Early growth response 2, a novel target of pelvic organ prolapse, is highly expressed in anterior vaginal wall tissues with pelvic organ prolapse.

Pelvic organ prolapse (POP) is a common disorder among women that negatively affects women's quality of life. Early growth response 2 (EGR2) is a transcription factor that regulates cell growth. The present study aimed to explore the role of EGR2 in POP progression and provided a new target for the treatment and prevention of POP. Firstly, we extracted primary vaginal anterior wall fibroblasts from POP tissues and non-POP tissues and then constructed an EGR2-silencing lentivirus for further study. Immunoblotting, qPCR, TUNEL assay, CCK-8 assay, dual luciferase assay, and ELISA assay were carried out. EGR2 expression was much higher in POP tissues than in control tissues, and EGR2 expression positively correlated with cytokine signaling 3 (SOCS3) expression. Knockdown of EGR2 increased cell proliferation, upregulated PCNA expression, and reduced apoptosis in POP fibroblasts. Moreover, we found that the knockdown of EGR2 increased COL1A1, COL3A1, and Elastin expression and decreased MMP2 and MMP9 activities, and knockdown of EGR2 increased TGF-ß/Smad pathway activity in POP fibroblasts. Interestingly, the results of dual luciferase assay demonstrated that EGR2 was able to increase SOCS3 transcriptional activity. EGR2 knockdown alleviated the apoptosis of POP fibroblasts by reducing SOCS3 expression and improving the proliferation and collagen synthesis of POP fibroblasts. Overall, our study illustrated that EGR2 was highly expressed in POP tissues, and knockdown of EGR2 alleviated apoptosis and reduced matrix degradation in POP fibroblasts. This study might provide a new insight into the pathogenesis of POP.

A general approach for automatic segmentation of pneumonia, pulmonary nodule, and tuberculosis in CT images.

Proposing a general segmentation approach for lung lesions, including pulmonary nodules, pneumonia, and tuberculosis, in CT images will improve efficiency in radiology. However, the performance of generative adversarial networks is hampered by the limited availability of annotated samples and the catastrophic forgetting of the discriminator, whereas the universality of traditional morphology-based methods is insufficient for segmenting diverse lung lesions. A cascaded dual-attention network with a context-aware pyramid feature extraction module was designed to address these challenges. A self-supervised rotation loss was designed to mitigate discriminator forgetting. The proposed model achieved Dice coefficients of 70.92, 73.55, and 68.52% on multi-center pneumonia, lung nodule, and tuberculosis test datasets, respectively. No significant decrease in accuracy was observed (p > 0.10) when a small training sample size was used. The cyclic training of the discriminator was reduced with self-supervised rotation loss (p < 0.01). The proposed approach is promising for segmenting multiple lung lesion types in CT images.

Effects of vaccination on mitigating COVID-19 outbreaks: a conceptual modeling approach.

This paper is devoted to investigating the impact of vaccination on mitigating COVID-19 outbreaks. In this work, we propose a compartmental epidemic ordinary differential equation model, which extends the previous so-called SEIRD model [1,2,3,4] by incorporating the birth and death of the population, disease-induced mortality and waning immunity, and adding a vaccinated compartment to account for vaccination. Firstly, we perform a mathematical analysis for this model in a special case where the disease transmission is homogeneous and vaccination program is periodic in time. In particular, we define the basic reproduction number $ \mathcal{R}_0 $ for this system and establish a threshold type of result on the global dynamics in terms of $ \mathcal{R}_0 $. Secondly, we fit our model into multiple COVID-19 waves in four locations including Hong Kong, Singapore, Japan, and South Korea and then forecast the trend of COVID-19 by the end of 2022. Finally, we study the effects of vaccination again the ongoing pandemic by numerically computing the basic reproduction number $ \mathcal{R}_0 $ under different vaccination programs. Our findings indicate that the fourth dose among the high-risk group is likely needed by the end of the year.

Ultrasound-guided Aspiration Combined with Medical Treatment for an Unexpected Rectal Endometriotic Cyst: A Case Report.

