Metabolism pathway-based subtyping in endometrial cancer: An integrated study by multi-omics analysis and machine learning algorithms.

Endometrial cancer (EC), the second most common malignancy in the female reproductive system, has garnered increasing attention for its genomic heterogeneity, but understanding of its metabolic characteristics is still poor. We explored metabolic dysfunctions in EC through a comprehensive multi-omics analysis (RNA-seq datasets from The Cancer Genome Atlas [TCGA], Cancer Cell Line Encyclopedia [CCLE], and GEO datasets; the Clinical Proteomic Tumor Analysis Consortium [CPTAC] proteomics; CCLE metabolomics) to develop useful molecular targets for precision therapy. Unsupervised consensus clustering was performed to categorize EC patients into three metabolism-pathway-based subgroups (MPSs). These MPS subgroups had distinct clinical prognoses, transcriptomic and genomic alterations, immune microenvironment landscape, and unique patterns of chemotherapy sensitivity. Moreover, the MPS2 subgroup had a better response to immunotherapy. Finally, three machine learning algorithms (LASSO, random forest, and stepwise multivariate Cox regression) were used for developing a prognostic metagene signature based on metabolic molecules. Thus, a 13-hub gene-based classifier was constructed to predict patients' MPS subtypes, offering a more accessible and practical approach. This metabolism-based classification system can enhance prognostic predictions and guide clinical strategies for immunotherapy and metabolism-targeted therapy in EC.

Current trends and emerging patterns in the application of nanomaterials for ovarian cancer research: a bibliometric analysis.

Introduction: Ovarian cancer remains to be a significant cause of global cancer-related mortality. In recent years, there has been a surge of studies in investigating the application of nanomaterials in the diagnosis and treatment of ovarian cancer. This study aims to conduct a comprehensive bibliometric analysis regarding nanomaterial-based researches on ovarian cancer to evaluate the current state and emerging patterns in this field. Methods: A thorough literature search on the Web of Science Core Collection database was conducted to identify articles focused on nanomaterial-based ovarian cancer researches. The studies that met the inclusion criteria were selected for further analysis. VOSviewer and CiteSpace were applied for the bibliometric and visual analyses of the selected publications. Results: A total of 2,426 studies were included in this study. The number of annual publications showed a consistent upward trend from 2003 to 2023. Notably, China, the United States, and India have emerged as the leading contributors in this field, accounting for 37.39%, 34.04%, and 5.69% of the publications, respectively. The Chinese Academy of Sciences and Anil K. Sood were identified as the most influential institution and author, respectively. Furthermore, the International Journal of Nanomedicine was the most frequently cited journal. In terms of the research focus, significant attention has been directed towards nanomaterial-related drug delivery, while the exploration of immunogenic cell death and metal-organic frameworks represented recent areas of interest. Conclusion: Through comprehensive analyses, an overview of current research trends and emerging areas of interest regarding the application of nanomaterials in ovarian cancer was illustrated. These findings offered valuable insights into the status and future directions of this dynamic field.

Mesh-less laparoscopic extraperitoneal linear suspension treatment of vaginal vault prolapse.

OBJECTIVES: To report the results of a mesh-less laparoscopic extraperitoneal linear suspension technique for the treatment of post-hysterectomy vaginal vault prolapse (PHVP). STUDY DESIGN: A retrospective observational study was conducted collecting medical records of 41 patients with symptomatic PHVP treated between November 2017 to November 2019 in Gynecologic department of China-Japan Friendship Hospital. All patients had Pelvic Organ Prolapse Quantification (POP-Q) scores indicating stage 3-4 PHVP and underwent mesh-less laparoscopic extraperitoneal linear suspension.The primary outcome was the subjective satisfaction rate based on responses to validated questionnaires. The secondary outcomes were the objective anatomical cure rate based on POP-Q scores and complication rates. All listed parameters were determined before the surgery and at control examinations in 1 year and 3 years after the treatment. RESULTS: The operation was completed successfully without serious complications in all patients. Mean operation time was 53.8 mins. Comparison of the scores by the questionnaires revealed a significant improvement in the quality of life in the postoperative period.The subjective satisfaction rates were 100 % (41/41) and 95 % (38/40) at 1 year and 3 years after surgery. The objective cure rates were 100 % (41/41) and 97.5 % (39/40) at 1 year and 3 years after surgery, respectively. During the follow-up, none of the patients experienced suture exposure, infection, chronic pelvic pain, or other related complications. CONCLUSION: The mesh-less laparoscopic extraperitoneal linear suspension technique avoids the use of implantable synthetic mesh. It has been shown to lead to favorable postoperative outcomes, considerable patient contentment, and low complication rates. It offers a new, cost-effective treatment option for PHVP patients.

