[Characterizing immune microenvironment cell composition of chronic rhinosinusitis with nasal polyps based on mass cytometry technology].

Objective: To analyze the cellular composition characteristics of the nasal tissue immune microenvironment in patients with control, chronic rhinosinusitis without nasal polyps (CRSsNP), non-eosinophilic chronic rhinosinusitis with nasal polyps (neCRSwNP), and eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) using mass cytometry flow technology. Methods: Thirteen CRS patients who underwent endoscopic nasal surgery at the Department of Otorhinolaryngology Head and Neck Surgery of Peking Union Medical College Hospital from March to December 2022 were recruited, including 8 males and 5 females, aged 22.3 to 58.3 years. Three control mucosae were obtained from normal ethmoid or sphenoid sinuses of patients with benign tumors of the temporal fossa or non-functional pituitary adenomas who underwent endoscopic surgery, excluding allergic rhinitis and sinusitis. Sixteen clinical tissue samples (3 of control, 3 of CRSsNP, 4 of neCRSwNP, and 6 of eCRSwNP) were prepared into single-cell suspensions. Mass cytometry flow detection was performed using a combination of 42 molecular markers to analyze the differences in cell subpopulations among the groups. Data were analyzed using GraphPad Prism 9. Results: Based on the mass cytometry flow results, cells from control, CRSsNP, neCRSwNP, and eCRSwNP were divided into seven main cell subgroups, with detailed subgrouping of T/NK cells and myeloid cells. In T/NK cells, compared with the control group, the number of NK CD56bright cells increased in the CRSsNP group, while NK CD56dim cells decreased; compared with the CRSsNP group, the eCRSwNP group showed a decrease in NKT cells and CD4+Tem cells; compared with the CRSsNP group, the eCRSwNP group showed a significant increase in CD25 expression within Treg cells; compared with the CRSsNP group, the eCRSwNP group showed a significant decrease in Tbet expression in CD8+Teff cells and CD8+TRM cells; in eCRSwNP, the expression of CD103 in CD8+TRM cells was significantly lower than in CRSsNP. In myeloid cells, compared with the other three groups, the eCRSwNP group showed a significant increase in macrophages and a significant decrease in cDC1 and monocytes; compared with the control group and CRSsNP, the eCRSwNP group also showed a significant decrease in resting state macrophages; compared with the CRSsNP group, the eCRSwNP group showed a significant decrease in the level of CX3CR1 within cDC2 and monocytes; the expression levels of NLRP3 in cDC2 and macrophages in the eCRSwNP group were significantly higher than in the other three groups; compared with the control group, the expression levels of Gata3 in cDC2 and macrophages in the eCRSwNP group were also significantly increased; additionally, the expression of CCR2 within monocytes in the eCRSwNP group was lower than in the CRSsNP group. In ILC, compared with the control group, the expression of CCR6 decreased in the eCRSwNP group. Conclusions: Compared with the control group, CRSsNP, and neCRSwNP, eCRSwNP shows an increase in macrophage number, a decrease in cDC1 and resting state macrophages, and depletion of protective cells CD103+CD8+TRM. Additionally, the expression levels of CCR2 and CX3CR1 in monocytes of eCRSwNP are decreased.

[Overview and prospects of an in vitro cell model for studying liver fibrosis].

Liver fibrosis incidence and adverse outcomes are high; however, there are no known chemical drugs or biological agents that are specific and effective for treatment. The paucity of a robust and realistic in vitro model for liver fibrosis is one of the major causes hindering anti-liver fibrosis drug development. This article summarizes the latest progress in the development of in vitro cell models for liver fibrosis, with a focus based on the analysis of induction and activation of hepatic stellate cells, cell co-culture, and 3D model co-construction, as well as concurrent potential methods based on hepatic sinusoidal endothelial cell establishment.

Metagenomic reconstructions of caecal microbiome in Landes, Roman and Zhedong White geese.

