Comparison of Hidden Blood Loss between Laparoendoscopic Single-Site Myomectomy and Conventional Laparoscopic Myomectomy.

OBJECTIVE: Laparoendoscopic single-site myomectomy (LESS-M) is widely applied for the treatment of uterine leiomyoma. The purposes of this study were to investigate differences in hidden blood loss between LESS-M and conventional laparoscopic myomectomy (CLM) during treatment of uterine leiomyoma and to identify the associated risk factors. DESIGN: This is a retrospective study. PARTICIPANTS: The participants of this study were patients who underwent laparoscopic myomectomy (114 and 156 for LESS-M and CLM, respectively) between July 1, 2019, and October 10, 2020, at the Second Affiliated Hospital of Wenzhou Medical University. SETTING: The study was conducted at the Second Affiliated Hospital of Wenzhou Medical University. METHODS: We enrolled a total of 114 and 156 patients who were treated with LESS-M and CLM, respectively, between July 1, 2019, and October 10, 2020. We collected clinical data, then applied the Nadler and Gross formula and multiple linear regression analysis to calculate the HBL and identify the associated risk factors, respectively. RESULTS: Patients in the LESS-M group had a VBL of 115.4 ± 180.6 mL and an HBL of 364.3 ± 252.6 mL, accounting for 74.4 ± 22.4% of true TBL. On the other hand, patients in the CLM group had VBL of 187.9 ± 198.5 mL, and HBL of 306.8 ± 304.7 mL, accounting for 58.9 ± 30.2% of true TBL. HBL was significantly higher in the LESS-M than the CLM group (p = 0.000). LIMITATIONS: This study was the small sample size used. CONCLUSIONS: HBL accounted for a significant percentage of TBL in laparoscopic myomectomy, especially in patients treated with LESS-M. Paying attention to perioperative blood changes coupled with fully understanding HBL might promote postoperative recovery of patients.

Chinese Medicines and Natural Medicine as Immunotherapeutic Agents for Gastric Cancer: Recent Advances.

BACKGROUD: According to the 2020 statistics from the World Health Organization's International Agency for Research on Cancer (IARC), it is projected that there will be over 1 million new cases of gastric cancer (GC) patients worldwide in 2020, resulting in approximately 770 000 deaths. Gastric cancer ranks fifth in terms of incidence rate and forth in death rate among malignant tumors. Despite advancements in early diagnostic techniques, the incidence of GC has exhibited a marginal decline; nevertheless, the mortality rate remains elevated for advanced inoperable patients with no currently available efficacious treatment options. RECENT FINDING: Chinese medicine (CM) has emerged as an efficacious treatment for GC, gradually gaining acceptance and widespread usage in China. It exhibits distinctive advantages in the prevention and treatment of metastasis. CM and natural medicine possess the ability to elicit antitumor effects by augmenting immune cell population, enhancing immune cell activity, and improving the tumor immune microenvironment. CMs and natural remedies encompass a diverse range of types, characterized by multiple targets, pathways, and extensive pharmacological effects. Consequently, they have become a prominent research area among oncologists worldwide. Numerous studies have demonstrated that CM and natural medicine can directly or indirectly enhance innate immune system components (including macrophages, natural killer cells, and myeloid suppressor cells), adaptive immune system elements (such as T lymphocytes and regulatory T cells), relevant cytokines (e.g., IL-2, IL-4, IL-10, TNF-α), and PD-1/PD-L1 axis regulation, thereby bolstering the cytotoxicity of immune cells against tumor cells. CONCLUSIONS: This ultimately leads to an improved tumor immune microenvironment facilitating superior antitumor efficacy. This paper critically examines the role of CM and natural medicine in regulating immunotherapy for GC, aiming to establish a new theoretical framework for the clinical treatment and prevention of gastric cancer within the realm of CM.

An Immune-Enhancing Injectable Hydrogel Loaded with Esketamine and DDP Promotes Painless Immunochemotherapy to Inhibit Breast Cancer Growth.

