[Pulmonary artery stenting in chronic thromboembolic pulmonary hypertension: a report of 2 cases].

Chronic thromboembolic pulmonary hypertension (CTEPH) is a pulmonary vascular disease characterized by an insidious onset, progressive deterioration, and poor prognosis. It is distinguished by the thrombotic organization within the pulmonary arteries, leading to vascular stenosis or occlusion. This results in a progressive increase in pulmonary vascular resistance and pulmonary arterial pressure, ultimately leading to right heart failure. In recent years, balloon pulmonary angioplasty (BPA) has emerged as an effective treatment option for patients ineligible for pulmonary endarterectomy (PEA). However, the use of stents in patients with suboptimal balloon dilation remains controversial. This article describes two cases of chronic thromboembolic pulmonary hypertension (CTEPH) in which balloon angioplasty yielded unsatisfactory results, subsequently leading to stent placement. Following stent implantation, there was improved blood flow, significant reduction in pulmonary arterial pressure, and notable alleviation of patient symptoms. One-year follow-up showed no recurrence of stenosis within the stent, suggesting potential guidance for the use of pulmonary artery stenting as a treatment modality for CTEPH. This report provided new insights into the therapeutic approach for CTEPH.

[Surgical treatment and prognosis analysis of hilar cholangiocarcinoma].

Objective: To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma. Methods: This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of (M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) µmol/L(range: 5.4 to 722.8 µmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 µmol/L to 85.5 µmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results: Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ (P=0.009), hemi-hepatectomy and extended resection (P=0.001),T1 and T2 patients without vascular invasion (T2 vs. T1:OR=1.43 (0.61-3.35),P=0.413;T3 vs. T1:OR=2.57 (1.03-6.41), P=0.010;T4 vs. T1, OR=3.77 (1.37-10.38), P<0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions: Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.

[A case of metastatic breast cancer complicated by pulmonary tumor thrombotic microangiopathy].

Pulmonary tumor thrombotic microangiopathy is a malignancy-related complication with rapid progression and high mortality. To improve the understanding of the disease, early diagnosis and treatment are key to successful treatment. A 39-year-old patient with pulmonary hypertension transferred from another hospital was admitted to the First Affiliated Hospital of Guangzhou Medical University on September 26, 2021. The patient developed shortness of breath and progressive exacerbation over the past month. No pulmonary artery embolism was seen on computed tomography pulmonary angiography (CTPA) at the outside hospital where the breast cancer was diagnosed. Pulmonary tumor thrombotic microangiopathy was immediately considered on admission and oncological endocrine therapy was started. After treatment, the patient's dyspnoea improved, PET-CT showed significant tumor regression, and cardiac ultrasound showed a significant decrease in pulmonary artery pressure. The successful treatment experience of this case was summarized for reference.

[Diagnosis and treatment procedures and health management for patients with hereditary angioedema].

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.

[Effects and clinical significance of NLRP3 inflammasome activated by IL-17A in CRSwNP].

Objective: To investigate the effects and clinical significance of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activated by interleukin (IL)-17A in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: Patients underwent nasal endoscopic surgery in the Third Affiliated Hospital of Sun Yat-sen University from January 2020 to December 2021 were collected, including 28 CRSwNP (including 19 males and 9 females, aged 19 to 67 years), 22 chronic rhinosinusitis without nasal polyps (CRSsNP) and 22 controls. qRT-PCR was used to detect the expressions of IL-17A, NLRP3, IL-1ß and IL-18 in the three groups, and their correlations were analyzed. The positions of IL-17A, NLRP3 and IL-18 in nasal polys were analyzed by immunofluorescence. Western Blotting and ELISA were employed to detect the expression of NLRP3, IL-1ß and IL-18 in the human nasal epithelial cells after using IL-17A stimulation or IL-17A receptor inhibitor. Immunofluorescence was used to observe the NLRP3, IL-1ß, and IL-18 protein expression after IL-17A stimulating human nasal epithelial cells, and after the use of IL-17A receptor inhibitor and NLRP3 inhibitor MCC950. The correlations between NLRP3, IL-1ß, IL-18 and CT scores, nasal endoscopic scores, visual analogue scale (VAS) scores, and sino-nasal outcome test (SNOT) 22 scores of CRSwNP patients were analyzed. SPSS 20.0 software was used for statistical analysis. Results: The expressions of IL-17A, NLRP3, IL-1ß and IL-18 in the tissues of CRSwNP patients were significantly higher than those in CRSsNP group(P=0.018,P<0.001,P=0.005, P=0.016) and the control group(all P<0.001). IL-17A was positively correlated with the expression of NLRP3, IL-1ß, and IL-18(r ralue was 0.643,0.650,0.629,respectively, all P<0.05). IL-17A, NLRP3, and IL-18 were co-localized in the epithelial propria of polyp tissue. IL-17A stimulated the expressions of NLRP3, IL-1ß, and IL-18 in human nasal epithelial cells. After the use of IL-17A receptor inhibitor, the expressions of NLRP3, IL-1ß, and IL-18 were significantly down-regulated. After the use of NLRP3 inhibitor MCC950, IL-17A was significantly down-regulated to promote the expression of NLRP3, IL-1ß, and IL-18. The expressions of NLRP3, IL-1ß and IL-18 were positively correlated with CT, nasal endoscopy, VAS, and SNOT22 scores in patients with CRSwNP. Conclusions: IL-17A promotes the release of IL-1ß and IL-18 by activating the NLRP3 inflammasome and aggravates the severity of the disease in CRSwNP.