Effect of esketamine on postpartum depression after labor analgesia and potential mechanisms: a randomized, double-blinded controlled trial.

BACKGROUND: To evaluate the effect of esketamine combined with ropivacaine hydrochloride on the occurrence of postpartum depression (PPD) after labor analgesia under epidural analgesia pump and explore the possible mechanisms. METHODS: A total of 120 women aged 24 to 36 years old who underwent labor analgesia by epidural analgesia pump, with American Society of Anesthesiologists (ASA) physical status II were enrolled. According to the formula of epidural analgesia pump, all participants were randomly divided into two groups: esketamine group (Group E) and control group (Group C). Epidural anaesthesia were operated in all women between L2 and L3 after cervical dilation up to 2 ~ 3 cm. After successful puncture, the epidural catheter was placed 3.5 cm toward the head and 1% lidocaine was injected for 3 ml. The epidural analgesia pump was connected. Esketamine (0.2 mg/kg) combined with 0.75% ropivacaine hydrochloride (20 ml) were diluted by normal saline up to 100 ml in Group E, when only the equal dose of ropivacaine hydrochloride was used in Group C. The visual analogue scale (VAS) before analgesia (T1), 5 (T2), 10 (T3) and 20 (T4) minutes after analgesia were measured. The duration of the first and second stage of labor, the Apgar score of fetus at delivery, postpartum hemorrhage, consumption of esketamine and ropivacaine were recorded. The incidence of PPD was recorded at 1 week and 6 weeks after delivering. The occurrence of side effects such as nausea and vomiting, dizziness, and nightmares were also recorded for 48 h after delivering. The levels of leptin, norepinephrine(NE), and epinephrine(E) in the peripheral venous blood were measured before labor analgesia and at 24 h, 1 week, and 6 weeks after delivering. RESULTS: Compared with Group C, the VAS score at T2, T3 and T4 were significantly lower in Group E (P < 0.01). Compared with Group C, the incidence of PPD was significantly lower at 1 week and 6 weeks after delivering in Group E (P < 0.01). Compared with Group C, the levels of leptin were significantly higher at 24 h and 1 week after delivering in Group E (P < 0.01), while NE and E (P < 0.01) were lower at the same time (P < 0.01). There were no significant difference of the duration of the first and second stage of labor, the Apgar score of fetus at delivery, postpartum hemorrhage, consumption of ropivacaine and the side effects for 48 h after delivering between the two groups. CONCLUSION: Esketamine combined with ropivacaine hydrochloride used in labor analgesia can significantly reduce the incidence of postpartum depression after delivering without increasing related side effects, which may be related to the regulation of leptin, norepinephrine, and epinephrine in the serum. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry on 30/05/2022 (CTRI registration number-ChiCTR2200060387). URL of registry: https://www.chictr.org.cn/bin/home .

AMEERA-4: a randomized, preoperative window-of-opportunity study of amcenestrant versus letrozole in early breast cancer.

BACKGROUND: Window-of-opportunity (WOO) studies provide insights into the clinical activity of new drugs in breast cancer. METHODS: AMEERA-4 (NCT04191382) was a WOO study undertaken to compare the pharmacodynamic effects of amcenestrant, a selective estrogen receptor degrader, with those of letrozole in postmenopausal women with newly diagnosed, operable estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer. Women were randomized (1:1:1) to receive amcenestrant 400 mg, amcenestrant 200 mg, or letrozole 2.5 mg once daily for 14 days before breast surgery. The primary endpoint was change in Ki67 between baseline and Day 15 (i.e., day of surgery). RESULTS: Enrollment was stopped early because of slow recruitment, in the context of the COVID-19 pandemic. The modified intent-to-treat population consisted of 95 study participants with baseline and post-treatment Ki67 values, whereas the safety population included 104 participants who had received at least one dose of study medication. Relative change from baseline in Ki67 was - 75.9% (95% confidence interval [CI] - 81.9 to - 67.9) for amcenestrant 400 mg, - 68.2% (- 75.7 to - 58.4) for amcenestrant 200 mg, and - 77.7% (- 83.4 to - 70.0) for letrozole (geometric least-squares mean [LSM] estimates). Absolute change in ER H-score from baseline (LSM estimate) was - 176.7 in the amcenestrant 400 mg arm, - 202.9 in the amcenestrant 200 mg arm, and - 32.5 in the letrozole arm. There were no Grade ≥ 3 treatment-related adverse events. CONCLUSIONS: Both amcenestrant and letrozole demonstrated antiproliferative activity in postmenopausal women with previously untreated, operable ER+/HER2- breast cancer and had good overall tolerability. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04191382 https://clinicaltrials.gov/ct2/show/NCT04191382 . Registered 9 December 2019.