1. The caecal microbiota in geese play a crucial role in determining the host's health, disease status and behaviour, as evidenced by extensive epidemiological data. The present investigation conducted 10× metagenomic sequencing of caecal content samples obtained from three distinct goose species, namely Landes geese, Roman geese and Zhedong White geese (n = 5), to explore the contribution of the gut microbiome to carbohydrate metabolism.2. In total, 337GB of Illumina data were generated, which identified 1,048,575 complete genes and construction of 331 metagenomic bins, encompassing 78 species from nine phyla. Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria and Bacteria were identified as the dominant phyla while Prevotella, Bacteroides, Streptococcus, and Subdoligranulum were the most abundant genera in the caecum of geese.3. The genes were allocated to 375 pathways using the Kyoto Encyclopedia of Genes and Genome (KEGG) analysis. The most abundant classes in the caecum of geese were confirmed to be glycoside hydrolases (GHs), glycosyl transferases (GTs), as identified through the carbohydrate-active enzyme (CAZyme) database mapping. Subdoligranulum variabile and Mediterraneibacter glycyrrhizinilyticus were discovered to potentially facilitate carbohydrate digestion in geese.4. Notwithstanding, further investigation and validation are required to establish a connection between these species and CAZymes. Based on binning analysis, Mediterraneibacter glycyrrhizinilyticus and Ruminococcus sp. CAG:177 are potential species in LD geese that contribute to the production of fatty liver.

Molecular characterisation, temporal expression and involvement of ANGPTL4 in fat deposition in Muscovy ducks.

1. Angiopoietin-like protein 4 (ANGPTL4) plays a key role in promoting fat metabolism and reducing blood lipid. This study characterised the ANGPTL4 gene in Muscovy ducks (Cairina moschata) and investigated its potential functions in fat metabolism in Muscovy ducks.2. The Muscovy duck ANGPTL4 cDNA was successfully cloned for the first time, showing a length of 2591 bp. After phylogenetic analysis by RT-qPCR analysis, it was found that the ANGPTL4 gene of Anas platyrhynchos shared the highest sequence similarity with that of Muscovy ducks.3. The ANGPTL4 gene was commonly expressed in 23 different tissues with the highest expression in the abdominal fat in Muscovy ducks. A significant association was observed between abdominal fat percentage (AFP) and the mRNA expression of the ANGPTL4 gene. Moreover, Muscovy ducks showed a peak of ANGPTL4 expression in the liver and abdominal fat at 1-2 weeks old.4. These findings suggest that the ANGPTL4 gene is related to fat deposition and regulation in Muscovy ducks.

[TXNDC17 protein overexpression in uterine papillary serous carcinoma is associated with clinicopathological characteristics and prognosis].

Objective: To analyze clinicopathological characteristics of patients with uterine papillary serous carcinoma (UPSC) in China, and investigate roles of TXNDC17 protein in UPSC clinicopathological characteristics and prognosis. Methods: Fifty-five patients with UPSC treated in Women's Hospital School of Medicine Zhejiang University from 2003 to 2016 were analysed retrospectively. Immunohistochemistry (IHC) were performed to TXNDC17 and BECN1 (Beclin 1 protein, a key regulator of autophagy) protein expression respectively. Kaplan-Meier was used to calculate the cumulative survival rate, Log-rank test was performed to compare the difference in cumulative survival rate among patients with different clinicopathological characteristics, and Cox regression model was used to analyze the related between TXNDC17 expression and prognosis of UPSC patients. Results: The median age of the 55 UPSC patients was 63(49, 79) years, 43.6%(24/55) with late stages (stage Ⅲ/Ⅳ), and 32.7 % (18/55) exhibiting more than half of myometrium invasion were enrolled. Notably, 28 (50.9%) patients had TXNDC17 protein overexpression, and associated with BECN1 overexpression(P=0.023). Besides, co-expression of TXNDC17 and BECN1 occurred at an advanced stage and deep myometrial invasion (P=0.013,0.009). The cumulative survival rate of TXNDC17 overexpression(37.4% vs 91.5%),FIGO Ⅲ/Ⅳ stage(44.1% vs 70.1%), deep myometrium invasion(36.1% vs 75.4%) and BECN1 overexpression(0 vs 83.0%)patients was low (P<0.05). The multivariate proportional hazards model revealed that myometrial invasion and TXNDC17 overexpression were associated with prognosis of UPSC patients. Conclusions: This study shows that TXNDC17 overexpression is associate with poor survival in UPSC patients. Co-expression of TXNDC17 and BECN1 shows characteristics of advanced stages and deep myometrial invasion. TXNDC17 may be a potential predictor or target in UPSC therapeutics..