[Efficacy of intravenous drug information management system on the improvement of anemia in maintenance hemodialysis patients].

Objective: To investigate the effect of information management of intravenous drugs on anemia in maintenance hemodialysis patients. Methods: The information management of intravenous drugs was a management system developed by the Hemodialysis Center of Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital in April 2020. The parameters six months before and after the use of the information management system were retrospectively collected and compared, including the rate of reaching the standard of hemoglobin, ferritin, transferrin saturation rate and the incidence of cardiovascular events. Specifically, the control stage was from October 2019 to March 2020, which was before the use of information management, and the study stage was from April to September 2020, which was after the use of information management. Results: There were 285 patients (190 males and 95 females) included in the control stage, with an average age of (62.4±13.2) years, while 278 patients (193 males and 85 females) were included in the study stage, with an average age of (62.8±13.2) years. Compared with the control stage, the rate of reaching the standard of hemoglobin [47.8% (797/1 668) vs 40.2% (687/1 710), P<0.001], ferritin [39.0% (217/556) vs 31.2% (178/570), P=0.006], and transferrin saturation [64.7% (360/556) vs 58.6% (334/570), P=0.034] increased in the study stage. The incidence of cardiovascular events in the study stage was 11.2% (31/278), which was significantly lower than that in the control stage [16.5% (47/285)] (P=0.043). Conclusion: The information management of intravenous drugs in the hemodialysis center may help improve the anemia status in maintenance hemodialysis patients.

[Efficacy and safety of dexcitabine combined with HAAG regimen in the treatment of recurrent acute myeloid leukemia].

Objective: To investigate the efficacy and safety of dexithabine (DAC) combined with HAAG regimen [harringtonine (HHT), cytarabine (Ara-C), aclarubicin (Acla) and recombinant human granulocyte colony stimulating factor (G-CSF)] in the treatment of acute myeloid leukemia (AML). Methods: The clinical data of 89 AML patients in People's Hospital Affiliated to Shandong First Medical University from January 2019 to January 2021 were retrospectively analyzed. The patients were divided into observation group (n=48) and control group (n=41) according to the treatment plan. The observation group included 25 males and 23 females, aged (44.4±9.3) years old, and was treated with DAC combined with HAAG. The control group included 24 males and 17 females, aged (42.2±10.1) years old, and was treated with DAC regimen. After 3 cycles of treatment, the treatment efficacy of the two groups was judged, including complete remission, partial remission and no remission. The level of serum P-glycoprotein (P-gp) in the two groups was detected by direct immunofluorescence-labeled monoclonal antibody flow cytometry. The enzyme-linked immunosorbent assay was used to detect the level of soluble urokinase-type plasminogen activator receptor (suPAR). Meanwhile, the incidence of adverse reactions such as digestive tract reaction, liver and kidney dysfunction, hemorrhage and infection during treatment were recorded. Results: After 3 cycles of treatment, the observation group had complete remission, partial remission and no remission in 10 cases, 21 cases and 17 cases, respectively, and the control group had 3 cases, 11 cases and 27 cases, respectively. The overall efficacy of the observation group was better than that of the control group (Z=-2.919, P=0.004). The levels of serum P-gp and suPAR in the observation group were (5.2±1.8) % and (464.4±103.4) ng/L, respectively, which were significantly lower than those in the control group [(8.8±1.9) % and (660.6±110.4) ng/L, respectively] (both P<0.05). During the treatment, the incidence of digestive tract reaction, liver and kidney dysfunction, hemorrhage and infection in the observation group was 29.2% (14/48), 22.9% (11/48), 16.7% (8/48) and 33.3% (16/48), respectively, while in the control group was 26.8% (11/41), 21.9% (9/41), 14.6% (6/41) and 24.4% (10/41), respectively, with no statistically significant difference (all P>0.05). Conclusions: The overall efficacy of DAC combined with HAAG in the treatment of AML is better than that of DAC alone. Moreover, the incidence of adverse reactions in DAC combined with HAAG is similar to that of DAC alone, with a high safety profile.