Role of Serum Inflammatory Cytokines in Sepsis Rats Following BMSCs Transplantation: Protein Microarray Analysis.

Bone marrow stromal cells (BMSCs) have emerged as a potential therapy for sepsis, yet the underlying mechanisms remain unclear. In this study, we investigated the effects of BMSCs on serum inflammatory cytokines in a rat model of lipopolysaccharide (LPS)-induced sepsis. Sepsis was induced by intravenous injection of LPS, followed by transplantation of BMSCs. We monitored survival rates for 72 h and evaluated organ functions, histopathological changes, and cytokines expression. Sepsis rats showed decreased levels of white blood cells, platelets, lymphocyte ratio, and oxygen partial pressure, along with increased levels of neutrophil ratio, carbon dioxide partial pressure, lactic acid, alanine aminotransferase, and aspartate aminotransferase. Histologically, lung, intestine, and liver tissues exhibited congestion, edema, and infiltration of inflammatory cells. However, after BMSCs treatment, there was improvement in organ functions, histopathological injuries, and survival rates. Protein microarray analysis revealed significant changes in the expression of 12 out of 34 inflammatory cytokines. These findings were confirmed by enzyme-linked immunosorbent assay. Pro-inflammatory factors, such as interleukin-1ß (IL-1ß), IL-1α, tumor necrosis factor-α (TNF-α), tissue inhibitor of metal protease 1 (TIMP-1), matrix metalloproteinase 8 (MMP-8), Leptin, and L-selectin were upregulated in sepsis, whereas anti-inflammatory and growth factors, including IL-4, ß-nerve growth factor (ß-NGF), ciliary neurotrophic factor (CNTF), interferon γ (IFN-γ), and Activin A were downregulated. BMSCs transplantation led to a decrease in pro-inflammatory cytokines and an increase in anti-inflammatory and growth factors. We summarized relevant molecular signaling pathways that resulted from cytokines in BMSCs for treating sepsis. Our results illustrated that BMSCs could promote tissue repair and improve organ functions and survival rates in sepsis through modulating cytokine networks.

Engineering exosomes derived from subcutaneous fat MSCs specially promote cartilage repair as miR-199a-3p delivery vehicles in Osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease involving cartilage. Exosomes derived from Mesenchymal stem cells (MSCs) therapy improves articular cartilage repair, but subcutaneous fat (SC) stromal cells derived exosomes (MSCsSC-Exos), especially engineering MSCsSC-Exos for drug delivery have been rarely reported in OA therapy. This objective of this study was to clarify the underlying mechanism of MSCsSC-Exos on cartilage repair and therapy of engineering MSCsSC-Exos for drug delivery in OA. MSCsSC-Exos could ameliorate the pathological severity degree of cartilage via miR-199a-3p, a novel molecular highly enriched in MSCsSC-Exos, which could mediate the mTOR-autophagy pathway in OA rat model. Intra-articular injection of antagomiR-199a-3p dramatically attenuated the protective effect of MSCsSC-Exos-mediated on articular cartilage in vivo. Furthermore, to achieve the superior therapeutic effects of MSCsSC-Exos on injured cartilage, engineering exosomes derived from MSCsSC as the chondrocyte-targeting miR-199a-3p delivery vehicles were investigated in vitro and in vivo. The chondrocyte-binding peptide (CAP) binding MSCsSC-Exos could particularly deliver miR-199a-3p into the chondrocytes in vitro and into deep articular tissues in vivo, then exert the excellent protective effect on injured cartilage in DMM-induced OA mice. As it is feasible to obtain human subcutaneous fat from healthy donors by liposuction operation in clinic, meanwhile engineering MSCsSC-Exos to realize targeted delivery of miR-199a-3p into chondrocytes exerted excellent therapeutic effects in OA animal model in vivo. Through combining MSCsSC-Exos therapy and miRNA therapy via an engineering approach, we develop an efficient MSCsSC-Exos-based strategy for OA therapy and promote the application of targeted-MSCsSC-Exos for drug delivery in the future.

Competition and synergistic mechanisms of species in Phyllostachys edulis-Alsophila spinulosa association based on niche theory.