[Predictive value of the product of plasma colchicine concentration and poisoning time for the prognosis of colchicine poisoning patients].

Objective: To investigate the predictive value of the product of first plasmacolchicine concentration and poisoning time for the prognosis of colchicine poisoning patients, and to provide a basis for early prognosis assessment. Methods: October 2021, patients with colchicine poisoning admitted in the First Affiliated Hospitol of Wenzhou Medical University from January 2017 to September 2021 were collected, including general information such as patient gender, age, oral colchicine dose, poisoning time, the first laboratory test index andplasma colchicine concentration after admission. The patients were divided into survival group and death group according to their prognosis. The differences in clinical indicators such as admission plasma colchicine concentration, blood routine, blood biochemistry, coagulation function, and blood gas analysis were compared between the two groups, and their predictive value for the prognosis of patients were analyzed. Results: A total of 23 patients with colchicine poisoning, aged 20-85 years, were included in this study, of which 15 cases (65.22%) survived and 8 cases (34.78%) died. The first plasma colchicine concentration at admision were 0.42-53.61 ng/ml. The plasma colchicine concentration and the concentration-time product were 10.08-2147.04 h·ng/ml.Compared with the survival group, the plasma colchicine concentration and the concentration-time product in the death group were significantly increased, and the differences were statistically significant (P<0.05). Univariate logistic regression analysis showed that first plasma concentration and poisoning time>132.48 h·ng/ml, high C-reactive protein, high D-dimer, high absolute value of BE were the risk factors for the prognosis of patients with colchicine poisoning (OR=12.000, 95%CI: 1.1181-128.836; OR=1.053, 95%CI: 1.009-1.098; OR=1.219, 95%CI: 1.039-1.429; OR=1.360, 95%CI: 1.1.044-1.773; P<0.05). High prothrombin time activity was protective factor affecting the prognosis of colchicine poisoning patients (OR=0.941, 95%CI: 0.892~0.993; P<0.05). ROC curve analysis showed that the areas under the curves of first plasma concentration and poisoning time, C-reactive protein, absolute value of BE, D-dimer for predicting the prognosis of patients with colchicine poisoning were 0.918, 0.888, 0.867, 0.837, respectively, and the areas under the curves of prothrombin time activityfor predicting the prognosis of patients with colchicine poisoning was 0.788 (P<0.05) . Conclusion: The product of the first plasma colchicine concentration at admission and poisoning time is closely related to the prognosis of patients with colchicine poisoning, it can be used as a predictor for early evaluation of the prognosis of poisoned patients.

[IL-1ß inhibitor sensitizes to olaparib in homologous recombination deficiency proficient ovarian cancer cells].

