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 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 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

OBJECTIVETo investigate the clinicopathologic features, diagnosis, treatment and prognosis of uterine mullerian adenosarcoma.

METHODSThe clinicopathological data of 9 cases of uterine mullerian adenosarcoma in PUMC hospital from January 2003 to February 2009 were retrospectively analyzed.

RESULTSThere were 6 uterine endometrial adenosarcomas and 3 cervical adenosarcomas. The main clinical manifestations were abnormal vaginal bleeding and pelvic pain. Physical examination showed cervical/vaginal mass, enlarged uterus or pelvic mass. The adenosarcoma was characterized by benign or atypical-appearing neoplastic glands within a sarcomatous stroma. This stroma could appear as periglandular cuffs or intraglandular polypoid projections of increased cellular structure. The primary diagnostic rate was 66.7% and the most common clinical stage was stage I (7/9). All patients received surgical treatment and seven had postoperative chemotherapy, radiotherapy or hormone therapy. Conservation of unilateral ovary or bilateral ovaries was performed in 5 cases. Three patients underwent local excision, which resulted in the preservation of reproductive function. During the follow-up, 2 cases of uterine endometrial adenosarcoma recurred. One patient of clinical stage III containing sarcomatous overgrowth died from recurrence 13 months after surgery. The other one recurred 2 years after local excision of the tumor in the uterine cavity and she remained healthy since hysterectomy.

CONCLUSIONUterine mullerian adenosarcoma is a rare tumor without specific clinical symptoms and signs. The diagnosis depends on pathomorphologic examination. The tumors show low malignant potential and the vast majority are at early stage. Surgical excision is the main treatment strategy with a good prognosis in the early stage disease with complete removal of tumors. The prognosis is poor in advanced adenosarcoma with sarcomatous overgrowth. Due to the relatively high rate of recurrence, long-term follow-up is recommended.

Adenosarcoma ; drug therapy ; pathology ; surgery ; Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Chemotherapy, Adjuvant ; Cisplatin ; therapeutic use ; Endometrial Neoplasms ; drug therapy ; pathology ; surgery ; Etoposide ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Hysterectomy ; methods ; Ifosfamide ; therapeutic use ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Retrospective Studies ; Uterine Cervical Neoplasms ; drug therapy ; pathology ; surgery ; Uterine Neoplasms ; drug therapy ; pathology ; surgery ; Young Adult

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

Objective To explore factors influencing the incidence of carotid atherosclerosis in different genders so as to provide reference for the specific prevention of the disease. Methods A nested case-control study was conducted to analyze factors influencing the incidence of carotid atherosclerosis in Jinchang cohort population who were randomly selected through stratified sampling by age and followed up. A risk prediction model was established and the goodness of fit was evaluated by the area under the receiver operator characteristic curve (ROC). Results The standardized incidence of carotid atherosclerosis in this follow-up population was 12.32%, and the incidence rate of males (13.65%) was greater than that of females (11.29%). The difference was statistically significant ( 2=4.267, P<0.001). Age, education, elevated systolic blood pressure, and elevated low-density lipoprotein cholesterol were common risk factors for carotid atherosclerosis in both men and women. Elevated fasting plasma glucose (OR=2.556, 95% CI: 1.618-4.038) and elevated triglyceride (OR=1.535, 95% CI: 1.058-2.227) were only associated with men. Abdominal obesity (OR=1.414, 95% CI: 1.013-1.974) was only associated with women. The area under ROC of male and female prediction models was 0.835 (95% CI: 0.815-0.856) and 0.809 (95% CI: 0.788-0.831), respectively. The sensitivity was 78.0% and 78.9%, the specificity was 78.8% and 73.1%, and the diagnostic coincidence rate was 91.3% and 82.4%, respectively. Conclusions There are different risk factors for carotid atherosclerosis in males and females, and targeted prevention and control measures should be taken according to gender. The risk prediction model established by Logistic regression had certain guiding value.

BACKGROUNDInvasive aspergillosis (IA), which is mainly caused by Aspergillus fumigatus (A. fumigatus), is a major cause of morbidity and mortality in immunocompromised patients. Despite considerable progress in currently available antifungals the mortality still remains high in critically ill patients. U0126 which is a highly selective inhibitor of MEK1 and MEK2 in the RAF/MEK/ERK pathway in mammalian cells has been demonstrated to have an anti-proliferative role in cancer cells. The purpose of this study was to explore the role of U0126 on growth inhibition and activation of mitogen-activated protein kinases (MAPKs) in A. fumigatus.

METHODSGermination percentage and hyphae growth in A. fumigatus treated with U0126 were observed and compared with untreated controls. Western blotting analysis was used to detect changes in activation of SakA, MpkA and MpkB.

RESULTSU0126 inhibited germination and hyphae growth in A. fumigatus and enhanced the phosphorylation of SakA and MpkA under oxidative stress. U0126 at 10 µmol/L did not block the activation of MpkB during nitrogen starvation stress.

CONCLUSIONU0126 shows promise as an antifungal candidate and the MAPK pathway may be a possible antifungal drug target for A. fumigatus.

Aspergillus fumigatus ; drug effects ; enzymology ; growth & development ; Butadienes ; pharmacology ; Enzyme Activation ; drug effects ; Enzyme Inhibitors ; pharmacology ; MAP Kinase Signaling System ; drug effects ; Mitogen-Activated Protein Kinases ; metabolism ; Nitriles ; pharmacology