Humans ; Child ; Primary Myelofibrosis/genetics* ; Prognosis ; Mutation

OBJECTIVES: To investigate the clinical phenotypes, genetic characteristics, and pathological features of children with disorders of sex development (DSD). METHODS: A retrospective analysis was conducted on epidemiological, clinical phenotype, chromosomal karyotype, gonadal pathology, and genotype data of 165 hospitalized children with DSD at Children's Hospital of Hebei Province and Tangshan Maternal and Child Health Hospital from August 2008 to December 2022. RESULTS: Among the 165 children with DSD, common presenting symptoms were short stature (62/165, 37.6%), clitoromegaly (33/165, 20.0%), cryptorchidism (28/165, 17.0%), hypospadias (24/165, 14.5%), and skin pigmentation abnormalities/exteriorized pigmented labia majora (19/165, 11.5%). Chromosomal karyotype analysis was performed on 127 cases, revealing 36 cases (28.3%) of 46,XX DSD, 34 cases (26.8%) of 46,XY DSD, and 57 cases (44.9%) of sex chromosome abnormalities. Among the sex chromosome abnormal karyotypes, the 45,X karyotype (11/57, 19%) and 45,X/other karyotype mosaicism (36/57, 63%) were more common. Sixteen children underwent histopathological biopsy of gonadal tissues, resulting in retrieval of 25 gonadal tissues. The gonadal tissue biopsies revealed 3 cases of testes, 3 cases of dysplastic testes, 6 cases of ovaries, 11 cases of ovotestes, and 1 case each of streak gonad and agenesis of gonads. Genetic testing identified pathogenic/likely pathogenic variants in 23 cases (23/36, 64%), including 12 cases of 21-hydroxylase deficiency congenital adrenal hyperplasia caused by CYP21A2 pathogenic variants. CONCLUSIONS Short stature, clitoromegaly, cryptorchidism, hypospadias, and skin pigmentation abnormalities are common phenotypes in children with DSD. 45,X/other karyotype mosaicism and CYP21A2 compound heterozygous variants are major etiological factors in children with DSD. The most commonly observed gonadal histopathology in children with DSD includes ovotestes, ovaries, and testes/dysgenetic testes.
Male ; Humans ; Child ; Disorders of Sex Development/pathology* ; Hypospadias/complications* ; Cryptorchidism/complications* ; Retrospective Studies ; Adrenal Hyperplasia, Congenital ; Steroid 21-Hydroxylase

OBJECTIVE To detect the reversal effect of Guizhi Fuling Wan on cisplatin-resistant ovarian cancer SKOV3/DDP cells and its relationship with protein expression of phosphatase and tensin homolog (PTEN) and metadherin (MTDH). METHODS Guizhi Fuling Wan (GFW) concentrated solution was prepared according to the Chinese Pharmacopoeia 2015 edition, Wistar rats were given GFW viagavage at 4 g·kg-1·d-1,8 g·kg-1·d-1,16 g·kg-1·d-1,or given saline as blank control for 5 days.Blood samples were taken and the corresponding drug-containing low-dose sera, medium-dose sear, high-dose sera and blank sera were prepared.The XCELLigence RTCA S16 real-time label-free cell analyzer was used to detect the reversal effect by the sera combined with cisplatin or paclitaxel in SKOV3/DDP cells. Annexin V-FITC and PI double-staining were used to detect the apoptosis-inducing effect of the sera in the cells. RT-qPCR and western blot were used to detect the mRNA and protein expression of PTEN and MTDH after the cells treated with the sera. RESULTS The inhibition rate of low-dose sera against SKOV3/DDP cells was less than 5%.After the low-dose sera combined with cisplatin or pacli-taxel, the IC50 of SKOV3/DDP cells against cisplatin and paclitaxel decreased by 3.01 and 1.79-fold, respectively.The total apoptosis rates induced by the low-dose sera,medium-dose sear,high-dose sera and blank sera in SKOV3/DDP cells were 11.08±0.13,19.42±0.30,24.23±0.31,and 3.21±0.24,respec-tively; there was a significant difference between the groups (P<0.01). RT-qPCR results showed that, compared with the blank serum, the sera can up-regulate the expression of PTEN mRNA and down-regulate the expression of MTDH mRNA in a dose-dependent manner. Western blot results showed that the induction effect to PTEN protein and the inhibition effect to MTDH protein by the sera were gradually enhanced with thesera dose increasement. CONCLUSION The resistance reversal effect of Guizhi Fuling Wan on ovarian cancer SKOV3/DDP cells may be related to the inhibition of MTDH, up-regulation of PTEN and induction of apoptosis, providing with an experiment basis for the applica-tion of Guizhi Fuling Wan as a reversal agent for chemotherapy resistance of ovarian cancer.