Chemotherapy is the cornerstone of triple-negative breast cancer. The poor effectiveness and severe neuropathic pain caused by it have a significant impact on the immune system. Studies confirmed that immune cells in the tumor microenvironment (TME), have critical roles in tumor immune regulation and prognosis. In this study, it is revealed that the painless administration of Esketamine, combined with Cisplatin (DDP), can exert an anti-tumor effect, which is further boosted by the hydrogel delivery system. It is also discovered that Esketamine combined with DDP co-loaded in Poloxamer Hydrogel (PDEH) induces local immunity by increasing mature Dendritic Cells (mDCs) and activated T cells in PDEH group while the regulatory T cells (Tregs) known as CD4+CD25+FoxP3+decreased significantly. Finally, , CD8+ and CD4+ T cells in the spleen exhibited a significant increase, suggesting a lasting immune impact of PDEH. This study proposes that Esketamine can serve as a painless immune modulator, enhancing an anti-tumor effect while co-loaded in poloxamer hydrogel with DDP. Along with improving immune cells in the microenvironment, it can potentially alleviate anxiety and depression. With its outstanding bio-safety profile, it offers promising new possibilities for painless clinical therapy.

Defective autophagy of pericytes enhances radiation-induced senescence promoting radiation brain injury.

BACKGROUND: Radiation-induced brain injury (RBI) represents a major challenge for cancer patients undergoing cranial radiotherapy. However, the molecular mechanisms and therapeutic strategies of RBI remain inconclusive. With the continuous exploration of the mechanisms of RBI, an increasing number of studies have implicated cerebrovascular dysfunction as a key factor in RBI-related cognitive impairment. As pericytes are a component of the neurovascular unit, there is still a lack of understanding in current research about the specific role and function of pericytes in RBI. METHODS: We constructed a mouse model of RBI-associated cognitive dysfunction in vivo and an in vitro radiation-induced pericyte model to explore the effects of senescent pericytes on the blood-brain barrier and normal CNS cells, even glioma cells. To further clarify the effects of pericyte autophagy on senescence, molecular mechanisms were explored at the animal and cellular levels. Finally, we validated the clearance of pericyte senescence by using senolytic drug and all-trans retinoic acid to investigate the role of radiation-induced pericyte senescence. RESULTS: Our findings indicated that radiation-induced pericyte senescence plays a key role in blood-brain barrier dysfunction, leading to RBI and subsequent cognitive decline. Strikingly, pericyte senescence also contributes to the growth and invasion of glioma cells. We further demonstrate that defective autophagy in pericytes is a vital regulatory mechanism for pericyte senescence. Moreover, autophagy activated by rapamycin can reverse pericyte senescence. Notably, the elimination of senescent cells by senolytic drugs significantly mitigated radiation-induced cognitive dysfunction. DISSCUSSION: Our results demonstrated that pericyte senescence may be a promising therapeutic target for RBI and glioma progression.

BCL6B-dependent suppression of ETV2 hampers endothelial cell differentiation.

BACKGROUND: B-cell CLL/lymphoma 6 member B (BCL6B) operates as a sequence-specific transcriptional repressor within the nucleus, playing crucial roles in various biological functions, including tumor suppression, immune response, stem cell self-renew, and vascular angiogenesis. However, whether BCL6B is involved in endothelial cell (EC) development has remained largely unknown. ETS variant transcription factor 2 (ETV2) is well known to facilitate EC differentiation. This study aims to determine the important role of BCL6B in EC differentiation and its potential mechanisms. METHODS: Doxycycline-inducible human induced pluripotent stem cell (hiPSC) lines with BCL6B overexpression or BCL6B knockdown were established and subjected to differentiate into ECs and vessel organoids (VOs). RNA sequencing analysis was performed to identify potential signal pathways regulated by BCL6B during EC differentiation from hiPSCs. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of pluripotency and vascular-specific marker genes expression. EC differentiation efficiency was determined by Flow cytometry analysis. The performance of EC was evaluated by in vitro Tube formation assay. The protein expression and the vessel-like structures were assessed using immunofluorescence analysis or western blot. Luciferase reporter gene assay and chromatin immunoprecipitation (ChIP)-PCR analysis were used to determine the regulatory relationship between BCL6B and ETV2. RESULTS: Functional ECs and VOs were successfully generated from hiPSCs. Notably, overexpression of BCL6B suppressed while knockdown of BCL6B improved EC differentiation from hiPSCs. Additionally, the overexpression of BCL6B attenuated the capacity of derived hiPSC-ECs to form a tubular structure. Furthermore, compared to the control VOs, BCL6B overexpression repressed the growth of VOs, whereas BCL6B knockdown had little effect on the size of VOs. RNA sequencing analysis confirmed that our differentiation protocol induced landscape changes for cell/tissue/system developmental process, particularly vascular development and tube morphogenesis, which were significantly modulated by BCL6B. Subsequent experiments confirmed the inhibitory effect of BCL6B is facilitated by the binding of BCL6B to the promoter region of ETV2, led to the suppression of ETV2's transcriptional activity. Importantly, the inhibitory effect of BCL6B overexpression on EC differentiation from hiPSCs could be rescued by ETV2 overexpression. CONCLUSIONS: BCL6B inhibits EC differentiation and hinders VO development by repressing the transcriptional activity of ETV2.