Most bowel endometriotic lesions are ill-defined serosal and subserosal nodules, and no case of cystic bowel endometriosis has been reported in the literature. This is the first report of an unexpected presentation of bowel endometriosis as a primary cyst located inside the posterior rectal wall. The patient was a 26-year-old nulliparous woman with progressive lower abdominal pain for 6 days and difficult defecation for 1 day. Colorectal surgeons recommended bowel resection owing to the giant rectal mass. However, the patient refused to undergo surgery. Ultrasound-guided aspiration of the rectal endometriotic cyst followed by gonadotropin-releasing hormone agonist injection was individually scheduled, which finally brought significant improvement both in symptoms and in the size of the rectal endometriotic lesion.

The efficacy and safety of temperature controlled dual-mode radiofrequency in women with vaginal laxity.

OBJECTIVE: Vaginal laxity could negatively influence women's sexual function. This study aimed to explore the efficacy and safety of temperature controlled dual-mode (monopolar and bipolar) radiofrequency (RF) in women with vaginal laxity. METHODS: A total of 102 patients with vaginal laxity were treated with temperature-controlled RF. The present study implemented Vaginal Laxity Questionnaire (VLQ), Female Sexual Function Index (FSFI) questionnaire and Sexual Satisfaction Questionnaire (SSQ) on all patients at baseline and after treatment. Pelvic Organ Prolapse Quantification System (POP-Q) system was applied to physical examination, and vaginal manometer to examine the strength of voluntary contractions of the pelvic floor muscles. RESULTS: The VLQ score was gradually increased after RF treatment at 1, 3, 6 and 12 months, accompanying by the significant improvement in total FSFI scores and the six domains (sexual desire, sexual arousal, lubrication, orgasm, satisfaction, pain). The increased sexual satisfaction based on the SSQ score was found after temperature-controlled RF. The result of POP-Q stage showed significant difference in women after treatment, with the women having Stage I of 45.10% at baseline, 36.27% at 1 month, 28.43% at 3 months, 19.61% at 6 months and 10.78% at 12 months. The mean pressure and mean duration of pelvic contractions were increased gradually at the 1-, 3-, 6- and 12- month follow-up. CONCLUSION: Temperature controlled dual-mode (monopolar and bipolar) radiofrequency may be associated with improvement of vaginal laxity, and contribute to enhancement to female sexual function and pelvic floor muscles.

Multidisciplinary treatment of retroperitoneal ectopic pregnancy: a case report and literature review.

BACKGROUND: Retroperitoneal ectopic pregnancy (REP) is an extremely rare type of ectopic pregnancy, with a total of less than 32 cases reported in the English literature. Early diagnosis of REP is very difficult and all treatments entail a high risk of life-threatening complications. CASE PRESENTATION: A 29-year-old nulliparous woman presented a history of 50-day amenorrhea and 7-day upper abdominal pain without vaginal spotting. The serum beta-human chorionic gonadotropin (ß-hCG) value was 65,004 m-international units per milliliter (mIU/mL), but no intrauterine gestational sac was found via transvaginal sonography (TVS). Then transabdominal ultrasonography (TAS) and abdominal contrast-enhanced computer tomography (CT) identified a retroperitoneal ectopic pregnancy (REP) tightly adjacent to the inferior vena cava and the abdominal aorta. After consultation from a multidisciplinary team, systemic methotrexate (MTX, intramuscular 20 mg daily for 5 consecutive days) combined with ultrasound-guided local potassium chloride solution injection into the gestational sac was scheduled firstly for the patient. However, serum ß-hCG continued to increase and the patient experienced worsening abdominal pain. Laparotomy was performed jointly by a gynecologist and a vascular surgeon. During the operation, the gestational sac with fetal bud measuring about 4.5 × 4.0x3.0 cm, tightly adherent to the surface of inferior vena cava and the left side of abdominal aorta, was carefully dissociated out from the surrounding tissues and removed en bloc. Histopathology examination confirmed the diagnosis of REP. The patient recovered uneventfully and her serum ß-hCG returned to normal range on the 23th postoperative day. CONCLUSIONS: Considering the possibility of REP and combined radiological examinations, such as ultrasonography and CT, are crucial for the early diagnosis of this rare condition. A multidisciplinary team is necessary to treat REP.

