2019, and tried to reveal the mechanism. Materials and Methods A total of 77 inpatients were grouped into sufficient control group (glycated hemoglobin [HbA1c] <6.5%, n = 49) and insufficient control group (HbA1c ≥6.5%, n = 28). Regression models were used to analyze the clinical data. Results Compared with patients with HbA1c <6.5, patients with HbA1c ≥6.5 showed higher heart rate (101 vs 89 b.p.m., P = 0.012), lower percutaneous oxygen saturation (93 vs 97%, P = 0.001), higher levels of multiple indicators of inflammation, such as white blood cell count (7.9 vs 5.9 × 109/L, P = 0.019), neutrophil count (6.5 vs 4.1 × 109/L, P = 0.001), high‐sensitivity C‐reactive protein (52 vs 30 mg/L, P = 0.025) and serum ferritin (1,287 vs 716 μg/L, P = 0.023), as well as lower levels of lymphocyte count (0.7 vs 0.8 × 109/L, P = 0.049) at hospital admission. Thus, patients with HbA1c ≥6.5 were more likely to develop secondary respiratory infections (25 [89%] vs 33 [67%], P = 0.032) and acute respiratory distress syndrome (17 [61%] vs 14 [29%], P = 0.006) than patients with HbA1c <6.5, resulting in a higher proportion of critically ill patients (19 [68%] vs 18 [37%], P = 0.009) and non‐survivors (13 [46%] vs 11 [22%], P = 0.029). After adjustment for potential risk factors, HbA1c was independently associated with in‐hospital death. Conclusion HbA1c was an independent risk factor for poor outcomes in coronavirus disease 2019 patients. Severe pulmonary infection and consequent acute respiratory distress syndrome might be the primary causes of death in insufficient glycemic control patients.

Rationale: Neonatal cholestasis is one of the most serious diseases in infancy. Progressive familial intrahepatic cholestasis (PFIC) is a disease that leads to intrahepatic cholestasis. It is one of the common causes of neonatal cholestasis in addition to biliary atresia (BA). The differential diagnosis of neonatal cholestasis is clinically challenging for pediatricians. Patient concerns: A 4-month-old female presented with severe jaundice, pruritus, and pale stool for 20 days. Abnormally strong echoes near the portal area, an abnormally small gallbladder with an irregularly stiff wall, and splenomegaly were identified on abdominal ultrasound. Blood tests showed elevated alanine aminotransferase, total bilirubin, conjugated bilirubin, gamma-glutamyltranspeptidase, and total bile acid levels. Diagnosis: Intraoperative cholangiography showed BA. ABCB4 gene mutation IVS13+6G>A/G was confirmed by genetic testing. The patient was diagnosed with BA combined with PFIC3. Interventions: Kasai portoenterostomy and ursodeoxycholic acid were used for treatment. Outcomes: Her clinical symptoms and blood tests improved gradually. No recurrence was noted during 1 year of follow-up. Lessons: Additional examinations, such as genetic testing, should be considered in patients with BA who had refractory jaundice after Kasai portoenterostomy in order to exclude intrahepatic cholestasis.

Until now, the recognition of sodium taurocholate cotransporting polypeptide (NTCP) deficiency has been mainly based on sporadic case reports. It was previously believed to be mildly symptomatic and resulting in mild liver dysfunction. However, to our knowledge, there have been no reports about the histopathologic and ultrastructural pathologic characteristics of the disease. The aim of the study was to analyze the clinical, histopathologic and ultrastructural pathologic characteristics of NTCP deficiency in 13 pediatric patients.From August 2012 to October 2018, this retrospective study conducted in the Department of Pediatrics of Tongji Hospital, China analyzed the data of 13 NTCP deficient patients with an SLC10A1 gene mutation. Except for NTCP deficiency, no other liver diseases were present in the patients, which was determined by both a genetic testing panel for jaundice and by reviewing medical records. The laboratory results, imaging, histopathologic, and ultrastructural pathologic information were recorded for analysis.The serum level of total bile acid was high in all 13 patients. All patients had adequate growth and development. Eight of the patients (8/13) presented with visible jaundice and 12 (12/13) were found to have hyperbilirubinemia. A needle liver biopsy was performed in 11 cases, which revealed slightly chronic inflammation in all 11 patients. One of the patients (1/13) was found to be suffering from gallstones.The data showed that although NTCP deficiency was often asymptomatic, some of the patients showed obvious clinical expressions, such as jaundice. Among the 13 pediatric patients with NTCP deficiency, both the biochemical and histopathologic features were similar to those of mild hepatocellular jaundice. In addition, it was determined that the clinical features in the patient with gallstones may have been caused by NTCP deficiency.

患者，男，18岁，因“烦渴、多饮、多尿伴体重下降10天”入院。患者入院前10天体重下降1．5 kg，随机静脉血糖23．0 mmol／L，给予预混人胰岛素30R 早餐前16 U，晚餐前10 U 皮下注射，治疗3天后，空腹血糖波动在8．6～13．0 mmol／L，餐后2小时血糖波动在10．7～15．7 mmol／L，门诊以“糖尿病”收入我科。患者出生为顺产，父母非近亲，无糖尿病家族史。嗅觉及视力正常，智力尚可，12～13岁后身高及体重高于同龄人，偶有夜间遗精现象，平素喜食零食，性格较暴躁。入院体检：血压124／87 mmHg，身高179 cm，体重92 kg，体重指数28．71 kg／m2，上部量84 cm，下部量95 cm，臂展185 cm，腰围103 cm，肤质细腻，无胡须，喉结不明显，音调较高，甲状腺无肿大，乳晕色淡，无乳腺增生，腹膨隆，双下腹可见紫纹，外生殖器 Tanner 2期：阴毛稀疏，双侧睾丸大小约3 ml，质偏硬，阴茎长约3．0 cm。

BACKGROUNDMultiple myeloma (MM), a clonal B cell malignancy characterized by the proliferation of plasma cells within the bone marrow, is still an incurable disease, and therefore, finding new therapeutic targets is urgently required. Although microRNA-137 (miR-137), which is involved in a variety of cellular processes, has been reported to be under-expressed in many types of solid tumors, its role in MM is less known.METHODSIn this study, the target gene and the potential effect of miR-137 in MM were investigated. .RESULTSThe results showed significantly down regulated expression of miR-137 in MM cell lines and in the CD138+ bone marrow mononuclear cells of MM patients. A dual luciferase reporter gene analysis revealed that MITF is a direct target of miR-137. The overexpression of miR-137 or transfection of MITF-shRNA had no significant effect on the expression of serine/ threonine protein kinase (AKT), but the expression of MITF, c-MET, p-AKT, and its phosphorylated substrate protein decreased significantly, which was accompanied by an increase in p53 expression. In addition, the overexpression of miR-137 or MITF-shRNA significantly improved the 36-hour inhibition rate and apoptosis rate in multiple myeloma cells treated with dexamethasone. The overexpression of MITF could counteract the biological effect of miR-137 in multiple myeloma cells.CONCLUSIONWe conclude that MITF is a direct target of miR-137. The miR-137 can improve the dexamethasone sensitivity in multiple myeloma cells by reducing the c-MET expression and further decreasing the AKT phosphorylation via targeting MITF.