Obesity is a worldwide health problem. An imbalance in energy metabolism is an important cause of obesity and related metabolic diseases. Our previous studies showed that inhibition of miR-429 increased the protein level of uncoupling protein 1 (UCP1) in beige adipocytes; however, whether local inhibition of miR-429 in subcutaneous adipose tissue affects diet-induced obesity and related metabolic disorders remains unclear. The aim of this study was to investigate the effect of local overexpression of miR-429 sponge in subcutaneous adipose tissue on obesity and related metabolic disorders. The control adeno-associated virus (AAV) or AAV expressing the miR-429 sponge was injected into mouse inguinal white adipose tissue. Seven days later, the mice were fed a high-fat diet for 10 weeks to induce obesity. The effects of the miR-429 sponge on body weight, adipose tissue weight, plasma glucose and lipid levels, and hepatic lipid content were explored. The results showed that the overexpression of miR-429 sponge in subcutaneous white adipose tissue reduced body weight and fat mass, decreased fasting blood glucose and plasma cholesterol levels, improved glucose tolerance, and alleviated hepatic lipid deposition in mice. Mechanistic investigation showed that the inhibition of miR-429 significantly upregulated the expression of UCP1 in adipocytes and adipose tissue. These results suggest that local inhibition of miR-429 in subcutaneous white adipose tissue ameliorates obesity and related metabolic disorders potentially by upregulating UCP1, and miR-429 is a potential therapeutic target for the treatment of obesity and related metabolic disorders.
Animals ; MicroRNAs/physiology* ; Obesity/metabolism* ; Mice ; Adipose Tissue, White/metabolism* ; Metabolic Diseases ; Subcutaneous Fat/metabolism* ; Male ; Uncoupling Protein 1/metabolism* ; Diet, High-Fat ; Mice, Inbred C57BL

Hereditary angioedema (HAE) is an autosomal dominant inherited disease characterized by recurrent and unpredictable episodes of subcutaneous or submucosal edema. These attacks could induce fatal risk when larynx is involved. The estimated prevalence of HAE is about 1 in 50 000. Due to its rarity and the diversity of clinical manifestations, HAE is known little by related physicians and misdiagnosis and mistreatment happens very often. Therefore, it is crucial to improve physicians′ understanding of HAE. To address this, a comprehensive management approach for the diagnosis and treatment of HAE have developed in our hospital. This approach includes intra-hospital multi-disciplinary treatment (MDT), collaboration with provincial network hospitals, patient education online and offline interacting with media propaganda. By implementing this approach, the diagnostic precision was significantly improved, the diagnostic time was significantly shortened, and the frequency of emergency interventions for severe laryngeal edema was significantly reduced. Additionally, the collection of data from HAE patients has provided valuable clinical insights for the diagnosis and treatment of HAE in China.

Hereditary angioedema (HAE) is an autosomal dominant inherited disease characterized by recurrent and unpredictable episodes of subcutaneous or submucosal edema. These attacks could induce fatal risk when larynx is involved. The estimated prevalence of HAE is about 1 in 50 000. Due to its rarity and the diversity of clinical manifestations, HAE is known little by related physicians and misdiagnosis and mistreatment happens very often. Therefore, it is crucial to improve physicians′ understanding of HAE. To address this, a comprehensive management approach for the diagnosis and treatment of HAE have developed in our hospital. This approach includes intra-hospital multi-disciplinary treatment (MDT), collaboration with provincial network hospitals, patient education online and offline interacting with media propaganda. By implementing this approach, the diagnostic precision was significantly improved, the diagnostic time was significantly shortened, and the frequency of emergency interventions for severe laryngeal edema was significantly reduced. Additionally, the collection of data from HAE patients has provided valuable clinical insights for the diagnosis and treatment of HAE in China.

