BACKGROUND: The new emerging avian influenza A H7N9 virus, causing severe human infection with a mortality rate of around 41%. This study aims to provide a novel treatment option for the prevention and control of H7N9. METHODS: H7 hemagglutinin (HA)-specific B cells were isolated from peripheral blood plasma cells of the patients previously infected by H7N9 in Jiangsu Province, China. The human monoclonal antibodies (mAbs) were generated by amplification and cloning of these HA-specific B cells. First, all human mAbs were screened for binding activity by enzyme-linked immunosorbent assay. Then, those mAbs, exhibiting potent affinity to recognize H7 HAs were further evaluated by hemagglutination-inhibiting (HAI) and microneutralization in vitro assays. Finally, the lead mAb candidate was selected and tested against the lethal challenge of the H7N9 virus using murine models. RESULTS: The mAb 6-137 was able to recognize a panel of H7 HAs with high affinity but not HA of other subtypes, including H1N1 and H3N2. The mAb 6-137 can efficiently inhibit the HA activity in the inactivated H7N9 virus and neutralize 100 tissue culture infectious dose 50 (TCID50) of H7N9 virus (influenza A/Nanjing/1/2013) in vitro, with neutralizing activity as low as 78 ng/mL. In addition, the mAb 6-137 protected the mice against the lethal challenge of H7N9 prophylactically and therapeutically. CONCLUSION The mAb 6-137 could be an effective antibody as a prophylactic or therapeutic biological treatment for the H7N9 exposure or infection.
Animals ; Antibodies, Monoclonal/therapeutic use* ; Antibodies, Neutralizing/therapeutic use* ; Antibodies, Viral ; Hemagglutinins ; Humans ; Influenza A Virus, H1N1 Subtype ; Influenza A Virus, H3N2 Subtype ; Influenza A Virus, H7N9 Subtype ; Influenza Vaccines ; Influenza in Birds ; Influenza, Human/prevention & control* ; Mice

Objective:s To evaluate the impacts of prior surgical scores(PSS) on the clinical efficacy and perioperative safety of cytoreductive surgery(CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC) for pseudomyxoma peritonei(PMP).Methods:From the comprehensive PMP database, we collect the cases treated for the first time by CRS+ HIPEC, to form this study cohort. The clinicopathological features, PSS, CRS+ HIPEC details, overall survival(OS), and serious adverse events(SAEs) are systematically analyzed, to study the correlations between PSS and OS or SAEs.Results:335 PMP cases received standardized CRS+ HIPEC in this study. The median OS is 58.2 months for PSS-0 patients, 63.7 months for PSS-1, and 55.4 months for PSS-2/3, with no statistically significant differences in OS among the different PSS groups(χ 2=0.499, P=0.779). Subgroup analysis by pathologic types also found no statistically significant differences among the different PSS groups. Moreover, no significantly statistical differences are observed in overall SAEs(χ 2=0.625, P=0.722), CRS-related SAEs(χ 2=0.267, P=0.901), and non-CRS-related SAEs(χ 2=0.677, P=0.715), among the different PSS groups. Conclusions:PSS does not pose significant impacts on the efficacy and safety of CRS+ HIPEC for PMP patients at experienced treatment center.

Objective:This study was to investigate the perioperative safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei (PMP), and analyze the risk factors of serious adverse events (SAEs).Methods:The occurrences of perioperative SAEs were retrospectively analyzed in 254 PMP patients treated with CRS plus HIPEC. Univariate and multivariate analysis were performed to identify independent risk factors.Results:Among the 272 CRS plus HIPEC procedures for 254 PMP patients, a total of 93 (34.2%) perioperative SAEs occurred, including 26 in infection, 22 in digestive system, 17 in respiratory system, 15 in cardiovascular system, 8 in hematological system, and 4 in urinary system. In terms of severity, the vast majority was grade Ⅲ with 76 cases, followed by grade Ⅳ with 13 cases and grade Ⅴ with 4 cases. Univariate analysis revealed 3 risk factors of perioperative SAEs: HIPEC regimen ( P=0.020), intraoperative red blood cell transfusion volume ( P=0.004), and intraoperative blood loss volume ( P=0.002). Multivariate analysis by logistic regression model analysis revealed that intraoperative red blood cell transfusion volume was an independent risk factor for perioperative SAEs ( OR=1.160, P=0.001). Conclusion:In conclusion, the perioperative safety of CRS plus HIPEC was acceptable. Moreover, intraoperative blood loss volume and red blood cell transfusion volume are expected to be reduced in order to prevent SAEs for PMP patients.

