OBJECTIVETo observe the change of PTEN/PI3K/AKT pathway hypoxia-inducible factor (HIF-1α), vascular endothelial growth factor (VEGF) in rats with adjuvant arthritis and to explore the mechanism of neovasculization in rheumatoid arthritis.

METHODSThirty rats were randomly divided into normal control group and model control group. The model control group were established the model of adjuvant arthritis using Freund's complete adjuvant. At 19 days after modeling, the expression of microvascular density (MVD), HIF-1α, VEGF were detected by ELISA assay and PTEN, PI3K, AKT were detected by Werstern Blotting.

RESULTSCompared with the normal control group, paw swelling, arthritic index were increased, and the expression of MVD, VEGF, HIF-1α of serum, PI3K, AKT of synovial tissue were significantly increased, PTEN was significantly decreased in model control group. PI3K, HIF-1α were positively correlated with MVD; VEGF, AKT were positively correlated with paw swelling; PTEN was negatively correlated with the arthritis index; HIF-1α was positively correlated with VEGF; PI3K was positively correlated with AKT, PTEN was negatively correlated with PI3K, AKT, VEGF.

CONCLUSIONImbalance of PTEN/PI3K/AKT pathway in rats with adjuvant arthritis is one of the mechanisms of synovial neovasculization.

Animals ; Arthritis, Experimental ; physiopathology ; Hypoxia-Inducible Factor 1, alpha Subunit ; physiology ; Neovascularization, Pathologic ; etiology ; PTEN Phosphohydrolase ; physiology ; Phosphatidylinositol 3-Kinases ; physiology ; Proto-Oncogene Proteins c-akt ; physiology ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; physiology

OBJECTIVETo observe the effect of Xinfeng Capsule (XFC) on ankylosing spondylitis (AS) patients' symptoms and signs, serum immunoglobulin levels, peripheral blood lymphocyte autophagy protein, autophagy gene, and to explore its mechanism.

METHODSTotally 59 AS patients were assigned to the treatment group (39 cases) and the control group (20 cases) according to random digit table. Patients in the treatment group received XFC, 0.5 g each pill, three pills each time, 3 times per day, while those in the control group received sulfasalazine (SASP), 0.25 g per tablet, 4 tablets each time, twice per day. Three months consisted of one therapeutic course. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) were statistically calculated. Serum immunoglobulins (IgG1, IgG2, IgG3, IgG4, IgA , SIgA, and IgM) were detected using ELISA. Changes of Beclin1, LC3-II, phosphatidylinositol 3-kinase (PI3K), Akt, the mammalian target of rapamycin (mTOR) were detected using Western blot. Serum autophagy related genes such as Atg1, Atg5, Atg12, Atg13, and Atg17 were detected using the polymerase chain reaction (PCR). The correlation between immunoglobulin subtypes and autophagy gene in AS patients using Spearman correlation.

RESULTSCompared with before treatment, BASDAI, IgG1, lgG3, and IgA decreased (P < 0.01); PI3K, Akt, and mTOR protein expressions decreased (P < 0.01); ATG1, ATG12, ATG13, and ATG17 mRNA expressions decreased, ATG5 mRNA expression increased (P < 0.01) in the treatment group. But BASDAI, IgG1, and IgA levels decreased (P < 0.05, P < 0.01); PI3K, Akt, and mTOR protein expressions decreased (P < 0.05); ATG1 and ATG13 mRNA expressions decreased (P < 0.05, P < 0.01) in the control group. Compared with the control group, BASDAI, IgG1, and IgA levels decreased (P < 0.05); PI3K, Akt, mTOR protein expressions decreased (P < 0.01); ATG12 and ATG17 mRNA expression decreased, ATG5 mRNA expression increased (P < 0.01) in the XFC group. Correlation analysis showed AS patients' IgG1, IgG2, IgG3, IgA, SIgA, IgM had negative correlation with ATG17; IgG4 and ATG17 were positively correlated (P < 0.05, P < 0.01).

CONCLUSIONXFC could elevate clinical efficacy of AS patients and enhance their autophagy, which might be achieved by acting on PI3K/Akt/mTOR signal, affecting autophagy gene and autophagy protein expression, taking part in the regulation of proliferation and differentiation of lymphocyte B, and strengthen humoral immunity.