Supramolecular Hydrogel Based on an Osteogenic Growth Peptide Promotes Bone Defect Repair.

Current bone defect treatment strategies are associated with several risks and have major limitations. Therefore, it is necessary to develop an inexpensive growth factor delivery system that can be easily produced in large quantities and can promote long-term bone regeneration. An osteogenic growth peptide (OGP) is a 14 amino acid peptide with a short peptide sequence active fragment. In this study, we developed two OGP-based self-assembling supramolecular hydrogels (F- and G-sequence hydrogels) and investigated the in vitro and in vivo effects on proliferation and osteogenesis, including the mechanism of hydrogel-mediated bone defect repair. The hydrogels presented excellent biocompatibility and cell proliferation-promoting properties (1.5-1.7-fold increase). The hydrogels could effectively upregulate the expression of osteogenic factors, including RUNX2, BMP2, OCN, and OPN, to promote osteogenesis differentiation. Interestingly, 353 differentially expressed genes were identified in hBMSCs treated with hydrogels. The hydrogels were proved to be involved in the inflammatory pathways and folate-related pathways to mediate the osteogenesis differentiation. Furthermore, the therapeutic efficiency (bone volume/total volume, trabecular number, and bone mineral density) of hydrogels on bone regeneration in vivo was evaluated. The results showed that the hydrogels promoted bone formation in the early stage of bone defect healing. Taken together, this study was the first to develop and evaluate the properties of OGP-based self-assembling supramolecular hydrogels. Our study will provide inspiration for the development of delivering OGP for bone regeneration.

Seroprevalence and infection attack rate of COVID-19 in Indian cities.

Objectives: Serological surveys were used to infer the infection attack rate in different populations. The sensitivity of the testing assay, Abbott, drops fast over time since infection which makes the serological data difficult to interpret. In this work, we aim to solve this issue. Methods: We collect longitudinal serological data of Abbott to construct a sensitive decay function. We use the reported COVID-19 deaths to infer the infections, and use the decay function to simulate the seroprevalence and match to the reported seroprevalence in 12 Indian cities. Results: Our model simulated seroprevalence matchs the reported seroprevalence in most of the 12 Indian cities. We obtain reasonable infection attack rate and infection fatality rate for most of the 12 Indian cities. Conclusions: Using both reported COVID-19 deaths data and serological survey data, we infer the infection attack rate and infection fatality rate with increased confidence.

Translabial ultrasound indices of failed pessary fittings in women with symptomatic pelvic organ prolapse.

OBJECTIVE: To investigate translabial ultrasound (TLUS) parameters that may predict failed pessary fittings in women with symptomatic pelvic organ prolapse (POP). METHODS: All participants in this retrospective study presented to the Pelvic Floor Disease Diagnosis and Treatment Center (Liaoning Province, China) between May 2018 and December 2020 seeking treatment for symptomatic POP. Each had chosen vaginal pessary as first-line treatment, undergoing TLUS in advance of placement. Participants were grouped by outcomes of pessary fittings as successful or failed. Group-wise demographic and clinical characteristics, including TLUS parameters, were then subjected to uni- and multi-variate logistic regression. RESULTS: A total of 373 women qualified for analysis, 255 (68.4%) achieved success, and were fitted with acceptable pessaries. Predictors of failed fittings included younger age (61.54 ± 10.25 y vs 64.72 ± 10.30 y; P = 0.006), premenopausal status (14.4% vs 5.9%; P = 0.006), sizeable hiatal circumference (20.36 ± 2.33 cm vs 19.70 ± 2.50 cm; P = 0.02) and hiatal area (HA) (29.67 ± 7.14 cm2 vs 27.27 ± 6.99 cm2; P = 0.003), levator ani muscle (LAM) avulsion (odds ratio [OR] = 3.23, 95% confidence interval [CI] = 1.62-6.46; P = 0.001), enterocele (OR = 2.51, 95% CI = 1.11-5.68; P = 0.03), and the inferiormost aspect of cervix situated below symphysis pubis (OR = 0.52, 95% CI = 0.29-0.95; P = 0.03). In multivariate logistic regression, younger age (OR = 0.98, 95% CI = 0.95-1.00; P = 0.04), sizeable HA on Valsalva (OR = 1.04, 95% CI = 1.01-1.08; P = 0.02), LAM avulsion (OR = 2.87, 95% CI = 1.32-6.25; P = 0.008), and enterocele (OR = 2.70, 95% CI = 1.12-6.50; P = 0.03) emerged as independent predictors of failed pessary fittings. CONCLUSIONS: Younger age, LAM avulsion, enterocele, and sizeable HA on Valsalva proved independently predictive of failed pessary fittings in women with symptomatic POP.