Objective To evaluate the operative outcomes of a triple procedure including simultaneous penetration keratoplasty (PKP),extracapsular cataract extraction (ECCE) and intraocular lens (IOL) implantation,and to investigate the relationship between postoperative corneal refractive power and preoperative lens diopter.Methods This retrospective analysis study involved 15 patients who had undergone a triple procedure surgery in Beijing You'an hospital from April to October 2016.Outcomes including the best corrected visual acuity (BCVA),intraocular pressure (IOP),corneal refractive power,axial length,postoperative complications,corneal endothelial cell counts and the survival of corneal graft were determined one year after surgery.Results All corneal grafts were transparent and corneal endothelium were (1974.20 ±472.82) cell · mm-2.The mean postoperative LogMAR visual acuity (0.80 ±0.27) had a significant improvement compared with the mean preoperative LogMAR visual acuity (2.63 ±0.62) (t =13.042,P ＜0.001).There were no statistically significant differences in preoperative IOP (15.27 ± 2.37) mmHg (1 kPa =7.5 mmHg) and postoperative data (14.53 ± 3.04) mmHg (t =0.685,P =0.505),preoperative axial length (23.69 ±2.01) mm and postoperative data (23.62 ±2.12)mm (t =-0.138,P=0.893)and preoperative keratometry (45.01 ± 1.66) D of the control eye and postoperative data (42.56 ± 5.48) D (t =1.202,P =0.260).The postoperative spherical equivalent refractive was (0.40 ±4.65) D,and the target refraction was (0.58 ±0.25)D.Conclusion The triple procedures are safe and effective for the treatment of patients with coexisting corneal pathologies and cataracts.Selection of emmetropia lens diopter may result in the satisfactory postoperative visual acuity.However,unpredictable postoperative corneal curvature changes will still affect the final refractive state.

The purpose of this research is to investigate the effects and mechanisms of paeonol (PL), a phenolic compound found in many traditional Chinese formulations, on reversing drug resistance in the ovarian cancer resistant SKOV3/DDP cells. The results showed that PL had significant drug-resistant reversal effect on SKOV3/DDP cells. Flow cytometry showed that PL could inhibit P-glycoprotein (P-gp) function in a concentration-dependent manner. Fluorescent quantitative PCR and cell immunofluorescence techniques were used to detect mechanisms of action. Results revealed that both the inhibitory effect on MDR1/P-gp and metadherin (MTDH) expression and the induction effect on phosphatase and tensin homolog (PTEN), by 15, 30, and 60 μmol·L^-1 PL, were increased with increased concentrations of PL (P < 0.01, P < 0.05). The inhibitory effect on MTDH mRNA and the induction effect on PTEN mRNA, by PI3K inhibitor LY294002, were stronger or equivalent to that of the 60 μmol·L^-1 PL treated group; however, the inhibition or induction effect on MTDH or PTEN protein were only comparable to the 15 μmol·L^-1 PL treated group. The present study shows that the effect of PL on SKOV3/DDP cells may be related to the inhibition of P-gp function and expression, the inhibition of MDR1, MTDH expression, and the induction of PTEN expression, all which can provide a theoretical foundation for PL as a drug resistance reversal agent on the treatment of ovarian cancer chemotherapy resistance.

