Clinical efficacy and safety of transvaginal natural orifice transluminal endoscopic surgery for benign adnexal disease: a prospective trial.

BACKGROUND: There is a scarcity of prospective clinical research evidence regarding the utilization of transvaginal natural orifice translumenal endoscopic surgery (vNOTES) as a treatment option for ovarian cysts. The objective of this study was to assess the feasibility and safety of employing vNOTES for the management of ovarian cysts. METHODS: Our study included women between the ages of 18 and 70 who intended to undergo surgical intervention for benign lesions. Stratified blocked randomization was employed to allocate participants into groups. The main objective was to assess whether the assigned group adhered to the recommended surgical technique for ovarian cystectomy or adnexectomy, without any deviation to alternative surgical methods. RESULTS: A total of 196 patients were included in the study, with all surgeries in each group being conducted according to the assigned procedures. Among them, the ovarian cystectomy layer included 58 cases in the vNOTES group and 58 cases in the conventional laparoscopy (CL) groups. The adnexectomy layer included 40 cases in the vNOTES group and 40 cases in the CL group. Utilizing a sensitivity analysis, the two-sided 95% lower confidence limit was determined to be 5.5% for the disparity in proportions between the vNOTES groups and CL groups. These lower limits fell below the predetermined non-inferiority margin of 10%. CONCLUSIONS: The study findings demonstrate that vNOTES was not inferior to CL in terms of adnexectomy or ovarian cystectomy. vNOTES can be considered a more minimally invasive surgical approach, as it results in reduced postoperative pain, faster recovery, and absence of visible incisions. Overall, vNOTES proves to be a safe, feasible, and less invasive treatment option. TRIAL REGISTRATION: This study retrospectively registered with the China Clinical Trial Registry with the registration number ChiCTR2100052223(22-10-2021).

RHBDF1 modulates cisplatin sensitivity of small cell lung cancer through YAP1/Smad2 signaling pathway.

Small cell lung cancer (SCLC) is a fatal tumor type that is prone to drug resistance. In our previous study, we showed that human rhomboid-5 homolog-1 (RHBDF1) was differentially expressed in 5 intrinsic cisplatin-resistant SCLC tissues compared with 5 intrinsic cisplatin-sensitive SCLC tissues by RNA sequencing, which intrigued us. We performed gain- and loss-of-function experiments to investigate RHBDF1 function, bioinformatics analysis, qRT-PCR, western blotting, and immunoprecipitation to elucidate the molecular mechanisms as well as detect RHBDF1 expression in SCLC by immunohistochemistry. We found that RHBDF1 knockdown promoted cell proliferation and cisplatin chemoresistance and inhibited apoptosis in vitro and in vivo. These effects could be reversed by overexpressing RHBDF1 in vitro. Mechanistically, RHBDF1 interacted with YAP1, which increased the phosphorylation of Smad2 and transported Smad2 to the nucleus. Among clinical specimens, the RHBDF1 was a low expression in SCLC and was associated with clinicopathological features and prognosis. We are the first to reveal that RHBDF1 inhibited cell proliferation and promoted cisplatin sensitivity in SCLC and elucidate a novel mechanism through RHBDF1/YAP1/Smad2 signaling pathway which played a crucial role in cisplatin chemosensitivity. Targeting this pathway can be a promising therapeutic strategy for chemotherapy resistance in SCLC.

Influence of malnutrition according to the glim criteria on the chemotherapy toxicities in patients with advanced lung cancer.