A predictive model of choosing pessary type for women with symptomatic pelvic organ prolapse.

OBJECTIVE: To investigate clinical factors including translabial ultrasound parameters, which are predictive for choosing pessary type (Ring or Gellhorn) in the fitting trial, and to establish a predictive model. METHODS: A retrospective study was conducted on symptomatic women with pelvic organ prolapse (POP) at the Pelvic Floor Disease Diagnosis and Treatment Center (Liaoning Province, China) between May 2018 and December 2020 who were successfully fitted with pessaries. This retrospective study was supplemented with a prospective cohort study on women seeking pessary for first-line treatment of POP at the above tertiary center between December 2020 and April 2021 for validation. Enrolled participants were grouped by their fitted type of pessary. Demographic and clinical parameters between groups, including pelvic organ prolapse quantification and translabial ultrasound, were analyzed using logistic regression. A receiver operating characteristic curve was calculated using predictive values obtained by regression as the predictor for choosing pessary type in the pessary fitting trial. RESULTS: The 181 participants included in the retrospective analysis were randomly divided into the "Development" and "Validation" datasets. In the "Development" set, multivariable logistic regression analyses showed that a younger age (odds ratio [OR]: 0.950; 95% confidence interval [CI]: 0.908-0.995; P = 0.026), a larger hiatal circumference on Valsalva (OR: 1.348; 95% CI: 1.103-1.647; P = 0.004), and a higher POP-Q stage (OR: 2.963; 95% CI: 1.210-7.255; P = 0.017) were independent predictors for successful fitting with the Gellhorn pessary. The predictive model was P = exp(Z)/[1 + exp(Z)], Z = -0.051 × Age (y) + 0.298 × hiatal circumference on Valsalva (cm) + 1.086 × pelvic organ prolapse stage (2, 3, or 4) - 5.490. The area under the receiver operating characteristic curves (AUC) was 0.776 (P < 0.001) and 0.705 (P < 0.001) based on the "Development" dataset and "Validation" datasets, respectively. The AUC was 0.815 (P < 0.001) based on the prospective cohort validation. CONCLUSIONS: For severe POP, women with younger age and larger hiatal circumference, Gellhorn pessaries should be their first choice instead of ring ones in pessary fitting trials.

Effects of the decrease of ß-catenin expression on human vaginal fibroblasts of women with pelvic organ prolapse.