Objective:This study was to investigate the perioperative safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei (PMP), and analyze the risk factors of serious adverse events (SAEs).Methods:The occurrences of perioperative SAEs were retrospectively analyzed in 254 PMP patients treated with CRS plus HIPEC. Univariate and multivariate analysis were performed to identify independent risk factors.Results:Among the 272 CRS plus HIPEC procedures for 254 PMP patients, a total of 93 (34.2%) perioperative SAEs occurred, including 26 in infection, 22 in digestive system, 17 in respiratory system, 15 in cardiovascular system, 8 in hematological system, and 4 in urinary system. In terms of severity, the vast majority was grade Ⅲ with 76 cases, followed by grade Ⅳ with 13 cases and grade Ⅴ with 4 cases. Univariate analysis revealed 3 risk factors of perioperative SAEs: HIPEC regimen ( P=0.020), intraoperative red blood cell transfusion volume ( P=0.004), and intraoperative blood loss volume ( P=0.002). Multivariate analysis by logistic regression model analysis revealed that intraoperative red blood cell transfusion volume was an independent risk factor for perioperative SAEs ( OR=1.160, P=0.001). Conclusion:In conclusion, the perioperative safety of CRS plus HIPEC was acceptable. Moreover, intraoperative blood loss volume and red blood cell transfusion volume are expected to be reduced in order to prevent SAEs for PMP patients.

Objective To study the clinical features,pathological characters,treatment and prognosis of patients with malignant solitary fibrous tumor (MSFT).Methods Retrospective analysis was made on the clinical data of 11 MSFT patients undergoing surgical resection in Beijing Shijitan Hospital from Jan 2010 to Dec 2017.Overall survival (OS) and disease-free survival (DFS) were assessed using Kaplan-Meier methods.Results One patient died of duodenal fistula within a month after surgery,and the other 10 patients recovered with no severe complications.Immunohistochemically,the tumor cells are all positive for CD34 (11/11) and vimentin (10/10) in a different degree.The median OS and DFS for the 10 patients were 49 and 26 months respectively.The 1-,3-,and 5-year OS rates were 89％,56％,42％ respectively.The 1-,3-,and 5-year DFS rates were 79％,34％,23％ respectively.Conclusion MSFT is a malignancy with high recurrence rate.Tumor recurrence was the main cause of death for patients with MSFT.

Objective: To establish the patient derived xenograft (PDX) model of pseudomyxoma peritonei (PMP), and identify the key characteristics of tumor biology of this model, in order to provide a reliable model for studying the pathological mechanisms and new therapeutic strategies of PMP. Methods: PMP tumor tissue was obtained from surgery and cut into pieces after washing. Then tumor pieces were implanted subcutaneously in BAL B/c-nu mice for 6 stable passages. In the 7th passage, tumor tissue was implanted orthotopically into abdomen. Subcutaneous tumor and orthotopic tumor were then homogenized to make tumor cell suspension, implanted into abdomen of 10 BAL B/c-nu mice through midline laparotomy, 100 μl for each. The key experimental parameters including body weight changes in the observation period, experimental peritoneal cancer index (ePCI) score at the autopsy, histopathological and immunohistochemical characteristics, and gene expression profiles by high-throughput whole-genome exon sequencing were detected and recorded. Results: The successful rate of established orthotopic PDX model of human PMP was 100% (10/10). The animals showed smooth body weight increases after tumor inoculation until day 27, then the body weight began to decrease steadily. Widespread tumor dissemination of PMP tumor through the whole abdomen was found by autopsy, including the diaphragm, liver, spleen, stomach, kidney, parietal peritoneum, bowel and mesenterium. Gelatinous ascites was also observed in abdominopelvic cavity. The ePCI score ranged from 5 to 9, with a 8 of median ePCI. Histopathological studies showed peritoneal mucinous carcinomatosis accompanied with signet ring cells (PMCA-S), obvious tumor cell atypia and parenchymal invasion.Immunohistochemistry showed the expressions of MUC1, MUC2, MUC5AC, CEA, CA199, CK20, CDX-2 and Ki-67 were positive, MUC6, CK7 and p53 were negative. Whole-exome sequencing identified that the most significant genetic alteration is the exon10 missense mutation c. 1621A>C of KIT gene, the mutation abundance was 89.7%. Conclusion PDX model of PMCA-S is successfully established, which displays the characters of high-degree malignancy, high proliferation and strong aggressiveness.