We examined the niche characteristics and interspecific covariant relationship of main species in Phyllostachys edulis-Alsophila spinulosa association in Chishui A. spinulosa National Nature Reserve under P. edulis disturbance condition, and analyzed the mechanism of competition and coexistence across different species. The results showed that there were 67 species from 53 genera and 40 families in the association. The importance values, Shannon niche breadth index (BS), and Levins niche breadth index (BL) of P. edulis were the largest, indicating its absolute dominant status in association. The importance value and BL of A. spinulosa ranked the second, while BS was the third. There were 190 pairs of 20 main species. The niche overlap between P. edulis and A. spinulosa was the largest, with niche overlap value of 0.64. 71.6% of species pairs had niche overlap of less than 0.2, indicating low niche overlap and high degree of niche differentiation among species. The overall association of main species in association was significantly positive, and the community was relatively stable. The correlation among the main species was not significant, the linkage was not strong, and the species were independent from each other. P. edulis showed significant positive correlation with A. spinulosa, Brassaiopsis glomerulata, Ficus virens, and Mallotus barbatus, while P. edulis showed significant negative correlation with Mallotus philippensis, Cinnamomum glanduliferum, and Machilus gamblei. Niche difference and fitness between P. edulis and natives affected the coexistence and competition among species. Controlling the expansion of P. edulis and limiting the size of species with negative correlation with A. spinulosa could create a favorable living environment for A. spinulosa.

Risk assessment of venous thromboembolism in head and neck cancer patients and its establishment of a prediction model.

IMPORTANCE: Venous thromboembolism (VTE) is closely relevant to head and neck cancer (HNC) prognosis, but little data exist on the risk prediction of VTE in patients with HNC. OBJECTIVE: To study the risk factors regarding VTE in HNC patients and construct a nomogram model for its prediction. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional retrospective study was implemented to comparatively analyze 220 HNC patients from January 2018 to December 2021. The Lasso algorithm was used to optimize the selection of variables. A nomogram model for predicting HNC-associated VTE was established using multivariate logistic regression analysis. Internal validation of the model was performed by bootstrap resampling (1000 times). Calibration plot and decision curve analysis (DCA) were applied to evaluate the calibration capability of the prediction model. MAIN OUTCOME AND MEASURE: The demographics, medical history, blood biochemical indicators, and modalities of treatment were included for analysis. RESULTS: The incidence of HNC-associated VTE was 2.8% (55/1967) in authors' affiliation. Five variables of risk factors, including surgery, radiochemotherapy, D-dimer, aspartate transaminase, and globulin, were screened and selected as predictors by Lasso algorithm. A prediction model that incorporated these independent predictors was developed and presented as the nomogram. The model showed good discrimination with a C-index of 0.972 (95% CI: 0.934-0.997), and had an area under the receiver operating characteristic curve value of 0.981 (p < 0.001, 95% CI: 0.964-0.998). The calibration curve displayed good agreement of the predicted probability with the actual observed probability for HNC-associated VTE. The DCA plot showed that the application of this nomogram was associated with net benefit gains in clinical practice. CONCLUSIONS AND RELEVANCE: The high-performance nomogram model developed in this study may help early diagnose the risk of VTE in HNC patients and to guide individualized decision-making on thromboprophylaxis.

Involvement in treatment decision-making and self-reported efficacy among patients with advanced colorectal cancer: a nationwide multi-center cross-sectional study.

Introduction: This cross-sectional study evaluated the involvement of patients with advanced colorectal cancer (CRC) in treatment decision-making, assessed the treatment efficacy according to their self-reports, and investigated the influencing factors. Methods: Patients with advanced CRC were recruited from 19 hospitals from March 2020 to March 2021 by a multi-stage multi-level sampling method. A self-designed questionnaire was used to collect demographic and clinical characteristics, involvement of CRC patients in treatment decision-making, treatment methods, and self-reported efficacy. Univariate and unordered multinomial logistic regression analyses were used to evaluate the factors affecting the involvement in treatment decision-making and self-reported efficacy. Results: We enrolled 4533 patients with advanced CRC. The average age at diagnosis was 58.7 ± 11.8 years. For the treatment method, 32.4% of patients received surgery combined with chemotherapy, 13.1% of patients underwent surgery combined with chemotherapy and targeted therapy, and 9.7% of patients were treated with surgery alone. For treatment decision-making, 7.0% of patients were solely responsible for decision-making, 47.0% of patients shared treatment decision-making with family members, 19.0% of patients had family members solely responsible for treatment decision-making, and 27.0% of patients had their physicians solely responsible for treatment decision-making. Gender, age, education level, family income, marital status, treatment cost, hospital type, and treatment method were significantly associated with the involvement of patients in treatment decision-making. A total of 3824 patients submitted self-reported efficacy evaluations during treatment. The percentage of patients with good self-reported efficacy was 76.5% (for patients treated for the first time), 61.7% (for patients treated for the second time), and 43.2% (for patients treated after recurrence and metastasis), respectively. Occupation, education level, average annual family income, place of residence, time since cancer diagnosis, hospital type, clinical stage, targeted therapy, and involvement in treatment decision-making were the main influencing factors of self-reported efficacy of treatment. Discussion: Conclusively, CRC patients are not highly dominant in treatment decision-making and more likely to make treatment decisions with their family and doctors. Timely and effective communication between doctors and patients can bolster patient involvement in treatment decision-making.

