Changes in menopausal symptoms comparing oral estradiol versus transdermal estradiol.

OBJECTIVE: This study aimed to compare the efficacy and safety of oral and transdermal estradiol in alleviating menopausal symptoms. METHOD: A total of 257 recently menopausal women were randomized into two groups. The t-E2 group received transdermal estradiol (2.5 g per day) (n = 128) and the o-E2V group received oral estradiol valerate (2 mg per day) (n = 129) for 24 weeks; both groups received micronized progesterone (200 mg per day). The primary outcome measure is the change in the modified Kupperman Menopausal Index (KMI) after 24 weeks of treatment. Menopausal symptoms were recorded at screening and at 4, 12 and 24 weeks using both the KMI and the Menopause Rating Scale (MRS). RESULTS: Significant amelioration was observed by KMI and MRS scores for both groups after treatment (p < 0.001). The mean KMI scores showed no difference between the two groups. The mean MRS scores were similar between the two groups at baseline and after 4 weeks of treatment. The results showed statistical differences after 12 weeks and 24 weeks of treatment (p = 0.005 and p = 0.011). Both the after-treatment scores minus the baseline scores of KMI and MRS and the incidence of adverse effects showed no difference between the two groups. CONCLUSIONS: This study shows that both transdermal and oral estradiol are effective in relieving menopausal symptoms, with little difference in treatment efficacy and safety. CLINICAL TRIAL NUMBER: ChiCTR2300073146.

[Analysis of efficacy and safety of daratumumab-containing regimen in relapsed and refractory multiple myeloma patients].

Objective: To investigate the efficacy and safety in relapsed and refractory multiple myeloma (RRMM) patients with combination regimen of daratumumab. Methods: The clinical data of 42 RRMM patients admitted to Qingdao Municipal Hospital from December 2020 to November 2023 were retrospectively analyzed, which included 26 males and 16 females, with a median age of 59 (47, 82) years old. According to the number of courses of treatment with Daratumumab, patients were divided into three groups: long course group (≥9 courses, n=21), medium course group (7-8 courses, n=12), and short course group (≤6 courses, n=9). The deadline for follow-up was November 10, 2023, and the follow-up period was 15.6 (6.0, 34.0) months. After completing at least 2 courses of treatment, patients were evaluated for efficacy, including stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR), stable disease (SD), and progressive disease (PD). Basic clinical characteristics of patients, overall response rate of treatment, and adverse reactions were statistically analyzed. Kaplan-Meier method was used to compare the differences of progression-free survival (PFS) in patients with different courses of treatment. Results: Among the 42 patients, 15 (35.7%) had extramedullary disease or plasmacytic leukemia, 7 (16.6%) had amyloidosis, and 18 (42.9%) had renal insufficiency. In Mayo stage, 25 patients (59.5%) were at high risk of myeloma cytogenetic stratification, 8 patients (19%) were standard risk, 9 patients (21.4%) had no cytogenetic data. There were 16 patients with second-line treatment (38.0%), 13 patients with third-line treatment (31%), and 13 patients with more than fourth-line treatment (31%). All patients received at least 2 courses of treatment, achieving the best degree of disease response in 4 cases of sCR (9.5%), 3 cases of CR (7.1%), 10 cases of VGPR (23.8%), 11 cases of PR (26.2%), and 6 cases of MR (14.2%). The overall response rate (ORR) was 80.9% (34/42). The overall response rate was 100% (21/21) in the long course group, 91.6% (11/12) in the medium course group and 22.2% (2/9) in the short course group. Kaplan-Meier survival analysis showed that the duration of PFS was 5.0 (95%CI: 3.1-6.9) months in the short course group,>8.0 months in the medium course group, and>38.0 months in the long course group, the difference was statistically significant (P<0.05). Grade≥3 adverse reactions were mainly neutropenia (3 cases) and thrombocytopenia (1 case). None of the patients discontinued treatment due to adverse reactions. Conclusion: Treatment of RRMM with a regimen containing Daratumumab requires a longer course of treatment to achieve maximum efficacy and the adverse reactions can be controlled.

[The diagnostic and evaluation value of plasma interleukin 9 in the mucosal healing in patients with inflammatory bowel disease treated with biological agents].

