Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

Objective: Autologous peripheral blood stem cells (PBSC) derived from bone marrow can promote liver regeneration and improve the liver function of patients, but there are few studies on its effect on the long-term outcomes in patients with decompensated cirrhosis. Based on previous work, this study observed the clinical outcomes of PBSC treatment in patients with decompensated cirrhosis for 10 years, in order to provide more data support for the safety and efficacy of stem cells in clinical applications. Methods: Data of patients with decompensated liver cirrhosis who completed PBSC treatment in the Department of Gastroenterology of the First Affiliated Hospital of Air Force Military Medical University from August 2005 to February 2012 were included. The follow-up endpoint was death or liver transplantation, and patients who did not reach the follow-up endpoint were followed-up for at least 10 years. The patients with decompensated liver cirrhosis who met the conditions for PBSC treatment but did not receive PBSC treatment in our hospital during the same period were used as controls. Results: A total of 287 cases with decompensated liver cirrhosis had completed PBSC treatment, and 90 cases were lost to follow-up within 10 years after surgery. A total of 151 cases with complete survival follow-up data were included in the control group. There were no statistically significant differences in baseline information such as gender, age, etiological composition and liver function score between the two groups. The 10-year survival rate was higher in PBSC than control group (37.56% vs. 26.49%, P<0.05). Cholinesterase, albumin, international normalized ratio, Child-Turcotte-Pugh score, model for end-stage liver disease score, and other indicators were gradually recovered within 3 months to 1 year after PBSC treatment, and stabilized at a more desirable level in the long-term after follow-up for up to 10 years. There was no statistically significant difference in the incidence of liver cancer between the two groups (25.22% vs.31.85%, P=0.267). The age of onset of hepatocellular carcinoma was later in PBSC than control group [(56.66±7.21) years vs. (52.69±8.42) years, P<0.05]. Conclusions: This long-term observational follow-up study of more than ten years confirms that PBSC treatment can bring long-term benefits to patients with decompensated cirrhosis, with good long-term safety, thus providing more data support on the safety and efficacy of stem cells for clinical applications.
End Stage Liver Disease ; Follow-Up Studies ; Humans ; Liver Cirrhosis/drug therapy* ; Middle Aged ; Peripheral Blood Stem Cells ; Severity of Illness Index ; Treatment Outcome

Objective:To evaluate the potential effects of serum lipid levels, appendicular skeletal muscle mass index (ASMI) and body mass index (BMI), together with its dynamic changes, on tumor progression in renal clear cell carcinoma patients, so as to inform body weight management.Methods:This prospective cohort study included a total of 100 patients with high-risk clear cell renal cell carcinoma. Serum lipid levels were detected, ASMI and BMI were measured using bioelectrical impedance analysis and the dynamic changes of BMI were tracked. The effects of BMI, ASMI and serum lipid levels on tumor progression within 2 years were explored.Results:Patients with normal BMI and low ASMI had 5.248 (95% CI: 1.946 to 14.153, P = 0.001) times higher risk of tumor progression than those who were overweight or obese. For every 0.1-unit increase in pre-operative HDL-C, the risk of tumor progression decreased by 0.771 (95% CI: 0.631 to 0.942, P = 0.011) times. Patients who experienced more than 5% decrease in BMI compared with baseline had 5.165 (95% CI: 1.735 to 15.370, P = 0.003) times the progression risk of patients whose BMI changed within ±5% from baseline. Conclusions:The advantage of obese clear cell carcinoma patients over normal-weight patients in tumor progression-free survival may be influenced by ASMI, pre-onset involuntary weight loss and lipid levels. Therefore, patient weight management should not merely focus on absolute BMI but tailor to individual characteristics, including cancer stage, body composition and metabolic status.