[Associations between multimorbidity patterns of 4 chronic diseases and physical activity with all-cause mortality].

Objective: To identify the prevalence of multimorbidity among a Chinese population, analyze the risk of all-cause mortality with different multimorbidity patterns, and the impact of exercise on the risk of multimorbidity-related mortality and life lost. Methods: The study was based on 437 408 MJ Health Management Center participants. The classification decision tree was used to explore multimorbidity patterns composed of hypertension, diabetes, chronic kidney disease (CKD), and chronic obstructive pulmonary disease (COPD). The Cox proportional hazards model was used to calculate the all-cause mortality hazard ratio (HR) for different multimorbidity patterns. Using Chiang's life table method, years of life lost were the difference in life expectancy for those with and without multimorbidity. Results: The prevalence rate of multimorbidity was 8.7%. Among multivariate patterns, the most common ones were "hypertension+CKD" (3.6%), "hypertension + diabetes + CKD" (1.1%) and "hypertension+diabetes+CKD+COPD" (0.1%). Compared with a healthy population, patterns with the highest mortality risk were "diabetes+CKD" (HR=3.80, 95%CI: 3.45-4.18), "diabetes+CKD+COPD" (HR=4.34, 95%CI: 3.43-5.49) and "hypertension+ diabetes+CKD+COPD" (HR=4.75,95%CI:4.15-5.43). Through low-intensity and moderate to high-intensity exercise, the increased HRs were attenuatedcompared with the inactive population. People with single disease and multimorbidity shortened life by 4.6 and 13.4 years, while exercise attenuated 2.3 and 4.6 years of life lost, of which low-intensity and moderate to high-intensity exercise saved 1.5 and 3.7 years of life lost due to chronic diseases. Conclusions: Multimorbidity patterns based on "diabetes + CKD" cause the highest mortality risk, and physical activity in reducing mortality was significant for either with or without multimorbidity. Higher exercise intensity leads to a greater relative reduction of mortality risk.

[Application of locating supratrochlear artery and supraorbital artery in combined transfrontal and intranasal endoscopic approaches].

Objective: To investigate the localization methods of supratrochlear artery (STA) and supraorbital artery (SOA), and to explore the clinical benefit of locating nerve via accompanying vascular localization in combined transfrontal and intranasal endoscopic approaches. Methods: From June 2019 to May 2021, 14 patients, including 11 males and 3 females, aging from 18 to 69 years old, were underwent frontal sinus surgery through the combined transfrontal and intranasal endoscopic approaches in the Department of Otorhinolaryngology Head and Neck Surgery of the Third Affiliated Hospital of Sun Yat-sen University. Before the surgery, localization of STA and SOA was determined by color doppler flow imaging (CDFI), computerized topographic angiography (CTA) and contrast enhanced magnetic resonance angiography (CE-MRA) respectively, and the distances between STA and SOA from facial midline were measured on 28 eyebrows. The position of external incision was determined according to the preoperative localization of STA and SOA. The examination time, cost and postoperative complications of the three methods were recorded. The accuracy of localization at 14 sides was verified by the surgery. GraphPad Prism 8.3 software was used for statistical analysis. Results: STA and SOA could be located by CDFI, CTA and CE-MRA. There was no significant difference in the measurement of the distance between STA and SOA from the facial midline among 3 methods (all P>0.05). Determining the position of external incision according to the localization of STA and SOA could protect both the blood vessels and accompanying nerves. No postoperative complications such as numbness of the forehead skin occurred. The measurement time of CDFI, CTA and CE-MRA was 22.50 (15.75, 30.00), 30.00 (28.00, 34.25) and 48.00 (44.00, 52.75) min (M (Q1, Q3)), respectively (all P<0.05). CDFI incurred the lowest costs and took the shortest time. Conclusions: CDFI is an efficient and economic localization method. The localization of STA and SOA facilitates the precise selection of the position of external incision, protects the accompanying nerve and reduces postoperative complications.