BACKGROUND: Cancer-associated malnutrition is highly prevalent in advanced lung cancer, and 50% of global cancer-related deaths are attributed to cancer-associated malnutrition. Platinum-containing chemotherapy is the standard treatment for advanced lung cancer. Unfortunately, it can cause exacerbated toxicities, which can also have a negative impact on patient's prognosis and quality of life. The Global Leadership Initiative on Malnutrition (GLIM) criteria have been proposed as the world's first accepted diagnostic criteria for malnutrition. However, the effectiveness of GLIM criteria in predicting chemotherapy toxicities in patients with advanced lung cancer is unclear. The aim of this study was to apply the GLIM criteria to assess the prevalence of pre-treatment diagnosis of malnutrition in patients with advanced non-small cell lung cancer (NSCLC) and to determine the impact of nutritional status on patient's chemotherapy toxicity. METHODS: We conducted a study of hospitalized patients with pathologically and clinically diagnosed advanced NSCLC who presented to our hospital from May 2021 to January 2022. Initially, the Nutritional Risk Screening-2002 (NRS-2002) was used for nutritional risk screening, and nutritional status was assessed using the Scored Patient-Generated Subjective Global Assessment (PG-SGA) and GLIM criteria. Chemotherapy toxicity was assessed and graded according to CTCAE5.0, and chemotherapy efficacy was assessed according to RECIST1.1. Kappa test was used to analyze the agreement between PG-SGA and GLIM criteria. Univariate and multivariate logistic regression analyses were used to determine the relationship between malnutrition and chemotherapy toxicity. RESULTS: A total of 215 patients with advanced NSCLC were evaluated for nutritional status. Most of the patients had normal BMI (61.86%) before the start of treatment, 40% were well-nourished as assessed by the PG-SGA tool, and 51.17% were well-nourished as assessed by GLIM criteria. Consistency analysis showed moderate agreement (Kappa = 0.463, P < 0.001) and their correlation was also moderate (Spearman, rs = 0.475, P < 0.001). The objective response rate (ORR) (P = 0.040) and disease control rate (DCR) (P < 0.001) were significantly lower in malnourished patients diagnosed according to GLIM criteria than in well-nourished patients. Multivariate analysis showed that malnutrition (OR = 1.531,95%CI 0.757-3.009; OR = 6.623,95%CI 1.390-31.567, P = 0.046) diagnosed by GLIM criteria was an independent predictor of chemotherapy toxicity. Conclusions Malnutrition diagnosed by GLIM criteria better predicts toxicity during chemotherapy, determines the degree of clinical benefit of chemotherapy, and may affect patient prognosis.

Efficacy and safety of combined anlotinib-oral etoposide treatment for patients with platinum-resistant ovarian cancer.

OBJECTIVE: Despite the availability of numerous treatment options, managing patients with platinum-resistant ovarian cancer (PROC) remains challenging, and the prognosis of PROC is notably unfavorable. This retrospective study aimed to assess the efficacy and safety of combined anlotinib-oral etoposide treatment for patients with PROC. METHODS: Data of 23 patients who were diagnosed with PROC from January 2020 to November 2022 and treated with anlotinib combined with oral etoposide for at least 2 cycles were retrospectively analyzed. RESULTS: Among per-protocol patients, 9 (45.0%; 95% confidence interval [CI]=21.1-68.9) of 20 patients achieved partial response and 17 (85.0%, 95% CI=67.9-100.0) of 20 patients achieved disease control. The median progression-free survival was 8.7 months (95% CI=5.3-11.6). The incidence of adverse events (any grade) was 100%, and the incidence of grade 3-4 adverse events was 54.5%. CONCLUSION: Anlotinib combined with etoposide emerged effective for the treatment of PROC.

A retrospective clinical analysis of 11 cases of PEComa from different sites.

PURPOSE: The objective of this paper is to offer a thorough examination of the clinical presentations, etiology, and treatment strategies associated with perivascular epithelioid cell tumors (PEComas). METHODS: This retrospective study examined the comprehensive archival data of PEComa cases diagnosed at Beijing Hospital from 2015 to 2023. The pathology slides of all patients were thoroughly reassessed by two experienced pathologists. A thorough retrospective analysis was undertaken, incorporating clinicopathological data including gender, age at diagnosis, initial clinical manifestations, signs, disease onset site, tumor markers, imaging findings, therapeutic modalities, pathological features, immunohistochemical profiles, treatment responses, and prognostic indicators. Patients were evaluated for disease severity according to established pathological classification criteria and were followed up until the designated analysis cut-off date. In instances where patients were unable to be monitored on-site, they were contacted via telephone for postoperative follow-up inquiries. RESULTS: This study included 11 patients with ages ranging from 17 to 66 years old, presenting with the disease in multiple anatomical sites, including the retroperitoneum (2/11), liver (4/11), kidney (4/11), lung (1/11), and broad ligament of the uterus (1/11). Most patients presented with non-specific clinical symptoms and were subsequently diagnosed with space-occupying lesions upon physical examination. The tumor demonstrated progressive growth and enlargement, which could result in compression of neighboring organs. Preoperative imaging alone is insufficient for a definitive diagnosis of PEComa, but MRI can provide an initial evaluation of the tumor's potential malignancy. Molecular marker testing specific to PEComa, such as HMB-45 (90.0%), SMA (81.8%), Melan-A (90.9%), vimentin (90.9%), and Desmin (36.3%), was conducted on all patients. No adjuvant therapies were administered postoperatively. Upon analysis, no instances of relapse at the primary site or the development of new tumors at other sites were observed. Regular imaging reviews of three patients with malignant PEComa post-surgery showed no evidence of recurrence. CONCLUSIONS: The clinical presentation, tumor biomarkers, and imaging characteristics of PEComa lack specificity, necessitating dependence on pathology and immunohistochemistry for precise diagnosis. The mainstay of treatment consists of surgical resection, with patients typically experiencing a favorable prognosis.