BACKGROUND: Pelvic organ prolapse (POP) lowers the quality of life in elderly women, and there have been no studies on its role in the pathogenesis of POP. The purpose of this study is to investigate the effect of ß-catenin on proliferation and collagen anabolism in human vaginal fibroblasts (HVFs). MATERIALS AND METHODS: The adherence and differential adherence methods were used to culture and purify HVFs. RNA interference was applied to knockdown ß-catenin and lithium chloride was used to activate Wnt/ß-catenin signaling pathway. ß-catenin nuclear translocation was tested by immunofluorescence, and HVF proliferation was detected by performing MTT assays. RESULTS: The expression of ß-catenin, phosphorylated-ß-catenin, phosphorylated-glycogen synthase kinase 3ß (p-GSK3ß), collagen I, matrix metalloproteinase 2 (MMP2), and tissue-derived inhibitors of metalloproteinases 2 (TIMP2) was assessed by western blot analysis. The expression of ß-catenin and collagen I was lower in HVFs of POP group than that of control group. The proliferation rate of HVFs in POP group was lower than that in control group. Knockdown of ß-catenin decreased the cell proliferation rate and the expression of collagen I. Lithium chloride can activate the Wnt/ß-catenin signaling pathway. CONCLUSION: ß-catenin participates in the proliferation and collagen I synthesis of HVFs. The decrease of ß-catenin expression may be closely related to the occurrence, and development of POP. LiCl can activate the Wnt/ß-catenin signaling pathway in HVFs and thus increase HVFs proliferation and collagen synthesis.

Diagnosis and Treatment of Renal Cell Carcinoma During Pregnancy.

Renal cell carcinoma during pregnancy is extremely rare, but it is the commonest urological malignancy reported in pregnancy. Currently, no uniform domestic or international diagnostic or treatment criteria exist for these patients, so their diagnosis and treatment are challenging for urologists. The health and reproductive needs of these patients have improved in recent years because of the continuous development of medical technology. This article reviews the epidemiology, risk factors, diagnosis, treatment, and prognosis of renal cell carcinoma during pregnancy.

The Application of Chemical Polishing in TEM Sample Preparation of Zirconium Alloys.

Hydride artefacts are commonly induced by the TEM sample preparation process in Zirconium alloys as hydrogen-sensitive metals, including electron polishing and focused ion beam (FIB) technology. In the research, we present the application of chemical polishing with a solution of 10HF:45HNO3:45H2O to prepare the disk samples for TEM observation in zirconium alloys. The thinning efficiency of chemical polishing is 25 µm per minute. XRD patterns indicate that the chemical polishing actually eliminates the macro- and micro-stress induced by mechanical grinding. TEM observation demonstrates that chemical polishing reduces the amount of hydride artefacts, especially hydrides with large size. It is proposed that induced stress provides driving force for hydride artefact formation. Compared with traditional mechanical grinding, the advantages of chemical polishing are high efficiency, free of induced stress, less induced hydride artefacts and bend contours.

Numerical well testing interpretation model and applications in crossflow double-layer reservoirs by polymer flooding.

This work presents numerical well testing interpretation model and analysis techniques to evaluate formation by using pressure transient data acquired with logging tools in crossflow double-layer reservoirs by polymer flooding. A well testing model is established based on rheology experiments and by considering shear, diffusion, convection, inaccessible pore volume (IPV), permeability reduction, wellbore storage effect, and skin factors. The type curves were then developed based on this model, and parameter sensitivity is analyzed. Our research shows that the type curves have five segments with different flow status: (I) wellbore storage section, (II) intermediate flow section (transient section), (III) mid-radial flow section, (IV) crossflow section (from low permeability layer to high permeability layer), and (V) systematic radial flow section. The polymer flooding field tests prove that our model can accurately determine formation parameters in crossflow double-layer reservoirs by polymer flooding. Moreover, formation damage caused by polymer flooding can also be evaluated by comparison of the interpreted permeability with initial layered permeability before polymer flooding. Comparison of the analysis of numerical solution based on flow mechanism with observed polymer flooding field test data highlights the potential for the application of this interpretation method in formation evaluation and enhanced oil recovery (EOR).

[Reasonable surgical approach for grade III cervical intraepithelial neoplasia].