This paper was to investigate the effect of Huanglian Jiedu Decoction(HLJD) on ulcerative colitis(UC) in mice, and determine the effective components in plasma, and virtually screen its therapeutic target, and predict its mechanism. Sixty Balb/c mice were randomly divided into blank group, model group, mesalazine treatment group(0.3 g·kg~(-1)), and HLJD treatment groups(24.66, 12.33, 6.17 g·kg~(-1)). Excepted for the blank group, all the mice in HLJD and mesalazine treatment groups were gavage administration. All mice freely drank 2.5% DSS solution for seven days to induce UC. The disease activity index(DAI) was detected each day. At the end of the experiment, HE staining was used to observe the pathological changes in colon. The content of IL-1β, IL-6 and TNF-α in colon were determined by ELISA. The effective components in plasma were determined by UPLC-Q-TOF-MS. The reverse docking in PharmMapper was used to screen the component targets. The disease targets of UC were collected by searching TTD, OMIM and GeneCards databases. The intersection of the component targets and disease targets was selected as the therapeutic targets. Then the therapeutic targets were imported into the STRING for GO and KEGG enrichment analysis. Discovery Studio was used to simulate the docking between the components and the targets. RESULTS:: showed that the DAI in the model group increased significantly(P<0.05), and the number of inflammatory cells and infiltration degree increased significantly compared with the blank group. The DAI in HLJD treatment group was significantly reduced(P<0.05), and the number and infiltration degree of inflammatory cells were reduced compared with the model group. The ELISA results showed that the levels of IL-1β, IL-6 and TNF-α were increased significantly in the model group(P<0.01) compared with the blank group, and significantly down regulated in the HLJD treatment group(P<0.05) compared with the model group. After UPLC-Q-TOF-MS analyse, ten components were identified. The network pharmacology analysis showed that the action targets were significantly enriched in 129 of biological processes, such as response to organic substance, chemical and oxygen-containing compound, etc., as well as 16 of signal pathways, such as IL-17, TNF and hepatitis B signal pathways, were enriched too. The results of molecular docking showed that limonin, palmatine and berberine could bind to CASP3 and MMP9 by hydrogen bond. In conclusion, HLJD could alleviate the colonic mucosal inflammatory infiltration and mucosal damage in UC mice. The mechanism may be related to the anti-inflammatory effect on UC mice by reducing the levels of IL-1β, IL-6 and TNF-α in colon through limonin, palmatine and berberine regulating IL-17 signal pathway and TNF signal pathway via CASP3 and MMP9 meditated.
Animals ; Anti-Inflammatory Agents/therapeutic use* ; Colitis, Ulcerative/drug therapy* ; Colon ; Dextran Sulfate/therapeutic use* ; Drugs, Chinese Herbal ; Mice ; Molecular Docking Simulation ; Plasma

Objective To investigate the expression of microRNA (miR)-513c-5p in cervical cancer and the mechanism of targeting histone deacetylase 1 (HDAC1) regulating cervical cancer cell migration and invasion. Methods Clinically collected 86 patients with cervical cancer. The levels of miR-513c-5p in tumor tissues and adjacent tissues were detected by Real-time PCR. The relationship between miR-513c-5p and pathological characteristics of cervical cancer was analyzed. It was verified that miR-513c-5p targets HDAC1 by a dual luciferase report. Cervical cancer HeLa cells were divided into four groups: control group, mimic group, mimic+HDAC1 group and HDAC1 group. MiR-513c-5p and(or) HDAC1 were overexpressed by plasmid transfection technology. Real-time PCR and Western blotting were used to detect the expression level of RNA or protein, respectively. The cell growth, migration, and invasion capabilities of each group were measured by CCK-8 method, cell scratch test, and Transwell test. Results The level of miR-513c-5p in cervical cancer tissues was significantly lower than that in adjacent tissues. Low levels of miR-513c-5p were associated with higher local invasion, lymphatic metastasis, and distal metastasis (P<0. 05). MiR-513-5p targeted HDAC1 expression. Overexpression of miR-513c-5p inhibited significantly the growth, migration and invasion of cervical cancer cells (P < 0. 05). Overexpression of HDAC1 promoted growth, migration and invasion (P<0. 05), and reversed the inhibitory effect of miR-513c-5p (P<0. 05). Conclusion Low levels of miR-513c-5p might be related to cervical cancer metastasis, and miR-513c-5p could inhibit the growth, migration and invasion of cervical cancer HeLa cells by targeted inhibition of HDAC1 protein expression.

OBJECTIVE: To detect the expression of CRLF2 in bone marrow mononuclear cells from children with newly diagnosed acute lymphoblastic leukemia(ALL) and to explore its clinical significance in pediatric ALL. METHODS: A total of 218 children with newly diagnosed ALL who achieveal the complete remission and had the complete follow-up information were selected, and the expression level of CRLF2 in bone marrow mononuclear cells of these children was detected by real-time fluorescent quantitative PCR, and the significance of CRLF2 expression level in clinical prognosis of ALL children was analyzed by using statistical method. RESULTS: 28 cases in 218 children with complete data showed high expression of CRLF2. The cumulative recurrence rate in the CRLF2 high expression group was significantly higher than that in the low expression group (53.6% vs 12.6%) (P＜0.01). The predicted 5-year recurrence-free survival rate (RFS) of ALL children with CRLF2 high expression was significantly higher than that of low expression group (P＜0.01). There was no significant difference in the predicted 5-year RFS between ALL children with CRLF2 low and high expression in the standard-risk(SR) group (P＞0.05). The predicted 5-year RFS of ALL children with CRLF2 low expression was higher than that of ALL children with CRLF2 high expression in the intermediate-risk (IR) and high-risk (HR) groups. (P＜0.05). Cox analysis showed that CRLF2 high expression is an independent risk factor for the relapse of children with ALL. CONCLUSION The recurrence rate of pediatric ALL with CRLF2 high expression is high, and CRLF2 high expression is an important prognostic factor for high risk of relapse in ALL children with IR and HR. It is necessary to use CRLF2 expression as an indicator of risk stratification in pediatric ALL.
Bone Marrow ; Child ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Receptors, Cytokine ; metabolism ; Recurrence ; Risk Factors