Objective: To investigate the inhibitory effect of combined strategy of poly adenosine diphosphate ribose polymerase (PARP) inhibitor and interleukin-1ß (IL-1ß) inhibitor on homologous recombination deficiency (HRD)-proficient ovarian cancer cells. Methods: (1) HRD-proficient ovarian cancer cell lines OVCAR3 and CAOV3 were treated with PARP inhibitor olaparib. Screening by RNA sequencing analysis, the expression level of IL-1ß was validated by enzyme-linked immunosorbent assay (ELISA) and western blot. (2) The dose-response curves of IL-1ß inhibitor diacerein were evaluated by cell counting kit-8 (CCK-8) assays in OVCAR3 and CAOV3 cells. CCK-8 assays were further applied to determine the viabilities of OVCAR3 and CAOV3 cells. (3) To evaluate the synergistic effects of olaparib and IL-1ß inhibitor in vivo, the transplanted ovarian cancer model was constructed. BALB/c-nude mice (n=16) were injected intraperitoneally with 1×107 OVACR3 cells labelled with luciferase (OVCAR3-Luc). Immunohistochemistry (IHC) assay was performed to determine nuclear antigen associated with cell proliferation (Ki-67) expression. (4) Blood routine tests, kidney and liver function tests were performed to analyze the toxic reaction of different drug treatments. The potential drug-induced injuries of vital organs including heart, liver, spleen, lungs and kidneys of nude mice were determined by hematoxylin-eosin (HE) staining. Results: (1) The RNA sequencing results showed that the mRNA level of IL-1ß was the most significantly increased among the 25 differentially expressed genes in OVCAR3 cells treated with olaparib, compared to the negative control group. Olaparib treatment significantly promoted the secretion and expression of IL-1ß protein in both OVACR3 and CAOV3 cells by ELISA [(36.2±3.5) and (49.5±3.5) pg/ml, respectively; all P<0.001] and western bolt (2.87±0.37 and 2.05±0.08, respectively; all P<0.01). (2) The half maximal inhibitory concentration (IC50) value of IL-1ß inhibitor was determined as follows: 75 µmol/L for OVACR3 cells and 100 µmol/L for CAOV3 cells. The treatments were divided into four groups including control group, olaparib monotherapy group, IL-1ß inhibitor monotherapy group and the combination therapy group. The cell viabilities of each group in OVCAR3 and CAOV3 were determined by CCK-8 assay. The data in each group were showed as follows for OVCAR3 and CAOV3 cells: (100.0±0.4)% and (100.0±3.5)% in control group; (63.1±6.2)% and (63.3±3.8)% in olaparib monotherapy group; (61.6±4.7)% and (63.8±3.5)% in IL-1ß inhibitor monotherapy group; and (32.9±5.2)% and (30.0±1.3)% in the combination therapy group. The viability assay showed that the combined strategy exhibited a significant inhibition effect on OVACR3 and CAOV3 cells, compared to the monotherapy group and the control group (all P<0.01). (3) All mice with transplanted tumors of HRD-proficient ovarian cancer cells were randomly divided into four groups, and treated with four different treatments as mentioned above, respectively. After 4 weeks (on day 29), the vivo fluorescence imaging were determined. The results showed that the amount of fluorescence of transplanted tumors was mostly decreased in the combination therapy group [(0.5±0.4)×1010 p/s], compared to the control group [(4.2±1.0)×1010 p/s] or the groups treated with any single drug [(3.1±0.9)×1010, (2.2±0.9)×1010 p/s; all P<0.05]. Mice were then sacrificed under anesthesia, and all transplanted tumors detached and weighed for further investigation. The weight of transplanted tumors was significantly decreased in the combination therapy group [(0.09±0.03) g], compared to that in control group [(0.25±0.05) g] or groups treated with any single drug [(0.17±0.03), (0.19±0.04) g; all P<0.05]. The measurement of the expression of Ki-67 showed that it was significantly decreased in the combination therapy group (0.33±0.10), compared to that in the control group (1.00±0.20) or monotherapy groups (0.76±0.07, 0.77±0.12; all P<0.05). (4) There were no significant differences of body weights, blood routine test, renal and liver function tests among mice with different treatments (all P>0.05). Moreover, no significant injuries were observed in the vital organs among the four groups. Conclusions: The combination of olaparib and IL-1ß inhibitor synergistically exhibits significant cytotoxicity in HRD-proficient ovarian cancer cells. Moreover, the blood routine and blood biochemistry results confirmed the biosafety of the combination of olaparib and IL-1ß inhibitor.

[Pay attention to the overall improvement of the quality of diagnosis and treatment of gynecological malignant tumors].

To further improve the survival rate of patients with gynecological malignancies, our paper currently propose to focus on the quality of diagnosis and treatment of gynecological malignancies. We suggest to promote the standardization of the diagnosis and treatment, to perform innovative clinical trial, and to construct a multidisciplinary model of diagnosis and treatment for patients with gynecological malignancies.

[Expression characteristics and diagnostic value of angiogenic molecules in intravenous leiomyomatosis].

