BACKGROUND:Ferroptosis and pyroptosis may play a role in the development of postmenopausal osteoporosis.There may be relevant biomarkers for the diagnosis of postmenopausal osteoporosis. OBJECTIVE:To search for the key genes related to ferroptosis and pyroptosis in postmenopausal osteoporosis using bioinformatics so as to further elucidate their biological mechanisms. METHODS:The data sets GSE56815 and GSE7429 of postmenopausal osteoporosis were downloaded from the GEO database,the national comprehensive gene expression database of the United States,and the two data sets were preprocessed.The differential expression analysis of the data was carried out by the limma package of R software,and the enrichment analysis was performed by DIVID and KOBAS.The protein-protein interaction network was mapped by STRING and Cytoscape,the Hub gene was selected by CytoHubba,and the key genes were screened by the ferroptosis database and pyroptosis database.The CIBERSORT package was used to determine the immune infiltration of postmenopausal osteoporosis samples and to analyze the correlation between key genes and immune cells RESULTS AND CONCLUSION:A total of 30 differential genes of postmenopausal osteoporosis were screened in the experimental samples,of which 9 genes were up-regulated and 21 genes were down-regulated.The enrichment of GO and KEGG pathways showed that the differences were mainly in"serine-type endopeptidase activity,""innate immune response,""special particle lumen,"and"renin secretion."The protein-protein interaction network showed the correlation of differential genes and the top 10 Hub genes with"Degree"value were selected using CytoHubba.Hub gene was intersected with the FerrDb database and cell pyroptosis dataset to obtain key genes ELANE and LCN2.Receiver operating characteristic curve and box diagram showed that the expression of ELANE and LCN2 in serum samples of postmenopausal osteoporosis was significantly lower than that in normal samples,indicating a good diagnostic value.Immune infiltration analysis showed that ELANE may be related to memory resting CD4+ T cells,M0 and M2 macrophages.LCN2 may be related to M0 macrophages.

Objective: This study aimed to investigate the impact of polycystic ovary syndrome (PCOS) on fertility-sparing treatment in young patients with atypical endometrial hyperplasia (AEH) or endometrioid endometrial cancer (EEC). Methods: A total of 285 patients with EEC (n=76, FIGO stage IA, without myometrium invasion) or AEH (n=209) who received progestin-based fertility-sparing treatment were evaluated retrospectively. Among the 285 patients, 103 (36.1%), including 70 AEH cases and 33 EEC cases, were diagnosed with PCOS. General characteristics, cumulative 16- and 32-week complete response (CR) rate, pregnancy outcome and recurrence were compared between patients with or without PCOS. Results: The cumulative 16-week CR rate was lower in the PCOS group than in the non-PCOS group (18.4% vs. 33.8%, p=0.006). Patients with PCOS took longer treatment duration to achieve CR (7.0 months vs. 5.4 months, p=0.006) and shorter time to relapse after CR (9.6 months vs. 17.6 months, p=0.040) compared with non-PCOS group. After adjusting for patient age, body mass index, PCOS, homeostasis model assessment-insulin resistance index, and serum testosterone levels, we found that body mass index ≥25 kg/m2 (HR=0.583; 95% CI=0.365–0.932; p=0.024) and PCOS (HR=0.545; 95% CI=0.324–0.917; p=0.022) were significantly correlated with lower 16-week CR rate. Conclusion PCOS was associated with lower 16-week CR rate, longer treatment duration and shorter recurrence interval in patients with AEH or EEC receiving fertility-preserving treatment.