P2X7R Modulates NEK7-NLRP3 Interaction to Exacerbate Experimental Autoimmune Prostatitis via GSDMD-mediated Prostate Epithelial Cell Pyroptosis.

Chronic prostatitis is one of the most common urologic diseases that troubles young men, with unclear etiology and ineffective treatment approach. Pyroptosis is a novel model of cell death, and its roles in chronic prostatitis are unknown. In this study, P2X7R, NEK7, and GSDMD-NT expression levels were detected in prostate tissues from benign prostate hyperplasia (BPH) patients and experiment autoimmune prostatitis (EAP) mice. P2X7R agonist, antagonist, NLRP3 inhibitor, and disulfiram were used to explore the roles of the P2X7R-NEK7-NLRP3 axis in prostate epithelial cell pyroptosis and chronic prostatitis development. We found that P2X7R, NEK7, and GSDMD-NT were highly expressed in the prostate epithelial cells of BPH patients with prostatic inflammation and EAP mice. Activation of P2X7R exacerbated prostatic inflammation and increased NLRP3 inflammasome component expressions and T helper 17 (Th17) cell proportion. Moreover, P2X7R-mediated potassium efflux promoted NEK7-NLRP3 interaction, and NLRP3 assembly and activation, which caused GSDMD-NT-mediated prostate epithelial cell pyroptosis to exacerbate EAP development. Disulfiram could effectively improve EAP by inhibiting GSDMD-NT-mediated prostate epithelial cell pyroptosis. In conclusion, the P2X7R-NEK7-NLRP3 axis could promote GSDMD-NT-mediated prostate epithelial cell pyroptosis and chronic prostatitis development, and disulfiram may be an effective drug to treat chronic prostatitis.

Effect of comfortable nursing on postoperative nausea and vomiting in patients with idiopathic scoliosis after posterior orthopedic surgery.

Objective: To evaluate the effect of comfort nursing on postoperative nausea and vomiting in patients with idiopathic scoliosis undergoing posterior correction surgery. Methods: 92 patients with idiopathic scoliosis were taken as the subjects and segmented into a control group and an experimental group (n = 46/each group). The former received routine care, while the latter one performed comfortable care. The observation period is 48 h after surgery. Record and compare the incidence, grade, frequency, and pain level of nausea and vomiting in both groups, as well as postoperative physical signs and symptoms, drug use, and postoperative recovery. Investigating the patient's satisfaction with nursing care. The research data is analyzed using SPSS26.0 software. P < 0.05 means statistical significance. Results: Within 48 h after surgery, the number of nausea and vomiting in the control is 24 and the experimental group is 8, with an incidence rate of 52% and 16%. The latter is significantly lower than that in the control. The average number of nausea and vomiting episodes in the control is 2.5, significantly higher than the 0.45 episodes in the experimental set. There is a significant difference in the frequency of nausea and vomiting/temperature and urine volume/scores of nausea, vomiting, dizziness, headache, decreased appetite, and discomfort between the two groups (P < 0.05). Conclusion: Comfortable care has a relieving effect on postoperative nausea and vomiting in patients with idiopathic scoliosis after posterior correction surgery. It can low down the incidence and frequency of nausea and vomiting, and reduce the score of related symptoms. Comfortable care can also help patients recover after surgery, increase dietary intake, and improve nutritional status. Comfortable care has a significant effect on postoperative nausea and vomiting in cases with idiopathic scoliosis undergoing posterior correction surgery, which can improve their postoperative recovery and quality of life.

Mitochondria-targeted polyprodrug nanoparticles induce mitochondrial stress for immunogenic chemo-photodynamic therapy of ovarian cancer.