Objective: To analyze the clinicopathological characteristics of ovarian pseudomyxoma peritonei (PMP). Methods: Clinical and pathological data from a total of 272 PMP patients diagnosed at Beijing Shijitan Hospital from January 2010 to January 2019 were collected from a database and retrospectively analyzed to study the origin of PMP tumors. Pathological slides marked with antigens were further studied using immunohistochemical staining, including CK7, CK20, CEA, Villin, CDX2, SATB2, CA125, ER, PR, MUC1, and MUC2. Results: Among the 272 PMP patients studied, the tumors of 245 (90.1%) originated from the appendix, while the remaining 27 (9.9%) originated from non-appendix tissues, including 5 (1.8%) from the ovaries. Ovarian cases included two ovarian teratomas, two ovarian mucinous cystadenomas, and one borderline ovarian mucinous cystadenoma. Histopathological analysis of peritoneal me-tastases further revealed two acellular mucins, two low-grade mucinous carcinoma peritonei, and one high-grade mucinous carcinoma peritonei, while immunohistochemistry revealed positive staining for CK20, CEA, Villin, and CDX2; SATB2 was also found to be partially positive in teratomas with mucinous tumors: negative in two cases and partially positive in one case. Conclusions: The occurrence of ovarian PMP is rare. Its precise diagnosis demands for a serial section of the whole appendix or suspected tissue to exclude any appen-diceal mucinous neoplasms, as well as the combination of a comprehensive analysis of its clinical signs and symptoms, imaging find-ings, surgical findings, histopathological characteristics, and immunohistochemistry.

Objective: To explore the relationship between liver controlled attenuation parameters (CAP) and body fat mass and its distribution. Methods: From May to December 2018, 978 adult patients visited at the fatty liver center of the Third People's Hospital of Changzhou were treated. The patient's liver controlled attenuation parameters were measured by transient elastography and the body fat mass and its distribution were measured by bioelectrical impedance technology. Pearson’s correlation coefficient was adopted to describe the correlation between liver CAP value and body mass index (BMI), body fat mass index (BFMI), trunk fat mass index (TFMI), limbs fat mass index (LFMI) and visceral fat area (VFA). Receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to evaluate BMI, BFMI, TFMI, LFMI and VFA to differentiate the cut-off points and efficacy of CAP for diagnosing grading of fatty liver changes in S0-1 and S2-3. Results: In 653 cases of male, S0 ~ S3 accounted for 4.90%, 3.37%, 22.36% and 69.37%, respectively, and in 325 cases of females, S0 ~ S3 accounted for 7.38%, 6.46%, 13.23% and 72.92%, respectively. Female patients had more visceral, trunk and limbs fat than male (P < 0.01). Body mass, body fat mass, body fat percentage, BMI, BFMI, TFMI, LFMI, and VFA were increased in male and female patients with increasing liver fat grade (P < 0.01). CAP values ​​of male and female patients were positively correlated with BMI, BFMI, TFMI, LFMI and VFA. Percentage of body fat mass increased with increasing liver fat grade (male: F = 13.42, P < 0.001; female: F = 3.22, P = 0.023); while limb fat mass percentage did not increase with liver fat grade (Male: F = 1.13, P = 0.34; female: F = 1.05, P = 0.37). Hepatic steatosis grading (S0 ~ 1 or S2 ~ 3) diagnosed with CAP were distinguished through BMI, BFMI, TFMI, LFMI and VFA. AUC was 0.80 ~ 0.82 in males (P < 0.01), and 0.75 ~ 0.78 in females (P < 0.01). Conclusion The liver CAP value is positively correlated with the body's limbs, trunk and visceral fat, and has a strong correlation with trunk and visceral fat. BMI, BFMI, TFMI, LFMI and VFA up to some extent can identify the CAP diagnosis of grading of fatty liver changes in S0-1 and S2-3.