OBJECTIVE: To analyze the clinical pathologic characteristics of cervical intraepithelial neoplasia grade III (CINIII ) and to explore optimal surgery for CINIII patients. METHODS: The clinical pathologic characteristics, surgical treatments, prognosis and history of 383 CINIII patients, who hospitalized from August 2005 to December 2010, were reviewed and analyzed. Among the patients, 213 (55.6%) received cold-knife conization surgery and 170 (44.4%) received ordinary electric knife conization surgery. RESULTS: There was no significant statistic difference between cold-knife conization group and ordinary electric-knife conization group on the level of clearance of the pathologic tissues and the cervical cone diameter and cone high. Intraoperative blood loss was (13.1±5.2) mL and (25.5±17.2) mL. Bleeding of electric knife conization group, compared with that of the cold knife conization group, decreased by nearly 50%. The difference between the 2 groups was significant (P<0.01). Pathological examination after conization operation indicated that 350 out of the 383 patients didn't show pathological upgrade while 33 patients showed pathological development, among which 21 were diagnosed with invasive cervical cancer at Ia1 clincal stage, 7 atIa2 clincal stage and 5 atIb1 clincal stage. In 3 cases (14.3%) Ia1 cervical cancer patients, fertility requirements and negative margins with cervical conization were closely followed up, and one patient (4.8%) with positive margin and fertility requirements had re-conecut. The remaining 17 (80.9%) had resected the uterus outside the fascia (or plus attachments) . All the 12 patients with invasive cervical cancer at Ia2 orIb1 clinical stage received radical hysterectomy. No tumor recurrence was observed in the 383 patients. CONCLUSION: Treatment optimazation of CINIII patients should be based on clinical pathological diagnosis and individual requirements. Both cervical conization surgery and total hysterectomy have been proved safe and practical for CINIII patients.

Analysis of clinical interventional strategy for women with urinary incontinence complicated with diabetes mellitus.

INTRODUCTION AND HYPOTHESIS: This study aims to investigate clinical therapeutic measures for women with urinary incontinence (UI) complicated with diabetes mellitus (DM). METHODS: We performed a retrospective cohort study, including 462 female patients with UI complicated with DM (group A) and 901 patients with UI without DM (group B). Both A and B groups were divided into three subgroups according to their UI types (pure stress UI, mixed UI dominated by urge UI, and by overactive bladder syndrome) and received corresponding treatments. The subjective and objective effective rates were analyzed statistically. RESULTS: The overall subjective effective rates were 62.99% and 85.23% and the overall objective effective rates were 67.53% and 87.24% for groups A and groups B, respectively; the subjective and objective effective rates were 73.68% and 89.47% for group A1 (patients with pure stress UI in group A). There was no statistical difference in group A1 between subjective and objective effective rates. CONCLUSION: Unsatisfactory clinical therapeutic efficacy was observed in women with UI complicated with DM; surgical operation should be deliberated cautiously for women with SUI complicated with DM.

Investigation of correlation between diameters of pelvic inlet and outlet planes and female pelvic floor dysfunction.

OBJECTIVE: To investigate correlation between key diameters of pelvic inlet and outlet planes and female pelvic floor dysfunction (FPFD). STUDY DESIGN: Correlation with incidence of FPFD was analyzed by measuring the two diameters of pelvic inlet and outlet planes (i.e. anteroposterior diameter of pelvic inlet and transverse diameter of pelvic outlet) in 298 patients with FPFD and 508 patients in control group taking into account of other relevant factors. RESULTS: The transverse diameter of pelvic outlet was significantly larger in experimental group than in control group (9.55cm vs. 8.50cm, P<0.01); while the difference in anteroposterior diameter of pelvic inlet between the two groups was not statistically significant (11.63cm vs. 11.26cm, P=0.205>0.01); Binary logistic regression analysis indicated that the anteroposterior diameter of pelvic inlet was not correlated with incidence of FPFD, but the transverse diameter of pelvic outlet was one of the influencing factor for FPFD. CONCLUSIONS: The transverse diameter of pelvic outlet is closely correlated with incidence of FPFD and represents one of the risk factors for FPFD; a transverse diameter of pelvic outlet greater than 9.5cm is the threshold for onset of FPFD and can be used as an early predictive index for FPFD.