[Efficacy and safety of neoadjuvant immunotherapy for hepatocellular carcinoma].

Objective: To study the surgical safety and efficacy of preoperative neoadjuvant therapy with immune checkpoint inhibitors combined with anti-angiogenic drugs in patients with China liver cancer staging(CNLC)-Ⅱb and Ⅲa resectable hepatocellular carcinoma. Methods: The data of 129 patients with Ⅱb and Ⅲa hepatocellular carcinoma who underwent surgery at the First Affiliated Hospital of Nanjing Medical University from January 2018 to December 2020 were analyzed. All patients were divided into two groups: the neoadjuvant therapy group(n=14,13 males and 1 female,aged (55.4±12.6)years(range:34 to 75 years)) received immune combined targeted therapy before surgery,immune checkpoint inhibitor camrelizumab was administered intravenously at a dose of 200 mg each time,every 2 weeks for 3 cycles,anti-angiogenesis drug apatinib was taken orally and continuously with a dose of 250 mg for 3 weeks and the conventional surgery group(n=115,103 males and 12 females,aged (55.8±12.0)years(range:21 to 83 years)) did not receive antitumor systemic therapy before surgery. There were 3 patients with CNLC-Ⅱb,11 with CNLC-Ⅲa in the neoadjuvant group;28 patients with CNLC-Ⅱb,87 with CNLC-Ⅲa in the conventional group. Student's t test or rank-sum test was used to compare the differences between two groups for quantitative data, Fisher's exact probability method was used to compare the differences of proportions between two groups, and Log-rank test was used to compare survival differences between two groups. Results: The 1-year recurrence rate in the neoadjuvant group was 42.9%,and the 1-year recurrence rate in the conventional group was 64.0%,with a statistically significant difference between the two groups(χ²=3.850,P=0.050);The 1-year survival rate in the neoadjuvant group was 100% and that in the conventional group was 74.2%,with a statistically significant difference between the two groups(χ²=5.170,P=0.023). According to the stratified analysis of the number of tumors,for single tumor,the 1-year recurrence rate in the neoadjuvant group was 25.0%,and that in the conventional surgery group was 71.0%,and the difference between the two groups was statistically significant(χ²=5.280, P=0.022). For multiple tumors, the 1-year recurrence rate in the neoadjuvant group was 66.7%,and the 1-year recurrence rate in the conventional surgery group was 58.9%,with no significant difference between the two groups(χ²=0.110,P=0.736). The operative time,intraoperative blood loss,and postoperative hospital stay in the neoadjuvant group were similar to those in the conventional group,and their differences were not statistically significant. Conclusions: Immune checkpoint inhibitors combined with anti-angiogenic targeted drugs as a neoadjuvant therapy for resectable hepatocellular carcinoma can reduce the 1-year recurrence rate and improve the 1-year survival rate,especially for those with solitary tumor. Limited by the sample size of the neoadjuvant group,the safety of immune combined targeted therapy before surgery cannot be observed more comprehensively,and further studies will be explored.

[Abnormal expression of CD44 aggravates liver disease progression in patients with non-alcoholic fatty liver disease accompanied with hepatitis B virus replication].