Hypoimmunogenicity and the immunosuppressive microenvironment of ovarian cancer severely restrict the capability of immune-mediated tumor killing. Immunogenic cell death (ICD) introduces a theoretical principle for antitumor immunity by increasing antigen exposure and presentation. Despite recent research progress, the currently available ICD inducers are still very limited, and many of them can hardly induce sufficient ICD based on traditional endoplasmic reticulum (ER) stress. Accumulating evidence indicates that inducing mitochondrial stress usually shows a higher efficiency in evoking large-scale ICD than that via ER stress. Inspired by this, herein, a mitochondria-targeted polyprodrug nanoparticle (named Mito-CMPN) serves as a much superior ICD inducer, effectively inducing chemo-photodynamic therapy-caused mitochondrial stress in tumor cells. The rationally designed stimuli-responsive polyprodrugs, which can self-assemble into nanoparticles, were functionalized with rhodamine B for mitochondrial targeting, cisplatin and mitoxantrone (MTO) for synergistic chemo-immunotherapy, and MTO also serves as a photosensitizer for photodynamic immunotherapy. The effectiveness and robustness of Mito-CMPNs in reversing the immunosuppressive microenvironment is verified in both an ovarian cancer subcutaneous model and a high-grade serous ovarian cancer model. Our results support that the induction of abundant ICD by focused mitochondrial stress is a highly effective strategy to improve the therapeutic efficacy of immunosuppressive ovarian cancer.

Trends in cardiovascular risk factor prevalence, treatment, and control among US adolescents aged 12 to 19 years, 2001 to March 2020.

BACKGROUND: Early-life cardiovascular risk factors (CVRFs) are known to be associated with target organ damage during adolescence and premature cardiovascular morbidity and mortality during adulthood. However, contemporary data describing whether the prevalence of CVRFs and treatment and control rates have changed are limited. This study aimed to examine the temporal trends in the prevalence, treatment, and control of CVRFs among US adolescents over the past 2 decades. METHODS: This is a serial cross-sectional study using data from nine National Health and Nutrition Examination Survey cycles (January 2001-March 2020). US adolescents (aged 12 to 19 years) with information regarding CVRFs (including hypertension, elevated blood pressure [BP], diabetes, prediabetes, hyperlipidemia, obesity, overweight, cigarette use, inactive physical activity, and poor diet quality) were included. Age-adjusted trends in CVRF prevalence, treatment, and control were examined. Joinpoint regression analysis was performed to estimate changes in the prevalence, treatment, and control over time. The variation by sociodemographic characteristics were also described. RESULTS: A total of 15,155 US adolescents aged 12 to 19 years (representing ≈ 32.4 million people) were included. From 2001 to March 2020, there was an increase in the prevalence of prediabetes (from 12.5% [95% confidence interval (CI), 10.2%-14.9%] to 37.6% [95% CI, 29.1%-46.2%]) and overweight/obesity (from 21.1% [95% CI, 19.3%-22.8%] to 24.8% [95% CI, 21.4%-28.2%]; from 16.0% [95% CI, 14.1%-17.9%] to 20.3% [95% CI, 17.9%-22.7%]; respectively), no improvement in the prevalence of elevated BP (from 10.4% [95% CI, 8.9%-11.8%] to 11.0% [95% CI, 8.7%-13.4%]), diabetes (from 0.7% [95% CI, 0.2%-1.2%] to 1.2% [95% CI, 0.3%-2.2%]), and poor diet quality (from 76.1% [95% CI, 74.0%-78.2%] to 71.7% [95% CI, 68.5%-74.9%]), and a decrease in the prevalence of hypertension (from 8.1% [95% CI, 6.9%-9.4%] to 5.5% [95% CI, 3.7%-7.3%]), hyperlipidemia (from 34.2% [95% CI, 30.9%-37.5%] to 22.8% [95% CI, 18.7%-26.8%]), cigarette use (from 18.0% [95% CI, 15.7%-20.3%] to 3.5% [95% CI, 2.0%-5.0%]), and inactive physical activity (from 83.0% [95% CI, 80.7%-85.3%] to 9.5% [95% CI, 4.2%-14.8%]). Sex and race/ethnicity affected the evolution of CVRF prevalence differently. Whilst treatment rates for hypertension and diabetes did not improve significantly (from 9.6% [95% CI, 3.5%-15.8%] to 6.0% [95% CI, 1.4%-10.6%]; from 51.0% [95% CI, 23.3%-78.7%] to 26.5% [95% CI, 0.0%-54.7%]; respectively), BP control was relatively stable (from 75.7% [95% CI, 56.8%-94.7%] to 73.5% [95% CI, 40.3%-100.0%]), while glycemic control improved to a certain extent, although it remained suboptimal (from 11.8% [95% CI, 0.0%-31.5%] to 62.7% [95% CI, 62.7%-62.7%]). CONCLUSIONS: From 2001 to March 2020, although prediabetes and overweight/obesity increased, hypertension, hyperlipidemia, cigarette use, and inactive physical activity decreased among US adolescents aged 12 to 19 years, whereas elevated BP, diabetes, and poor diet quality remained unchanged. There were disparities in CVRF prevalence and trends across sociodemographic subpopulations. While treatment and control rates for hypertension and diabetes plateaued, BP control were stable, and improved glycemic control was observed.