Objective: To compare the effects and safety of dydrogesterone (DG) and medroxyprogesterone acetate (MPA) on the treatment in patients with endometrial hyperplasia without atypia (EH). Methods: This was a single-center, open-label, prospective non-inferior randomized controlled phase Ⅲ trial. From February 2019 to November 2021, patients with EH admitted to the Obstetrics and Gynecology Hospital of Fudan University were recruited. Enrolled patients were stratified according to the pathological types of simple hyperplasia (SH) or complex hyperplasia (CH), and were randomised to receive MPA or DG. Untill May 14, 2022, the median follow-up time after complete response (CR) was 9.3 months (1.1-17.2 months). The primary endpoint was the 6-month CR rate (6m-CR rate). The secondary endpoints included the 3-month CR rate (3m-CR rate), adverse events rate, recurrence rate, and pregnancy rate in one year after CR. Results: (1) A total of 292 patients with EH were enrolled in the study with the median age of 39 years (31-45 years). A total of 135 SH patients were randomly assigned to MPA group (n=67) and DG group (n=68), and 157 CH patients were randomly assigned to MPA group (n=79) and DG group (n=78). (2) Among 292 patients, 205 patients enrolled into the primary endpoint analysis, including 92 SH patients and 113 CH patients, with 100 patients in MPA group and 105 in DG group, respectively. The 6m-CR rate of MPA group and DG group were 90.0% (90/100) and 88.6% (93/105) respectively, and there were no statistical significance (χ²=0.11, P=0.741), with the rate difference (RD) was -1.4% (95%CI:-9.9%-7.0%). Stratified by the pathology types, the 6m-CR rate of SH patients was 93.5% (86/92), and MPA group and DG group were respectively 91.1% (41/45) and 95.7% (45/47); and the 6m-CR rate of CH patients was 85.8% (97/113), and MPA group and DG group were 89.1% (49/55) and 82.8% (48/58) respectively. The 6m-CR rates of the two treatments had no statistical significance either (all P>0.05). A total of 194 EH patients enrolled into the secondary endpoint analysis, including 88 SH patients and 106 CH patients, and 96 patients in MPA group and 98 in DG group, respectively. The 3m-CR rate of SH patients were 87.5% (77/88), while the 3m-CR rates of MPA group and DG group were 90.7% (39/43) and 84.4% (38/45), respectively; the 3m-CR rate of CH patients was 66.0% (70/106), and MPA group and DG group had the same 3m-CR rate of 66.0% (35/53). No statistical significance was found between the two treatments both in SH and CH patients (all P>0.05). (3) The incidence of adverse events between MPA group and DG group had no statistical significance (P>0.05). (4) A total of 93 SH patients achieved CR, and the cumulative recurrence rate in one year after CR were 5.9% and 0 in MPA group and DG group, respectively. While 112 CH patients achieved CR, and the cumulative recurrence rate in one year after CR were 8.8% and 6.5% in MPA group and DG group, respectively. There were no statistical significance between two treatment groups (all P>0.05). Among the 93 SH patients, 10 patients had family planning but no pregnancy happened during the follow-up period. Among the 112 CH patients, 21 were actively preparing for pregnancy, and the pregnancy rate and live-birth rate in one year after CR in MPA group were 7/9 and 2/7, while in DG group were respectively 4/12 and 2/4, and there were no statistical significance in pregnancy rate and live-birth rate between the two treatment groups (all P>0.05). Conclusions: Compared with MPA, DG is of good efficacy and safety in treating EH. DG is a favorable alternative treatment for EH patients.
Female ; Humans ; Adult ; Medroxyprogesterone Acetate/adverse effects* ; Endometrial Hyperplasia/pathology* ; Dydrogesterone/adverse effects* ; Hyperplasia ; Prospective Studies