Platinum Nanoparticles-Enhanced Ferritin-Mn2+ Interaction for Magnetic Resonance Contrast Enhancement and Efficient Tumor Photothermal Therapy.

Nanoplatforms with high Mn2+ coordination can display efficient T1 magnetic resonance imaging (MRI) contrast enhancement. Herein, an earth gravity-like method for enhanced interaction between Ferritin (Fn) and Mn2+ by the growth of platinum nanoparticles (PNs) in Fn's cage structure via a biomineralization method is first proposed. Fn has good biocompatibility and can provide a suitable growth site for PNs. PNs with negative charge have certain attraction to Mn2+ with positive charge, improving Fn's loading capacity of Mn2+ by attraction force; and thus, achieving efficient MRI contrast enhancement. In addition, PNs can be applied for efficient photothermal therapy (PTT) under near infrared ray (NIR) irradiation. Systemic delivery of this nanoplatform shows obvious MRI contrast enhancement and tumor progression inhibition after NIR irradiation, as well as no obvious side effects. Therefore, this nanoplatform has the potential to contribute to nanotheranostic for clinical transformation.

Anticancer effect of hUC-MSC-derived exosome-mediated delivery of PMO-miR-146b-5p in colorectal cancer.

Antisense oligonucleotide (ASO) is a novel therapeutic platform for targeted cancer therapy. Previously, we have demonstrated that miR-146b-5p plays an important role in colorectal cancer progression. However, a safe and effective strategy for delivery of an ASO to its targeted RNA remains as a major hurdle in translational advances. Human umbilical cord mesenchymal cell (hUC-MSC)-derived exosomes were used as vehicles to deliver an anti-miR-146b-5p ASO (PMO-146b). PMO-146b was assembled onto the surface of exosomes (e) through covalent conjugation to an anchor peptide CP05 (P) that recognized an exosomal surface marker, CD63, forming a complex named ePPMO-146b. After ePPMO-146b treatment, cell proliferation, uptake ability, and migration assays were performed, and epithelial-mesenchymal transition progression was evaluated in vitro. A mouse xenograft model was used to determine the antitumor effect and distribution of ePPMO-146b in vivo. ePPMO-146b was taken up by SW620 cells and effectively inhibited cell proliferation and migration. The conjugate also exerted antitumor efficacy in a xenograft mouse model of colon cancer by systematic administration, where PPMO-146b was enriched in tumor tissue. Our study highlights the potential of hUC-MSC-derived exosomes anchored with PPMO-146b as a novel safe and effective approach for PMO backboned ASO delivery.

Osimertinib versus comparator first-generation epidermal growth factor receptor tyrosine kinase inhibitors as first-line treatment in patients with advanced EGFR-mutated non-small cell lung cancer: a Chinese, multicenter, real-world cohort study.