Real-World Utilization, Barriers, and Factors Associated With the Targeted Treatment of Metastatic Colorectal Cancer Patients in China: A Multi-Center, Hospital-Based Survey Study.

Objectives: To explore the utilization, barriers, and factors associated with the targeted treatment of Chinese metastatic colorectal cancer (mCRC) patients. Methods: A total of 1,688 mCRC patients from 19 hospitals in 14 cities were enrolled from March 2020 to March 2021 using stratified, multistage cluster sampling. The use of targeted therapy and any barriers patients experienced were collected. Logistic regression analyses were conducted to identify the factors associated with initiating targeted treatment. Results: About 51.6% of the patients initiated targeted therapy, of whom 44.5%, 20.2%, and 35.2% started first-, second-, and third-line treatment, respectively. The most reported barriers were high medical costs and a lack of belief in the efficacy of targeted therapy. Patients treated in the general hospital, diagnosed at an older age, less educated, and who had a lower family income, no medical insurance, poor health-related quality of life, metastasis outside the liver/lung or systemic metastasis, a shorter duration of mCRC were less likely to initiate targeted therapy. Conclusion: Reduced medical costs and interventional education to improve public awareness could facilitate the use of targeted treatment for mCRC.

Risk of leakage with a new detachable multi-hard-port containment system for power morcellation during gynecologic laparoscopy: An in vitro study.

BACKGROUND: Laparoscopic surgery has been a milestone for minimally invasive surgeries. But safe removal of large uterine tissue is a challenge for minimally invasive procedures, and there still exists concern about the dissemination of benign or occult malignant uterine tissue during the use of the morcellator. Different tissue containment systems have been used in laparoscopic power morcellation. However, a risk of leakage still exists in clinical practice. In this study, we aimed to evaluate leakage and tissue dissemination associated with a new detachable multi-hard-port containment system for tissue removal during laparoscopic myomectomy morcellation. METHODS: Beef tongue specimens were stained with methylene blue solution and morcellated in a plastic trainer box under laparoscopic guidance. The morcellation test in vitro conditions comprised two different containment systems to simulate laparoscopic power morcellation, specifically a polyurethane bag with two pipes (control group) and a detachable multi-hard-port containment system (experimental group). Insufflation pressure was set at 14 mmHg. Three methods are used to detect the leakage The procedure times were recorded. Thirty trials were performed using a multi-port approach and the two tissue containment systems. RESULTS: The leakage rate was 0.03% (n = 30) for the experimental group and 26.6% (n = 30) for the control group (p < 0.005). Morcellation time was significantly shorter in the experimental group than in the control group (p < 0.001). Median bag introduction time was shorter in the experimental group than in the control group; however, removal time differences were not significant. CONCLUSIONS: This study quantified the low leakage rate during morcellation and the improved convenience of operation provided by a new tissue containment system.

Effect of intraoperative mild hyperventilation on the incidence of shoulder pain after laparoscopic sleeve gastrectomy: A randomized, controlled trial.

BACKGROUNDS: To observe the effect of using mild intraoperative hyperventilation on the incidence of postlaparoscopic shoulder pain (PLSP) in patients undergoing laparoscopic sleeve gastrectomy. METHODS: Eighty patients undergoing laparoscopic sleeve gastrectomy, aged 22 to 36 years, with American Society of Anesthesiologists grade I or II, were divided into 2 groups according to method of random number table. A mild hyperventilation was used in group A with controlling pressure of end-tidal carbon dioxide (PETCO2) of 30 to 33 mm Hg, while conventional ventilation was used in group B with PETCO2 35 to 40 mm Hg during the operation. The incidence and severity of PLSP, dosage of remedial analgesia and adverse reactions such as nausea and vomiting at 12, 24, 48, 72 hours and 1 week after surgery were recorded. Arterial blood gas was recorded before anesthesia induction, 20 minutes after pneumoperitoneum, during suture skin, and 24 hours after surgery. RESULTS: Compared with 12, 24, 48, and 72 hours after operation, the incidence of PLSP at 1 week decreased significantly (P < .01). Compared with group B, the incidence of PLSP, pain score, and dosage of remedial analgesic at 12, 24,48, 72 hours, and 1 week after surgery were significantly decreased (P < .01). There was no significant difference between the 2 groups in arterial blood gas analysis before anesthesia induction, 20 minutes after pneumoperitoneum, during suture skin, and 24 hours after surgery (P > .05). There were no significant difference of the occurrence of adverse reactions such as nausea and vomiting between the 2 groups within 1 week after surgery (P > .05). CONCLUSION: Mild hyperventilation can reduce the incidence and severity of PLSP after laparoscopic sleeve gastrectomy without increasing the associated adverse effects.

