Objective To explore the effect of microRNAs 224 and 21 on human glioma stem cells survival and the possible molecular mechanisms.Methods qPCR was used to detect the dysregulated expression of microRNAs in malignant glioma samples, human GBM stem cells, artificially established GBM stem cell lines and human tissues.Caspase 3/7 assay, Annexin V apoptosis/fluorescence assay were performed to determine the effect of miR-21 or miR-224 mimics and inhibitor on cell apoptosis.Living cells count was used to assess miR-21 or miR-224 mimics and inhibitor on cell growth.TargetScan was used to explore potential targets of miR-21 and miR-224, and dual luciferase reporter assay was used to identify whether the 3’UTR of Caspase 3, Caspase 9 and Bim mRNA was a binding target of miR-21 or miR-224.Western blot was used to detect the expression of Caspase 3, Caspase 9 and Bim protein after transfection of miR-21 or miR-224 mimics or inhibitors.Results miR-21 and miR-224 are strongly upregulated in GSC samples, multiple GBM human tumor specimens, and GBM neurosphere stem cell lines ( P<0.05 ) .Caspase 3/7 assay and Annexin V apoptosis/fluorescence assay results showed that miR-224 and miR-21 regulated GSC apoptosis.Living cells count results demonstrated that miR-224 and miR-21 regulated GSC growth.miR-224 and miR-21 regulate pro-apoptotic gene expression by directly targeting Caspase 3, Caspase 9, and Bim 3’-UTRs. Conclusion These results indicate that miR-224 and miR-21 are important physiologic drivers of GSC resistance to apoptosis, providing new points of therapeutic leverage against these treatment-resistant cells.

Objective:To analyze the epidemiological, clinical characteristics and treatment of coronavirus disease 2019 (COVID-19) in Northeastern Sichuan, and summarize experience in time to provide reference for clinical diagnosis and treatment.Methods:A retrospective study was conducted. Fifty-nine patients with COVID-19 admitted to Bazhong Central Hospital and Dazhou Central Hospital from January 27th to February 9th, 2020 were selected as the subjects. The data of demography, epidemiology, laboratory examination, chest CT and related clinical treatment were collected. According to the severity of the disease, the patients were divided into three types: mild, general and severe types, and the differences of the above indices among different clinical types were compared.Results:① General information and epidemiology: 31 cases (52.5%) were male, 28 cases (47.5%) were female, the average age was (42.0±16.4) years old, and the patients over 40 years old accounted for the largest proportion (35 cases, 59.3%). The proportion of clinical type was 72.9% (43 cases) in general type, and 62.7% (37 cases) were imported type. With the increase of disease severity, the average age of patients also showed a significant increase trend [the age of the mild, general and severe patients were (30.9±13.6), (42.7±15.3), (55.8±18.9) years old, P < 0.01]. The proportion of patients with more than one basic disease in severe patients was significantly higher than those in mild and general patients [66.7% (4/6) vs. 20.0% (2/10), 9.3% (4/43), both P < 0.05]. In the distribution of clinical symptoms, the proportion of severe patients with chest distress/dyspnea was significantly higher than those in mild and general patients [66.7% (4/6) vs. 10.0% (1/10), 11.6% (5/43), both P < 0.05]. ② Laboratory examination index: the total number of white blood cell count (WBC), neutrophils count (NEU), C-reactive protein (CRP) in severe patients were higher than those in mild patients and general patients [WBC (×10 9/L): 7.21±4.35 vs. 5.85±1.69, 5.43±2.04; NEU (×10 9/L): 6.09±4.43 vs. 3.95±1.45, 3.54±1.83; CRP (mg/L): 16.00 (8.20, 46.43) vs. 5.00 (0.00, 16.13), 15.00 (3.13, 28.58)], the albumin (Alb) level in severe patients was lower than those in mild and general patients (g/L: 38.00±5.35 vs. 49.23±5.27, 39.81±2.15, both P < 0.05), while the hemoglobin (Hb) level in mild patients was higher than that in severe and general patients (g/L:155.2±12.1 vs. 141.3±6.8, 131.1±11.7, both P < 0.05). ③ Chest imaging: the CT manifestations of typical cases were single or multiple ground glass shadows. With the progress of the disease, the focus gradually increased, the scope gradually expanded, and multiple solid shadows of lung lobes were involved. ④ Treatment: all patients received at least 2 kinds of antiviral therapy, and the application rate of Interferon and Ribavirin in severe patients were higher than those in mild and general patients [100.0% (6/6) vs. 80.0% (8/10), 97.7% (42/43); 83.3% (5/6) vs. 0% (0/10), 20.9% (9/43); all P < 0.05]. ⑤ Prognosis: until March 6th 2020, 50 patients (84.8%) were discharged from the hospital after rehabilitation, and the remaining 9 patients were still under treatment, none deaths. Conclusions:The proportion of severe patients with chest distress/dyspnea is higher, the older the patients are and the more basic diseases are, the more likely they are to develop into severe type. High resolution chest CT could be considered for suspected cases or even fever patients, which may show the progress of the disease.