OBJECTIVES: Although patients with grade I and II endometrioid endometrial adenocarcinoma (EEA) are considered with good prognosis, among them 15%–25% died in 5 years. It is still unknown whether integrating estrogen receptor (ER) and progesterone receptor (PR) into clinical risk stratification can help select high-risk patients with grade I–II EEA. This study was to investigate the prognostic value of ER and PR double negativity (ER/PR loss) in grade I–II EEA, and the association between ER/PR loss and The Cancer Genome Atlas (TCGA) classification. METHODS: ER and PR were assessed by immunohistochemistry on hysterectomy specimens of 903 patients with grade I–II EEA. ER and PR negativity were determined when < 1% tumor nuclei were stained. Gene expression data were obtained from the TCGA research network. RESULTS: Compared with ER or PR positive patients (n=868), patients with ER/PR loss (n=35) had deeper myometrial infiltration (p=0.012), severer FIGO stage (p=0.004), and higher rate of pelvic lymph node metastasis (p=0.020). In univariate analysis, ER/PR loss correlated with a shorter progression-free survival (PFS; hazard ratio [HR]=5.25; 95% confidence interval [CI]=2.21–12.52) and overall survival (OS; HR=7.59; 95% CI=2.55–22.60). In multivariate analysis, ER/PR loss independently predicted poor PFS (HR=3.77; 95% CI=1.60–10.14) and OS (HR=5.56; 95% CI=1.37–22.55) for all patients, and poor PFS for patients in stage IA (n=695; HR=5.54; 95% CI=1.28–23.89) and stage II–IV (n=129; HR=5.77; 95% CI=1.57–21.27). No association was found between ER/PR loss and TCGA classification. CONCLUSION: Integrating ER/PR evaluation into clinical risk stratification may improve prognosis for grade I–II EEA patients.
Adenocarcinoma* ; Carcinoma, Endometrioid ; Classification ; Disease-Free Survival ; Endometrial Neoplasms ; Estrogens* ; Female ; Gene Expression ; Genome ; Humans ; Hysterectomy ; Immunohistochemistry ; Lymph Nodes ; Multivariate Analysis ; Neoplasm Metastasis ; Progesterone* ; Prognosis ; Receptors, Progesterone*

OBECTIVE： To study the mechanism of Wutou decoction in the treatment of osteoarthritis， and to provide a new direction and target for the treatment of osteoarthritis. METHODS： Using oral bioavailability （OB）≥30％， drug like （DL）≥0.18％ as index， active components were screened from Wutou decoction by using TCM systematic pharmacological analysis platform （TCMSP）， such as Aconitum carmichaelii， Ephedra sinica， Astragalus propinquus， Paeonia tactilora， Glycyrrhiza uralensis. Targets of osteoarthritis were obtained by retrieving therapeutic targets database （TTD） and mining thip data from gene expression database （GEO）. Target genes were analyzed by GO and KEGG pathway enrichment analysis were performed by using DAVID database. RESULTS： A total of 30 active components were screened， including quercetin， terpenoids and gardenol； 31 targets related to osteoarthritis were obtained， including β2 adrenergic receptor， arachidonate 5-lipoxygenase and androgen receptor. The biological process of Wutou decoction in treatment of osteoarthritis was mainly related to the IL-1 receptor signal transduction， synergistic activation of peroxidase proliferation activated receptor， signal transduction of tyrosine kinase receptor 2. It mainly regulated tumor necrosis factor signaling pathway， vascular endothelial growth factor signaling pathway， osteoclasts differentiation signaling pathway， nuclear factor κB signaling pathway， Toll-like receptor signaling pathway so as to play a role in the treatment of osteoarthritis. CONCLUSIONS： The study analysis the potential mechanism of Wutou decoction in the treatment of osteoarthritis based on network pharmacology， which can provide reference for further study on the material basis and target of Wutou decoction in the treatment of osteoarthritis.