Apoptosis Regulatory Proteins ; metabolism ; Autophagy ; drug effects ; Beclin-1 ; Capsules ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Immunoglobulin A ; blood ; Immunoglobulin G ; blood ; Immunoglobulin M ; blood ; Lymphocytes ; drug effects ; Membrane Proteins ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Spondylitis, Ankylosing ; drug therapy ; Sulfasalazine ; therapeutic use ; TOR Serine-Threonine Kinases ; metabolism

OBJECTIVETo provide genetic diagnosis and counseling for a 2-year-old girl with typical Rett syndrome through analyzing the methyl-CpG binding protein 2 (MECP2) gene.

METHODSPotential mutation of the MECP2 gene was screened by DNA sequencing and multiplex ligation-dependent probe amplification (MLPA) analysis of members of the family as well as normal controls. Lymphocyte culture for karyotype analysis was carried out for the patient to exclude chromosomal abnormalities.

RESULTSThe karyotype of the girl was normal. No variation of the MECP2 gene was detected in the patient by direct sequencing. A heterozygosis variation, c.1072G>A in exon 4 of the MECP2 gene was detected in a normal female control, which was not found in other controls. The son and daughter of the female control were respectively heterozygous and homozygous carriers of the same mutation. By MLPA analysis, a heterozygosis deletion of exon 3 and part of exon 4 was detected in the patient. cDNA amplification and sequencing confirmed the presence of a 1176 bp deletion (c.27-1202del1176). The same deletion was not detected in the parents.

CONCLUSIONA large deletion in MECP2 gene was detected with MLPA in a patient featuring typical Rett syndrome. The same deletion was missed by sequencing analysis. With cDNA sequencing, the breakage point of the mutation can be mapped precisely.

Base Sequence ; Child, Preschool ; Exons ; Female ; Genetic Testing ; Genotype ; Humans ; Karyotyping ; Methyl-CpG-Binding Protein 2 ; genetics ; Mutation ; Rett Syndrome ; genetics

OBJECTIVETo detect the changes of the antioxidant level, cell cycle progression, necrosis and apoptosis, calcium ion concentration ([Ca2+] i) and mitochondrial membrane potential (deltapsim) in the model rats of impaired glucose regulation (IGR) induced by long-range high-fat diet, and to explore IGR-induced male reproductive injury and its mechanisms.

METHODSForty male Wistar rats were randomly divided into a normal control (n = 10) and an IGR model group (n = 30), and the IGR model was established by 20 weeks of long-range high-fat diet. Pathological changes in the rat spermatogenic cells were detected by HE staining; the content of malondialdehyde (MDA) and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were measured with biochemical methods; changes in the cell cycle progression, necrosis and apoptosis were determined using flow cytometry with propidium iodide (PI) dyeing and the Annexin V-FITC kit, respectively, and [Ca2+]i and deltapsim were detected by flow cytometry with Fluo-3 and Rhodamine probe labeling, respectively.

RESULTSAfter 20 weeks of continuous high-fat diet, fasting blood glucose was kept at 6.1 - 7.0 mmol/L and blood glucose at 7.8 - 11.1 mmol/L after 2 h glucose load in 12 rats, with a 40% success rate of modeling. Lots of dividing spermatocytes and spermatids were seen in the tissue sections of the normal control rats under the microscope, but few or none in the IGR models. Compared with the normal controls, the IGR model rats showed remarkably increased MDA content and decreased SOD, CAT and GSH-Px activities in the testis tissue (P < 0.05 or P < 0.01) , reduced G0/G1 cells and increased G2/M cells (P < 0.05 or P < 0.01), decreased necrotic cells and increased apoptotic cells (P < 0.05 or P < 0.01), increased [Ca2+]i and decreased deltapsim (P < 0.01), but no significant changes in the percentages of S cells and normal cells.

CONCLUSIONIGR can cause spermatogenic cell division disorder in rats, which may be attributed to increased oxidative damage, decreased antioxidant enzyme activities, G2/M phase arrest, [Ca2+]i elevation, deltapsim reduction, and apoptosis of testicular cells.

