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Objective: To compare the effects and safety of dydrogesterone (DG) and medroxyprogesterone acetate (MPA) on the treatment in patients with endometrial hyperplasia without atypia (EH). Methods: This was a single-center, open-label, prospective non-inferior randomized controlled phase Ⅲ trial. From February 2019 to November 2021, patients with EH admitted to the Obstetrics and Gynecology Hospital of Fudan University were recruited. Enrolled patients were stratified according to the pathological types of simple hyperplasia (SH) or complex hyperplasia (CH), and were randomised to receive MPA or DG. Untill May 14, 2022, the median follow-up time after complete response (CR) was 9.3 months (1.1-17.2 months). The primary endpoint was the 6-month CR rate (6m-CR rate). The secondary endpoints included the 3-month CR rate (3m-CR rate), adverse events rate, recurrence rate, and pregnancy rate in one year after CR. Results: (1) A total of 292 patients with EH were enrolled in the study with the median age of 39 years (31-45 years). A total of 135 SH patients were randomly assigned to MPA group (n=67) and DG group (n=68), and 157 CH patients were randomly assigned to MPA group (n=79) and DG group (n=78). (2) Among 292 patients, 205 patients enrolled into the primary endpoint analysis, including 92 SH patients and 113 CH patients, with 100 patients in MPA group and 105 in DG group, respectively. The 6m-CR rate of MPA group and DG group were 90.0% (90/100) and 88.6% (93/105) respectively, and there were no statistical significance (χ2=0.11, P=0.741), with the rate difference (RD) was -1.4% (95%CI:-9.9%-7.0%). Stratified by the pathology types, the 6m-CR rate of SH patients was 93.5% (86/92), and MPA group and DG group were respectively 91.1% (41/45) and 95.7% (45/47); and the 6m-CR rate of CH patients was 85.8% (97/113), and MPA group and DG group were 89.1% (49/55) and 82.8% (48/58) respectively. The 6m-CR rates of the two treatments had no statistical significance either (all P>0.05). A total of 194 EH patients enrolled into the secondary endpoint analysis, including 88 SH patients and 106 CH patients, and 96 patients in MPA group and 98 in DG group, respectively. The 3m-CR rate of SH patients were 87.5% (77/88), while the 3m-CR rates of MPA group and DG group were 90.7% (39/43) and 84.4% (38/45), respectively; the 3m-CR rate of CH patients was 66.0% (70/106), and MPA group and DG group had the same 3m-CR rate of 66.0% (35/53). No statistical significance was found between the two treatments both in SH and CH patients (all P>0.05). (3) The incidence of adverse events between MPA group and DG group had no statistical significance (P>0.05). (4) A total of 93 SH patients achieved CR, and the cumulative recurrence rate in one year after CR were 5.9% and 0 in MPA group and DG group, respectively. While 112 CH patients achieved CR, and the cumulative recurrence rate in one year after CR were 8.8% and 6.5% in MPA group and DG group, respectively. There were no statistical significance between two treatment groups (all P>0.05). Among the 93 SH patients, 10 patients had family planning but no pregnancy happened during the follow-up period. Among the 112 CH patients, 21 were actively preparing for pregnancy, and the pregnancy rate and live-birth rate in one year after CR in MPA group were 7/9 and 2/7, while in DG group were respectively 4/12 and 2/4, and there were no statistical significance in pregnancy rate and live-birth rate between the two treatment groups (all P>0.05). Conclusions: Compared with MPA, DG is of good efficacy and safety in treating EH. DG is a favorable alternative treatment for EH patients.
Subject(s)
Female , Humans , Adult , Medroxyprogesterone Acetate/adverse effects , Endometrial Hyperplasia/pathology , Dydrogesterone/adverse effects , Hyperplasia , Prospective StudiesABSTRACT
Objective: To explore the occupational protective effect of different protective devices on the operators during manual cleaning and oiling of dental handpieces, and to provide a basis for the selection of appropriate protective methods. Methods: From November 2020 to December 2021, 20 high-speed dental handpieces of the same brand were selected and randomly divided into disposable protective bag group and small aerosol safety cabinet group by drawing lots, with 10 in each group. After recording the model, they were distributed to the clinical fixed consulting room for use, and were collected by specially-assigned personnel every day for manual cleaning under the protection of the two devices. By measuring the number of airborne colonies, the concentrations of particulate matter and the satisfaction of operators, the occupational protection effect of the two protective devices on operators was evaluated. Results: Under the protection of the two devices, the average number of airborne colonies after operation was less than 1 CFU/ml. When no protective device was used, the number concentration of particulate matter produced during operation was (21595.70±8164.26) pieces/cm(3). The number concentrations of particles produced by disposable protective bag group [ (6800.24±515.05) pieces/cm(3)] and small aerosol safety cabinet group [ (5797.15±790.50) pieces/cm(3)] were significantly lower than those without any protective device (P<0.001). The number concentration of particle matter of small aerosol safety cabinet group was significantly lower than that of disposable protective bag group (P<0.001). In the satisfaction evaluation of operators, small aerosol safety cabinet group [ (3.53±0.82) points] was significantly better than disposable protective bag group [ (2.23±1.10) points] (P<0.001) . Conclusion: The use of small aerosol safety cabinet during manual cleaning and oiling of dental handpieces has good protective effect, superior safety performance and strong clinical applicability, and has advantages in occupational protection of clinical operators.