Objective: To analyze the expression of CD44 in non-alcoholic fatty liver disease (NAFLD) accompanied with hepatitis B virus (HBV) infection and its clinical significance. Methods: Blood sample of hospitalized patients with NAFLD, chronic hepatitis B, cirrhosis, and healthy population (control) was collected. The study was approved by the hospital ethics committee. Serum CD44 level and clinopathological characteristics were analyzed quantitatively by enzyme-linked immunosorbent-assay. Flow cytometry was used to analyze the proportion of CD44(+)T lymphocytes in patients with NAFLD and chronic hepatitis B. NAFLD model was prepared with high-fat diet to verify the abnormal expression of CD44. Results: Compared with the healthy control group, the expression of serum CD44 in the cirrhosis group, chronic hepatitis B group and NAFLD group was increased, and the difference between the groups were statistically significant (P < 0.01). NAFLD patients graded as mild or severe group were equally accompanied by hepatocyte injury, abnormal blood glucose, lipid or CD44. In NAFLD patients accompanied with HBV infection, serum CD44 concentrations were significantly higher in HBsAg, HBeAg and HBV DNA positive group than HBsAg, HBeAg and HBV DNA negative group (P < 0.01). The proportion of CD44(+)T lymphocytes in peripheral blood of NAFLD and chronic hepatitis B group were 78.2% ± 16.3% and 68.5% ± 20.9%, respectively, and both groups (NAFLD and chronic hepatitis B) were significantly higher than the healthy control group (46.5% ± 20.5%) (P < 0.05). The high-fat diet model confirmed that in rat liver tissues the CD44 was overexpressed with fat deposition accompanied with liver cell damage, especially remarkable in liver tissues containing carcinogens. Conclusion: The abnormal expression of CD44 in patients with NAFLD may be related to the malignant transformation of HBV-related liver disease.

Novel chemotherapeutic agent FX-9 activates NF-κB signaling and induces G1 phase arrest by activating CDKN1A in a human prostate cancer cell line.

BACKGROUND: The aminoisoquinoline FX-9 shows pro-apoptotic and antimitotic effects against lymphoblastic leukemia cells and prostate adenocarcinoma cells. In contrast, decreased cytotoxic effects against non-neoplastic blood cells, chondrocytes, and fibroblasts were observed. However, the actual FX-9 molecular mode of action is currently not fully understood. METHODS: In this study, microarray gene expression analysis comparing FX-9 exposed and unexposed prostate cancer cells (PC-3 representing castration-resistant prostate cancer), followed by pathway analysis and gene annotation to functional processes were performed. Immunocytochemistry staining was performed with selected targets. RESULTS: Expression analysis revealed 0.83% of 21,448 differential expressed genes (DEGs) after 6-h exposure of FX-9 and 0.68% DEGs after 12-h exposure thereof. Functional annotation showed that FX-9 primarily caused an activation of inflammatory response by non-canonical nuclear factor-kappa B (NF-κB) signaling. The 6-h samples showed activation of the cell cycle inhibitor CDKN1A which might be involved in the secondary response in 12-h samples. This secondary response predominantly consisted of cell cycle-related changes, with further activation of CDKN1A and inhibition of the transcription factor E2F1, including downstream target genes, resulting in G1-phase arrest. Matching our previous observations on cellular level senescence signaling pathways were also found enriched. To verify these results immunocytochemical staining of p21 Waf1/Cip1 (CDKN1A), E2F1 (E2F1), PAI-1 (SERPNE1), and NFkB2/NFkB p 100 (NFKB2) was performed. Increased expression of p21 Waf1/Cip1 and NFkB2/NFkB p 100 after 24-h exposure to FX-9 was shown. E2F1 and PAI-1 showed no increased expression. CONCLUSIONS: FX-9 induced G1-phase arrest of PC-3 cells through activation of the cell cycle inhibitor CDKN1A, which was initiated by an inflammatory response of noncanonical NF-κB signaling.

[The expression of Notch pathway in nasal polyps and its correlation with the decreased Treg percentage and eosinophil infiltration].

