Baicalein Relieves Ferroptosis-Mediated Phagocytosis Inhibition of Macrophages in Ovarian Endometriosis.

Iron overload and oxidative stress have been reported to contribute to ferroptosis in endometriotic lesions. However, the possible roles of iron overload on macrophages in endometriosis (EMs) remain unknown. Based on recent reports by single-cell sequencing data of endometriosis, here we found significant upregulations of ferroptosis-associated genes in the macrophage of the endometriotic lesion. Additionally, there was an elevated expression of HMOX1, FTH1, and FTL in macrophages of peritoneal fluid in EMs, as well as iron accumulation in the endometriotic lesions. Notably, cyst fluid significantly up-regulated levels of intracellular iron and ferroptosis in Phorbol-12-myristate-13-acetate (PMA)-stimulated THP-1 cells. Additionally, high iron-induced ferroptosis obviously reduced PMA-stimulated THP-1 cells' phagocytosis and increased the expression of angiogenic cytokines, such as vascular endothelial growth factor A (VEGFA) and interleukin 8 (IL8). Baicalein, a potential anti-ferroptosis compound, increased GPX4 expression, significantly inhibited ferroptosis, and restored phagocytosis of THP-1 cells in vitro. Collectively, our study reveals that ferroptosis triggered by high iron in cyst fluid promotes the development of EMs by impairing macrophage phagocytosis and producing more angiogenic cytokines (e.g., IL8 and VEGFA). Baicalein displays the potential for the treatment of EMs, especially in patients with high ferroptosis and low phagocytosis of macrophages.

Anatomical Partition-Based Deep Learning: An Automatic Nasopharyngeal MRI Recognition Scheme.

BACKGROUND: Training deep learning (DL) models to automatically recognize diseases in nasopharyngeal MRI is a challenging task, and optimizing the performance of DL models is difficult. PURPOSE: To develop a method of training anatomical partition-based DL model which integrates knowledge of clinical anatomical regions in otorhinolaryngology to automatically recognize diseases in nasopharyngeal MRI. STUDY TYPE: Single-center retrospective study. POPULATION: A total of 2485 patients with nasopharyngeal diseases (age range 14-82 years, female, 779[31.3%]) and 600 people with normal nasopharynx (age range 18-78 years, female, 281[46.8%]) were included. SEQUENCE: 3.0 T; T2WI fast spin-echo sequence. ASSESSMENT: Full images (512 × 512) of 3085 patients constituted 100% of the dataset, 50% and 25% of which were randomly retained as two new datasets. Two new series of images (seg112 image [112 × 112] and seg224 image [224 × 224]) were automatically generated by a segmentation model. Four pretrained neural networks for nasopharyngeal diseases classification were trained under the nine datasets (full image, seg112 image, and seg224 image, each with 100% dataset, 50% dataset, and 25% dataset). STATISTICAL TESTS: The receiver operating characteristic curve was used to evaluate the performance of the models. Analysis of variance was used to compare the performance of the models built with different datasets. Statistical significance was set at P < 0.05. RESULTS: When the 100% dataset was used for training, the performances of the models trained with the seg112 images (average area under the curve [aAUC] 0.949 ± 0.052), seg224 images (aAUC 0.948 ± 0.053), and full images (aAUC 0.935 ± 0.053) were similar (P = 0.611). When the 25% dataset was used for training, the mean aAUC of the models that were trained with seg112 images (0.823 ± 0.116) and seg224 images (0.765 ± 0.155) was significantly higher than the models that were trained with full images (0.640 ± 0.154). DATA CONCLUSION: The proposed method can potentially improve the performance of the DL model for automatic recognition of diseases in nasopharyngeal MRI. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 1.

Analysis of Cross-Reactivity and Allergic Symptoms of 19 Allergens: Results from NHANES 2005-2006.