Objective: This study aims to analyze the clinicopathological characteristics of patients with intravenous leiomyoma (IVL), and to explore the expression characteristics and diagnostic value of angiogenesis related molecules in IVL. Methods: The clinicopathological data of 40 patients with IVL at Women's Hospital, School of Medicine, Zhejiang University from January 2013 to April 2021 were reviewed. Log-rank test was performed to compare the difference in recurrence-free survival (RFS) rates among patients with different clinicopathological characteristics. Immunohistochemistry (IHC) staining was performed on 10 angiogenesis related molecules to analyze their expression characteristics in IVL. The sensitivity and specificity of molecules with high expression rates in the diagnosis of IVL were calculated, the receiver operating characteristic curve (ROC) was plotted and the area under ROC (AUC) was calculated to evaluate the diagnostic value. Results: Median age of the 40 patients was 47 (43, 50) years. The clinical manifestations of IVL were atypical with the diagnostic accuracy of preoperative ultrasound was 12.5% (5/40), CT and/or MRI was 26.7% (8/30), and intraoperative frozen section was 30.0% (12/40). The overall recurrence rate of IVL was 10.0% (4/40). The Log-rank test showed that the cumulative recurrence-free survival rate of IVL patients with previous cesarean section (40.9%) was lower than that of those without cesarean section (96.4%) (P<0.05); and their median RFS time was shorter than those without cesarean section (16.4 months vs 22.2 months). The overall positive rates of adrenomedullin (ADM), fibroblast growth factor receptor 1 (FGFR1), vascular endothelial growth factor receptor 3 (VEGFR3) and angiogenin receptor tyrosine kinase receptor 1 (TIE1) were 65.0% (26/40), 75.0% (30/40), 57.5% (23/40) and 50.0% (20/40), respectively. FGFR1 expression intensity and positive rate were higher in tumors with a maximum diameter greater than 5 cm than in tumors with a maximum diameter smaller than 5 cm (P<0.05). The AUC of FGFR1 combined with ADM, VEGFR3, and TIE1 was 0.876 (95%CI: 0.788-0.964, P<0.001). Conclusions: There was no typical clinical manifestation of IVL. A history of the previous cesarean section indicated a lower cumulative recurrence-free survival rate and shorter recurrence interval. It was hard to diagnose IVL by sonography, radiography, or frozen section pathology. FGFR1, ADM, VEGFR3, and TIE1 were all highly expressed in IVL, and the efficacy of the combination of the four molecules in diagnosing IVL was higher than that of imaging and classical vascular endothelial markers, which are expected to be promising molecular diagnostic markers.

[Study on human fatigue during monotonous sitting-posture work].

Objective: In this study, the occupational fatigue caused by long-time sitting-posture work was studied. Also, the physical and psychological factors which affect on human fatigue of workers suffering from monotonous sitting-position were analyzed. Methods: In 2021, a total of 30 subjects, including 15 males and 15 females, were selected to complete a 4-hour simulated sitting-position assembly task in the laboratory. The "Borg's RPE" was used to measure the subjects' subjective fatigue and feeling of monotony, the polyconductive physiological recorder was used to measure the subjects' EMG, and the wireless motion-capture evaluation system was used to measure the kinematics of the subjects. Results: When engaged in monotonous work tasks, there was a significant positive correlation between workers' monotony and subjective fatigue, with correlation coefficients ranging from 0.976 to 0.988 (P<0.050) . At the beginning of work, the subjective fatigue of the neck was more significant (P=0.046) . As working time increased, the back fatigue was significantly higher than that of the neck (P=0.029) . After 4 hours of work, the MPF value of the back erector spinae EMG decreased significantly (P=0.025) . The body posture data showed that the shoulder and neck indicators began to change significantly after about 2 hours of work (P(neck)=0.032, P(shoulder)=0.021) . The waist and hip indicators began to change significantly after about 4 hours of work (P(left hip)=0.031, P(right hip)=0.028) . The flexion angle of the neck first increased and then decreased; the flexion angle of the waist and hip continued to increase with the working time. Conclusion: It was found that the fatigue effect of monotonous sitting-posture work on the operator is mainly reflected in the lower back. The monotony of the work exacerbates the operator's subjective fatigue feeling. The operator should be given corresponding protection and set the work content reasonably. It is recommended to have appropriate activities or short breaks every 2 work-hour.