OBJECTIVE: Our previous study showed that insulin resistance (IR) was related to endometrial hyperplasia as well as endometrial cancer. But the exact impact of IR on fertility-sparing treatment in endometrial hyperplasic disease is unclear. This study investigated how IR affects fertility-sparing treatment in endometrial atypical hyperplasia (EAH) patients. METHODS: The 151 EAH patients received fertility-sparing treatment were retrospectively investigated. All patients received high-dose progestin combined with hysteroscopy. Therapeutic effects were evaluated by hysteroscopy every 3 months during the treatment. RESULTS: The median age was 33.0 years old (range, 21–54 years old). Sixty-one patients (40.4%) were insulin resistant. Three patients were excluded from the analysis because they chose hysterectomy within 3 months after initiation of progestin treatment. The 141 out of 148 (95.3%) patients achieved complete response (CR). No difference was found in cumulative CR rate between those with or without IR (90.2% vs. 95.6%, p=0.320). IR significantly affected therapeutic duration to achieve CR (8.1±0.5 months with IR vs. 6.1±0.4 months without IR, p=0.004). Overweight (body mass index [BMI]≥25 kg/m2) was associated with higher risk of treatment failure (odds ratio=5.61; 95% confidence interval=1.11–28.35; p=0.040) and longer therapeutic duration to achieve CR (7.6±0.5 months vs. 6.3±0.4 months, p=0.019). EAH patients with both IR and overweight (IR+BMI+) had the longest therapeutic time compared with other patients (8.8±0.6 months vs. 5.6±0.7, 6.3±0.4, and 6.4±0.8 months for IR−BMI+, IR−BMI−, and IR+BMI−, respectively, p=0.006). CONCLUSION: IR and overweight were associated with longer therapeutic duration in EAH patients receiving progestin-based fertility-sparing treatment.
Endometrial Hyperplasia ; Endometrial Neoplasms ; Female ; Humans ; Hyperplasia* ; Hysterectomy ; Hysteroscopy ; Insulin Resistance* ; Insulin* ; Overweight* ; Retrospective Studies ; Therapeutic Uses ; Treatment Failure

Apolipoprotein A-Ⅰ (ApoA-Ⅰ), the predominant protein in plasma HDL, regulates cholesterol metabolism and exhibits anti-in-flammatory and antioxidant functions. Multiple clinical studies suggest that serum ApoA-Ⅰ levels are associated with the occurrence, development, and prognosis of malignant tumors. Laboratory research also shows that ApoA-Ⅰ and ApoA-Ⅰ mimetics exert antitumor ef-fects through antioxidation, immunoregulation, cholesterol metabolism, lysophosphatidic acid binding, and anti-angiogenesis. This pa-per reviews the role of ApoA-Ⅰ and ApoA-Ⅰ peptides in tumorigenesis and their potential value in diagnosis, treatment, and prognosis.

Objective To evaluate the value of serum procalcitonin (PCT ) in the diagnosis of liver cirrhosis complicating sponta‐neous bacterial peritonitis (SBP) .Methods The patients with cirrhosis were divided into non‐SBP group and complicating SBP group according to whether complicating SBP ,and the patients with common hepatitis served as the control group .Serum expres‐sion levels of PCT ,CRP and IL‐6 were detected by electrocheniluminescence and Immunoturbidimetry methods .The receiver operat‐ing characteristic curve (ROC) curve was drawn for evaluating the diagnostic efficiency of each indicator .Results The levels of ser‐um PCT ,CRP and IL‐6 in the complicating SBP group were significantly higher than those in the non‐SBP group and control group , the differences were statistically significant (P<0 .01);The ROC curve analysis showed that the diagnostic value of PCT at the op‐timum threshold value of 0 .51 ng/mL for diagnosing cirrhosis complicating SBP was superior to CRP and IL‐6 ,the sensitivity of se‐rum PCT for diagnosing SBP in 3 groups was 62 .68% ,the specificity was 76 .59% and the accuracy was 80 .01% .Conclusion The serum PCT level has an important value for the early diagnosis of liver cirrhosis complicating SBP .