Animals ; Apoptosis ; Cell Cycle ; Cell Division ; Diet, High-Fat ; Glucose Metabolism Disorders ; metabolism ; Glutathione Peroxidase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Oxidative Stress ; Rats ; Rats, Wistar ; Superoxide Dismutase ; metabolism ; Testis ; cytology ; metabolism

Objective To analyze the economic burden due to healthcare-associated infection(HAI)in low birth weight(LBW)infants,and provide theoretical basis for formulating HAI related policies.Methods The data of LBW infants in a tertiary first-class hospital from January 2018 to December 2022 were retrospectively collected.Propensity score matching method and marginal analysis were adopted to evaluate the economic losses in LBW in-fants and hospitals due to HAI.Results A total of 1 048 LBW infants were included in analysis,124 of whom had HAI,with HAI incidence of 11.8％.A total of 109 pairs were successfully matched using the propensity score matching method.The median length of hospital stay for LBW infants in the HAI group and non-HAI group were 34.0 and 11.0 days,respectively,the length of hospital extended 23 days in LBW infants in the HAI group(P＜0.001).The median hospitalization expenses for LBW infants in HAI group and non-HAI group were 38 067.6 and 12 375.7 Yuan,respectively,the hospitalization expense for LBW infants in HAI group was 25 691.9 Yuan more than non-HAI group(P＜0.001).The major increased expenses were examination,treatment and medication fees.The total hospitalization expenses in different birth weight LBW infants in HAI group were all higher than non-HAI group,and the differences were all statistically significant(all P＜0.05).LBW infants with gestational age＜32 weeks had longer length of hospital stay and higher total hospitalization expense,differences were all statistically significant(all P＜0.05).When the marginal profit ratios were 5％,10％,and 15％,respectively,the economic losses caused by HAI were 371 000 Yuan,742 000 Yuan,and 1 114 000 Yuan,respectively;The ratios of loss-profit and loss-profit to infection coefficient were 0.33 and 2.79,respectively.Conclusion HAI cause significant economic losses to both LBW infants and hospitals.Infants with a birth weight ≤1 000 g and those with a gestational age＜32 weeks are key populations for prevention and control.The lost-profit to infection coefficient can be used to estimate the economic loss of the hospital,timely adjust infection control measures,and reduce the incidence of HAI.

BACKGROUNDMitochondrial dysfunction is linked to the pathogenesis of Parkinson's disease (PD). However, the precise role of mitochondrial DNA (mtDNA) variations is obscure. On the other hand, mtDNA haplogroups have been inconsistently reported to modify the risk of PD among different population. Here, we try to explore the relationship between mtDNA haplogroups and sporadic PD in a Han Chinese population.

METHODSNine single-nucleotide polymorphisms, which define the major Asian mtDNA haplogroups (A, B, C, D, F, G), were detected via polymerase chain reaction-restriction fragment length polymorphism or denaturing polyacrylamide gel electrophoresis in 279 sporadic PD patients and 510 matched controls of Han population.

RESULTSOverall, the distribution of mtDNA haplogroups did not show any significant differences between patients and controls. However, after stratification by age at onset, the frequency of haplogroup B was significantly lower in patients with early-onset PD (EOPD) compared to the controls (odds ratio [OR] =0.225, 95% confidence interval [CI]: 0.082-0.619, P = 0.004), while other haplogroups did not show significant differences. After stratification by age at examination, among subjects younger than 50 years of age: Haplogroup B also showed a lower frequency in PD cases (OR = 0.146, 95% CI: 0.030-0.715, P = 0.018) while haplogroup D presented a higher risk of PD (OR = 3.579, 95% CI: 1.112-11.523, P = 0.033), other haplogroups also did not show significant differences in the group.

CONCLUSIONSOur study indicates that haplogroup B might confer a lower risk for EOPD and people younger than 50 years in Han Chinese, while haplogroup D probably lead a higher risk of PD in people younger than 50 years of age. In brief, particular Asian mtDNA haplogroups likely play a role in the pathogenesis of PD among Han Chinese.

Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; genetics ; DNA, Mitochondrial ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Haplotypes ; genetics ; Humans ; Male ; Middle Aged ; Parkinson Disease ; genetics ; Pedigree ; Polymorphism, Single Nucleotide ; genetics

Adenosarcoma ; mortality ; pathology ; therapy ; Adolescent ; Adult ; Female ; Humans ; Middle Aged ; Mixed Tumor, Mullerian ; mortality ; pathology ; therapy ; Prognosis ; Uterine Neoplasms ; mortality ; pathology ; therapy

OBJECTIVETo evaluate the clinical effect of a 10-day sequential therapy which was made up of omeprazole, clarithromycin, amoxicillin-clavulanate and metronidazole for the eradication of Helicobacter pylori (Hp) infection in children.