ADSCs increase the autophagy of chondrocytes through decreasing miR-7-5p in Osteoarthritis rats by targeting ATG4A.

BACKGROUND: Osteoarthritis (OA) is a highly degenerative joint disease, mainly companying with progressive destruction of articular cartilage. Adipose-derived stromal cells (ADSCs) therapy enhances articular cartilage repair, extracellular matrix (ECM) synthesis and attenuates joints inflammation, but specific mechanisms of therapeutic benefit remain poorly understood. This study aimed to clarify the therapeutic effects and mechanisms of ADSCs on cartilage damage in the keen joint of OA rat model. METHODS: Destabilization of the medial meniscus (DMM) and anterior cruciate ligament transection (ACLT) surgery-induced OA rats were treated with allogeneic ADSCs by intra-articular injections for 6 weeks. The protective effect of ADSCs in vivo was measured using Safranin O and fast green staining, immunofluorescence and western blot analysis. Meanwhile, the miRNA-7-5p (miR-7-5p) expression was assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The mechanism of increased autophagy with ADSCs addition through decreasing miR-7-5p was revealed using oligonucleotides, and adenovirus in rat chondrocytes. The luciferase reporter assay revealed the molecular role of miR-7-5p and autophagy related 4A (ATG4A). The substrate of mTORC1 pathway: (p-)p70S6 and (p-)S6 in OA models with ADSCs addition were detected by western blotting. RESULTS: The ADSCs treatment repaired the articular cartilage and maintained chondrocytes ECM homeostasis through modulating chondrocytes autophagy in the OA model, indicators of the change of autophagic proteins expression and autophagic flux. Meanwhile, the increased autophagy induced by ADSCs treatment was closely related to the decreased expression of host-derived miR-7-5p, a negative modulator of OA progression. Functional genomics (overexpression of genes) in vitro studies demonstrate the inhibition of host-derived miR-7-5p in mediating the benefit of ADSCs administration in OA model. Then ATG4A was defined as a target gene of miR-7-5p, and the negative relation between miR-7-5p and ATG4A was investigated in the OA model treated with ADSCs. Furthermore, miR-7-5p mediated chondrocyte autophagy by targeting ATG4A in the OA model treated with ADSCs was confirmed with the rescue trial of ATG4A/miR-7-5p overexpression on rat chondrocyte. Finally, the mTORC1 signaling pathways mediated by host-derived miR-7-5p with ADSCs treatment were decreased in OA rats. CONCLUSIONS: ADSCs promote the chondrocytes autophagy by decreasing miR-7-5p in articular cartilage by targeting ATG4A and a potential role for ADSCs based therapeutics for preventing of articular cartilage destruction and extracellular matrix (ECM) degradation in OA.

Treatment of FIGO 2018 stage IIIC cervical cancer with different local tumor factors.

BACKGROUND: To compare the oncological outcomes of patients with FIGO 2018 stage IIIC cervical cancer (CC) involving different local tumor factors who underwent abdominal radical hysterectomy (ARH), neoadjuvant chemotherapy and radical surgery (NACT), or radical chemoradiotherapy (R-CT). METHODS: Based on tumor staging, patients with stage IIIC were divided into T1, T2a, T2b, and T3 groups. Kaplan-Meier and Cox proportional hazards regression analysis were used to compare their overall survival (OS) and disease-free survival (DFS) of 5 years. RESULTS: We included 4,086 patients (1,117, 1,019, 869, and 1,081 in the T1, T2a, T2b, and T3 groups, respectively). In the T1 group, NACT was correlated with a decrease in OS (hazard ratio [HR] = 1.631, 95% confidence interval [CI]: 1.150-2.315, P = 0.006) and DFS (HR = 1.665, 95% CI: 1.255-2.182, P < 0.001) than ARH. ARH and NACT were not correlated with OS (P = 0.226 and P = 0.921) or DFS (P = 0.343 and P = 0.535) than R-CT. In the T2a group, NACT was correlated with a decrease in OS (HR = 1.454, 95% CI: 1.057-2.000, P = 0.021) and DFS (HR = 1.529, 95% CI: 1.185-1.974, P = 0.001) than ARH. ARH and NACT were not correlated with OS (P = 0.736 and P = 0.267) or DFS (P = 0.714 and P = 0.087) than R-CT. In the T2b group, NACT was correlated with a decrease in DFS (HR = 1.847, 95% CI: 1.347-2.532, P < 0.001) than R-CT nevertheless was not correlated with OS (P = 0.146); ARH was not correlated with OS (P = 0.056) and DFS (P = 0.676). In the T3 group, the OS rates of ARH (n = 10), NACT (n = 18), and R-CT (n = 1053) were 67.5%, 53.1%, and 64.7% (P = 0.941), and the DFS rates were 68.6%, 45.5%, and 61.1%, respectively (P = 0.761). CONCLUSION: R-CT oncological outcomes were not entirely superior to those of NACT or ARH under different local tumor factors with stage IIIC. NACT is not suitable for stage T1, T2a, and T2b. Nevertheless ARH is potentially applicable to stage T1, T2a, T2b and T3. The results of stage T3 require confirmation through further research due to disparity in case numbers in each subgroup.