Objective: To investigate the diagnostic and evaluation value of plasma interleukin 9 (IL9) in the mucosal healing (MH) in patients with inflammatory bowel disease (IBD) treated with biological agents. Methods: Cohort study. IBD patients (137 cases) treated in the Affiliated Suzhou Hospital to Nanjing Medical University (Suzhou Municipal Hospital) from September 2019 to January 2022 were prospective selected. Each patient was treated with biological agents [Infliximab (IFX, 56 cases), Adalimumab (ADA, 20 cases), Ustekinumab (UST, 18 cases), Vedolizumab (VDZ, 43 cases)]. According to different therapeutic drugs, the IFX, ADA, UST, and VDZ group were divided. Clinical symptoms, inflammatory indicators and imaging examinations etc. were evaluated every 8 weeks, and the degree of MH was evaluated by endoscopy at the 54th week. The expression of plasma IL9 was detected by ELISA after initial enrollment (W 0) and 8 weeks of biological treatment (W 8). Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of IL9 for MH. Select the cut off value for the optimal ROC threshold based on the highest value of the Youden index. Spearman's rank correlation was used to analyze the correlation between IL9 and Simple Endoscopic Score for CD (SES-CD) and Mayo Endoscopic Score (MES), so as to evaluate the predictive value of IL9 for MH in IBD patients treated with biologic agents. Results: Among the 137 patients, there were 97 Crohn's disease (CD) patients, 53 males and 44 females, aged (31.6±10.3) years (18-60 years). There were 40 ulcerative colitis (UC) patients, 22 males and 18 females, aged (37.5±14.7) years (18-67 years). Among the CD patients, 42 cases (43.3%) achieved MH on endoscopy at the 54th week, and 60 patients (61.9%) achieved clinical remission. Among the UC patients, 22 cases (55.0%) achieved MH and 30 cases (75.0%) achieved clinical remission. At W 0, the relative expression of IL9 in patients in IBD patients who achieved MH after 54 weeks of biological treatment was lower than that in the non-MH patients [x¯±s, (127.42±34.43) vs (146.82±45.64) ng/L, (113.01±44.88) vs (146.12±48.66) ng/L, respectively, both P<0.05]. At W 8, the relative expression of IL9 in the MH group was lower than that in the non-MH patients (both P<0.05). The relative expression of IL9 in the MH patients after IFX treatment was lower than that in the non-MH group (P<0.05). There was no significant difference among the other groups between MH and non-MH patients (all P>0.05). IL9 at W 8 showed high value in predicting MH in IBD [CD patients: area under curve (AUC)=0.716(95%CI: 0.616-0.817, P<0.001), sensitivity and specificity were 80.77%(95%CI:67.64%-88.45%) and 48.89%(95%CI: 35.53%-64.47%), respectively; UC patients: AUC=0.821, sensitivity and specificity were 77.78% and 72.73%, respectively]. At W 8, the cut off values for CD and UC patients were IL9>80.77 ng/L and IL9>77.78 ng/L, respectively. IL9 was positively correlated with endoscopic MH score parameters [M(Q1,Q3),SES-CD: 3.0(8.5, 18.5); MES: 2.0(1.0, 3.0)] (r=0.55, 0.72, respectively, both P<0.001) at W8. Conclusion: The plasma IL-9 at the week 8 after biological agents treatment can be used to diagnose and evaluate the MH of patients with IBD.

[Effects of in vivo targeted carboxylesterase 1f gene knockdown on the Kupffer cells polarization activity in mice with acute liver failure].