INTRODUCTION: We explored the cross-reactivity among 19 common allergen sources and evaluated the influence of serum IgE concentrations and the number of sensitized allergens on the incidence of allergic symptoms. METHODS: We conducted this cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2006 which is a program of studies designed to assess the health and nutritional status of adults and children in the USA. After excluding participants with missing data from the allergen IgE test, allergy questionnaire, and respiratory health questionnaire, a total of 7,224 participants aged 6 years and older were included, as children younger than 6 years old did not complete all 19 allergen-specific IgE tests. Spearman correlation analysis was used to analyze the cross-reactivity between allergen sources. An independent sample Kruskal-Wallis test was performed to investigate the relationship between the serum-specific IgE levels of 19 allergens and the incidence of allergic symptoms. RESULTS: The cross-reactivity between D. farinae and D. pteronyssinus was the strongest (ρ = 0.88), and cross-reactivity of cross-species was universal. With the increase in serum-specific IgE levels of D. farinae, D. pteronyssinus, oak, and birch, the incidence of sneezing increased (p < 0.05). With the increase in serum-specific IgE levels of cats, dogs, peanuts, Aspergillus, and Alternaria, the incidence of wheezing increased (p < 0.05). The incidence of rash was positively correlated with serum-specific IgE levels of D. farinae, D. pteronyssinus, shrimp, and peanut (p < 0.05). The incidence of wheezing continued to increase with an increase in sensitized allergens. When participants were sensitized to <10 allergens, the incidence of sneezing continued to increase as the number of sensitized allergens increased, whereas the incidence of rash did not have a clear association with the number of sensitized allergens. CONCLUSION: Species that are biologically close are more likely to have antigen cross-reactivity, while cross-reactivity among different species is common. Different allergens tend to cause different allergic symptoms. Different allergic sites in the body have inconsistent responses to the number of sensitized allergens.

A Comprehensive Review on Radiomics and Deep Learning for Nasopharyngeal Carcinoma Imaging.

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumours of the head and neck, and improving the efficiency of its diagnosis and treatment strategies is an important goal. With the development of the combination of artificial intelligence (AI) technology and medical imaging in recent years, an increasing number of studies have been conducted on image analysis of NPC using AI tools, especially radiomics and artificial neural network methods. In this review, we present a comprehensive overview of NPC imaging research based on radiomics and deep learning. These studies depict a promising prospect for the diagnosis and treatment of NPC. The deficiencies of the current studies and the potential of radiomics and deep learning for NPC imaging are discussed. We conclude that future research should establish a large-scale labelled dataset of NPC images and that studies focused on screening for NPC using AI are necessary.

Baicalein inhibits FURIN-MT1-MMP-mediated invasion of ectopic endometrial stromal cells in endometriosis possibly by reducing the secretion of TGFB1.

PROBLEM: Endometriosis (EMs) is characterized by the presence of endometrial stroma and glands outside the uterus. Our previous study showed that baicalein inhibited proliferation and induced apoptosis in EMs. However, the effects of baicalein on the invasiveness of ectopic endometrial stromal cells (EcESCs) remain unclear. The aim of this study was to assess the potential anti-invasive effect of baicalein and determine the underlying mechanism. METHODS: The invasive and migratory properties of EcESCs were assessed in vitro using Transwell and wound healing assays. The expression of functional markers of EcESCs, including matrix metalloproteases (MMPs), FURIN, and TGFB1, was analyzed using WB and ELISA. Additionally, a mouse model of EMs was treated with baicalein (10 mg/kg/d and 35 mg/kg/d) for 4 weeks. The weight and number of ectopic lesions were determined, and the expression of markers was assessed using immunohistochemistry. RESULTS: Baicalein inhibited the invasion of EcESCs and the expression of certain invasion-related proteins, including MMP9, MMP2, and MT1-MMP. Exposure to baicalein reduced the extracellular levels of TGFB1 in EcESCs and the reduced expression of TGFB1, resulting in decreased expression of FURIN in EcESCs, which serves a pivotal role in the transformation of pro-MT1-MMP to activated MT1-MMP. In the mouse model of EMs, intraperitoneal injection of baicalein inhibited the growth of ectopic lesions and reduced MT1-MMP, FURIN, and TGFB1 expression. CONCLUSIONS: Baicalein reduced the invasion of EMs, potentially by restricting the FURIN-MT1-MMP-mediated cell invasion of EcESCs maybe through reduction of the autocrine of TGFB1.