METHODA total of 214 children with abdominal pain, who were confirmed to have Hp infection through endoscopy, biopsy, and Hp culture. The 214 cases were randomly divided into four groups. A 10-day sequential therapy group accepted omeprazole 0.8 - 1.0 mg/(kg·d) plus amoxicillin-clavulanate 50 mg/(kg·d) for five days and omeprazole 0.8 - 1.0 mg/(kg·d), clarithromycin 20 mg/(kg·d) and metronidazole 20 mg/(kg·d) for the remaining five days. The 7-day triple therapy group, 10-day triple therapy group and 14-day triple therapy group received omeprazole 0.8 - 1.0 mg/(kg·d), amoxicillin-clavulanate 50 mg/(kg·d) and clarithromycin 20 mg/(kg·d) for 7 days,10 days,14 days, respectively. All drugs were given twice daily. All these patients received (13)C urea breath test ((13)C-UBT) four weeks after the treatment.

RESULTFinally, 199 patients were followed up, and the total rate of loss to follow-up was 7.0% (15/214). Hp eradication rate was 85.2% and 90.2% in the 10-day sequential therapy group on intention to treat (ITT) and per protocol (PP) analyses, 66.0% and 71.4% in the 7-day triple therapy group on ITT and PP analyses; 60.0% and 67.3% in 10-day triple therapy group on ITT and PP analyses, and 78.8% and 82.0% in patients who received the 10-day sequential regimen on ITT and PP analyses, respectively. By ITT analysis, there was significantly difference between the 10-day sequential therapy group and 7-day or 10-day triple therapy group (P < 0.05), while no significant difference was found between the 10-day sequential therapy group and 14-day triple therapy group (P > 0.05). The results of the ITT analysis and the PP analysis were the same. The four groups had neither significant difference in abdominal pain relief (P > 0.05) nor in incidence of adverse reactions (P > 0.05).

CONCLUSIONThe 10-day sequential regimen was significantly more effective than both 7-day triple regimen and 10-day triple regimen, while had the same eradication rate compared with the 14-day sequential therapy. But 10-day triple regimen to eradicate Hp infection in children had the advantages such as short course of treatment and better compliance.

Administration, Oral ; Adolescent ; Amoxicillin ; administration & dosage ; adverse effects ; Anti-Bacterial Agents ; administration & dosage ; adverse effects ; Anti-Ulcer Agents ; administration & dosage ; Breath Tests ; methods ; Child ; Child, Preschool ; Clarithromycin ; administration & dosage ; adverse effects ; Drug Administration Schedule ; Drug Therapy, Combination ; Female ; Helicobacter Infections ; drug therapy ; Helicobacter pylori ; drug effects ; isolation & purification ; Humans ; Male ; Metronidazole ; administration & dosage ; adverse effects ; Microbial Sensitivity Tests ; Omeprazole ; administration & dosage ; adverse effects ; Time Factors ; Treatment Outcome

Objective To evaluate the bias of creatinine testing by external quality assessment (EQA) and analyze the effects of calibration on the bias of tested values using Jaffe assay.Methods The EQA data from The Clinical Laboratory Centre of Chongqing City were utilized to investigate the frozen pooled-human serum in which the value of creatinine was determined by reference method.The differences between Jaffe assay and creatine oxidase method were analyzed and the bias was evaluated.After the routine measurement systems were calibrated using the frozen pooled-human sera with double levels,the EQA samples were tested.Results The number of the laboratories using Jaffe method for creatinine measurement reduced significantly in Chongqing from 2012 to 2016.The robust average values of Jaffe assay were different from enzymatic assay significantly and the difference of the values were correlated with the concentration of creatinine (r =0.774 6).The results of the investigation using frozen pooled human serum and the trueness verification program of National Center for Clinical Laboratories indicated the positive bias of Jaffe assay was observed in low levels of creatinine with maximum of 10.39％ and 13.31％ and the bias correlated with the concentration of creatinine (r =0.988 9),by contrast the bias was low in enzymatic assay with maximum of 1.04％ and 1.49％ only.After the measurement systems were calibrated by frozen pooled human sera with double-levels,the positive bias of Jaffe assay in the low concentration of creatinine could be corrected.Conclusion There may be a positive bias of Jaffe assay for the samples with low concentration of creatinine,which could be corrected by using the calibrators with double-levels.