Objective: To investigate the effect of targeted carboxylesterase 1f (Ces1f) gene knockdown on the polarization activity of Kupffer cells (KC) induced by lipopolysaccharide/D-galactosamine (LPS/D-GalN) in mice with acute liver failure. Methods: The complex siRNA-EndoPorter formed by combining the small RNA (siRNA) carrying the Ces1f-targeting interference sequence and the polypeptide transport carrier (Endoporter) was wrapped in ß-1, 3-D glucan shell to form complex particles (GeRPs). Thirty male C57BL/6 mice were randomly divided into a normal control group, a model group (LPS/D-GalN), a pretreatment group (GeRPs), a pretreatment model group (GeRPs+LPS/D-GalN), and an empty vector group (EndoPorter). Real-time fluorescent quantitative PCR and western blot were used to detect Ces1f mRNA and protein expression levels in the liver tissues of each mouse group. Real-time PCR was used to detect the expression levels of KC M1 polarization phenotypic differentiation cluster 86(CD86) mRNA and KC M2 polarization phenotypic differentiation cluster 163 (CD163) mRNA in each group. Immunofluorescence double staining technique was used to detect the expression of Ces1f protein and M1/M2 polarization phenotype CD86/CD163 protein in KC. Hematoxylin-eosin staining was used to observe the pathological damage to liver tissue. A one-way analysis of variance was used to compare the means among multiple groups, or an independent sample nonparametric rank sum test was used when the variances were uneven. Results: The relative expression levels of Ces1f mRNA/protein in liver tissue of the normal control group, model group, pretreatment group, and pretreatment model group were 1.00 ± 0.00, 0.80 ± 0.03/0.80 ± 0.14, 0.56 ± 0.08/0.52 ± 0.13, and 0.26 ± 0.05/0.29 ± 0.13, respectively, and the differences among the groups were statistically significant (F = 9.171/3.957, 20.740/9.315, 34.530/13.830, P < 0.01). The percentages of Ces1f-positive Kupffer cells in the normal control group, model group, pretreatment group, and pretreatment model group were 91.42%, ± 3.79%, 73.85% ± 7.03%, 48.70% ± 5.30%, and 25.68% ± 4.55%, respectively, and the differences between the groups were statistically significant (F = 6.333, 15.400, 23.700, P < 0.01). The relative expression levels of CD86 mRNA in the normal control group, model group, and pretreatment model group were 1.00 ± 0.00, 2.01 ± 0.04, and 4.17 ± 0.14, respectively, and the differences between the groups were statistically significant (F = 33.800, 106.500, P < 0.01). The relative expression levels of CD163 mRNA in the normal control group, the model group, and the pretreatment model group were 1.00 ± 0.00, 0.85 ± 0.01, and 0.65 ± 0.01, respectively, and the differences between the groups were statistically significant (F = 23.360, 55.350, P < 0.01). The percentages of (F4/80(+)CD86(+)) and (F4/80(+)CD163(+)) in the normal control group and model group and pretreatment model group were 10.67% ± 0.91% and 12.60% ± 1.67%, 20.02% ± 1.29% and 8.04% ± 0.76%, and 43.67% ± 2.71% and 5.43% ± 0.47%, respectively, and the differences among the groups were statistically significant (F = 11.130/8.379, 39.250/13.190, P < 0.01). The liver injury scores of the normal control group, the model group, and the pretreatment model group were 0.22 ± 0.08, 1.32 ± 0.36, and 2.17 ± 0.26, respectively, and the differences among the groups were statistically significant (F = 12.520 and 22.190, P < 0.01). Conclusion: Ces1f may be a hepatic inflammatory inhibitory molecule, and its inhibitory effect production may come from the molecule's maintenance of KC polarization phenotypic homeostasis.

[Establishment and validation of nomogram prediction model for complicated acute appendicitis].

Objective: To establish and internally validate a nomogram model for predicting complicated acute appendicitis (CA). Methods: The clinical data from 663 acute appendicitis patients from the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from October 2015 to October 2022 were retrospectively analyzed. There were 411 males and 252 females, aged (M (IQR)) 41 (22) years (range: 18 to 84 years). There were 516 cases of CA and 147 cases of uncomplicated acute appendicitis. The minimum absolute contraction and selection operator regression model was used to screen the potential relative factors of CA, and the screened factors were included in the Logistic regression model for multivariate analysis. Software R was used to establish a preoperative CA nomogram prediction model, the receiver operating characteristic curve of the model was drawn, and the value of area under the curve (AUC) was compared to evaluate its identification ability, and the Bootstrap method was used for internal verification. Results: The elderly (age≥60 years) (OR=2.428, 95%CI: 1.295 to 4.549), abdominal pain time (every rise of 1 hour) (OR=1.089, 95%CI: 1.072 to 1.107), high fever (body temperature≥39 ℃) (OR=1.122, 95%CI: 1.078 to 1.168), total bilirubin (every rise of 1 µmol/L) (OR=2.629, 95%CI: 1.227 to 5.635) were independent relative factors of CA (all P<0.05). The AUC of this model was 0.935 (95%CI: 0.915 to 0.956). After internal verification using the Bootstrap method, the model still had a high discrimination ability (AUC=0.933), and the predicted CA curve was still in good agreement with the actual clinical CA curve. Conclusion: The clinical prediction model based on the elderly (age≥60 years), prolonged abdominal pain time, high fever (body temperature≥39 ℃), and increased total bilirubin can help clinicians effectively identify CA.

