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Purpose Endometrial cancer(EC) is an estrogen-dependent tumor, the occurrence of which is closely related to an imbalance of estrogen homeostasis. Our previous studies explored the effects of resveratrol on estrogen metabolism.However, systematic research on the exact mechanism of action of resveratrol is still lacking.Based on network pharmacology, molecular docking and animal experiments, the effects and molecular mechanisms of resveratrol on endometrial cancer were investigated. Methods The target of resveratrol was obtained from HERB and ECTM databases, and the target of endometrial cancer was obtained by using Genecards database.Use of Veeny map to obtain the intersection target of resveratrol in the treatment of EC, and the protein interaction network of the intersection target was constructed by importing the STRING database,then construct the drug-disease-target interaction network based on Cytoscape 3.9.1 software.GO and KEGG pathway enrichment analysis were performed for intersection targets using OmicShare cloud platform. Resveratrol and core target were analyzed by molecular docking. EC mice model induced by MNNG were randomly divided into Control group, Res group, MNNG group, and MNNG + Res group. MNNG + Res + MAPK/ERKi group.The protein expression levels of ERK and p-ERK in mouse uterus were detected by Western blot.The contents of E1, E2, E3, 16-epiE3, 17-epiE3, 2-MeOE1, 4-MeOE1, 2-MeOE2, 4-MeOE2, 3-MeOE1, 2-OHE1, 4-OHE1, 2-OHE2, 4-OHE2, 16α-OHE1 in serum and endometrial tissue of mice were detected by LC-MS/MS. Results A total of 174 intersection targets of resveratrol anti EC were obtained. Signaling pathways analyzed by KEGG enrichment included AGE-RAGE signaling pathway in diabetic complications, PI3K-Akt signaling pathway and MAPK signaling pathway.The top 10 core targets were MAPK3, JUN, TP53, CASP3, TNF, IL1B, AKT1, FOS, VEGFA and INS.Molecular docking showed that except TNF, other targets had good affinity with resveratrol, and the binding activity with MAPK3 was stable.Western blot results showed that resveratrol increased the phosphorylation level of ERK, and MAPK/ERKi decreased the activation of ERK.Using LC-MS/MS analysis,the contents of 2-MeOE1,2-MeOE2 and 4-MeOE1 in serum and uterine tissue were showed significantly decreasing trend in MNNG group, while the content of 4-OHE2 was increased (P༜0.05).The concentration levels of 4-MeOE1 in serum and 2-MeOE1 and 2-MeOE2 in endometrial tissue of mice were significantly increased after resveratrol treatment,the content of 4-OHE2 in serum and uterus of mice was significantly decreased (P༜0.05). Meanwhile, MAPK/ERKi intervention group showed that the effect of resveratrol on the reversal of estrogen homeostasis imbalance was obviously weakened. Conclusion Resveratrol has the characteristics of multiple targets and multiple approaches in the treatment of endometrial cancer. In this study, it was found that resveratrol regulates estrogen metabolism by activating MAPK pathway, which provides a new perspective for subsequent research on the treatment of endometrial cancer.

The loss of inner ear hair cells leads to irreversible acoustic injury in mammals, and regeneration of inner ear hair cells to restore hearing loss is challenging.

Objectives To identify the predictors of anatomical and functional outcomes following tympanoplasty. Study Design A retrospective cohort study. Methods Patients with chronic suppurative otitis media (CSOM) who underwent a tympanoplasty at Peking Union Medical College Hospital from January 1, 2015 to December 31, 2019 were retrospectively included. Outcome measures included graft success and postoperative pure tone audiometry air‐bone gap (PTA‐ABG) at last follow‐up (≥6 months). PTA‐ABG and MERI were calculated. Descriptive, univariable, and multivariable logistic regression analyses were conducted to evaluate the predictors of the graft and hearing outcomes. Results During the study, 385 patients (167 male, 218 female, median age 44 years) undergoing 413 procedures were studied. Out of this, 219 ears underwent tympanoplasty, 45 ears had tympanoplasty with canal wall up mastoidectomy, and 149 ears had tympanoplasty with canal wall down mastoidectomy. At the last follow‐up, the overall graft success rate was 91.3% (377/413) and the overall hearing success rate was 40% (165/413). Multivariable analysis results showed that the obstructed aditus ad antrum (OR 2.67, 95%CI 1.13‐6.30; P = .025) was an independent prognostic factor for graft failures. Moreover, the obstructed aditus ad antrum (OR 2.18, 95%CI 1.16‐4.08; P = .015) and MERI >3 (OR 6.53, 95%CI 3.55‐12.02; P 20 dB). Conclusions Aditus ad antrum patency was an independent predictor of both graft and hearing success among patients following tympanoplasty. MERI score greater than three was found to be a significant predictor of postoperative hearing and could serve as a useful tool for assisting clinicians in perioperative risk assessment. Level of Evidence 4.