Objective: To investigate the correlation between Notch pathway expression in nasal polyps and Treg percentage and Eos infiltration. Methods: Patients with chronic sinusitis and simple nasal septum deviation who received nasal endoscopic surgery in the Third Affiliated Hospital of Sun Yat-Sen University between November 2012 and August 2018 were selected and enrolled in CRS group and control group respectively. Nasal mucosa tissues were collected from 30 CRSsNP patients (14 males and 16 females aged from 18 to 63), 58 CRSwNP patients (38 males and 20 females aged from 18 to 65) and 29 patients (19 males and 10 females aged from 20 to 57), who underwent nasal endoscopic surgery for correction of simple nasal septum deviation. Hematoxylin-eosin(HE) staining was used to observe the infiltration of eosinophilic granulocytes in the tissues and to classify chronic sinusitis with polyps (CRSwNP) into eosinophilic chronic rhinosinusitis with nasal polyps (Eos-CRSwNP)and non-eosinophilic chronic rhinosinusitis with nasal polyps (Eos-CRSwNP). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of Notch pathway receptors (Notch-l, 2, 3, 4) and their ligands (Jagded-l, Jagded-2, Delta-l, Delta-3and Delta-4) in the nasal mucosa of each group, as well as the expression of Th2 cytokines (IL-4, IL-5, IL-13), eosinophilic cationic protein (ECP)and the key transcription factor Foxp3 in Treg cells. Finally, flow cytometry was used to detect CD4+CD25+Foxp3+ Treg cells in nasal mucosa of each group. Results: Compared with controls, the expression of Th2 cytokines (IL-4, IL-5, IL-13) in CRSsNP and non-Eos-CRSwNP patients was the highest in Eos-CRSwNP (F=16.930,9.197,9.116, all P<0.05). Foxp3 had the lowest expression in Eos-CRSwNP patients and was lower than non-Eos-CRSwNP patients (F=2.780,P<0.05), and was negatively correlated with ECP (r=-0.326,P<0.05). Compared with controls, Eos-CRSwNP patients in CRSsNP patients and non-Eos-CRSwNP patients exhibited a significantly lower frequency of CD4+CD25+Foxp3+Treg cells (F=13.140, all P<0.01). The expression of Notch-l and Jagged-l in Eos-CRSwNP was significantly higher than that of the controls, CRSsNP patients and non-Eos-CRSwNP patients (F=5.953/F=6.380, P<0.05). In the nasal polyp group, the expression of Notch-l and Jagged-l showed significantly negative correlation with Foxp3 (r=-0.611/-0.346, all P<0.05), and positive correlation with Th2 cytokines (IL-4, IL-5, IL-13) and ECP, respectively (r=0.781/0.459,0.621/0.601,0.605/0.490,0.464/0.668, all P<0.05). There was no significant difference in the expression of receptor and ligand of the other Notch pathway among the groups. Conclusion: Abnormal activation of Notch-l/Jagged-l pathway may be involved in decreasing Treg ratio in Eos-CRSwNP, thereby promoting Th2 inflammatory response and Eosinophil infiltration.

[Surgical treatment of primary liver cancer:a report of 10 966 cases].