Ultra-low-dose estradiol and dydrogesterone: a phase III study for vasomotor symptoms in China.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of ultra-low-dose estradiol plus dydrogesterone for vasomotor symptoms in postmenopausal women in China (trial registration CTR20160689). METHODS: A total of 332 patients were randomized to continuous combined estradiol 0.5 mg + dydrogesterone 2.5 mg or placebo for 12 weeks. The primary efficacy endpoint was change in the number of hot flushes per day from baseline to end of treatment. Secondary efficacy endpoints included change in the number of moderate-to-severe hot flushes per day, menopausal symptoms from baseline and quality of life. RESULTS: Between baseline and end of treatment, change in the mean number of hot flushes per day was -5.9 (95% confidence interval [CI] - 6.6, -5.2) with estradiol + dydrogesterone and -4.5 (95% CI -5.1, -3.8) with placebo, with a mean difference of -1.4 hot flushes per day (95% CI -2.2, -0.7; p < 0.001). Significant differences in favor of estradiol + dydrogesterone were also observed in several secondary efficacy endpoints. The study treatment was well tolerated. CONCLUSION: Continuous combined estradiol 0.5 mg + dydrogesterone 2.5 mg reduced hot flushes in postmenopausal women in China. This ultra-low-dose regimen provides an additional option for women experiencing the vasomotor symptoms of menopause. These data are consistent with previous results in other populations.

Impacts of menopause hormone therapy on mood disorders among postmenopausal women.

OBJECTIVE: This study aimed to explore the modulatory effects of menopause hormone therapy (MHT) on mood disorders among postmenopausal women. METHODS: A cross-sectional study was conducted to recruit postmenopausal women, including patients (arranged MHT for over 3 years as the medication group) and non-MHT controls. All participants were asked to respond to the Center for Epidemiological Studies Depression Scale (CES-D) and Generalized Anxiety Disorder Screener (GAD-7) questionnaires to assess their depression and anxiety status. RESULTS: A total of 230 cases from the two groups were determined based on propensity score matching analysis by matching the menopausal age and menopausal durations. We found that MHT served as a favorable modulator in the depression status of postmenopausal women. Among the four factors of the CES-D questionnaire, our data indicated that the differences between the two groups fell primarily into two aspects: depressive emotion, and somatic symptoms or retarded activities. MHT was mainly involved in improving the depression of overweight women. However, no substantial effects of MHT were observed on the regulation of anxiety. CONCLUSION: Postmenopausal women, especially the overweight population, who have experienced MHT exhibited an improved depressive status but not their anxiety condition.

Ultralight type I transvaginal mesh: an alternative for recurrent severe posterior vaginal prolapse.

OBJECTIVE: This study aimed to analyze the medium-term outcomes of ultralight type I mesh for postmenopausal women with recurrent severe posterior vaginal prolapse (PVP). METHODS: All participants underwent transvaginal ultralight type I mesh repair between April 2016 and April 2021 and were followed until May 2022. Pelvic Organ Prolapse Quantification System (POP-Q) staging, mesh-related complications, Patient Global Impression of Improvement (PGI-I) scale and quality of life questionnaire responses were evaluated. The primary outcome was composite surgical success rate at the last follow-up, composite success being defined as no vaginal bulge symptoms, no POP-Q point at or beyond the hymen and no re-treatment for POP. Secondary outcomes included anatomic outcomes (POP-Q score), symptomatic relief and complications. RESULTS: The median follow-up was 37.3 months. At the last follow-up, the composite success rate was 75%, and POP-Q scores for the vault and posterior wall and quality of life questionnaire scores were significantly improved (p < 0.01). The subjective satisfaction (PGI-I ≤ 2) rate was 83.3%. There were no mesh-related complications. CONCLUSIONS: Ultralight mesh can achieve good clinical outcomes and substantially improve the quality of life of patients with severe recurrent PVP in the medium term, and may thus be a viable alternative for treating this condition.

[Efficacy of endoscopic treatment oncolorectal laterally spreading tumor and risk factors of delayed bleeding after operation].