Objective To evaluate the efficacy of hot water drinking, isosorbide dinitrate and combination of both in achalasia.Methods The patients with untreated achalasia admitted to Peking Union Medical College Hospital in the period of October 2012 to May 2013 were enrolled and randomly divided into group A ( hot water drinking and combined therapy) and group B (isosorbide dinitrate and combined therapy).Patients in group A received hot water drinking only during the first week, then combined with isosorbide dinitrate from the second to the fourth week.Patients in group B received isosorbide dinitrate only during the first week, then combined with hot water drinking from the second to the fourth week.Clinical symptoms were evaluated at baseline ( 2 weeks before treatment) as well as after 1-week and 4-week treatment.High-resolution manometry and X-ray barium esophagram were evaluated at both baseline and after 4-week treatment.Results A total of 41 patients were in-cluded in this study, 19 in group A and 22 in group B.There was no significant difference in gender, age and course of disease between the two groups ( P>0.05) .Compared with baseline, symptoms were significantly alle-viated after 1-week treatment and after 4-week treatment in group A (P<0.05), and symptoms were significantly mitigated after 4-week treatment than after 1-week treatment ( P<0.05 ) .Compared with baseline, symptoms were significantly alleviated after 4-week treatment in group B ( P<0.05) .There was no difference in scales of symptoms between the two groups (P>0.05).Compared with baseline, there was no significant reduction in lower esophageal sphincter pressure ( LESP) and integrated relaxation pressure ( IRP) after 4-week treatment in both groups (P>0.05).However, at both baseline and after 4-week treatment, LESP and IRP were significantly decreased after hot water drinking or sublingual isosorbide dinitrate compared with pre-intervention levels in both groups ( P<0.05 ) .There was no change in the width of the esophagus after 4-week treatment in both groups ( P>0.05) .Conclusions Hot water drinking or sublingual isosorbide dinitrate could alleviate clinical symp-toms by temporarily decreasing LESP and IPR, which could be amplified by the combination of these two treat-ments, but the effect is not sustained.Hot water drinking combined with sublingual isosorbide dinitrate provides an option of conservative therapy for those intolerant to or relapsing after invasive treatment.

OBJECTIVETo investigate the ability of Fuzhenghuayu capsule to improve markers of liver fibrosis when provided as supplemental therapy in patients with chronic hepatitis B (CHB) who achieved complete virological response but unsatisfactory resolution of fibrosis markers with nucleos(t)ide analog (NAs) monotherapy.

METHODSOne-hundred-and-ten patients with CHB-related liver fibrosis who had received NA for more than or equal to 2 years and achieved sustained virological response (SVR) but no improvement in liver fibrosis index were randomly divided into two equal groups: experimental group, continued oral NAs (one tablet, 1 time/day) with simultaneous Fuzhenghuayu capsule (1.5 g, 3 times/day) for 48 weeks; control group, continued oral NAs only for 48 weeks. Serum fibrosis markers (hyaluronic acid (HA), laminin (LN), amino terminal propeptide of type III procollagen (PIIIP) and IV collagen (IV-C)), liver fibrosis stages, B ultrasonic wave, and liver function were observed before (baseline) and after treatment and compared by statistical analysis.