Objective: To analyze the pathological features of pseudomyxoma peritonei (PMP) in correlation with the survival status and independent prognostic factors. Methods: One-hundred and fifty-five PMP specimens were collected at Beijing Shijitan Hospital, Capital Medical University, from 2012 to 2018. Conventional histopathological evaluation was performed to document the primary tumor site, histopathological type, lymph nodes metastasis, tumor emboli in the blood and lymph vessels, nerve invasion and cellular density. The immunohistochemical parameters including Ki-67, p53, MMR-related protein, MUC2 and MUC5AC were analyzed. Clinical follow-up data were reviewed to correlate with pathological prognostic factors using Kaplan-Meier estimator and Cox proportional hazards regression model for univariate and multivariate analysis. Results: Among 155 PMP patients, there were 77 males and 78 females. There were 98 cases (63.2%) of low-grade peritoneal mucinous carcinomatosis, 49 cases (31.6%) of high-grade peritoneal mucinous carcinomatosis, 8 cases (5.2%) of high-grade mucinous carcinoma peritonei with signet ring cells; only 15 cases (9.7%) with lymph node metastasis; 18 cases (11.6%) with tumor emboli in the blood and lymph vessels; 8/126 (6.3%) were positive dMMR; 100 cases (64.5%) had Ki-67 label index <50%, and 56 cases(36.1%) presented with mutant type p53. Univariate analysis revealed 11 survival-related pathological parameters including gender, age, primary tumor site, histopathological type, lymph node metastasis, tumor emboli in the blood and lymph vessels, nerve invasion, cellular density, Ki-67 label index rate, p53 and dMMR. Multivariate analysis identified 4 independent prognostic factors including the histopathological type (HR 59.78, P<0.01), lymph node metastasis (HR 3.74, P=0.028), nerve invasion (HR 7.81, P=0.007) and dMMR (HR 9.82, P<0.01). Conclusions Histopathological type is the most important prognostic factor of PMP with dMMR as an independent molecular prognostic indicator.

Objective To establish the patient derived xenograft ( PDX) model of pseudomyxoma peritonei (PMP), and identify the key characteristics of tumor biology of this model, in order to provide a reliable model for studying the pathological mechanisms and new therapeutic strategies of PMP. Methods PMP tumor tissue was obtained from surgery and cut into pieces after washing. Then tumor pieces were implanted subcutaneously in BAL B／c?nu mice for 6 stable passages. In the 7th passage, tumor tissue was implanted orthotopically into abdomen. Subcutaneous tumor and orthotopic tumor were then homogenized to make tumor cell suspension, implanted into abdomen of 10 BAL B／c?nu mice through midline laparotomy, 100 μl for each. The key experimental parameters including body weight changes in the observation period, experimental peritoneal cancer index (ePCI) score at the autopsy, histopathological and immunohistochemical characteristics, and gene expression profiles by high?throughput whole?genome exon sequencing were detected and recorded. Results The successful rate of established orthotopic PDX model of human PMP was 100%(10／10). The animals showed smooth body weight increases after tumor inoculation until day 27, then the body weight began to decrease steadily. Widespread tumor dissemination of PMP tumor through the whole abdomen was found by autopsy, including the diaphragm, liver, spleen, stomach, kidney, parietal peritoneum, bowel and mesenterium. Gelatinous ascites was also observed in abdominopelvic cavity.The ePCI score ranged from 5 to 9, with a 8 of median ePCI. Histopathological studies showed peritoneal mucinous carcinomatosis accompanied with signet ring cells ( PMCA?S ), obvious tumor cell atypia and parenchymal invasion. Immunohistochemistry showed the expressions of MUC1, MUC2, MUC5AC, CEA, CA199, CK20, CDX?2 and Ki?67 were positive, MUC6, CK7 and p53 were negative. Whole?exome sequencing identified that the most significant genetic alteration is the exon10 missense mutation c.1621A＞C of KIT gene, the mutation abundance was 89.7%. Conclusion PDX model of PMCA?S is successfully established, which displays the characters of high?degree malignancy, high proliferation and strong aggressiveness.