Objectives The hospital environment has been implicated in the enrichment and exchange of pathogens and antibiotic resistance, but its potential in shaping the symbiotic microbial community of hospital staff is unclear. This study was designed to evaluate the alteration of the gut microbiome in medical workers compared to non-medical controls. Methods A prospective cross-sectional cohort study was conducted in the intensive care unit (ICU) and other departments of a centre in north-eastern China. Faecal samples of 175 healthy medical workers—short-term (1–3 months) workers (n = 80) and long-term (>1 year) workers (n = 95)—and 80 healthy non-medical controls were analysed using 16S rRNA amplicon sequencing. The hospital environmental samples (n = 9) were also analysed. Results The gut microbiomes of medical workers exhibited marked deviations in diversity and alteration in microbial composition and function. Short-term workers showed significantly higher abundances of taxa such as Lactobacillus, Butyrivibrio, Clostridiaceae, Clostridium, Ruminococcus, Dialister, Bifidobacterium, Odoribacter, and Desulfovibrio and lower abundances of Bacteroides and Blautia than the controls. Long-term workers showed higher abundances of taxa such as Dialister, Veillonella, Clostridiaceae, Clostridium, Bilophila, Desulfovibrio, Pseudomonas, and Akkermansia and lower abundances of Bacteroides and Coprococcus than the controls. The medical workers' department (ICU versus non-ICU) and position (resident doctor versus nursing staff) also impacted their gut microbiome. Compared with the non-ICU workers, workers in the ICU showed a significant increase in the abundances of Dialister, Enterobacteriaceae, Phascolarctobacterium, Pseudomonas, Veillonella, and Streptococcus and a marked depletion of Faecalibacterium, Blautia, and Coprococcus. In contrast with the nursing staff, the resident doctors showed a significant increase in Erysipelotrichaceae and Clostridium and a decrease in Bacteroides, Blautia, and Ruminococcus in the gut microbiome. Moreover, we found that the microbiota of hospital environments potentially correlated with the workers' gut microbiota. Conclusions Our findings demonstrated structural changes in the gut microbial community of medical workers.