[Different concentrations of specialized pro-resolving mediators in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps].

Objective: To investigate the difference of concentrations of specialized pro-resolving mediators (SPMs) derived from fatty acids in eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) and non-eosinophilic chronic rhinosinusitis with nasal polyps (nECRSwNP). Methods: A total of 36 patients with bilateral chronic rhinosinusitis with nasal polyps (CRSwNP) who underwent endoscopic nasal surgeries in Peking Union Medical College Hospital from May 2019 to September 2020 were enrolled, including 27 males and 9 females, with the age from 13 to 67 years. There were 23 cases of ECRSwNP and 13 cases of nECRSwNP. At the same time, 12 control subjects were enrolled. The concentrations of multiple SPMs, including lipoxins (LXA4 and LXB4), resolvins (RvD1, RvD2, RvD3, RvD5 and RvE1), protectins (PDX) and maresins (Mar-1) in nasal polyps with different histological subtypes and normal nasal mucosa were analyzed using liquid chromatography-tandem mass spectrometry. The concentrations of SPMs between groups were compared using Mann-Whitney U test. Spearman's rank correlation coefficient was used to measure the correlation between the concentrations of SPMs in nasal polyps and tissue eosinophil counts. Results: The concentrations of RvD2, RvD3, RvD5, LXA4, LXB4, Mar-1 and PDX in ECRSwNP group were significantly higher than that in controls (Z value was -2.276, -2.313, -3.371, -2.094, -2.051, -3.104 and -2.294, respectively, all P<0.05). The concentrations of RvD2, RvD5, Mar-1 and PDX in ECRSwNP group were significantly higher than those in nECRSwNP group (Z value was -2.175, -2.289, -2.243 and -2.124, respectively, all P<0.05). There was no significant difference in all these SPMs between nECRSwNP and controls (all P>0.05). The concentrations of RvD2, RvD3, RvD5, LXB4, Mar-1 and PDX in nasal polyps correlated positively with tissue eosinophil counts (r value was 0.443, 0.436, 0.371, 0.502, 0.340 and 0.386, respectively, all P<0.05). Conclusions: A varienty of SPMs are elevated in ECRSwNP. Dysregulation of fatty acid metabolism might play an important role in the chronic inflammation of ECRSwNP.

[Incidence of unintended pregnancy within 2 years after delivery and its influencing factors in China].

Objective: To investigate the present situation of unintended pregnancy within two years postpartum and its influencing factors in China. Methods: Participants who delivered a live birth at 60 hospitals in 15 provinces in the eastern, central and western regions of China during July 2015 to June 2016 were interviewed by using structured questionnaire. Information on occurrence of unintended pregnancy within 2 years after delivery, postpartum contraceptive use, sexual resumption, breastfeeding, and women's socio-demographic characteristics, and so on, were collected. Life-table analysis, cluster log-rank tests and a 2-level Cox regression model were used for data analysis. Results: A total of 18 045 postpartum women were investigated. The cumulative 1- and 2-year unintended pregnancy rates after delivery were 5.3% (95%CI: 4.5%－6.1%) and 13.1% (95%CI: 11.3%－14.8%), respectively. Cox regression model analysis showed that the risk of unintended pregnancy within 2 years postpartum were increased in younger women, ethnic minorities, women with abortion history, and those who had a vaginal delivery with short lactation time and late postpartum contraceptive initiation (all P<0.01). The risk of postpartum unintended pregnancy was not associated with geographic regions and hospitals where women gave a birth (all P>0.05). Conclusions: In China, the risk of unintended pregnancy within 2 years after delivery is relatively high. Service institutions and service providers should improve the quality of postpartum family planning services, promote the use of high effect contraceptive methods, and educate women to use a method at the time of their sexual resumption or even before.