Paris saponin VII reverses resistance to PARP inhibitors by regulating ovarian cancer tumor angiogenesis and glycolysis through the RORα/ECM1/VEGFR2 signaling axis.

The emergence of Poly (ADP-ribose) polymerase inhibitors (PARPi) has marked the beginning of a precise targeted therapy era for ovarian cancer. However, an increasing number of patients are experiencing primary or acquired resistance to PARPi, severely limiting its clinical application. Deciphering the underlying mechanisms of PARPi resistance and discovering new therapeutic targets is an urgent and critical issue to address. In this study, we observed a close correlation between glycolysis, tumor angiogenesis, and PARPi resistance in ovarian cancer. Furthermore, we discovered that the natural compound Paris saponin VII (PS VII) partially reversed PARPi resistance in ovarian cancer and demonstrated synergistic therapeutic effects when combined with PARPi. Additionally, we found that PS VII potentially hindered glycolysis and angiogenesis in PARPi-resistant ovarian cancer cells by binding and stabilizing the expression of RORα, thus further inhibiting ECM1 and interfering with the VEGFR2/FAK/AKT/GSK3ß signaling pathway. Our research provides new targeted treatment for clinical ovarian cancer therapy and brings new hope to patients with PARPi-resistant ovarian cancer, effectively expanding the application of PARPi in clinical treatment.

P62 promotes FSH-induced antral follicle formation by directing degradation of ubiquitinated WT1.

In females, the pathophysiological mechanism of poor ovarian response (POR) is not fully understood. Considering the expression level of p62 was significantly reduced in the granulosa cells (GCs) of POR patients, this study focused on identifying the role of the selective autophagy receptor p62 in conducting the effect of follicle-stimulating hormone (FSH) on antral follicles (AFs) formation in female mice. The results showed that p62 in GCs was FSH responsive and that its level increased to a peak and then decreased time-dependently either in ovaries or in GCs after gonadotropin induction in vivo. GC-specific deletion of p62 resulted in subfertility, a significantly reduced number of AFs and irregular estrous cycles, which were same as pathophysiological symptom of POR. By conducting mass spectrum analysis, we found the ubiquitination of proteins was decreased, and autophagic flux was blocked in GCs. Specifically, the level of nonubiquitinated Wilms tumor 1 homolog (WT1), a transcription factor and negative controller of GC differentiation, increased steadily. Co-IP results showed that p62 deletion increased the level of ubiquitin-specific peptidase 5 (USP5), which blocked the ubiquitination of WT1. Furthermore, a joint analysis of RNA-seq and the spatial transcriptome sequencing data showed the expression of steroid metabolic genes and FSH receptors pivotal for GCs differentiation decreased unanimously. Accordingly, the accumulation of WT1 in GCs deficient of p62 decreased steroid hormone levels and reduced FSH responsiveness, while the availability of p62 in GCs simultaneously ensured the degradation of WT1 through the ubiquitin‒proteasome system and autophagolysosomal system. Therefore, p62 in GCs participates in GC differentiation and AF formation in FSH induction by dynamically controlling the degradation of WT1. The findings of the study contributes to further study the pathology of POR.

Pan-cancer transcriptional atlas of minimal residual disease links DUSP1 to chemotherapy persistence.

Chemotherapy is a commonly effective treatment for most types of cancer. However, many patients experience a relapse due to minimal residual disease (MRD) after chemotherapy. Previous studies have analyzed the changes induced by chemotherapy for specific types of cancer, but our study is the first to comprehensively analyze MRD across various types of cancer. We included both bulk and single-cell RNA sequencing datasets. We compared the expression of the entire genome and calculated scores for canonical pathway signatures and immune infiltrates before and after chemotherapy across different types of cancer. Our findings revealed that DUSP1 was the most significantly and widely enriched gene in pan-cancer MRD. DUSP1 was found to be essential for MRD formation and played a role in T cell-fibroblast communications and the cytotoxic function of CD4 + T cells. Overall, our analysis provides a comprehensive understanding of the changes caused by chemotherapy and identifies potential targets for preventing and eliminating MRD, which could lead to long-term survival benefits for patients.