RESULTSThe baseline levels of fibrosis markers were not significantly different between the experimental and control groups. After treatment, the levels of all of the fibrosis markers were lower in the experimental group (P less than 0.05 vs. control group; HA t = 19.548, LN t = 2.264, PIIIP t = 2.230, and IV-C t = 6.649) and lower than the baseline levels (P less than 0.01; HA t = 12.458, LN t = 7.402, PIIIP t = 4.620, IV-C t = 8.937). The control group also showed a significant reduction in HA and LN levels after treatment (P less than 0.01 vs. baseline; t = 5.202 and 3.444), but PIIIP and IV-C were unaffected. The baseline liver fibrosis stages were not significantly different between the experimental and control groups. After treatment, only the experimental group showed significant improvement in liver fibrosis stages (P less than 0.01). The rates of excellent therapeutic outcome, effectiveness, and non-effectiveness were significantly different between the experimental group (11.3%, 43.4%, and 45.3%) and the control group (1.0%, 22.2%, and 75.6%) (x2 = 9.408, P less than 0.01). Similar trends were observed for improvements in B ultrasonic wave for liver and spleen and in markers of liver function. Finally, neither treatment group experienced adverse effects.

CONCLUSIONFor CHB patients who achieve SVR by antiviral treatment with NAs, but unsatifactory improvement in liver fibrosis indices, administration of supplemental Fuzhenghuayu capsule with continued NAs therapy may represent a safe and effective treatment.

Adult ; Antiviral Agents ; administration & dosage ; therapeutic use ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Female ; Hepatitis B, Chronic ; drug therapy ; Humans ; Liver ; pathology ; Liver Cirrhosis ; drug therapy ; metabolism ; Male ; Middle Aged ; Nucleotides ; therapeutic use ; Phytotherapy ; Prospective Studies ; Treatment Outcome

OBJECTIVETo determine the differentially expressed serum proteins in patients with hepatoma carcinoma and identify a putative diagnostic marker.

METHODThe isobaric tags for relative and absolute quantitation (iTRAQ) labeling method and LC-MALDI-TOF/TOF MS detection method were used to quantify serum proteins in hepatocellular carcinoma patients (n =20) and healthy individuals (n =20). Real-time reverse transcription-polymerase chain reaction was used to verify the differentially expressed proteins by analyzing the corresponding mRNA expression levels in the hepatic carcinoma and healthy hepatocyte samples, as well as in 30 pairs of patient-matched hepatic carcinoma and adjacent normal tissue samples. Western blot analysis was used to verify the protein expression in hepatic carcinoma cells.

RESULTFifty-one proteins were significantly differentially expressed between the hepatic carcinoma group and healthy controls. The iTRAQ protein profile showed that the serum level of clusterin was significantly lower in hepatoma carcinoma patients. The mRNA level of clusterin was 20-fold lower in hepatic carcinoma cells than in healthy hepatocytes, and was 2.38-fold lower in hepatoma tissues than that in adjacent normal tissues. The clusterin protein levels were significantly lower in hepatic carcinoma cells (8.06 vs normal hepatocytes: 27.81; P less than 0.01).

CONCLUSIONThe serum expression of clusterin is significantly decreased in both serum and tissues of hepatic carcinoma patients. The relationship between hepatic carcinoma and clusterin should be evaluated in future studies.

Biomarkers ; Carcinoma, Hepatocellular ; metabolism ; Case-Control Studies ; Clusterin ; blood ; metabolism ; Humans ; Liver Neoplasms ; metabolism ; Mass Spectrometry ; RNA, Messenger ; genetics ; Tumor Cells, Cultured