Objective:To summarize the clinical features and gene phenotype of children with spondyloenchondrodysplasia with immune dysregulation (SPENCDI) caused by ACP5 gene mutation. Methods:The medical data and genetic phenotype of a child diagnosed with SPENCDI in the Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University in February 23, 2017 were analyzed retrospectively.Besides, " spondyloenchondrodysplasia" were taken as the search terms to perform the retrieval in CNKI, Wanfang Data, and PubMed, in an attempt to conduct the literature review.χ 2 test was used to compare the factors among children with different mutations. Results:The 4.5-year-old girl was admitted to hospital for complaint of " fever and chilblain-like rash" when she was 2 years old.She was diagnosed with systemic lupus erythematosus (SLE) concomitant with lupus nephritis.Methylprednisolone combined with cyclophosphamide, mycophenolate mofetil was used for the treatment.However, she experienced multiple infections, thrombocytopenia, limp, and growth retardation during the treatment.Genetic detection identified ACP5 gene compound hybrid mutation: c.779C>A and c. 770T>C.She was diagnosed with SPENCDI, and was subjected to follow-up.A total of 78 SPENCDI patients were retrieved from the databases, with various clinical manifestations of SPENCDI, commonly with skeletal involvement and immune phenotypes; 73.08% of the cases were positive for antinuclear antibodies, 57.69% of cases were positive for anti-double stranded-DNA antibodies and 34.62% of cases had neurological symptoms.In 58 cases, ACP5 gene mutations were detected, including 44 homozygous mutations and 14 compound heterozygous mutations.Patients with ACP5 gene homozygous mutation had a higher probability of consanguineous marriage in parents [56.82% (25/44 cases) vs.14.29% (2/14 cases)]; patients with ACP5 gene heterozygous mutation were more likely to develop SLE [64.29% (9/14 cases) vs.34.09% (15/44 cases)]( χ2=7.722, 3.992; all P<0.05). Conclusions:The majority of the ACP5 gene mutations are homozygous mutations in patients with SPENCDI, and heterozygous mutations are rare.The clinical manifestations of SPENCDI are various and complex, it is prone to develop autoimmune diseases, and there was no clear correlation between clinical features and gene phenotype in SPENCDI patients.