Tea-Derived Polyphenols Enhance Drought Resistance of Tea Plants (Camellia sinensis) by Alleviating Jasmonate-Isoleucine Pathway and Flavonoid Metabolism Flow.

Extreme drought weather has occurred frequently in recent years, resulting in serious yield loss in tea plantations. The study of drought in tea plantations is becoming more and more intensive, but there are fewer studies on drought-resistant measures applied in actual production. Therefore, in this study, we investigated the effect of exogenous tea polyphenols on the drought resistance of tea plant by pouring 100 mg·L-1 of exogenous tea polyphenols into the root under drought. The exogenous tea polyphenols were able to promote the closure of stomata and reduce water loss from leaves under drought stress. Drought-induced malondialdehyde (MDA) accumulation in tea leaves and roots was also significantly reduced by exogenous tea polyphenols. Combined transcriptomic and metabolomic analyses showed that exogenous tea polyphenols regulated the abnormal responses of photosynthetic and energy metabolism in leaves under drought conditions and alleviated sphingolipid metabolism, arginine metabolism, and glutathione metabolism in the root system, which enhanced the drought resistance of tea seedlings. Exogenous tea polyphenols induced jasmonic acid-isoleucine (JA-ILE) accumulation in the root system, and the jasmonic acid-isoleucine synthetase gene (TEA028623), jasmonic acid ZIM structural domain proteins (JAMs) synthesis genes (novel.22237, TEA001821), and the transcription factor MYC2 (TEA014288, TEA005840) were significantly up-regulated. Meanwhile, the flavonoid metabolic flow was significantly altered in the root; for example, the content of EGCG, ECG, and EGC was significantly increased. Thus, exogenous tea polyphenols enhance the drought resistance of tea plants through multiple pathways.

[Efficacy and Prognosis of Chemotherapy Regimen Containing BTK Inhibitor in Treatment of Recurrent/Refractory Mantle Cell Lymphoma].

OBJECTIVE: To investigate the efficacy and prognosis of chemotherapy regimen containing Bruton's tyrosine kinase (BTK) inhibitor in the treatment of relapsed/refractory mantle cell lymphoma (R/R MCL). METHODS: The clinical data of 134 patients with R/R MCL were collected and analyzed retrospectively. The clinical characteristics of patients and effect of chemotherapy regimen on efficacy, overall survival (OS) and progression-free survival (PFS) were observed. RESULTS: The median age of the patients was 58(56-61) years old, and male to female ratio was about 2.9∶1. Patients with Ann Arbor stage III-IV accounted for 77.6%, extranodal involvement > 2 for 43.3%, bone marrow involvement for 60.4%, gastrointestinal involvement for 24.6%, and hepatosplenomegaly for 38.1%. The median follow-up time was 30 (2-103) months, overall response rate (ORR) was 41.8%, 3-year PFS was not reached, and 3-year and 5-year OS rate was 62.7% and 53.8%, respectively. The ORR of BTK inhibitor group was 56.9%, which was higher than 32.5% of non-BTK inhibitor group (P =0.006). The difference was statistically significant in PFS between the two groups (P =0.002), but was not in OS (P>0.05). The difference was statistically significant in OS between classical and special morphology (P < 0.001), but was not in PFS (P >0.05). Ki-67 was an influencing factor for OS and PFS. Multivariate analysis showed that Ki-67, B symptoms, MIPI score, and Ann Arbor stage were independent prognostic factors affecting patients' OS. The second-line treatment regimen was an independent prognostic factor affecting patients' PFS. CONCLUSIONS: The chemotherapy regimen containing BTK inhibitors can effectively improve the efficacy and prolong the PFS of R/R MCL patients. Ki-67, B symptoms, MIPI score, and Ann Arbor stage are independent prognostic factors for R/R MCL patients.

Unraveling the molecular mechanisms driving enhanced invasion capability of extravillous trophoblast cells: a comprehensive review.

Precise extravillous trophoblast (EVT) invasion is crucial for successful placentation and pregnancy. This review focuses on elucidating the mechanisms that promote heightened EVT invasion. We comprehensively summarize the pivotal roles of hormones, angiogenesis, hypoxia, stress, the extracellular matrix microenvironment, epithelial-to-mesenchymal transition (EMT), immunity, inflammation, programmed cell death, epigenetic modifications, and microbiota in facilitating EVT invasion. The molecular mechanisms underlying enhanced EVT invasion may provide valuable insights into potential pathogenic mechanisms associated with diseases characterized by excessive invasion, such as the placenta accreta spectrum (PAS), thereby offering novel perspectives for managing pregnancy complications related to deficient EVT invasion.