[Endocervical adenocarcinomas classified by International Endocervical Adenocarcinoma Criteria and Classification: a clinicopathological and prognostic analysis of 286 cases].

Objectives: To investigate the clinicopathological and prognostic significance of International Endocervical Adenocarcinoma Criteria and Classification (IECC) in classifying endocervical adenocarcinomas among Chinese women. Methods: A total of 286 endocervical adenocarcinomas diagnosed from January 2013 to December 2019 at the Women's Hospital, Zhejiang University School of Medicine were identified and included. The cases were reviewed and reclassified based on IECC. The histological types were correlated with p16 immunostaining, human papilloma virus (HPV) mRNA status, the clinicopathological parameters including the International Federation of Gynecologic Oncology (FIGO) stage, and clinical follow-up data. Results: The patients aged from 19 to 77 (median 47) years. There were 223 patients at FIGO stage Ⅰ, 22 at stage Ⅱ, 38 at stage Ⅲ and 3 at stage Ⅳ. The IECC types included 213 (74.5%) HPV-related adenocarcinomas (HPVA), 60 (21%) non-HPV-related adenocarcinomas (NHPVA), and 13 (4.5%) adenocarcinomas, no other specified (NOS). The major histological subtypes in HPVA and NHPVA were common type (n=156, 54.5%) and gastric type (GAC, n=46, 15.9%), respectively. The p16 positive rates in HPVA, NHPVA and adenocarcinoma, NOS were 92% (173/188), 26.6% (17/64) and 61.5% (8/13), respectively, and those of HPV mRNA hybridization in situ were 89.4% (144/161), 0/18 and 7/13, respectively. Compared to HPVA, NHPVA was more frequently associated with older age, FIGO stage Ⅱ-Ⅳ, neural involvement, lymphovascular invasion and aberrant p53 expression (P<0.05). Univariate survival analysis showed that age (>47 years), NHPVA, GAC, FIGO stage Ⅱ-Ⅳ, neural involvement, lymphovascular invasion and aberrant p53 expression were indicators for a poorer overall survival and tumor recurrence (P<0.05). Mucinous HPVA showed worse clinical outcomes compared to usual-type HPVA (P<0.01). Multivariate survival analysis demonstrated that FIGO stage Ⅱ-Ⅳ, NHPVA and aberrant p53 expression were independent indicators for poor overall survival while FIGO stage Ⅱ-Ⅳ and GAC were independently associated with tumor recurrence (P<0.05). Conclusions: The two broad IECC categories, HPVA and NHPVA, not only provide morphological links to the etiology (HPV infection), but also have significant clinicopathological and prognostic relevance.

[Factors affecting long-term survival of advanced high-grade serous ovarian cancer].

Objective: To identify the factors associated with long-term survival and guide the decision for primary surgery in patients with advanced high-grade serous ovarian cancer(HGSOC). Methods: In this case-control study, clinical parameters, including surgical and non-surgical associated factors, were collected and compared between the patients with short-term (<2 years) and long-term (>5 years) survival who all underwent primary debulking surgery (PDS) followed by carboplatin and paclitaxel chemotherapy from January 2004 to December 2016. Univariate analysis was examined by chi-square test and multivariate analysis was performed by logistic regression analysis. Results: There were 95 cases long-term survival (LTS group) and 77 cases short-term survival (STS group) in 698 newly diagnosed HGSOC patients with International Federation of Gynecology and Obstetrics (FIGO) stage Ⅲc and Ⅳ who met include and exclude criteria. (1) Univariate analysis showed that the proportion of complete cytoreduction with no visible residual disease (R0) at PDS and platinum sensitivity in LTS group were significantly higher than those in STS group (P<0.01). The surgical complexity score (SCS), the preoperative serum CA125 level and the ascites volume in the LTS group were significantly lower than those of the STS group (all P<0.05). In the LTS group, the preoperative incidence of lesions in retrograde peritoneum of the bladder, serosal and mesangial membrane of the small intestine, upper abdominal peritoneum and liver parenchyma were significantly lower than those in the STS group (all P<0.05). Multivariate logistic regression analysis showed that platinum sensitivity (OR=0.016, 95%CI: 0.004-0.063, P<0.01), ascites volume >500 ml (OR=3.193, 95%CI: 1.285-7.930, P=0.012), and SCS ≥8 (OR=17.433, 95%CI: 2.281-133.25, P=0.003) were independent factors affecting long-term survival (P>0.05). (2) Totally 37 of 95 in long-term survival and 16 of 77 in short-term survival achieved R0 cytoreduction at PDS. Univariate analysis showed that preoperative serum CA125 level, preoperative lesion score, preoperative lesion (DS) score, ascites volume, platinum sensitivity,and SCS were significantly correlated with the R0 PDS (all P<0.05). Multivariate analysis showed that ascites volume >500 ml (OR=5.199, 95%CI: 2.015-13.409, P=0.001), DS >2 (OR=15.264, 95%CI: 5.843-39.874, P<0.01) and SCS ≥4 (OR=4.176, 95%CI: 1.618-10.777, P=0.003) were independent factors associated with R0 cytoreduction. In patients with DS ≤2 or SCS <4, but not those with DS >2 or SCS ≥4, R0 cytoreduction was significantly associated with long-term survival. Conclusion: The intrinsic biology of tumor is the factor influencing long-term survival of advanced HGSOC patients, and those who present with wide intraperitoneal metastases and need to remove multiple organs may not benefit from R0 cytoreduction.