Yongli Zhang,1,2 Mengyao Xie,1,2 Ruoyan Xue,1,2 Qi Tang,1,2 Xiaohui Zhu,1,2 Jian Wang,1,2 Hua Yang,1,2 Chao Ma3– 5 1Department of Otolaryngology, Chinese Academy of Medical Sciences and Peking Union Medical College, Peking Union Medical College Hospital, Beijing, 100730, People’s Republic of China; 2Translational Medicine Center, Peking Union Medical College Hospital, Beijing, 100730, People’s Republic of China; 3Institute of Basic Medical Sciences, Department of Human Anatomy, Histology and Embryology, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, 100005, People’s Republic of China; 4Joint Laboratory of Anesthesia and Pain, Peking Union Medical College, Beijing, 100730, People’s Republic of China; 5Chinese Institute for Brain Research, Beijing, 102206, People’s Republic of ChinaCorrespondence: Jian Wang; Hua YangDepartment of Otolaryngology, Peking Union Medical College Hospital, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, People’s Republic of ChinaTel +86 13673164261; +86 13701127757Fax +86-10-69156311Email wangjianent@163.com; dr_yanghua2021@163.comPurpose: Rapid and accurate diagnosis of the pathological characteristics of head and neck cancer and tumor resection margins is important. The DiveScope cell morphology analyzer (DiveScope) is a new endomicroscope that can rapidly image living tissues and cells. In this study, we preliminarily examined the accuracy of the DiveScope for determining the malignancy of head and neck cancers and the positivity/negativity of tumor resection margins and determined the consistency between diagnostic results with the DiveScope and those of frozen section pathology to provide a foundation for further clinical trials in pathological diagnosis of head and neck cancers and tumor resection margins.Methods: Head and neck cancer samples and resection margin samples were rapidly stained ex vivo before observation under the DiveScope cell morphology analyzer. Experienced pathologists distinguished the benignity and malignancy of the tumors based on images obtained by the DiveScope in a double-blind manner to validate the diagnostic performance of the analyzer.Results: We found that the cell morphology, cell nucleus morphology, karyoplasmic ratio, and even the nucleolus could be clearly distinguished. The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of benign and malignant head and neck cancer according to DiveScope results were 10.55 and 0.04, respectively. The PLR and NLR of the head and neck cancer resection margins according to the DiveScope were 19.01 and 0, respectively.Conclusion: The DiveScope showed high accuracy in determining the benignity and malignancy of head and neck cancer and the positivity/negativity of resection margins, and its results were highly consistent with those of intraoperative frozen section pathology tests.Keywords: the DiveScope cell morphology analyzer, head and neck cancer, resection margins, pathological diagnosis

Coal spontaneous combustion (CSC) has a devastating effect on the environment and human health. CSC primarily involves oxygen-lean oxidation and combustion states. In this study, to investigate the evolution of the coal microstructure during CSC in an oxygen-lean atmosphere, coal for oxygen-lean combustion was obtained and combusted at characteristic temperatures by using an independently developed electric tube furnace. Through Fourier-transform infrared spectroscopy, the relative contents of the active functional group of the initial-state oxidation coal were explored, and the main active functional groups, namely aromatic hydrocarbon, the oxygen functional group, aliphatic hydrocarbon, and the hydroxyl group, with the characteristic temperature, were determined. The sensitivities of different active functional groups to oxygen concentrations were analysed. In practice, a 10 vol% oxygen concentration was the key factor, inhibiting and promoting various active functional groups and exhibiting distinct dominance at various stages. Finally, the oxygen concentrations affected the gas concentration release characteristics, thereby determining the correlation degree of the key group and the oxygen concentration, as well as verifying the oxygen concentration sensitivity of the microstructure. The groups highly correlated with CSC characteristic parameters were mainly –CH2 and –CH3. The research results suggested remarkable explanatory potential to further elucidate the evolution of microstructures in oxygen-lean CSC.

The immunoproteasomes are specific proteasomes that clear oxidant-damaged proteins under inflammatory conditions in various diseases. Toxoplasma gondii (T. gondii) infects the central nervous system and causeencephalitis. However, the relationship between the immunoproteasomes and brain inflammation during T. gondii infection is not well characterized. In this study, we established an in vivo mouse model of T. gondii PLK strain infection via intraperitoneal injection and evaluated the expression of immunoproteasome subunits in the brains of infected mice. The results demonstrated that first, pathological changes in the brains of infected mice increase in severity over time. Second, following T. gondii infection, activated microglia and astrocytes undergo a series of functional alterations and morphological transformations, including proliferation and migration. Third, T. gondii infection induces expression of inflammatory cytokines, including IFN-γ, IL-1β, TNF-α, and IL-6. Fourth, the immunoproteasome subunits low-molecular-weight polypeptide 2 (LMP2), LMP7, and LMP10 mRNA and protein levels are significantly upregulated in T. gondii-infected mouse brains, as shown by RT-qPCR and western blot analysis, compared with that in vehicle-treated brains, and their expression is localized in the microglia, astrocytes, and neurons of T. gondii-infected brains, as determined via immunofluorescence staining. Furthermore, the western blot mean gray value for the immunoproteasome subunits and the positive microglia and astrocyte immunohistochemical signals in the brains of T. gondii-infected mice were positively correlated, indicating that the observed relationships were highly significant. Therefore, it was concluded that the induction of the immunoproteasomes is a pathogenic mechanism underlying T. gondii infection-induced inflammation.