Modified R-BAC plus BTK inhibitor regimen in newly diagnosed young patients with mantle cell lymphoma: a real-world retrospective study.

To explore the optimal treatment for young patients with untreated mantle cell lymphoma (MCL), we compared the efficacy and safety of R-CHOP/R-DHAP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone/rituximab, dexamethasone, cytarabine and cisplatin) and R-BAP (rituximab, bendamustine, cytarabine, and prednisone) plus BTK (Bruton's tyrosine kinase) inhibitors in newly diagnosed patients. Eighty-three young patients (≤ 65 years old) with newly diagnosed MCL admitted to the First Affiliated Hospital of Zhengzhou University from January 1, 2014, to June 1, 2023, using R-CHOP/R-DHAP or R-BAP plus BTK inhibitor were assessed in this study. The median age at presentation was 60 (42-65) years in 83 patients, including 64 males and 19 females; 59 were treated with R-CHOP/R-DHAP regimen chemotherapy, and 24 were treated with R-BAP in combination with the BTK inhibitor regimen. The median follow-up was 17 months (2-86 months) in 83 patients, and the median PFS (progression-free survival) time was not reached. The CRR (complete response rate) of the R-BAP group was higher than that of the R-CHOP/R-DHAP group (87.5% vs. 54.2%, P = 0.005). The ORR (overall response rate) was not significantly different between the two groups (ORR: 91.7% vs. 84.7%, P = 0.497). The PFS (progression-free survival) of the R-BAP group was longer than that of the R-CHOP/R-DHAP group (P = 0.013), whereas OS was not significantly different between the two groups (P = 0.499). The most common adverse effect in both groups was hematotoxicity, with a higher incidence of grade 3-4 lymphopenia and grade 3-4 thrombocytopenia in the R-BAP group than in the R-CHOP/R-DHAP group (P = 0.015 and P = 0.039). Male sex (HR = 4.257, P = 0.013), LDH (lactate dehydrogenase) ≥ 245 U/L (HR = 3.221, P = 0.012), pleomorphic-blastoid (HR = 2.802, P = 0.043) and R-CHOP/R-DHAP regimen (HR = 7.704, P = 0.047) were independent risk factors for PFS. Ki67 ≥ 30% (HR = 8.539, P = 0.005) was an independent risk factor for OS. First-line treatment with R-BAP in combination with BTK inhibitor improved CRR and prolonged PFS in young patients with mantle cell lymphoma and adverse events were tolerable.

Transcription factor EB-mediated autophagy affects cell migration and inhibits apoptosis to promote endometriosis.

Autophagy has emerged as an important process of cell metabolism. With continuous in-depth research on autophagy, TFEB has been a key transcription factor regulating autophagy levels in recent years. Studies have established that TFEB regulates autophagy and apoptosis in various diseases. However, the relationship between TFEB and the pathogenesis of endometriosis remains unclear. This study aimed to investigate the effect of TFEB on the mechanism of endometriosis progression. The results showed that TFEB and autophagy-related protein LC3 are highly expressed in ectopic endometrium of patients with endometriosis, overexpression of TFEB in cultured human endometrial stromal cells (HESCs) by lentivirus not only promoted autophagy but also inhibited apoptosis. In addition, the migration and invasion ability of HESCs were enhanced by TFEB overexpression. Furthermore, inhibiting autophagy with specific inhibitors can attenuate migration and invasion of HESCs induced by TFEB. The rat models of endometriosis show that TFEB knockdown can suppress lesion growth in vivo. Our results suggest that autophagy may be involved in the progression mechanism of endometriosis, and the mechanism of autophagy disorder in endometriosis is probably related to TFEB. TFEB may be a key molecule in promoting endometriosis.

LSD1 promotes the FSH responsive follicle formation by regulating autophagy and repressing Wt1 in the granulosa cells.