Subject(s)
Aerosols , Particulate Matter , Protective DevicesABSTRACT
Objective@#To explore the relationship between father s emotional symptoms with offspring s emotional and behavioral problems, so as to provide reference for the prevention and intervention of emotional and behavioral problems in preschool children.@*Methods@#Using the method of multi stage sampling, two kindergartens from each of the two counties, two districts and two development zones were selected from Hefei during February to April 2023. A total of 3 672 children aged 3 to 6 years old and their fathers were selected from 12 kindergartens. Fathers filled out the Depression Anxiety and Stress Scale (DASS-21) and mothers filled out the Strength and Difficulty Questionnaire (SDQ). Multivariate Logistic regression model was established to analyze the relationship between father s emotional symptoms and preschool children s emotional and behavioral problems.@*Results@#The detection rate of emotional and behavioral problems in preschool children was 18.65%, and the detection rates of stress, anxiety and depression in fathers were 4.82%, 10.05% and 6.64%, respectively. Multivariate Logistic regression model analysis showed when fathers had negative emotions of stress, anxiety and depression, the detection rate of emotional and behavioral problems in their offspring was higher than children with father without negative emotion group ( OR =1.77-2.13, P <0.01). Father s stress symptoms were associated with increased risk of emotional and behavioral problems in boys, while father s anxiety and depressive symptoms were associated with increased risk of emotional and behavioral problems in boys and girls ( OR =1.45-2.69, P <0.05). Father s stress symptoms were associated with increased risk of emotional and behavioral problems in the first child, while father s anxiety and depressive symptoms were associated with increased risk of emotional and behavioral problems in the first child, second child and above ( OR =1.81-2.49, P <0.05).@*Conclusions@#Father s negative emotional symptoms are important factors affecting preschool children s emotional and behavioral problems. Early detection and targeted intervention of father s negative emotional symptoms are beneficial to the prevention and control of preschool children s emotional and behavioral problems.
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Objective: To investigate the impact of molecular classification and key oncogenes on the oncologic outcomes in patients with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) receiving fertility-preserving treatment. Methods: Patients with EC and AEH undergoing progestin-based fertility-preserving treatment and receiving molecular classification as well as key oncogenes test at Obstetrics and Gynecology Hospital, Fudan University from January 2021 to March 2023 were reviewed. Hysteroscopic lesion resection and endometrial biopsy were performed before initiating hormone therapy and every 3 months during the treatment to evaluate the efficacy. The risk factors which had impact on the treatment outcomes in EC and AEH patients were further analyzed. Results: Of the 171 patients analyzed, the median age was 32 years, including 86 patients with EC and 85 patients with AEH. The distribution of molecular classification was as follows: 157 cases (91.8%) were classified as having no specific molecular profile (NSMP); 9 cases (5.3%), mismatch repair deficient (MMR-d); 3 cases (1.8%), POLE-mutated; 2 cases (1.2%), p53 abnormal. No difference was found in the cumulative 40-week complete response (CR) rate between the patients having NSMP or MMR-d (61.6% vs 60.0%; P=0.593), while the patients having MMR-d had increased risk than those having NSMP to have recurrence after CR (50.0% vs 14.4%; P=0.005). Multi-variant analysis showed PTEN gene multi-loci mutation (HR=0.413, 95%CI: 0.259-0.658; P<0.001) and PIK3CA gene mutation (HR=0.499, 95%CI: 0.310-0.804; P=0.004) were associated with a lower cumulative 40-week CR rate, and progestin-insensitivity (HR=3.825, 95%CI: 1.570-9.317; P=0.003) and MMR-d (HR=9.014, 95%CI: 1.734-46.873; P=0.009) were independent risk factors of recurrence in EC and AEH patients. Conclusions: No difference in cumulative 40-week CR rate is found in the patients having NSMP or MMR-d who received progestin-based fertility-preserving treatment, where the use of hysteroscopy during the treatment might be the reason, while those having MMR-d have a higher risk of recurrence after CR. Oncogene mutation of PTEN or PIK3CA gene might be associated with a lower response to progestin treatment. The molecular profiles help predict the fertility-preserving treatment outcomes in EC and AEH patients.