Objective: To analyze three different integrated scoring schemes of prostate biopsy and to compare their concordance with the scoring of radical prostatectomy specimens. Methods: A retrospective analysis of 556 patients with radical prostatectomy performed in Nanjing Drum Tower Hospital, Nanjing, China from 2017 to 2020. In these cases, whole organ sections were performed, the pathological data based on biopsy and radical prostatectomy specimens were summarized, and 3 integrated scores of prostate biopsy were calculated, namely the global score, the highest score and score of the largest volume. Results: Among the 556 patients, 104 cases (18.7%) were classified as WHO/ISUP grade group 1, 227 cases (40.8%) as grade group 2 (3+4=7); 143 cases (25.7%) as grade group 3 (4+3=7); 44 cases (7.9%) as grade group 4 (4+4=8) and 38 cases (6.8%) as grade group 5. Among the three comprehensive scoring methods for prostate cancer biopsy, the consistency of global score was the highest (62.4%). In the correlation analysis, the correlation between the scores of radical specimens and the global scores was highest (R=0.730, P<0.01), while the correlations of the scores based on radical specimens with highest scores and scores of the largest volume based on biopsy were insignificant (R=0.719, P<0.01; R=0.631, P<0.01, respectively). Univariate and multivariate analyses showed tPSA group and the three integrated scores of prostate biopsy were statistically correlated with extraglandular invasion, lymph node metastasis, perineural invasion and biochemical recurrence. Elevated global score was an independent prognostic risk factor for extraglandular invasion and biochemical recurrence in patients; increased serum tPSA was an independent prognostic risk factor for extraglandular invasion; increased hjighest score was an independent risk factor for perineural invasion. Conclusions: In this study, among the three different integrated scores, the overall score is most likely corresponded to the radical specimen grade group, but there is difference in various subgroup analyses. Integrated score of prostate biopsy can reflect grade group of radical prostatectomy specimens, thereby providing more clinical information for assisting in optimal patient management and consultation.
Male ; Humans ; Prostate/pathology* ; Retrospective Studies ; Prostatectomy/methods* ; Biopsy ; Prostatic Neoplasms/pathology*

Objective: To investigate the expression of glycoprotein non metastatic melanoma protein B (GPNMB) in renal eosinophilic tumors and to compare the value of GPNMB with CK20, CK7 and CD117 in the differential diagnosis of renal eosinophilic tumors. Methods: Traditional renal tumor eosinophil subtypes, including 22 cases of renal clear cell carcinoma eosinophil subtype (e-ccRCC), 19 cases of renal papillary cell carcinoma eosinophil subtype (e-papRCC), 17 cases of renal chromophobe cell carcinoma eosinophil subtype (e-chRCC), 12 cases of renal oncocytoma (RO) and emerging renal tumor types with eosinophil characteristics [3 cases of eosinophilic solid cystic renal cell carcinoma (ESC RCC), 3 cases of renal low-grade eosinophil tumor (LOT), 4 cases of fumarate hydratase-deficient renal cell carcinoma (FH-dRCC) and 5 cases of renal epithelioid angiomyolipoma (E-AML)], were collected at the Affiliated Drum Tower Hospital of Nanjing University Medical School from January 2017 to March 2022. The expression of GPNMB, CK20, CK7 and CD117 was detected by immunohistochemistry and statistically analyzed. Results: GPNMB was expressed in all emerging renal tumor types with eosinophil characteristics (ESC RCC, LOT, FH-dRCC) and E-AML, while the expression rates in traditional renal eosinophil subtypes e-papRCC, e-chRCC, e-ccRCC and RO were very low or zero (1/19, 1/17, 0/22 and 0/12, respectively); the expression rate of CK7 in LOT (3/3), e-chRCC (15/17), e-ccRCC (4/22), e-papRCC (2/19), ESC RCC (0/3), RO (4/12), E-AML(1/5), and FH-dRCC (2/4) variedly; the expression of CK20 was different in ESC RCC (3/3), LOT(3/3), e-chRCC(1/17), RO(9/12), e-papRCC(4/19), FH-dRCC(1/4), e-ccRCC(0/22) and E-AML(0/5), and so did that of CD117 in e-ccRCC(2/22), e-papRCC(1/19), e-chRCC(16/17), RO(10/12), ESC RCC(0/3), LOT(1/3), E-AML(2/5) and FH-dRCC(1/4). GPNMB had 100% sensitivity and 97.1% specificity in distinguishing E-AML and emerging renal tumor types (such as ESC RCC, LOT, FH-dRCC) from traditional renal tumor types (such as e-ccRCC, e-papRCC, e-chRCC, RO),respectively. Compared with CK7, CK20 and CD117 antibodies, GPNMB was more effective in the differential diagnosis (P<0.05). Conclusion: As a new renal tumor marker, GPNMB can effectively distinguish E-AML and emerging renal tumor types with eosinophil characteristics such as ESC RCC, LOT, FH-dRCC from traditional renal tumor eosinophil subtypes such as e-ccRCC, e-papRCC, e-chRCC and RO, which is helpful for the differential diagnosis of renal eosinophilic tumors.
Humans ; Kidney Neoplasms/pathology* ; Carcinoma, Renal Cell/pathology* ; Diagnosis, Differential ; Angiomyolipoma/diagnosis* ; Biomarkers, Tumor/metabolism* ; Leukemia, Myeloid, Acute/diagnosis* ; Membrane Glycoproteins