Background: In the phase 3 FLAURA trial, osimertinib was compared with first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) as a first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib showed longer progression-free survival (PFS), overall survival (OS), and a similar safety profile. However, more studies demonstrating the effectiveness and safety of osimertinib as a first-line strategy are needed in real-world populations. Methods: We enrolled 1,556 patients with EGFR-mutated stage IIIc-IV NSCLC from the CAPTRA-Lung database. All patients received either osimertinib (n=202) or a first-generation EGFR-TKI (n=1,354) as their initial treatment. To adjust for differences in baseline characteristics between two groups, 1:2 propensity score matching (PSM) was performed. Propensity scores included gender, age, Eastern Cooperative Oncology Group performance status score, smoking history, family history of tumor, pathology, EGFR mutations, and central nervous system (CNS) metastases. The standardized mean differences (SMD) before and after PSM were calculated to examine the balance of covariate distributions between two groups. Results: After PSM, 202 patients receiving osimertinib and 404 patients receiving first-generation EGFR-TKIs were finally identified. SMD of each matched variable is less than 0.10. The median PFS was 19.4 months [95% confidence interval (CI): 14.3-24.4] in the osimertinib arm and 10.9 months (95% CI: 9.3-12.5) in the comparator arm [hazard ratio (HR) for progression, 0.47; 95% CI: 0.38-0.59; P<0.001). The median OS was 40.5 months (95% CI: 27.1-54.0) vs. 34.3 months (95% CI: 30.6-38.0) in two groups, respectively (HR for death, 0.76; 95% CI: 0.58-1.00; P=0.045). The incidence of grade 3 adverse events (AEs) between the two groups was 1% and 4.2%, respectively. No grade 4 AEs and treatment-related deaths were reported in both groups. Conclusions: In real-world settings, osimertinib demonstrates longer PFS and OS, with a similar safety profile to that of comparator EGFR-TKIs when used as a first-line strategy in NSCLC patients.

Metabolic reprogramming of three major nutrients in platinum-resistant ovarian cancer.

Metabolic reprogramming is a phenomenon in which cancer cells alter their metabolic pathways to support their uncontrolled growth and survival. Platinum-based chemotherapy resistance is associated with changes in glucose metabolism, amino acid metabolism, fatty acid metabolism, and tricarboxylic acid cycle. These changes lead to the creation of metabolic intermediates that can provide precursors for the biosynthesis of cellular components and help maintain cellular energy homeostasis. This article reviews the research progress of the metabolic reprogramming mechanism of platinumbased chemotherapy resistance caused by three major nutrients in ovarian cancer.

Preoperative small airway dysfunction is associated with skeletal muscle loss in early-stage non-small cell lung cancer.

BACKGROUND: Postoperative skeletal muscle loss (SM loss) was reported to be associated with a poor prognosis in early-stage non-small cell lung cancer (NSCLC). Small airway dysfunction (SAD) is a common but neglected respiratory abnormality. Little information is known about the association between preoperative SAD and postoperative SM loss in early-stage NSCLC. Therefore, this study aimed to investigate the correlation between preoperative SAD and SM loss after surgery in early-stage NSCLC patients. METHODS: There were 348 NSCLC patients with stages I-IIIA in this study from January 2017 to December 2020. All CT images were contrast-enhanced scans, and the skeletal muscle index (SMI) was measured using CT images. A 10.0% decrease in SMI over 12 months was determined as the cut-off value to define excessive SM loss. Logistic regression analyses were used to examine the relationship between SAD and SM loss. RESULTS: This study included 348 subjects who underwent pulmonary operation (159 males and 189 females; mean age: 57.5 ± 8.8 years). 152 (43.7%) patients were identified as having SAD before surgery, and 179 patients (51.4%) were identified as having SM loss after 1 year. Moreover, a higher incidence of SAD was found in the SM loss group compared with that in the non-SM loss group (52.0% vs. 34.9%, p = 0.001). The patients with SAD were older, had larger tumor size, and had lower albumin levels. Furthermore, there were significant correlations between the lung function parameters manifesting SAD and the percentage change in SMI (for the forced expiratory flow when 75% of forced vital capacity has been exhaled (FEF75%), Pearson r=-0.107, p = 0.046; for FEF50%, r = -0.142, p = 0.008; and for FEF25-75%, r=-0.124, p = 0.021; respectively). However, no significant correlations were found between SMI and the lung function parameters reflecting proximal airway obstruction (p > 0.05). Logistic regression analysis revealed that preoperative SAD (HR, 2.465; 95% CI, 1.256-4.838; p = 0.009) was independent risk factor for postoperative SM loss in early-stage NSCLC. In addition, multivariable analysis revealed that SAD (HR, 1.816; 95% CI, 1.025-3.216, P = 0.041) were associated with postoperative complications. CONCLUSION: Preoperative SAD is significantly associated with postoperative complications and SM loss in early NSCLC patients. Our results suggest that preoperative assessment of SAD may be useful for risk stratification of surgical candidates with potential for targeted interventions.