Objective: To summarize the experience of surgical treatment of primary liver cancer. Methods: The clinical data of 10 966 surgically managed cases with primary liver cancer, from January 1986 to December 2019 at Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, were retrospectively analyzed. The life table method was used to calculate the survival rate and postoperative recurrence rate. Log-rank test was used to compare the survival process of different groups, and the Cox regression model was used for multivariate analysis. In addition, 2 884 cases of hepatocellular carcinoma(HCC) with more detailed follow-up data from 2009 to 2019 were selected for survival analysis. Among 2 549 patients treated with hepatectomy, there were 2 107 males and 442 females, with an age of (56.6±11.1) years (range: 20 to 86 years). Among 335 patients treated with liver transplantation, there were 292 males and 43 females, with an age of (51.0±9.7) years (range: 21 to 73 years). The outcomes of hepatectomy versus liver transplantation, anatomic versus non-anatomic hepatectomy were compared, respectively. Results: Of the 10 966 patients with primary liver cancer, 10 331 patients underwent hepatectomy and 635 patients underwent liver transplantation. Patients with liver resection were categorized into three groups: 1986－1995(712 cases), 1996－2008(3 988 cases), 2009‒2019(5 631 cases). The 5-year overall survival rate was 32.9% in the first group(1986－1995). The 5-year overall survival rate of resected primary liver cancer was 51.7% in the third group(2009-2019), among which the 5-year overal survival rates of hepatocellular carcinoma, intrahepatic cholangiocarcinoma and mixed liver cancer were 57.4%, 26.6% and 50.6%, respectively. Further analysis was performed on 2 549 HCC patients with primary hepatectomy. The 1-, 3-, 5-, and 10-year overall survival rates were 88.1%, 71.9%, 60.0%, and 41.0%, respectively, and the perioperative mortality rate was 1.0%. Two hundred and forty-seven HCC patients underwent primary liver transplantation, with 1-, 3-, 5-, and 10-year overall survival rates of 84.0%, 64.8%, 61.9%, and 57.6%, respectively. Eighty-eight HCC patients underwent salvage liver transplantation, with the 1-, 3-, 5-, and 10-year overall survival rates of 86.8%, 65.2%, 52.5%, and 52.5%, respectively. There was no significant difference in survival rates between the two groups with liver transplantation (P>0.05). Comparing the overall survival rates and recurrence rates of primary hepatectomy (2 549 cases) with primary liver transplantation (247 cases), the 1-, 3-, 5-, and 10-year overall survival rates in patients within Milan criteria treated with hepatectomy and transplantation were 96.3%, 87.1%, 76.9%, 54.7%, and 95.4%, 79.4%, 77.4%, 71.7%, respectively (P=0.754). The 1-, 3-, 5-year recurrence rates were 16.3%, 35.9%, 47.6% and 8.1%, 11.7%, 13.9%, respectively(P<0.01). The 1-, 3-, 5-, 10-year overall survival rates in patients with no large vessels invasion beyond the Milan criteria treated with liver resection and transplantation were 87.2%, 65.9%, 53.0%, 33.0% and 87.6%, 71.8%, 71.8%, 69.3%, respectively(P=0.003); the 1-, 3-, 5-year recurrence rate were 39.2%, 57.8%, 69.7% and 29.7%, 36.7%, 36.7%, respectively (P<0.01). The 1-, 3-, 5-, and 10-year overall survival rates in patients with large vessels invasion treated with liver resection and transplantation were 62.1%, 36.1%, 22.2%, 15.0% and 62.9%, 31.8%,19.9%, 0, respectively (P=0.387); the 1-, 3-, 5-year recurrence rates were 61.5%, 74.7%, 80.8% and 59.7%, 82.9%, 87.2%, respectively(P=0.909). Independent prognostic factors for both overall survival and recurrence-free survival rates of HCC patients treated with liver resection included gender, neoadjuvant therapy, symptoms, AST, intraoperative or postoperative blood transfusion, tumor number, tumor size, cirrhosis, macrovascular invasion, microvascular invasion, and pathological differentiation. Propensity score matching analysis of 443 pairs further showed that there was no significant difference in overall survival rate between anatomical liver resection and non-anatomical liver resection(P=0.895), but the recurrence rate of non-anatomical liver resection was higher than that of anatomical liver resection(P=0.035). Conclusions: In the past decade, the overall survival rate of HCC undergoing surgical treatment is significantly higher than before. For HCC patients with good liver function reservation, surgical resection can be performed first, and salvage liver transplantation can be performed after recurrence. The effect of salvage liver transplantation is comparable to that of primary liver transplantation. As for the choice of liver resection approaches, non-anatomical resection can reserve more liver tissue and can be selected as long as the negative margin is guaranteed.

[Clinical efficacy and prognostic factors analysis following curative hepatectomy for hepatocellular carcinoma patients with different China Liver Cancer Staging].

Objective: To examine clinical efficacy and prognostic factors of hepatocellular carcinoma(HCC) patients with different China Liver Cancer Staging (CNLC) after hepatectomy. Methods: From January 2010 to December,2019,549 patients underwent surgical resection and pathologically proven HCC were retrospectively reviewed in the First Affiliated Hospital of Nanjing Medical University. There were 462 males(84.2%) and 87 females(15.8%);the median age was 57 years (range: 21-84 years). Preoperative parameters,intraoperative and postoperative conditions,and postoperative pathological examination were observed.Survival analysis was performed by Kaplan-Meier method and the Log-rank test. Factors associated with disease-free survival(DFS) and overall survival(OS) of HCC patients were identified using univariate and multivariate Cox proportional hazards regression models. Results: Among the 549 patients underedwent liver resection,200 patients(36.4%) belonged to CNLC Ⅰa,whiles 148 patients(27.0%) belonged to CNLC Ⅰb. Furthermore,there were 49 patients(8.9%) with CNLC Ⅱa,32 patients(5.8%) with CNLC Ⅱb, 101 patients(18.4%) with CNLC Ⅲa and 19 patients(3.5%) with CNLC Ⅲb.The 1-,3-,5-,10-year OS for the entire cohort was 83.8%,69.0%,54.2%,37.7%,respectively,while 1-,3-, 5-year DFS was 61.0%,44.2%,36.0%, respectively. The 1-,3-, 5-year OS and DFS for CNLC Ⅰa were 97.3%,90.6%,80.5% and 83.9%,65.0%,54.0%,respectively;The 1-, 3-, 5-years OS and DFS for CNLC Ⅰb were 87.9%,71.0%,47.7%,and 58.4%,42.3%,33.4%,respectively.The 5-year OS for CNLC Ⅱa (37.2%) and Ⅱb(44.3%) were similar to CNLC Ⅰb. The 1-, 3-, 5-year OS and DFS for CNLC Ⅲb were 35.3%,13.2%,0 and 23.5%,0 and 0,respectively. Univariate analysis showed that preoperative symptoms,AFP level,total protein level,AST level,total bilirubin level,intraoperative blood loss,intraoperative or postoperative blood transfusion,postoperative complications,tumor number and size,microvascular invasion,macrovascular invasion and tumor differentiation were prognostic factors for long-term survival(≥5 years)(all P<0.05). The multivariate analysis suggested that AST level,intraoperative blood loss,tumor number and size,macrovascular invasion and tumor differentiation were the independent prognostic factors of long-term OS (all P<0.05). Conclusions: HCC patients with different stages of CNLC have different recurrence patterns and prognosis.After strict preoperative evaluation,patients with CNLC Ⅱa-Ⅲb can also benefit from radical resection. AST level,intraoperative blood loss,tumor number,tumor size,macrovascular invasion and tumor differentiation were independent factors that affect long-term survival. This will provide an important basis for the choice of treatment and the evaluation of surgical prognosis for patients with HCC.