Objective:To investigate the correlation between intrahepatic triglyceride content (IHTC) and glucose metabolism in patients with non-alcoholic fatty liver disease (NAFLD) diagnosed by proton magnetic resonance spectroscopy ( 1H-MRS). Methods:A total of 239 subjects without diabetes mellitus were previously enrolled and underwent 1H-MRS scans. Anthropometric indexes including height, weight, waist and blood pressure, and laboratory findings as plasma glucose (PG), insulin (INS), C-peptide (CP), liver enzymes [alanine aminotransferase (ALT), aspartate transaminase (AST), γ-glutamyl transpeptidase (GGT)] and lipid profiles were collected. According to IHTC levels, participants were divided into three groups: the non-NAFLD group (IHTC<5.56%), the mild NAFLD group (IHTC 5.56%-<33%), and the moderate and severe NAFLD group (IHTC ≥ 33%). The clinical characteristics of each group were analyzed, and the correlation between IHTC and glucose metabolism were assessed. Results:Compared with those in the non-NAFLD group, male proportion, waist, 120 min postprandial PG (PG120), CP, liver enzymes and total cholesterol (TC) levels were greater in the NAFLD group, whereas insulin sensitivity index-Cederholm (ISI-Cederholm) and high density lipoprotein cholesterol (HDL-C) levels were lower in the NAFLD groups. Subjects in the moderate and severe NAFLD group had higher levels of 120 min postprandial INS (INS120) and Stumvoll indexes, and lower ISI-Cederholm than those in the mild NAFLD group [80.37 (57.68, 112.70) mU/L vs.110.50(71.78, 172.80)mU/L, 1453(1178, 1798)vs.1737(1325, 2380), 358(297, 446) vs.441(318, 594), 2.27(2.01, 2.53) vs.2.06(1.81, 2.39), respectively, all P<0.05]. Correlation analyses showed that IHTC was significantly positively correlated with waist hip ratio (WHR), PG120, INS120, HOMA insulin resistance (HOMA-IR), Stumvoll 1st-insulin secretion, Stumvoll 2nd-insulin secretion, ALT, AST, GGT and TC ( r=0.197, 0.274, 0.334, 0.162, 0.199, 0.211, 0.406, 0.361, 0.215, and 0.196, respectively, all P<0.05), and negatively correlated with ISI-Cederholm and HDL-C ( r=-0.334, and-0.237, respectively, all P<0.05). Furthermore, a multiple linear stepwise regression analysis indicated that ISI-Cederholm (Standardized β =-0.298, P<0.001) and Stumvoll 1st insulin secretion (Standardized β = 0.164, P = 0.024) were independent factors of IHTC. Conclusions:Peripheral insulin resistance occurs in the early stage of NAFLD and becomes worse with the progression of the disease. IHTC was independently associated with insulin sensitivity and first-phase insulin secretion.

Objective:To analyze the clinicopathological features and prognosis of idiopathic membranous nephropathy (IMN) in children, and to investigate the factors influencing their prognosis.Methods:The clinical and pathological data of 128 children with IMN hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2012 to December 2019 were retrospectively analyzed.They were divided into 2 groups according to the pathological manifestations: group A[typical membranous nephropathy(MN) group] and group B (atypical MN group), and the clinicopathological characteristics of the 2 groups were compared.Different treatment regimens and their efficacy were summarized, and the prognosis and its influencing factors were analyzed.The primary endpoint event at follow-up was the occurrence of end stage renal disease (ESRD), and the secondary endpoint event was the occurrence of renal insufficiency.Children with IMN were further divided into endpoint event group and non-endpoint event group according to the presence or absence of endpoint events at the last follow-up.Survival analysis was performed using the Kaplan-Meier survival curve method.The Cox proportional risk model method was used to analyze the factors influencing the prognosis of poor kidney outcomes in children with IMN. Results:(1)A total of 128 children were included, with the male-to-female ratio of 1.13∶1.00.The median age of onset and peak age of onset were 13.0 (10.3, 15.0) years, and 12-16 years (68.8%), respectively.Massive proteinuria was detected in 119 cases (93.0%), including 103 cases (80.5%) with massive proteinuria and hematuria, 4 cases(3.1%) with simple hematuria, and 5 cases (3.9%) with non-renal proteinuria.There were 29 cases (22.7%) in group A and 99 cases (77.3%) in group B. (2)Blood triacylglycerol level was significantly higher in group B than that of group A[2.1 (1.5, 3.0) mmol/L vs.1.7(1.1, 2.5) mmol/L], while high-density lipoprotein[1.5(1.1, 1.8) mmol/L vs.1.8(1.4, 2.1) mmol/L], serum albumin[22.0(17.0, 27.3) g/L vs.25.5 (21.0, 32.5) g/L] and complement C3[(1.1±0.2) g/L vs.