MicroRNA-375 restrains the progression of lung squamous cell carcinoma by modulating the ERK pathway via UBE3A-mediated DUSP1 degradation.

MiRNA-375 has been reported to play critical roles in a variety of cancers. To unravel its biological roles, especially its specific mechanisms of action in lung squamous cell carcinoma (LUSC), LUSC tissue microarrays and miRNAscope were performed to identify the miR-375 expression. Associations with clinicopathologic features, survival, and the prognostic value of miR-375 in LUSC were clarified in a retrospective study of 90 pairs of LUSC tissues. In vitro and in vivo gain- and loss-of-function assays were conducted to validate the effects and mechanism of miR-375 in LUSC. The mechanism responsible for interactions was verified by dual-luciferase reporter gene assay, immunoprecipitation (IP) analysis, immunofluorescence (IF) assay and ubiquitination assay. We found that miR-375 had higher expression in noncancerous adjacent tissues than in LUSC tissues. Clinicopathologic analyses showed that miR-375 expression was correlated with pathologic stage and was an independent predictor of overall survival (OS) for LUSC. MiR-375, as a tumor inhibitor, inhibited proliferation and metastasis while promoting apoptosis of LUSC cells. Mechanistic research indicated that miR-375 targeted ubiquitin-protein ligase E3A (UBE3A), which in turn promoted the activity of the ERK signaling pathway via ubiquitin-mediated dual-specificity protein phosphatase 1 (DUSP1) degradation. Collectively, we propose a novel mechanism of tumorigenesis and metastasis of LUSC via the miR-375/UBE3A/DUSP1/ERK axis, which could potentially facilitate new strategies for the treatment of LUSC.

NIR-IIb fluorescence-image guided synergistic surgery/starvation/chemodynamic therapy: an innovative treatment paradigm for malignant non-small cell lung cancers.

Background: Currently, the prognosis and survival rate for patients bearing non-small cell lung cancer (NSCLC) is still quite poor, mainly due to lack of efficient theranostic paradigms to exert in time diagnostics and therapeutics. Methods: Herein, for NSCLC treatment, we offer a customized theranostic paradigm, termed NIR-IIb fluorescence diagnosis and synergistic surgery/starvation/chemodynamic therapeutics, with a newly designed theranostic nanoplatform PEG/MnCuDCNPs@GOx. The nanoplatform is composed of brightly NIR-II emissive downconversion nanoparticles (DCNPs)-core and Mn/Cu-silica shell loaded with glucose oxidase (GOx) to achieve synergistic starvation and chemodynamic therapy (CDT). Results: It is found that 10% Ce3+ doped in the core and 100% Yb3+ doped in the middle shell greatly improves the NIR-IIb emission up to even 20.3 times as compared to the core-shell DCNPs without Ce3+ doping and middle shell. The bright NIR-IIb emission of the nanoplatform contributes to sensitive margin delineation of early-stage NSCLC (diameter < 1 mm) with a signal-to-background ratio (SBR) of 2.18, and further assists in visualizing drug distribution and guiding surgery/starvation/chemodynamic therapy. Notably, the starvation therapy mediated by GOx-driven oxidation reaction efficiently depletes intratumoral glucose, and supplies H2O2 to boost the CDT mediated by the Mn2+ and Cu2+, which consequently realized a highly effective synergistic treatment for NSCLC. Conclusion: This research demonstrates an efficient treatment paradigm for NSCLC with NIR-IIb fluorescence diganosis and image-guided synergistic surgery/starvation/chemodynamic therapeutics.

CCR2-overexpressing biomimetic carrier-free nanoplatform for enhanced cascade ferroptosis tumor therapy.