Objective: To evaluate the endoscopic treatment efficacy of colorectal laterally spreading tumor (LST) and analyze the risk factors for delayed post-polypectomy bleeding (DPPB). Methods: Between January 2015 and December 2020, patients underwent colorectal endoscopic submucosal dissection (ESD) or hybrid ESD were recruited from the Second Affiliated Hospital of Zhejiang University. Complete resection rate, perforation rate, bleeding rate, operation time and lesion adhesion were compared between the ESD and hybrid ESD groups. Patients were divided into bleeding and non-bleeding groups based on the presence of DPPB. Multivariate logistic regression analysis was used to analyze the risk factors of DPPB. Results: A total of 665 patients with colorectal LST were enrolled, including 376 males and 289 females, with an average age of (57.4±0.4) years. There were 471 cases underwent ESD and 194 cases underwent hybridized ESD. There were no significant differences in gender, age, history of smoking and drinking, and prevalence of hypertension between the two groups (all P>0.05). Likewise, the rate of lesion adhesion (4.2% vs 7.7%, P=0.067), lesion complete resection (96.8% vs 93.8%, P=0.418), perforation (0.6% vs 1.0%, P=0.594), delayed bleeding (2.8% vs 2.1%, P=0.605) were not statistically significant between the two groups. Seventeen patients (2.6%) developed DPPB after endoscopic treatment. Multivariate logistic regression analysis showed that the lesion was in the rectum (OR=3.594, 95%CI: 1.237-10.443, P=0.019) and the diameter of the lesion>2 cm (OR=3.776, 95%CI: 1.411-10.106, P=0.008) were risk factors for DPPB. Conclusions: Both ESD and hybrid ESD are successful treatments for colorectal LST. Colorectal LST lesion site and lesion size>2 cm are risk factors of DPPB.

[Association between urinary arsenic levels and anemia among older adults in nine longevity areas of China].

Objective: To investigate the association between urinary arsenic levels and anemia among older adults in nine longevity areas of China. Methods: A total of 1 896 subjects aged 65 years and above who participated in the Healthy Aging and Biomarkers Cohort Study (HABCS) in 2017-2018 were included. A self-made questionnaire was used to collect demographic characteristics, lifestyle and other information from the subjects. Through physical examination, data including height, weight and blood pressure were determined and body mass index (BMI) was calculated. Blood and urine samples were collected for the detection of hemoglobin (Hb), blood glucose, blood lipids, plasma vitamin B12 and urinary arsenic concentrations. The urinary arsenic levels were divided into four groups according to the quartiles of urinary arsenic concentrations (µg/g creatinine): Q1 (<18.7), Q2 (18.7-34.5), Q3 (34.6-69.5) and Q4(≥69.6). Multivariate logistic regression model and restricted cubic spline fitting logistic regression model were used to analyze the association between urinary arsenic levels and anemia. Results: The age of the 1 896 subjects (M (Q1, Q3)) was 83 (74, 92) years, including 952 females (50.21%), and the concentration of Hb (M (Q1, Q3)) was 135 (124, 147)g/L. The prevalence of anemia was 24.89% (472 cases). The geometric mean and M (Q1, Q3) of urinary arsenic concentrations were 37.5 and 34.6 (18.7, 69.6)µg/g creatinine, respectively. Multivariate logistic regression model analysis showed that after adjusting for age, gender, BMI, education level, smoking and drinking status, residence, economic level, ethnicity, the status of vitamin B12 deficiency, consumption frequency of aquatic products and meat, the prevalence of hypertension, diabetes and dyslipidemia, urinary arsenic levels were positively associated with anemia (Taking group Q1 as a reference, OR (95%CI) values in Q2, Q3 and Q4 groups were 1.73 (1.20-2.50), 2.08 (1.43-3.02) and 1.52 (1.02-2.28), respectively). The results of restricted cubic spline fitting logistic regression analysis showed a non-linear association between urinary arsenic concentrations and anemia (P<0.001). Subgroup analysis showed there was a negative multiplicative interaction between the prevalence of chronic diseases and urinary arsenic levels with OR (95%CI) was 0.55 (0.30-0.99), while no multiplicative interaction was found between age, gender, residence, smoking status, drinking status and urinary arsenic levels (P>0.05). There was a positive association between urinary arsenic levels and anemia in participants who were absence of chronic diseases,male, living in rural, smoking and drinking with OR (95%CI) values of 3.62 (1.30-10.06),2.46 (1.34-4.52), 1.70 (1.03-2.80), 2.21 (1.01-4.82) and 2.79 (1.23-6.33), respectively. Conclusion: There is a positive association between urinary arsenic levels and anemia among older adults in nine longevity areas of China.