Blocking Effect of Demethylzeylasteral on the Interaction between Human ACE2 Protein and SARS-CoV-2 RBD Protein Discovered Using SPR Technology.

The novel coronavirus disease (2019-nCoV) has been affecting global health since the end of 2019, and there is no sign that the epidemic is abating. Targeting the interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor is a promising therapeutic strategy. In this study, surface plasmon resonance (SPR) was used as the primary method to screen a library of 960 compounds. A compound 02B05 (demethylzeylasteral, CAS number: 107316-88-1) that had high affinities for S-RBD and ACE2 was discovered, and binding affinities (KD, µM) of 02B05-ACE2 and 02B05-S-RBD were 1.736 and 1.039 µM, respectively. The results of a competition experiment showed that 02B05 could effectively block the binding of S-RBD to ACE2 protein. Furthermore, pseudovirus infection assay revealed that 02B05 could inhibit entry of SARS-CoV-2 pseudovirus into 293T cells to a certain extent at nontoxic concentration. The compoundobtained in this study serve as references for the design of drugs which have potential in the treatment of COVID-19 and can thus accelerate the process of developing effective drugs to treat SARS-CoV-2 infections.

Intranasal Vasopressin Relieves Orthopedic Pain After Surgery.

BACKGROUND: Orthopedic pain after surgery is very common and difficult to manage. Although intranasal arginine vasopressin (AVP) relieves headache (tension-type headache and migraine mostly), the effect of intranasal AVP on the orthopedic pain after surgery is unknown. AIMS: This study investigated the effect of intranasal AVP on orthopedic pain after surgery in a randomized controlled trial with a double-blind design. PARTICIPANTS: The study included 653 orthopedic patients and 661 health volunteers. METHODS: Orthopedic pain was analyzed by the visual analogue scales (VAS) and AVP concentration was determined by radioimmunoassay. RESULTS: (1) intranasal AVP decreased the VAS level in orthopedic patients 2-4 weeks after surgery in a dose-dependent manner; (2) the cerebrospinal fluid (CSF) AVP concentration in orthopedic patients after surgery was higher than that in the health volunteers (38.57 ± 6.11 pg/mL vs 11.74 ± 2.85 pg/mL, p < .01), but had no change in plasma (p > .05); (3) CSF AVP concentration increased significantly in orthopedic patients during 24 hours after the intranasal AVP (p < .05 or .01), which related with VAS level negatively (all p < .01); (4) during 24 hours, intranasal AVP did not influence not only plasma AVP concentration, but also blood pressure, heart rate, respiratory rate and body temperature in orthopedic patients. COUCLUSIONS: The findings contribute valuable information that intranasal AVP can treat orthopedic pain after surgery, and AVP could be an option for pain relief by intranasal administration.

A Novel Nitrobenzoate Microtubule Inhibitor that Overcomes Multidrug Resistance Exhibits Antitumor Activity.

Multidrug resistance is a major limitation for microtubule-binding agents in cancer treatment. Here we report a novel microtubule inhibitor (2-morpholin-4-yl-5-nitro-benzoic acid 4-methylsulfanyl-benzyl ester, IMB5046), its cytotoxicity against multidrug-resistant cell lines and its antitumor efficacy in animal models. IMB5046 disrupted microtubule structures in cells and inhibited purified tubulin polymerization in vitro. It bound to the colchicine pocket of tubulin. IMB5046 displayed potent cytotoxicity against multiple tumor cell lines with an IC50 range of 0.037-0.426 µM. Notably, several multidrug-resistant cell lines which were resistant to colchicine, vincristine and paclitaxel remained sensitive to IMB5046. IMB5046 was not a P-glycoprotein substrate. IMB5046 blocked cell cycle at G2/M phase and induced cell apoptosis. Microarray assay indicated that the differentially expressed genes after IMB5046 treatment were highly related to immune system, cell death and cancer. In a mouse xenograft model IMB5046 inhibited the growth of human lung tumor xenograft by 83% at a well-tolerated dose. It is concluded that IMB5046 is a tubulin polymerization inhibitor with novel chemical structure and can overcome multidrug resistance. It is a promising lead compound for cancer chemotherapy, especially for treatment of multidrug-resistant tumors.