Ferroptosis-based nanoplatforms have shown great potential in cancer therapy. However, they also face issues such as degradation and metabolism. Carrier-free nanoplatforms consisting of active drugs can effectively avoid the security issues associated with additional carrier ingredients. Herein, a biomimetic carrier-free nanoplatform (HESN@CM) was designed to treat cancer by modulating cascade metabolic pathways of ferroptosis. CCR2-overexpressing macrophage membrane-modified HESN can target cancer cells via the CCR2-CCL2 axis. The acidic tumor microenvironment (TME) can disrupt the supramolecular interaction of HESN, releasing hemin and erastin. Then, erastin could induce cancer cells ferroptosis by inhibiting system XC- pathways, while hemin, a vital component of blood to transport oxygen, could be broken down by heme oxygenase-1 (HO-1), increasing the intracellular Fe2+ concentration to induce cancer cells' ferroptosis further. Meanwhile, erastin could enhance the activity of HO-1, further promoting the release of Fe2+ from hemin. As a result, HESN@CM demonstrated superior therapeutic efficacy in both primary and metastatic tumors in vitro and in vivo. The carrier-free HESN@CM provided cascade ferroptosis tumor therapy strategies for potential clinical application. STATEMENT OF SIGNIFICANCE: CCR2-overexpressing biomimetic carrier-free nanoplatform (HESN@CM) was designed for cancer treatment by modulating metabolic pathways of ferroptosis. HESN modified with CCR2-overexpressing macrophage membrane can target tumor cells via the CCR2-CCL2 axis. HESN was composed of hemin and erastin without additional vectors. Erastin could directly induce ferroptosis, while hemin could be broken down by heme oxygenase-1 (HO-1), increasing the intracellular Fe2+ concentration to enhance ferroptosis further. Meanwhile, erastin could improve the activity of HO-1, promoting the release of Fe2+ from hemin. Therefore, HESN@CM with good bioavailability, stability, and simple preparation can realize cascade ferroptosis tumor therapy and have the potential prospect of clinical translation.

Resveratrol alleviates oxidative stress induced by oxidized soybean oil and improves gut function via changing gut microbiota in weaned piglets.

BACKGROUND: Oxidized soybean oil (OSO) has been shown to impair growth and exacerbate inflammation, leading to intestinal barrier injury in animals. Recent evidence suggests important roles for resveratrol (RES) in the promoting growth performance, antioxidant capacity, anti-inflammatory, and regulate intestinal barriers in animals. Therefore, The objectives of this study are to investigate the effects of dietary RES (purity 98%) supplementation on the growth performance, antioxidant capacity, inflammatory state, and intestinal function of weaned piglets challenged with OSO. METHODS: A total of 28 castrated weaned male piglets with a similar body weight of 10.19 ± 0.10 kg were randomly assigned to 4 dietary treatments for 28-d feeding trial with 7 replications per treatment and 1 piglet per replicate. Treatments were arranged as a 2 × 2 factorial with oil type [3% fresh soybean oil (FSO) vs. 3% OSO] and dietary RES (0 vs. 300 mg/kg). RESULTS: The results showed that relative to the FSO group, OSO stress tended to decrease the average daily feed intake (ADFI), and decreased the activity levels of lipase, villus/crypt ratio (VCR), the mRNA expression of FABP1, SOD2, IL-10 and ZO-1 in the jejunum, and SOD2, GPX1, occludin and ZO-1 in the colon, the levels of acetic acid in the colonic digesta, whereas up-regulated the mRNA expression of IL-1ß and TNF-α in the jejunum (P < 0.05). Moreover, dietary supplementation with RES increased ether extract (EE), the activity levels of sucrase, lipase, α-amylase, villus height (VH) and VCR, the mRNA expression of FABP1, SOD2, IL-10 and occludin in the jejunum, and FABP1, PPAR-γ, GPX1, occludin and ZO-1 in the colon, and the abundance of Firmicutes, acetic and propionic acid, but decreased the levels of D-lactic acid in the plasma, the abundance of Bacteroidetes in the colonic digesta of weaned piglets compared to the non-RES group (P < 0.05). Meanwhile, in the interaction effect analysis, relative to the OSO group, dietary RES supplementation in the diets supplemented with OSO increased the activity levels of trypsin, VH in the jejunum, the abundance of Actinobacteria, the levels of butyric acid of weaned piglets, but failed to influence the activity levels of trypsin and VH, Actinobacteria abundance, the levels of butyric acid when diets were supplemented with FSO (interaction, P < 0.05). Relative to the OSO group, dietary RES supplementation in the diets supplemented with OSO decreased the activity levels of DAO in the plasma of weaned piglets but failed to influence the activity levels of DAO when diets were supplemented with FSO (interaction, P < 0.05). Relative to the FSO group, dietary RES supplementation in the diets supplemented with FSO decreased the level of propionic acid, whereas RES supplementation failed to influence the level of propionic acid when the diet was supplemented with OSO (interaction, P < 0.01). CONCLUSIONS: Inclusion of OSO intensified inflammatory states and impaired the intestinal health characteristics of weaned piglets. Dietary RES supplementation improved the antioxidant capacity, anti-inflammatory activity, and intestinal morphology. Further studies showed that the protective effects of RES on gut health could be linked to the decreased abundance of Prevotella_1, Clostridium_sensu_stricto_6, and Prevotellaceae_UCG003 and increased levels of acetic and propionic acid.