In a growing follicle, the survival and maturation of the oocyte largely depend on support from somatic cells to facilitate FSH-induced mutual signaling and chemical communication. Although apoptosis and autophagy in somatic cells are involved in the process of FSH-induced follicular development, the underlying mechanisms require substantial study. According to our study, along with FSH-induced antral follicles (AFs) formation, both lysine-specific demethylase 1 (LSD1) protein levels and autophagy increased simultaneously in granulosa cells (GCs) in a time-dependent manner, we therefore evaluated the importance of LSD1 upon facilitating the formation of AFs correlated to autophagy in GCs. Conditional knockout of Lsd1 in GCs resulted in significantly decreased AF number and subfertility in females, accompanied by marked suppression of the autophagy in GCs. On the one hand, depletion of Lsd1 resulted in accumulation of Wilms tumor 1 homolog (WT1), at both the protein and mRNA levels. WT1 prevented the expression of FSH receptor (Fshr) in GCs and thus reduced the responsiveness of the secondary follicles to FSH induction. On the other hand, depletion of LSD1 resulted in suppressed level of autophagy by upregulation of ATG16L2 in GCs. We finally approved that LSD1 contributed to these sequential activities in GCs through its H3K4me2 demethylase activity. Therefore, the importance of LSD1 in GCs is attributable to its roles in both accelerating autophagy and suppressing WT1 expression to ensure the responsiveness of GCs to FSH during AFs formation.

Cuprotosis clusters predict prognosis and immunotherapy response in low-grade glioma.

Cuprotosis, an emerging mode of cell death, has recently caught the attention of researchers worldwide. However, its impact on low-grade glioma (LGG) patients has not been fully explored. To gain a deeper insight into the relationship between cuprotosis and LGG patients' prognosis, we conducted this study in which LGG patients were divided into two clusters based on the expression of 18 cuprotosis-related genes. We found that LGG patients in cluster A had better prognosis than those in cluster B. The two clusters also differed in terms of immune cell infiltration and biological functions. Moreover, we identified differentially expressed genes (DEGs) between the two clusters and developed a cuprotosis-related prognostic signature through the least absolute shrinkage and selection operator (LASSO) analysis in the TCGA training cohort. This signature divided LGG patients into high- and low-risk groups, with the high-risk group having significantly shorter overall survival (OS) time than the low-risk group. Its predictive reliability for prognosis in LGG patients was confirmed by the TCGA internal validation cohort, CGGA325 cohort and CGGA693 cohort. Additionally, a nomogram was used to predict the 1-, 3-, and 5-year OS rates of each patient. The analysis of immune checkpoints and tumor mutation burden (TMB) has revealed that individuals belonging to high-risk groups have a greater chance of benefiting from immunotherapy. Functional experiments confirmed that interfering with the signature gene TNFRSF11B inhibited LGG cell proliferation and migration. Overall, this study shed light on the importance of cuprotosis in LGG patient prognosis. The cuprotosis-related prognostic signature is a reliable predictor for patient outcomes and immunotherapeutic response and can help to develop new therapies for LGG.

A meta-analysis of treatment for early-stage cervical cancer: open versus minimally invasive radical trachelectomy.

BACKGROUND: In previous systematic reviews, meta-analysis was lacking, resulting in the statistical difference between the data of different surgeries being impossible to judge. This meta-analysis aims to contrast the fertility results and cancer outcomes between open and minimally invasive surgery. METHOD: We systematically searched databases including PubMed, Embase, Cochrane, and Scopus to collect studies that included open and minimally invasive radical trachelectomy. A random-effect model calculated the weighted average difference of each primary outcome via Review Manager V.5.4. RESULT: Eight studies (1369 patients) were incorporated into our study. For fertility results, the Open group excels MIS group in pregnancies-Third trimester delivery [OR = 2.68; 95% CI (1.29, 5.59); P = 0.008]. Nevertheless, there is no statistical difference in clinical pregnancy, miscarriage, and second-trimester rate. Concerning cancer outcomes, no difference was detected in the overall survival [OR = 1.56; 95% CI (0.70, 3.45); P = 0.27] and recurrence [OR = 0.63; 95% CI (0.35, 1.12); P = 0.12]. Concerning surgery-related outcomes, the comprehensive effects revealed that the estimated blood loss of the Open group was higher than that of the MIS group[MD = 139.40; 95% CI (79.05, 199.75); P < 0.0001]. However, there was no difference between the postoperative complication rate in the two groups [OR = 1.52; 95% CI (0.89, 2.60); P = 0.12]. CONCLUSION: This meta-analysis suggested that the fertility result of the Open group may be better than the MIS group, while the MIS group has better surgery-related outcomes. Owing to the poor cases of our study, a more robust conclusion requires more relevant articles in the future. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022352999.