Vascular endothelial growth factor receptor-2 inhibitor cediranib causes regression of endometriotic lesions in a rat model.

Vascular endothelial growth factor (VEGF) receptor-2 plays an essential role in angiogenesis, and it also expressed in the glandular epithelium and stromal cells of ectopic endometrium. Cediranib is a protein tyrosine kinase inhibitor that potently inhibits VEGF receptor-2, but there is no study about its effects on the endometriosis. We induced endometriosis on both sides of the abdominal wall in 20 female Sprague-Dawley rats and randomly divided them into 2 groups. They were administered: cediranib 4 mg/kg/day (group 1), equal saline (group 2) for 12 days. Then, the lesion volumes were calculated, and Masson trichrome was used to detect fibrosis. Angiogenesis was evaluated by CD-31 immunohistochemistry and serum VEGF levels. Proliferation was indicated by proliferating cell nuclear antigen immunohistochemistry. Apoptosis was measured by a TUNEL assay and cleaved caspase-3 immunohistochemistry. In the treatment group, the lesion volumes were smaller (P < 0.05), and the degree of fibrosis was greater. The microvessel density was lower (P < 0.05) than control, however, serum VEGF was up-regulated by a negative feedback mechanism (P < 0.01). In addition, proliferation was significantly suppressed (P < 0.01), and apoptosis in the lesions was more obvious in the treatment group. These data indicated that cediranib can inhibit development of endometriotic lesions in rats.

[Studies on causes of gynecology postoperative urinary retention and its acupuncture treatment].

Urinary retention is a frequent-encountered complication after gynaecological surgery. It affects the postoperative recovery and decreases the life quality of patients. In recent years, extensive researches on causes and treatments of postoperative urinary retention are carried out in clinic. And it is approved that acupuncture treatment, which includes body needling, moxibustion, combination of acupuncture and moxibustion, acupoint injection and medication plasters, has reliable effects and less side-effects. Acupuncture treatment on postoperative urinary retention keeps developing and innovating. And it is held to have better effect when compare with western medicine.

[Comparison outcomes of three surgical procedures in treatment of severe pelvic organ prolapse and analysis of risk factors for genital prolapse recurrence].

OBJECTIVE: To investigate clinical significance and application of modified pelvic floor reconstruction developed by Peking Union Medical College Hospital (MPFR) in treatment of severe pelvic organ prolapse (POP) by comparing the effectiveness, quality of postoperative sexual life, life satisfaction and risk factors for POP recurrence with the following two surgical procedures: traditional total vaginal hysterectomy with anterior-posterior colporrhaphy (TVH-APC) and total vaginal hysterectomy with lateral colporrhaphy and sacrospinous ligament fixation and vaginal bridge repair and episiotomy (TVH-LC-SSLF-VBR-EP). METHODS: Totally 173 patients with severe POP and at least two compartments defects of pelvic floor underwent surgeries in the study, 86 patients (group A) were treated by MPFR with polypropylene mesh application, 58 (group B) were treated by TVH-APC, and 29 patients (group C) were treated by TVH-LC-SSLF-VBR-EP. Peri-operative data and outcomes of postoperative courses at 6, 12, 18 months were collected and analyzed, in the meantime, the risk factors of recurrence were studied. RESULTS: (1) No statistical difference was observed among the above 3 groups in terms of length of operation, amount of blood loss, length of hospital stay, and morbidity after surgery (P > 0.05). (2) Cost hospitalization was (11 448 ± 3049) Yuan in group A, which was significantly higher than (7262 ± 1607) Yuan in group B and (7140 ± 1817) Yuan in group C (P < 0.05). (3) The length of vaginal cuff of (7.5 ± 1.4) cm in group A and (5.6 ± 1.1) cm in group C were significantly longer than (7.1 ± 0.6) cm in group B (P < 0.05). The width of vaginal cuff of (4.3 ± 0.3) cm in group A was larger than (3.4 ± 0.3) cm in group B and (3.3 ± 0.4) cm in group C (P < 0.05). (4) The recurrence rate at 12 months after surgery was 12.8% (11/86) in group A, which was similar with 17.2% (5/29) in group C (P > 0.05) and significantly less than 36.2% (21/58) in group B (P < 0.05). The rate of active sexual life of 16.3% (14/86) in group A was significantly higher than 1.7% (1/58) in group B and 0 in group C (P < 0.05). The index of life quality improvement at 12 months after surgery was 48 ± 12 in group A, which was no less than 53 ± 16 in group C (P > 0.05) and higher than 27 ± 9 in group B (P < 0.05). (5) Mesh rejection was observed in 6 patients in group A within 3 months after surgery, while the posterior vaginal wall was exclusively involved. No difference was found in urinary retention or urinary incontinence among three groups (P > 0.05). (6) The severe degree of POP, type of surgical procedure (TVT-APC), anterior compartment defect of pelvic floor, and early days of performing pelvic floor reconstruction surgeries were high risk factors for POP recurrence (P < 0.05). CONCLUSIONS: MPFR has a better curative effect and lower recurrence rate on patients with POP. It can help patients regain integrity of anatomical structure and functions of pelvic floor. TVH-LC-SSLF-VBR-EP is also effective.