No pulsed radio emission during a bursting phase of a Galactic magnetar.

Fast radio bursts (FRBs) are millisecond-duration radio transients of unknown physical origin observed at extragalactic distances1-3. It has long been speculated that magnetars are the engine powering repeating bursts from FRB sources4-13, but no convincing evidence has been collected so far14. Recently, the Galactic magnetar SRG 1935+2154 entered an active phase by emitting intense soft γ-ray bursts15. One FRB-like event with two peaks (FRB 200428) and a luminosity slightly lower than the faintest extragalactic FRBs was detected from the source, in association with a soft γ-ray/hard-X-ray flare18-21. Here we report an eight-hour targeted radio observational campaign comprising four sessions and assisted by multi-wavelength (optical and hard-X-ray) data. During the third session, 29 soft-γ-ray repeater (SGR) bursts were detected in γ-ray energies. Throughout the observing period, we detected no single dispersed pulsed emission coincident with the arrivals of SGR bursts, but unfortunately we were not observing when the FRB was detected. The non-detection places a fluence upper limit that is eight orders of magnitude lower than the fluence of FRB 200428. Our results suggest that FRB-SGR burst associations are rare. FRBs may be highly relativistic and geometrically beamed, or FRB-like events associated with SGR bursts may have narrow spectra and characteristic frequencies outside the observed band. It is also possible that the physical conditions required to achieve coherent radiation in SGR bursts are difficult to satisfy, and that only under extreme conditions could an FRB be associated with an SGR burst.

[Relationship between cognitive impairment and sleep-related respiratory indexes in patients with obstructive sleep apnea].

Objectives: To investigate the cognitive impairment in patients with obstructive sleep apnea (OSA), and it's relationship with sleep-related respiratory indexes. Methods: A total of 126 patients who were diagnosed with OSA and received treatment in the Sichuan Mental Health Center from March 2018 to September 2018 were selected as the OSA group, and 92 healthy volunteers with matched age, gender and education level were also recruited as the control group. All participants were assessed by polysomnography and the montreal cognitive assessment scale (MOCA). Results: (1) The total score of MOCA, visual space/executive function score, attention score, language function score and memory score in OSA group were significantly lower than those in the control group (23±4 vs 25±4, 2.0±1.7 vs 2.9±1.5, 5.4±1.0 vs 5.7±0.7, 2.7±0.6 vs 2.9±0.3, 2.6±1.4 vs 3.0±1.4, all P<0.05). The correlation analysis showed that MOCA score was in positive correlation with education level (r=0.585, P<0.001) and mean oxygen saturation (r=0.207, P=0.020). However, the MOCA score was in negative correlation with age (r=-0.564, P<0.001) and time in bed (TIB) (r=-0.205, P=0.021). There was no correlation between MOCA score and apnea-hypopnea index (AHI) (r=-0.006, P=0.949). Multiple linear regression analysis revealed that age (t=-4.133, P<0.001), education level (t=4.001, P<0.001) and mean oxygen saturation (t=2.036, P=0.044) were the major factors that contributed to the cognitive impairment of OSA patients. Conclusions: Patients with OSA have cognitive impairment. The impairment gets more obvious when more severe hypoxia occurs at night, but it's not related to AHI.