Subject(s)
Pregnancy , Female , Humans , Adult , Hyperplasia , Progestins , Fertility Preservation , Endometrial Neoplasms/pathology , Endometrial Hyperplasia/surgery , Treatment Outcome , Precancerous Conditions , Fertility , Class I Phosphatidylinositol 3-Kinases , Retrospective StudiesABSTRACT
Glycogen synthase kinase-3β (GSK-3β) is an important serine/threonine kinase that implicates in multiple cellular processes and links with the neurodegenerative diseases including Alzheimer’s disease (AD). In this study, structure-based virtual screening was performed to search database for compounds targeting GSK-3β from Enamine’s screening collection. Of the top-ranked compounds, 7 primary hits underwent a luminescent kinase assay and a cell assay using human neuroblastoma SH-SY5Y cells expressing Tau repeat domain (TauRD) with pro-aggregant mutation ΔK280. In the kinase assay for these 7 compounds, residual GSK-3β activities ranged from 36.1% to 90.0% were detected at the IC50 of SB-216763. In the cell assay, only compounds VB-030 and VB-037 reduced Tau aggregation in SH-SY5Y cells expressing ΔK280 TauRD-DsRed folding reporter. In SH-SY5Y cells expressing ΔK280 TauRD, neither VB-030 nor VB-037 increased expression of GSK-3α Ser21 or GSK-3β Ser9. Among extracellular signal-regulated kinase (ERK), AKT serine/threonine kinase 1 (AKT), mitogen-activated protein kinase 14 (P38) and mitogenactivated protein kinase 8 (JNK) which modulate Tau phosphorylation, VB-037 attenuated active phosphorylation of P38 Thr180/ Tyr182, whereas VB-030 had no effect on the phosphorylation status of ERK, AKT, P38 or JNK. However, both VB-030 and VB-037 reduced endogenous Tau phosphorylation at Ser202, Thr231, Ser396 and Ser404 in neuronally differentiated SH-SY5Y expressing ΔK280 TauRD. In addition, VB-030 and VB-037 further improved neuronal survival and/or neurite length and branch in mouse hippocampal primary culture under Tau cytotoxicity. Overall, through inhibiting GSK-3β kinase activity and/or p-P38 (Thr180/Tyr182), both compounds may serve as promising candidates to reduce Tau aggregation/cytotoxicity for AD treatment.
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OBJECTIVES@#To develop a prediction model for postoperative prognosis in patients with cholangiocarcinoma (CCA) based on the expression of silence information regulator 2 (SIRT2).@*METHODS@#The differential expression of SIRT2 between CCA and normal tissues was analyzed using TCGA and GEO databases. Gene set enrichment analysis (GSEA) was used to explore potential mechanisms of SIRT2 in CCA. The expression of SIRT2 protein in CCA tissues and normal tissues (including 44 pairs of specimens) was also detected by immunohistochemistry (IHC) staining in 89 resectable CCA patients who underwent surgical treatment in The First Affiliated Hospital of Bengbu Medical College between January 2016 and December 2021. The relationship between SIRT2 expression and clinicopathological characteristics and prognosis of CCA patients was analyzed. A survival prediction model for patients with resectable CCA was constructed with COX regression results, the calibration curve and the time-dependent receiver operating characteristic curve (ROC) were used to evaluate the performance of the constructed model, and the predictive power between this model and the AJCC/TNM staging system (8th Edition) was compared.@*RESULTS@#SIRT2 mRNA was overexpressed in CCA tissues as shown in TCGA and GEO databases. IHC staining showed that SIRT2 protein expression in CCA tissues was significantly higher than that in adjacent non-tumor tissues. GSEA results showed that elevated SIRT2 expression may be involved in multiple metabolism-related signaling pathway, such as fatty acid metabolism, oxidative phosphorylation, amino acid metabolism, etc. SIRT2 expression level was related to serum triglycerides level, tumor size and lymph node metastasis (all P<0.05). The survival analysis results showed that the patients with higher SIRT2 expression had a significant lower overall survival (OS) than patients with lower SIRT2 expression (P<0.05). Univariate COX regression analysis suggested that pathological differentiation, clinical stage, postoperative treatment and SIRT2 expression level were associated with the prognosis of CCA patients (all P<0.05). Multivariate regression analysis confirmed that clinical stage and SIRT2 expression level were independent predictors of OS in postoperative CCA patients (both P<0.05). A nomogram based on SIRT2 for prediction of survival in postoperative CCA patients was constructed. The C-index of the model was 0.675, and the area under the time-dependent ROC curve (AUC) for predicting survival in the first, second, and third years was 0.879, 0.778, and 0.953, respectively, which were superior to those of AJCC/TNM staging system (8th Edition).@*CONCLUSIONS@#SIRT2 is highly expressed in CCA tissues, which is associated with poor prognosis in patients with resectable CCA. The nomogram developed based on SIRT2 may have better predictive power than the AJCC/TNM staging system (8th Edition) in prediction of survival of postoperative CCA patients.