Leucine Supplementation Alleviates Immune and Antioxidant Function Damage in Adult Rats Induced by Early Weaning.

BACKGROUND: Early weaning (EW) can lead to stress and destroy intestinal integrity. Leucine has functional diversity in antioxidant, immune, and metabolic regulation. OBJECTIVES: This study aimed to explore the lifelong impact of EW on intestinal, immune, and antioxidant functions of adult rats and the role of leucine supplementation in the alleviation of the damage caused by EW. METHODS: In this 211-d study, 36 Sprague Dawley (SD) rat pups were divided into 3 groups: 21-d weaning normal group, 17-d EW group, and 17-d EW group with 2-mo leucine supplementation. The content of amino acids in serum, immune and antioxidant indexes, intestinal morphology, liver transcriptomics, messenger RNA (mRNA), and protein expression of signaling pathway were determined. RESULTS: EW reduced the protein expression level of secretory immunoglobulin A (IgA) and reduced glutathione (GSH) in the jejunum and increased the protein expression concentrations of IgA, IgM, and interleukin 17 (IL-17) in serum, and tumor necrosis factor α and IL-1ß in the jejunum. The impairment by EW was activated via nuclear transcription factor κB (NF-κB) signal pathway. In terms of antioxidation, EW reduced the concentration of GSH in the jejunum. After leucine supplementation, the damage induced by EW was partially repaired. CONCLUSIONS: EW causes long-term damage to the intestinal barrier function, immunity, apoptosis factor, and antioxidant function in rats and leucine supplementation could alleviate the impairment, suggesting a possible approach to EW.

Efficacy of Chinese Herbal Medicines on Pregnancy Outcomes in Patients with Endometriosis in Long-Term Management: A Multicenter Retrospective Cohort Study.

OBJECTIVE: To analyze the factors related to pregnancy of endometriosis and whether Chinese herbal medicines (CHMs) can improve pregnancy outcomes in patients with endometriosis in long-term management. METHODS: This multicenter cohort study retrospectively analyzed the clinical data of endometriosis patients with fertility needs from January 2019 to November 2019. A total of 252 patients with endometriosis from 5 level-III Grade A hospitals in Beijing were included in this study. Univariate and multivariate logistic regression analysis were performed for the relevant factors. The propensity score matching (PSM) function of SPSS software was used to match the CHMs group with the non-CHMs group. The pregnancy rate and live birth rate were analyzed. RESULTS: The results of univariate analysis showed that age, disease course, presence of infertility, presence of adenomyosis, time after surgery or use of gonadotropin-releasing hormone agonist (GnRH-a), use of CHMs and follow-up time were influencing factors of pregnancy in endometriosis patients (P<0.05). The results of multivariate analysis showed that age, presence of adenomyosis, time after surgery or use of GnRH-a, use of CHMs and follow-up time were independent factors affecting pregnancy in endometriosis patients, among which, age ⩾35 years old, presence of adenomyosis and follow-up time >6 months were independent risk factors (OR=0.445, 0.348, 0.140, respectively, P<0.05), time after surgery or use of GnRH-a ⩽6 months and use of CHMs were independent protective factors (OR=3.839, 3.842, respectively, P<0.05). After PSM, 99 pairs of two groups were matched successfully. The pregnancy rate of the CHMs group was higher than that of the non-CHMs group [55.56% (55/99) vs. 36.36% (36/99), P<0.05]. The live birth rate of the CHMs group was higher than that of the non-CHMs group [49.49% (49/99) vs. 35.35% (35/99), P<0.05]. CONCLUSION: CHMs can effectively improve clinical pregnancy rate and live birth rate of patients with endometriosis in the chronic disease management.