[Causes of death and influencing factors of atrial fibrillation patients undergoing anticoagulation therapy].

Objective: To investigate the causes of death and predictors in patients with nonvalvular atrial fibrillation (AF) undergoing anticoagulation therapy. Methods: Consecutive anticoagulated nonvalvular AF patients were recruited from the China Atrial Fibrillation Registry (China-AF) Study from August 2011 to December 2018. After exclusion of patients with hypertrophic cardiomyopathy, dilated cardiomyopathy, or loss of follow-up within 1 year, 2 248 patients were included in this analysis. Enrolled patients were followed up were followed up for 3 and 6 months, and then every 6 months. The primary endpoint was death, including cardiovascular death, non-cardiovascular death and undetermined death. The patients were divided into survival group and death group according to the survival status after follow-up. Clinical information such as age and sex was collected. Cox proportional hazards regression was performed to identify associated risk factors for all-cause mortality, and Fine-Gray competing risk model was used to identify associated risk factors for cardiovascular mortality. Results: A total of 2 248 patients with atrial fibrillation receiving anticoagulant therapy died over a mean follow-up of (42±24) months, mean age was (67±10) years old and 41.1% (923/2 248) patients were female. The mortality rate was 2.8 deaths per 100 patient-years. The most common cause of death was cardiovascular deaths, accounted for 55.0% (120/218). Worsening heart failure was the most common cause of cardiovascular deaths (18.3% (40/218)), followed by bleeding events (12.9% (28/218)) and ischemic stroke (8.7% (19/218)). Multivariate Cox regression analysis showed that age (HR = 1.05, 95%CI 1.04-1.07, P<0.001), anemia (HR = 1.81, 95%CI 1.02-3.18, P = 0.041), heart failure (HR=2.40, 95%CI 1.75-3.30, P<0.001), ischemic stroke/transient ischemic attack (TIA)(HR = 1.59, 95%CI 1.21-2.13, P = 0.001) and myocardial infarction (HR = 2.93, 95%CI 1.79-4.81, P<0.001) were independently associated with all-cause death. Fine-Gray competing risk model showed that age (HR=1.05, 95%CI 1.02-1.08, P<0.001), heart failure (HR=2.81, 95%CI 1.79-4.39, P<0.001), ischemic stroke/TIA (HR=1.50, 95%CI 1.02-2.22, P=0.041) and myocardial infarction (HR=3.31, 95%CI 1.72-6.37, P<0.001) were independently associated with cardiovascular death. Conclusions: In anticoagulated nonvalvular AF patients, ischemic stroke represents only a small subset of deaths, whereas worsening heart failure is the most common cause of cardiovascular deaths. Heart failure, ischemic stroke/TIA, and myocardial infarction are associated with increased mortality.