ObjectiveTo find out if the immune system derived thyroid stimulating hormone(TSH) β splice variant(TSHβ-Ⅴ) would be regulated by circulating thyroid hormone levels to get a further understanding of the function and mechanism of this TSHβ-Ⅴ in thyroid homeostasis.MethodsA total of 20 weaning Balb/c mice (half male and half female) were selected and randomly divided into two groups according to their body mass and gender(n =10).Mice of control group were fed with common diet and deionized water.Mice of the low-iodine(LI) group were fed with low-iodine diet(containing iodine 20 - 40 μg/kg,iodine-intake about 0.25 μg/d) and deionized water.The experimental period was 3 months.At the end of the experiment,mice were executed and the blood was collected to observe the levels of TSH and thyroid hormone by chemiluminescence immunoassay (CIA) ; bone marrow (BM),peripheral blood(PBL),thyroid gland and pituitary were collected to assay the TSHβ-Ⅴ mRNA expression by real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR).ResultsThe serum free thyroxine(FT4) and total thyroxine(TT4) levels in LI group of mice[(0.47 ± 0.70)nmol/L,(2.41 ± 0.28)pmol/L] were significantly lower than that of the control group of mice [(55.2 ± 3.68) nmol/L, (32.72 ± 1.02) pmol/L,t =43.81,86.04 、all P ＜ 0.01 ] and the serum total triiodothyronine(TT3) and free triiodothyronine(FT3) reduction in LI group of mice[ (0.76 ± 0.08)nmol/L,(4.01 ± 0.40)pmol/L] were significantly lower than that of the control group of mice [ (1.10 ± 0.06)nmol/L,(5.40 ± 0.38)pmol/L,t =9.81,7.5 1,P ＜ 0.01 ].Iodine insufficiency strongly elevated the serum TSH in LI group of mice[ (35.67 ± 17.39)mU/L] than that in control group of mice[ (0.24 ± 0.10)mU/L,t =- 6.11,P ＜ 0.01 ].The mRNA levels of TSH β-Ⅴ in BM (9.62 ± 0.60) and in PBL( 9.25 ± 0.83 ) of LI group of mice were lower than those in control group of mice (7.69 ± 0.36,7.11 ± 0.41,t =6.77,5.64,P ＜ 0.01),while the mRNA level of TSH β-Ⅴ in pituitary of LI group of mice (1.99 ± 0.61) was increased compared with that in control group of mice (5.75 ± 0.98,t =- 8.02,P＜ 0.01).Compared with control group of mice(9.12 ± 0.62),the level of thyroid TSH β-Ⅴ mRNA in LI group of mice (9.32 ± 0.91 ) was not significantly changed (t =0.45,P ＞ 0.05).There was no detectable native TSHβ in BM,PBL and thyroid.The mRNA level of native TSHβ in pituitary in LI group of mice( - 7.17 ± 1.78) was dramatically elevated compared to that in control group of mice( - 1.43 ± 0.51,t =- 7.60,P ＜ 0.01 ).ConclusionsThe mRNA levels of TSHβ-Ⅴ are suppressed in BM and PBL in low iodinediet induced hypothyroidism mice,which suggest that immune system derived TSHβ-Ⅴ may be more important thannative TSHβ in immune-thyroid regulation.

Objective To determine the predictive value of HATCH score on recurrence of atrial fibrillation (AF) after radiofrequency catheter ablation (RFCA).Methods The data of 123 consecutive AF patients (74 paroxysmal and 49 persistent AF) who underwent RFCA between April 2009 and December 2010 in our department were retrospectively analyzed.Of theses patients,65 (52.9％) patients had HATCH score =0,41 (33.3％) patients had HATCH score =1,and 17 (13.8％) patients had HATCH score ≥2 (HATCH =2 in 11 patients,HATCH =3 in 5 patients,HATCH =4 in 1 patient).The recurrence was defined as atrial tachyarrhythmia lasting more than 30 seconds after 3 months post RFCA.The patients were divided into recurrence group and no recurrence group.Relationship between HATCH score and recurrence was observed.Results There were 43 cases in recurrence group and 80 cases in no recurrence group.After 12 months follow-up,HATCH score was significant higher in recurrence group than in nonrecurrence group[(0.91 ±0.94) score vs.(0.53 ± 0.80) score,P ＜ 0.05].The ratio of patients with HATCH≥2 in recurrence group was higher than in non-recurrence group [23.3％ (10/43) vs.8.8％ (7/80),P ＜ 0.01].The sensitivity and specificity of HATCH ≥ 2 to define the risk of recurrence was 25.0％,92.4％ respectively.Cumulative non-recurrence rate of patients with HATCH score≥2 was lower than patients with HATCH score =0 and 1 (P ＜ 0.05).Conclusion Higher HATCH score is associated with increased risk of AF recurrence post RFCA.