(1.2±0.2) g/L] were significantly lower in group B than those of group A (all P<0.05). (3)Complete clinical data during hospitalization and follow-up data were obtained from 91 children with IMN, with a median follow-up time of 87.0 (49.0, 104.5) months.Among them, 5 cases (5.5%) progressed to ESRD, involving 3 cases received renal transplantation, and 9 cases (9.9%) had secondary endpoints.Cumulative renal survival rate for ESRD at 5 and 10 years were 96.2% and 92.9%, respectively, which, for the secondary endpoints at 5 and 10 years were 95.2% and 84.8%, respectively.(4)Kaplan-Meier survival analysis showed no significant difference in the cumulative renal survival between group A and group B ( P>0.05). Multifactorial Cox regression analysis showed that tubular atrophy/interstitial fibrosis was an independent risk factor for renal insufficiency in children with IMN ( HR=0.102, 95% CI: 0.011-0.940, P<0.05). Conclusions:Massive proteinuria combined with hematuria is the major clinical manifestation of IMN in children, and atypical MN is the major pathological manifestation.Tubular atrophy/interstitial fibrosis is an independent risk factor for renal insufficiency in children with IMN.

BackgroundDepression， anxiety， impulse control disorders， insomnia are prevalent non-motor symptoms of Parkinson's disease， severely impairing the quality of life of patients. Cognitive behavioral therapy （CBT） is a common psychological intervention for various clinical psychological conditions， which can improve anxiety， insomnia and depression in patients with Parkinson's disease. However， the current research evidence on the effects of CBT in improving quality of life in patients with Parkinson's disease remains inconsistent. ObjectiveTo assess the effects of CBT on the quality of life among patients with Parkinson's disease， so as to provide references for the clinical application of CBT in this population. MethodsOn May 25， 2023， a systematic search was conducted across PubMed， PsycINFO， Embase， CNKI， Wanfang Database and VIP Database to identify randomized controlled trials investigating the impact of CBT on the quality of life in patients with Parkinson's disease. Literature screening， quality evaluation and data extraction were performed， focusing on variables related to quality of life， anxiety， and depression. Meta-analysis was performed using Stata 13.0 and RevMan 5.3. ResultsA total of 11 studies with 456 participants were included， comprising 241 in the CBT group and 215 in the control group. The CBT group exhibited significantly higher quality of life compared with the control group （SMD=0.47， 95% CI： 0.27~0.67， P<0.01）. Anxiety and depression scores in CBT group were significantly lower than those in the control group （SMD=-0.63，95% CI：-0.84~-0.43， P<0.01； SMD=-0.83， 95% CI： -1.15~-0.51， P<0.01）. Among the 11 studies， 6 studies delivered CBT remotely and 5 studies implemented CBT face-to-face. Meta-analysis results revealed that remote CBT group yielded significantly higher quality of life （SMD=0.43， 95% CI： 0.17~0.70， P<0.01）， and lower anxiety and depression scores （SMD=-0.62， 95% CI： -0.91~-0.34， P<0.01； SMD=-0.78， 95% CI： -1.34~-0.21， P<0.01） compared with the control group. Similarly， face-to-face CBT group showed better outcomes than the control group in terms of quality of life， anxiety and depression （SMD=0.51， 95% CI： 0.22~0.81， P<0.01； SMD=-0.64， 95% CI： -0.93~-0.35， P<0.01； SMD=-0.90， 95% CI： -1.20~-0.60， P<0.01）. ConclusionCBT may contribute to alleviating anxiety and depression levels of patients with Parkinson's disease， and improving their quality of life.｛Funded by Shanghai 13th Five-Year Key Specialty Construction Project （number， shslczdzk04901）； Nature Fund Project of Shanghai Science and Technology Commission （number， 22ZR1459300）； Shanghai Municipal Health Commission Traditional Chinese Medical Science Non-drug Therapy Demonstration Center Project ［number， ZY（2021-2023） -0204-03］｝