Tumor Microenvironment CD8 T and Treg Cells-related Genes Signature Distinguishes Distinct Prognosis and Targeted Therapies Response in Endometrial Cancer.

Although most endometrial cancer (EC) patients have a favorable prognosis, the overall survival (OS) of metastatic and recurrent EC could hardly be improved by the current chemoradiotherapy. We aimed to reveal the tumor microenvironment immune infiltration characteristics to elucidate the underlying mechanism of EC progression and guide clinical decisions. In the Cancer Genome Atlas (TCGA) cohort, Kaplan-Meier survival curves confirmed Tregs and CD8 T cells were prognosis-protective factors in OS of EC ( P <0.05). Weighted gene coexpression network analysis identified 2 gene modules closely correlated with Tregs and CD8 T-cell infiltration. We randomly split the TCGA EC cohort into the training and testing cohorts at a ratio of 7:3. An immune-related prognosis risk index (IRPRI), including NR3C1, E2F1, OTOG, TTK, PPP1R16B, and FOXP3, was established by univariate, Least Absolute Shrinkage and Selection Operator, and multivariate Cox regression with area under the curve >0.67. Distinct clinical, immune, and mutation characteristics existed between IRPRI groups by multiomics analysis. Cell proliferation and DNA damage repair-related pathways were activated, and immune-related pathways were inactivated in the IRPRI-high group. Furthermore, patients in the IRPRI-high group had lower tumor mutation burden, programmed death-ligand 1 expression, and Tumor Immune Dysfunction and Exclusion scores, indicating a poor response to immune checkpoint inhibitors therapy ( P <0.05), which was also validated in the TCGA testing cohort and independent cohorts, GSE78200, GSE115821, and GSE168204. Also, the higher mutation frequencies of BRCA1, BRCA2, and genes enrolled in homologous recombination repair in the IRPRI-low group predicted a good response to PARP inhibitors. Finally, a nomogram integrating the IRPRI group and prognosis significant clinicopathological factors for EC OS prediction was developed and validated with good discrimination and calibration.

Effect of pre-administration of esketamine intraoperatively on postpartum depression after cesarean section: A randomized, double-blinded controlled trial.

BACKGROUND: To evaluate the effect of pre-administration of esketamine intraoperatively on the occurrence of postpartum depression after cesarean section under combined spinal-epidural anesthesia. METHODS: A total of 120 women aged 24 to 36 years undergoing cesarean section by spinal-epidural anesthesia with American Society of Anesthesiologists physical status II were enrolled. According to the intraoperative use of esketamine, all participants were randomly divided into 2 groups: test group (group E) and control group (group C). Esketamine was administered intravenously at a dose of 0.2 mg/kg after the infant was delivered in group E and equal volume of normal saline was given in group C. The incidence of postpartum depression was recorded at 1 week and 6 weeks after the operation. The occurrence of adverse reactions such as postpartum bleeding, nausea and vomiting, drowsiness, and nightmares were also recorded at 48 hours after surgery. RESULTS: Compared with group C, the incidence of postpartum depression was significantly lower at 1 week and 6 weeks after surgery in group E (P < .01). There was no significant difference of the adverse effects at 48 hours after the operation between the 2 groups. CONCLUSION: Intravenous infusion of 0.2 mg/kg esketamine in women during cesarean section can significantly reduce the incidence of postpartum depression at 1 week and 6 weeks after surgery without increasing related adverse effects.

Comparison between laparoscopic and abdominal radical hysterectomy for cervical adenosquamous carcinoma at stage IA2 to IIA2: A multicenter retrospective study.