Objective To evaluate the anti-diabetic effect and mechanism of a novel G protein coupled receptor 40 (GPR40) agonist SZZ15 -11. Methods Transactivation assay based on luciferase reporter gene was performed to explore the agonist activity of the compounds to GPR40. The primary mouse islets were used to evaluate the insulinotropic ability of the compounds. After oral administration of the tested compounds once,the plasma concentrations of glucose,insulin and glucagon like peptide 1 (GLP-1) were determined in normal mice followed oral glucose loading. The effect of the compounds on gastric emptying was also evaluated in normal mice given orally once. In spontaneous type 2 diabetic KKAy mice orally administrated compound for one month,the plasma glucose concentration were measured. Results The compound SZZ15 -11 activated GPR40 with EC50 of 1. 2 μmol·L-1. It significantly promoted glucose-stimulated insulin secretion (GSIS) in mouse primary islets by 61. 1％ (P < 0. 05) under high glucose conditions (16. 8 mmol·L-1). Oral administration of SZZ15-11 (50 mg·kg-1) once decreased the plasma concentrations of glucose in normal ICR mice followed oral glucose loading,reduced the area under the curve (AUC) by 13. 1％ (P < 0. 05) ,and increased insulin secretion after oral glucose load by 46. 6％ (P < 0. 05). SZZ15-11 also obviously delayed the gastric emptying rate in normal mice at a dose of 50 mg·kg-1,which reduced the area of the serum acetaminophen concentration-time curve (P <0. 05). At two doses of 50 and 100 mg·kg-1,plasma GLP -1 levels in normal mice after oral glucose load was increased (P <0. 05). In the type 2 diabetic KKAy mice administrated with SZZ15 -11 at the dose of 50 and 100 mg·kg-1 for 4 weeks,the fasting blood glucose was decreased significantly decreased (P < 0. 01 and P < 0. 05). Conclusion The novel GPR40 agonist SZZ15 -11 promoted glucose-dependent insulin and GLP-1 secretion,thus ameliorated glucose metabolism in type 2 diabetic mice. It will be a potential anti-diabetic compound candidate which is worth of further exploration.

OBJECTIVETo investigate the clinical features, diagnosis and treatment of glucose transporter 1 deficiency syndrome (GLUT1-DS), as well as the diagnostic value of movement disorders.

METHODSThe clinical data of four children with GLUT1-DS were collected, and their clinical features, treatment, and follow-up results were analyzed.

RESULTSThere were two boys and two girls, with an age of onset of 2-15 months. Clinical manifestations included movement disorders, seizures, and developmental retardation. Seizures were the cause of the first consultation in all cases. The four children all had persistent ataxia, dystonia, and dysarthria; two had persistent tremor, two had paroxysmal limb paralysis, and two had eye movement disorders. Paroxysmal symptoms tended to occur in fatigue state. All four children had reductions in the level of cerebrospinal fluid glucose and its ratio to blood glucose, as well as SLC2A1 gene mutations. The four children were given a ketogenic diet, at a ketogenic ratio of 2:1 to 3:1, and achieved complete remission of paroxysmal symptoms within 5 weeks.

CONCLUSIONSGLUT1-DS should be considered for epileptic children with mental retardation and motor developmental delay complicated by various types of movement disorders. The ketogenic diet is effective at a ketogenic ratio of 2:1 to 3:1 for the treatment of GLUT1-DS.

Carbohydrate Metabolism, Inborn Errors ; diagnosis ; genetics ; therapy ; Child ; Child, Preschool ; Female ; Humans ; Male ; Monosaccharide Transport Proteins ; deficiency ; genetics ; Movement Disorders ; diagnosis ; genetics ; therapy

OBJECTIVETo investigate the effects of different hemapheresis procedures on the components of hematopoietic stem cells(HSCs) collected from helathy donors.

METHODStwelve donors were underwent stem cell collection from January 2015 to August 2016, and the stem cells were randomly colleted by AutoPBSC procedure of COBE spectra and MNC procedure of the Spectra Optia blood cell separator, the mononuclear cells, CD34cells, granulocytes, lymphocytes and platelets in the collections were compared.

RESULTSThe circulating blood volume, the acquisition time and dosage of anticoagulants were not significantly different between two procedures. The volume and the mononuclear cell count collected by AutoPBSC procedure were lower than those by the MNC procedure, while the CD34cell count by AutoPBSC procedure was higher than that by the MNC procedure. More lymphocytes and platelets were collected by AutoPBSC procedure as compared with that by the MNC procedure (P<0.05).

CONCLUSIONCompared with MNC procedure of the Spectra Optia blood cell separator, the number of collected stem cells, lymphocytes and platelets are higher by using AutoPBSC procedure of the COBE spectra blood cell separator.