Male ; Humans ; Prostate/pathology* ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Adenocarcinoma/pathology*

Objective: To investigate how plasma exchange (PE) and double plasma molecular adsorption combined with half-volume plasma exchange (DPMAS + half-volume PE) affect the curative effect and short-term survival rate in liver failure. Methods: Data from 181 cases of liver failure caused by different etiologies from January 1, 2017 to September 31, 2020, were selected. Patients were divided into a PE treatment alone group and a DPMAS + half-dose PE treatment group. The laboratory indicators with different models of artificial liver before and after treatment and the survival rates of 7, 14, 28, and 90 days after discharge were observed in the two groups. Measurement data were analyzed by t-tests and rank sum tests. Categorical data were analyzed by χ (2) test. Results: Non-biological artificial liver therapy with different models improved the liver and coagulation function in the two groups of patients with liver failure (P < 0.05 in PTA% intra-group). The coagulation function was significantly improved in the PE treatment alone group compared with that in the DPMAS + half-dose PE group [PT after treatment: (20.15 ± 0.88) s in the PE treatment alone group, (23.43 ± 1.02) s, t = -2.44, P = 0.016 in the DPMAS+half-dose PE group; PTA: 44.72% ± 1.75% in the PE treatment alone group, 35.62% ± 2.25%, t = 3.215 P = 0.002 in the DPMAS + half-dose PE group]. Bilirubin levels were significantly decreased in the DPMAS+half-dose PE group compared to the PE treatment alone group [total bilirubin after treatment: (255.30 ± 15.64) μmol/L in the PE treatment alone group, (205.46 ± 9.03) μmol/L, t = 2.74, P = 0.07 in the DPMAS + half-dose PE group; direct bilirubin after treatment: (114.74 ± 7.11) μmol/L in the PE treatment alone group, (55.33 ± 3.18) μmol/L, t = 7.54, P < 0.001) in the DPMAS + half-dose PE group]. However, there was no significant effect on leukocytes and neutrophils after treatment with different models of artificial liver (P > 0.05) in the two groups, and platelets decreased after treatment, with no statistically significant difference between the groups (t = -0.15, P = 0.882). The inflammatory indexes of the two groups improved after treatment with different models of artificial liver (P < 0.05], and the 28 and 90 d survival rates were higher in the DPMAS+half-dose PE group than those of the PE treatment alone group (28 d: 60.3% vs. 75.0%, χ (2) = 4.315, P = 0.038; 90 d: 56.2% vs. 72.5%. χ (2) = 10.355 P < 0.001). DPMAS + half-dose PE group plasma saving was 1385 ml compared with PE treatment alone group (Z = -7.608, P < 0.05). Conclusion: Both DPMAS+half-dose PE and PE treatment alone have a certain curative effect on patients with liver failure. In DPMAS+half-dose PE, the 28-day survival rate is superior to PE treatment alone, and it saves plasma consumption and minimizes blood use in clinic.