Struma ovarii associated with pseudo-Meigs' syndrome and elevated serum CA 125: a case report and review of the literature.

The association of pseudo-Meigs' syndrome, elevation of CA 125 to the struma ovarii is a rare condition. So far only nine cases have been reported in English literature through MEDLINE search. Here we report a 46-year-old case of the struma ovarii, presented with ascites, hydrothorax, right ovarian mass and elevated serum CA 125 level. These findings were misdiagnosed for an ovarian malignancy at the first impression. Immediate resolution of the ascites, hydrothorax and normalization of the serum CA 125 level were followed by ovarian mass removal. Struma ovarii could be a rare cause of ascites, hydrothorax, ovarian mass and elevated CA 125. This rare condition should be considered in the differential diagnosis in patents with ascites and pleural effusions but with negative cytology.

[Evaluation of laparoscopic surgery in the early stage-malignant tumor of ovary with lower risk].

OBJECTIVE: To evaluate the laparoscopic operation for early ovarian malignant tumor with low risk. METHODS: Ten patients with ovarian malignant tumor who underwent laparoscopic total hysterectomy, pelvic lymph nodes dissection, bilateral adnexectomy, ovarian aortic and vein high ligation, omentectomy, and additional appendectomy. Eleven patients with the same diagnosis who underwent operation by laparotomy were served as control group. The operation time, intraoperative blood loss, number of pelvic lymph nodes excised, and postoperative recovery were analyzed retrospectively. RESULTS: Frozen section method during operation proved the diagnosis of ovarian malignant tumor and cytological examination proved a negative result of the peritoneal irrigation liquid. The operation time was 298 min +/- 60 min for the laparoscopy group and 182 min +/- 43 min for the laparotomy group (P < 0.05). The intraoperative blood loss was 280 ml +/- 156 ml for the laparoscopy group and 346 ml +/- 170 ml for the laparotomy group (P < 0.05). The number of pelvic lymph node resected was 25 +/- 5 and 27 +/- 7 for the laparoscopy group and laparotomy group respectively (P > 0.05). The postoperative illness rate was 20.0% and 72.7% for the laparoscopy group and laparotomy group respectively (P < 0.01). Seven patients and 1 case in the laparoscopy group and laparotomy group left their beds 48 hours after operation (P < 0.05). The right obtuator nerve was injured and was sutured on 1 patient in the laparoscopy group. CONCLUSION: The whole procedure of total hysterectomy, bilateral adnexectomy, pelvic lymph node dissection, ovarian aortic and vein high ligation, omentectomy, and additional appendectomy may be performed under laparoscope in the treatment of early stage ovarian malignant tumor with lower risk. The laparoscopic operation has the advantage of less intraoperative bleeding, less morbidity and rapid recovery.