Objective To evaluate combined effect on different population through 2 459 data of SAA,hs-CRP and PCT from 8 three-level hospitals in Guangdong region.Methods Subjects were divided into five groups by ages,and every group had bacterial and virus type.In order to confirm diagnostic effect on infection,methods were performed including in tendency of SAA and hs-CRP,Paired t test between bacterial and virus group,efficiency of 3 indexes in judging infection depending on ROC and parameters,multiple logistic regression,consistency between positive bacterial infection and bacterial culture.Re-sults There were statistically significant differences in SAA and hs-CRP between bacterial and virus in infants and children (P <0.001).SAA had the biggest AUC area 0.824 with sensibility 71.8% and specificity 82.6% in younger group.Corre-sponding,hs-CRP had the biggest area 0.806 with sensibility 84%.There was the accuracy of 78.8% for differential diagno-sis in younger group,while 65.1% in elder group.AUC of SAA was 0.883 for positive bacterial culture with sensibility 71.2% and specificity 90.7%,accuracy of 95.2% for differential diagnosis.Conclusion There was obvious trend of age in SAA and hs-CRP,3 indexes could be used for differential diagnosis alone or combined,especially in younger group.SAA is the best index as a separated index.There is less value at ratio of SAA and hs-CRP.

OBJECTIVE: To compare the efficacy of metformin plus megestrol acetate (MA) with that of MA alone for treating endometrial atypical hyperplasia (EAH). METHODS: This pilot study included 16 EAH patients who met at least one metabolic syndrome (MS) criterion and received either adjunctive metformin plus MA (MET group) or MA monotherapy (MA group). Each patient in the MA group received 160 mg of MA daily, whereas patients in the MET group received the same dose of MA plus 0.5 g of metformin thrice daily. Treatment response was assessed by histological examination of dilation and curettage specimens obtained after 12 weeks of therapy. RESULTS: Each group had eight patients, and half of the patients in each group were diagnosed with MS. The complete response (CR) rate was 75% (6/8) in the MET group and 25% (2/8) in the MA group (p=0.105). Complications of MS did not affect the response rates in either group. In the MET group, 75% (3/4) of the patients had CR in the presence or absence of MS. In the MA group, 50% (2/4) of the patients with MS had CR, whereas no patient without MS had CR. No irreversible toxicities were observed. CONCLUSION: Metformin plus MA may be a potential alternative therapy for treating EAH, and the MS status of patients may have no effect on the efficacy of metformin plus MA therapy.
Adult ; Antineoplastic Agents, Hormonal/*therapeutic use ; Drug Therapy, Combination ; Endometrial Hyperplasia/complications/*drug therapy/metabolism ; Female ; Humans ; Hypoglycemic Agents/*therapeutic use ; Megestrol Acetate/*therapeutic use ; Metabolic Syndrome X/complications/metabolism ; Metformin/*therapeutic use ; Pilot Projects ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Single-Blind Method ; Treatment Outcome

Objective To investigate the release pattern of insulin after the load of glucose in patients with polycystic ovary syndrome ( PCOS ) and normal oral glucose tolerance.Methods Sixty-three patients with PCOS were undertaken oral glucose tolerance test (OGTT) and insulin release test,while 34 women with normal menstrual cycle served as control.Results Among 63 patients with PCOS,33 cases were obese with body mass index over 25 kg/m2,including 5 with abnormal OGTT.All 30 non-obese patients with PCOS had normal OGTT.The prevalences of insulin resistance were 78.8％,16.7％,and 9.0％ in obese PCOS,non-obese PCOS,and control groups,respectively.Abnormal insulin release curve were found in 84.5％,70.0％,and 14.7％ of subjects in these 3 groups,respectively.In 58 PCOS patients with normal OGTT,the prevalence of insulin resistance was 44.8％,and 75.9％with abnormal insulin release curve. Among them,body mass index of 32 patients,whose homeostasis model assessment for insulin resistance (HOMA-IR) and fasting insulin remained in normal range,was similar to those of control group [ ( 20.52 ± 2.86 vs 20.01 ± 2.54 ) kg/m2,P＞0.05].Conclusion These findings indicate that insulin release test is useful in detecting insulin resistance.Insulin release is elevated in PCOS patients even with normal OGTT.