Objective:To investigate the prognosis of childhood adrenoleukodystrophy (ALD) with cognitive disorder after haploidentical allogenic hematopoietic stem cell transplantation (haplo-HSCT), and to identify risk factors affecting the prognosis.Methods:It was a single-center retrospective study involving 31 ALD children receiving haplo-HSCT in Peking University People′s Hospital from January 2014 to October 2022.Survival analysis was performed by Kaplan-Meier method. Cox regression analysis was performed to identify risk factors for the prognosis of childhood ALD following haplo-HSCT. Results:Among the 31 children with ALD, 1 case died of cardiogenic shock during the transplantation, and the remaining had a successful haplo-HSCT.Ten children with ALD had cognitive disorder before haplo-HSCT, including 3 cases with the minimal LOES score ≥10 points and 8 cases with the Neurologic Function Score (NFS)>0 point before haplo-HSCT.Six children had major functional disability (MFD) and 2 cases died due to progression of ALD after haplo-HSCT.Twenty children did not have cognitive disorder before haplo-HSCT, of whom 3 cases had the LOES score≥10 points and 6 cases had NFS>0 before haplo-HSCT.Four children had MFD and 2 cases died due to progression of ALD after haplo-HSCT.For ALD patients without cognitive disorder after haplo-HSCT, the 3-year and 5-year survival rate were 100.0% and 72.9%, respectively, and the 5-year MFD-free survival was 61.6%.For ALD patients with cognitive disorder after haplo-HSCT, the 3-year survival rate was 83.3%.Compared with ALD patients with the LOES score<10 points before haplo-HSCT, those with the LOES score≥10 points had 9.243 times the risk of developing MFD after haplo-HSCT ( P=0.024, 95% CI: 1.332-64.127). Compared with ALD patients without cognitive disorder before haplo-HSCT, ALD patients with cognitive disorder had 9.749 times the risk of developing MFD after haplo-HSCT ( P=0.023, 95% CI: 1.358-66.148). Conclusions:Cognitive disorder and LOES score≥10 points before haplo-HSCT are risk factors for developing MFD in children with ALD following haplo-HSCT.

Objective:To analyze the intervention effect of rehabilitation platform-based online psycho-education on patients with bipolar disorder (BD) in remission stage.Methods:In this randomized controlled study, 91 patients with BD in remission stage who attended the community health center in Xicheng District, Beijing from July to August 2021 were randomly divided into a test group (46 cases) and a control group (45 cases) according to a 1∶1 ratio using the random number table. Baseline data were collected from both groups, and the control group received conventional medication and community telephone follow-up, while the test group was given online mental health education in the form of a WeChat subscription number on this basis, including BD mental health education course push (twice a week) and disease self-management (daily recording of mood, sleep, medication, exercise and gratitude diary), and the intervention period was 6 months in both groups. During the intervention, one patient in the test group was admitted to hospital due to exacerbation of mental illness and the trial was terminated. A total of 90 cases were included in the study. The scores of Medication Adherence Rating Scale (MARS), Hamilton Depression Scale (HAMD), Young Mania Rating Scale (YMRS) and Perceived Devaluation-Discrimination Scale (PDD) were assessed at baseline, after 3 months and 6 months of intervention in both groups, respectively. And the differences in baseline data between the two groups were compared using two independent samples t test and χ2 test, and the repeated-measures ANOVA was used to compare the differences in MARS, HAMD, YMRS, and PDD scores between the two groups before and after the intervention, and to analyze the intervention effects of network mental health education based on the rehabilitation platform on patients in remission stage of BD. Results:After 6 months of intervention, MARS scores in the test group was significantly higher than that in the control group [(8.47±1.75) vs (7.47±1.85)], and was significantly higher than that at baseline (7.36±2.13) and after 3 months of intervention (8.04±1.68) (all P<0.05). YMRS and PDD scores in the test group were significantly lower than those at baseline after 3 and 6 months of intervention [YMRS, 2.0(1.0,4.0),2.0(0,3.0) vs 3.0(1.0,5.5); PDD, (31.18±4.65), (30.13±4.76) vs (32.51±4.51)] (all P<0.05); the differences in YMRS and PDD scores in the control group were not statistically significant (all P>0.05). There was no statistically significant difference in HAMD scores between the two groups before and after the intervention (all P>0.05). Conclusion:Combining mental health education based on rehabilitation platform with conventional medication and community management can significantly improve the medication compliance of patients with BD in remission stage, and improve their manic symptoms and reduce the stigma of the disease.