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AIM: To investigate the visual fatigue of patients with accommodative asthenopia and the difference in scores before and after treatment by using the asthenopia survey scale(ASS), and to evaluate its reliability, validity and responsiveness in this population.METHODS: A total of 112 patients with accommodative asthenopia were admitted to the department of ophthalmology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine and recruited online were investigated using the ASS questionnaire, and 48 subjects were randomly selected and retested 1wk later. A variety of reliability, validity and responsiveness indicators were used to evaluate the scale.RESULTS: The overall Cronbach's α coefficients of the scale entries was 0.91; The split-half reliability coefficients was 0.86; Repeated measurement correlation coefficient of the scale total score was 0.74, there was no significant difference before and after(P>0.05); The results of confirmatory factor analysis showed that the absolute fit index of the three-factor structural model was χ2/df<2.0, RMSEA=0.08; The correlation coefficients of each dimension's total score and the scale's total score were 0.92, 0.90 and 0.83 respectively; The standard association validity analysis showed statistically significant differences between groups(P<0.01). Response analysis was statistically significant before and after treatment(P<0.01).CONCLUSION: The ASS has high reliability, validity and responsiveness in the clinical evaluation of accommodative asthenopia, and it's an effective tool for clinical research and screening of asthenopia in this population.
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Background Acute drug poisonings are increasing year by year and have become the leading cause of acute poisoning in Shanghai in recent years, and the related prevention and control work is faced with a tough situation. Objective To understand the composition of drugs leading to acute poisonings and describe the epidemiological tendency of reported acute drug poisonings in Shanghai. Methods We collected registered acute drug poisoning case information from the Shanghai Health Information System under Shanghai Health Statistics Center, including demographic characteristics and clinical diagnosis. There were totally 86476 cases reported from 2019 to 2021. The distributions of drugs and victims were described by year. Incidence tendency of acute drug poisonings was analyzed by chi-square test and the analysis focused on analgesic, hypnotics, and antidepressant drug-associated poisonings. Spatial autocorrelation analysis was performed by GeoDa1.20 through calculating global and local Moran's I. Results There was an ascendant tendency in both case count (22132 cases in 2019, 29071 cases in 2020, and 35273 cases in 2021) and crude morbidity (0.89‰ in 2019, 1.21‰ in 2020, and 1.46‰ in 2021) of patients who received outpatient service or emergency treatment for acute drug poisonings from 2019 to 2021 in Shanghai. The top 3 kinds of acute poisoning drugs were analgesics, hypnotics, and antidepressants. The morbidity rates of acute drug poisonings associated with antidepressants (χ2=2700.15, P<0.05) and analgesics (χ2=2294.01, P<0.05) increased year by year. The leading 3 kinds of drugs associated with acute drug poisonings in the same age group were similar. Analgesics showed high frequency staying in the top 3 acute poisoning drugs in most age groups for the 3 years (the highest morbidity was 0.84‰ in male or 1.07‰ in female). Antidepressants were in the top 3 acute poisoning drugs in the under 59 years age groups for the 3 years (male morbidity rate was 0.12‰-0.44‰, and female morbidity rate was 0.06‰-0.45‰). Hypnotics were in the top 3 acute poisoning drugs in the ≥ 18 years age groups for the 3 years (morbidity rate in male was 0.28‰-0.98‰, and morbidity rate in female was 0.21‰-0.92‰). Cardiovascular drugs were in the top 3 acute poisoning drugs in the > 60 years age group for the 3 years (male morbidity rate was 0.40‰-1.03‰, and female morbidity rate was 0.66‰-0.81‰). Regarding the causes of poisonings, accidental poisoning and exposure was the main cause in the ≤ 17 years groups (male constituent ratio was 57.64%-67.12%, and female constituent ratio was 55.27%-68.27%); suicide (male constituent ratio was 20.28%-43.51%, and female constituent ratio was 25.18%-52.02%) had a higher percentage than accidental poisoning and exposure (male constituent ratio was 16.97%-23.62%, and female constituent ratio was 12.76%-17.63%) in the 18-59 years age groups; accidental poisoning and exposure (male constituent ratio was 24.38%-45.18%, and female constituent ratio was 32.69%-38.11%) had a higher percentage than suicide (male constituent ratio was 12.35%-14.02%, and female constituent ratio was 11.92%-12.31%) in the > 60 years age group. The spatial autocorrelation analysis showed that the distribution of acute poisoning cases caused by analgesics, hypnotics, or antidepressants was not random. It was mostly positive spatial clustering. The high-morbidity area was always in the outer-ring circle, especially in Xuhui, Changning, and Jing'an districts, which suggested a high-high cluster pattern. Conclusion In view of the increasing morbidity rate of acute drug poisoning cases in Shanghai in this study, it is urgent to take prevention and control actions. We should plan further studies and different strategies toward different victims with distinct drug poisoning characteristics and areas with high morbidity rates.