Objective·To evaluate the changes in cognitive function in overweight and obese adolescents,and explore the association between cognitive function and fibroblast growth factor 21(FGF21).Methods·A total of 175 adolescents from a senior high school in Shanghai were divided into normal weight group(n=50),overweight group(n=50)and obese group(n=75)based on their body mass index(BMI).General information,anthropometric data and laboratory testing indicators of the adolescents were collected and compared.The cognitive function of the three groups of adolescents was assessed by using the accuracy(ACC)and reaction time of Flanker task and n-back task.Enzyme-linked immunosorbent assay(ELISA)was used to detect the serum FGF21 level of the three groups of adolescents.Partial correlation analysis and multiple linear regression model were used to evaluate the correlation between cognitive task performance and anthropometric data and laboratory testing indicators.Results·Compared with the normal weight group,systolic blood pressure,diastolic blood pressure,and the levels of fasting plasma glucose,glycosylated hemoglobin and triacylglycerol in the obese group were higher(all P<0.05).Under congruent or incongruent stimulus conditions in the Flanker task,there was no significant difference in ACC between any two groups;compared with the normal weight and overweight groups,the reaction time of the adolescents in the obese group was prolonged(all P<0.05).In the n-back task,there were no significant differences in ACC between any two groups,while the obese group had longer reaction time in the 1-back and 2-back tasks compared to the normal weight and overweight groups(all P<0.05).Compared with the normal weight group,serum FGF21 levels of the adolescents in the obese group were higher(P=0.000).Partial correlation analysis showed that the reaction time of the adolescents in Flanker and n-back tasks was correlated with their BMI,body fat mass,waist circumference,waist-to-hip ratio and FGF21 level(all P<0.05).Multiple linear regression analysis further confirmed that BMI was associated with prolonged reaction time in cognitive-related behavioral tasks in the adolescents(all P<0.05),and FGF21 level was associated with ACC in the 2-back task(P=0.000)and reaction time in the incongruent stimulus condition(P=0.048).Conclusion·Overweight and obese adolescents have cognitive impairments,and BMI and serum FGF21 levels are associated with changes in their cognitive function.

As a rare Chinese medicinal material， Paridis Rhizoma is mainly distributed in Yunnan， Guangxi， and Guizhou in southwestern China， with the effect of clearing heat and detoxifying， alleviating edema and relieving pain， cooling liver and tranquilizing mind. It is particularly effective for injuries from falls， fractures， contusions and strains， snake bites， cold wind-induced convulsion， and other diseases， which has been used for more than 2 000 years. According to modern research， polyphyllin Ⅱ， one of the main active components of Paridis Rhizoma， belongs to diosgenin in structure. It has the anti-tumor， anti-inflammatory， antiviral， antibacterial， immune-regulating， antioxidant， and multidrug resistance-reversing activities， showing good application prospect. Especially， the anti-tumor effect of polyphyllin Ⅱ has attracted wide attention， and the mechanism is inhibiting proliferation， migration， and invasion of tumor cells， inducing cell cycle arrest， apoptosis， and autophagy， suppressing angiogenesis， and modulating tumor microenvironment. However， the pharmacokinetic results show that polyphyllin Ⅱ has low bioavailability in vivo due to the low solubility， poor absorption， unsatisfactory distribution， and slow metabolism， which limit the clinical application. In recent years， there has been an explosion of research on the adverse reactions of polyphyllin Ⅱ， such as the strong hemolytic activity and obvious cytotoxicity to liver， kidney， myocardium and cardiovascular cells. Thus， papers were retrieved from "CNKI"， "VIP"， "Wanfang Data"， "PubMed"， "Web of Science"， and "Elsevier SD" with "Paris saponin Ⅱ"， "Polyphyllin Ⅱ" as the main keywords， and the pharmacological activities and mechanisms， pharmacokinetics， and adverse reactions were summarized. The findings are expected to serve as a reference for the in-depth research， development， and utilization of polyphyllin Ⅱ.