OBJECTIVE: We aimed to compare the 5-year oncological outcomes of laparoscopic/abdominal radical hysterectomy (LRH/ARH) in patients with cervical adenosquamous carcinoma at stage IA2 to IIA2 based on the 2009 or 2018 International Federation of Gynecology and Obstetrics (FIGO) staging criteria. METHODS: Based on the clinical diagnosis and treatment of cervical cancer in China (Four C) database, Cox risk regression models were applied to analyze tumor prognosis treated with ARH/LRH in FIGO 2009 and 2018 IA2-IIA2 patients and stratified findings according to tumor diameter (≤4 and >4 cm subgroups). And to avoid bias, propensity score matching (PSM) was also used for the cohort study. RESULTS: Based on FIGO 2009 staging criteria (n = 474), there was no significant difference between the ARH and LRH groups in 5-year disease-free survival (DFS) or overall survival (OS). Lymph node metastasis was a risk factor for 5-year DFS in this stage. After PSM, lymphovascular space invasion (LVSI) was an independent risk factor for 5-year OS in the tumors ≤4 cm subgroup. Based on FIGO2018 staging criteria (n = 322), cervical interstitial infiltration depth was an independent risk factor for 5-year OS in the total population and the tumor diameter ≤4 cm subgroup. CONCLUSIONS: Laparoscopic surgery was not a risk factor affecting the oncologic prognosis of adenosquamous carcinoma of the cervix based on either FIGO 2009 or 2018 staging of stage IA2-IIA2. In addition, LRH may be considered for patients with early-stage cervical adenosquamous carcinoma.

The Biological Characteristics of Eutopic and Ectopic Endometrial Progenitor Cells in Endometriosis.

AIM: The aim of this study was to identify the biological characteristics and potential roles of endometrial progenitor cells in the pathogenesis of endometriosis. BACKGROUND: It is generally believed that progenitor cells in human endometrium are responsible for rapid endometrial regeneration. However, the biological characteristics and potential roles of the paired eutopic and ectopic endometrial progenitor cells in endometriosis remain unclear. OBJECTIVE: This study intends to isolate the epithelial progenitor (EP) cells and endometrial mesenchymal stem cells (eMSCs) from the eutopic and ectopic endometria from endometriosis patients, further to reveal their features and functions respectively. METHODS: The distributions of EP cells and eMSCs and the expression of steroid hormone receptors in the endometrium and endometriotic tissues were assessed by immunohistochemistry. EP cells and eMSCs were sorted from paired eutopic and ectopic endometria with epithelial cell adhesion molecule (EpCAM) magnetic beads. The clonogenicity, cell viability after being treated with estradiol and progesterone, and cell markers expression were evaluated with colony forming on Matrigel, CCK-8 and immunofluorescence staining, respectively. The differentially expressed genes (DEGs) were further identified with RNA sequencing. RESULTS: SSEA-1- and PDGFRß-positive cells were distributed in the epithelial and stromal layers. The ERß staining was much more intense in endometriotic tissues, but PR expression was almost absent. The ectopic EP cells exhibit strong clonogenicity and ERß expression but weak PR expression, leading to progesterone resistance. There are 12604 and 13242 DEGs revealed by RNA sequencing between eutopic and ectopic EP cells or eMSCs. GO and KEGG analyses revealed that the functions and pathways of DEGs enriched in cellular energy metabolism and regulation of the immune response, respectively. Additionally, ERß targets were mainly enriched in ectopic EP cells. CONCLUSION: Both EP cells and eMSCs may engage in ectopic lesion formation in endometriosis by modifying the metabolic mode and immune tolerance. These data not only help to understand the molecular mechanism of endometriosis but also could potentially contribute to the discovery of therapeutic targets for endometriosis.

Laparoscopically assisted ovarian cystectomy with totally enclosed protective device for tumor isolation.

OBJECTIVE: To present a novel totally enclosed protective device for tumor isolation in laparoscopic ovarian cystectomy. METHODS: A retrospective study was conducted of 16 patients with unilateral ovarian teratoma in the Department of Obstetrics and Gynecology of the China-Japan Friendship Hospital. Laparoscopic surgery was performed with a totally enclosed protective device for tumor isolation, followed by a case series retrospective study. The indexes measured included size of cyst, rate of intraoperative rupture, duration of operation, amount of intraoperative blood loss, and postoperative length of stay in the hospital. An intact cyst resected in the device with no spillage seen indicated a successful surgery. RESULTS: A total of 16 operations were performed successfully. The mean diameter of the cysts was 7.2 ± 1.4 cm. Of them, 12 (75%) had an intraoperative cyst rupture without spillage. The mean duration of surgery was 1.3 ± 0.1 h and the mean amount of intraoperative blood loss was 12.5 ± 3.2 ml. All postoperative histology tests showed benign cysts. The mean length of stay after surgery was 2.4 ± 0.5 days. No peritonitis-related symptoms or complaints were reported. CONCLUSION: Laparoscopically assisted ovarian cystectomy with a totally enclosed protective device for tumor isolation was confirmed safe and feasible.