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D-allulose-3-epimerase (DPEase) is the key enzyme for isomerization of D-fructose to D-allulose. In order to improve its thermal stability, short amphiphilic peptides (SAP) were fused to the N-terminal of DPEase. SDS-PAGE analysis showed that the heterologously expressed DPEase folded correctly in Bacillus subtilis, and the protein size was 33 kDa. After incubation at 40 °C for 48 h, the residual enzyme activity of SAP1-DSDPEase was 58%. To make the recombinant B. subtilis strain reusable, cells were immobilized with a composite carrier of sodium alginate (SA) and titanium dioxide (TiO2). The results showed that 2% SA, 2% CaCl2, 0.03% glutaraldehyde solution and a ratio of TiO2 to SA of 1:4 were optimal for immobilization. Under these conditions, up to 82% of the activity of immobilized cells could be retained. Compared with free cells, the optimal reaction temperature of immobilized cells remained unchanged at 80 °C but the thermal stability improved. After 10 consecutive cycles, the mechanical strength remained unchanged, while 58% of the enzyme activity could be retained, with a conversion rate of 28.8% achieved. This study demonstrated a simple approach for using SAPs to improve the thermal stability of recombinant enzymes. Moreover, addition of TiO2 into SA during immobilization was demonstrated to increase the mechanical strength and reduce cell leakage.
Subject(s)
Bacillus subtilis/metabolism , Carbohydrate Epimerases/genetics , Enzyme Stability , Enzymes, Immobilized/metabolism , Fructose , Hydrogen-Ion Concentration , Racemases and Epimerases , TemperatureABSTRACT
BACKGROUND@#Endometrial cancer (EC) has been one of the most general cancers with respect to gynecological malignancies; however, there are debates on clinical strategies concerning treatments especially for patients with grade 3 (G3) endometroid endometrial cancer (EEC). Present study aimed to evaluate the lymphatic metastasis (LM) related factors and figure out the necessity of lymphadenectomy for G3 EEC patients.@*METHODS@#From January 2009 to April 2019, 3751 EC patients were admitted to Obstetrics and Gynecology Hospital of Fudan University. Clinical characteristics include age, grade, stage, and clinical pathological features. A total of 1235 EEC patients were involved in the multivariable analysis. Three hundred and eighty-one patients were involved in the survival analysis and the data attributed to sufficient follow-up information. Kaplan-Meier curve and log-rank test were utilized to analyze the survival rate.@*RESULTS@#Among the 1235 EEC patients, 181 (14.7%) were categorized as G3 and 1054 (85.3%) were grade 1 to grade 2 (G1-2). Multivariate analysis demonstrated that lymphovascular space invasion, adnexal involvement, and cervical stroma involvement were independent risk factors of LM in G3 cohort with odds ratio 3.4, 5.8, and 8.9; 95% confidence interval 1.1-10.6, 1.5-22.4, and 2.8-28.0, respectively. LM rates increased from 3.3% (3/92) to 75% (9/12) for G3 EEC cohort as related factor numbers increased from one to three. There were no differences between G3 and G1-2 EEC in overall survival and progression free survival. Additionally, no survival advantage was observed for G3 EEC patients at early stage with different plans of adjuvant treatment.@*CONCLUSIONS@#For G3 EEC patients without other pathological positive factor, the LM rate is lower than those with other pathological positive factor. Survival analysis showed no difference between G3 cohort and G1-2 cohort. Also, different adjuvant treatments had no impact on the overall survival for G3 EEC patients.