Objective: To compare the biological characteristics of human induced pluripotent stem cell-derived platelet exosomes (hiPSC-Plt-Exos) with those of conventional apheresis platelet exosomes (Plt-Exos), specifically focusing on their differential abilities to enhance the proliferation and migration of human umbilical cord mesenchymal stem cells (hUC-MSCs). Methods: Exosomes were isolated from hiPSC-derived Plt and apheresis Plt concentrate using size exclusion chromatography. These exosomes were then characterized through nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blotting. Co-culture experiments into hUC-MSCs were conducted with hiPSC-Plt-Exos and apheresis Plt-Exos, respectively. Their effects on the proliferation and migration of hUC-MSCs were assessed via cell proliferation assays and scratch tests. Results: hiPSC-Plt-Exos and apheresis Plt-Exos exhibited comparable particle sizes, morphological features (such as the characteristic cup-shaped structure), and surface markers (including CD9 and HSP70). Notably, hiPSC-Plt-Exos demonstrated a significantly greater ability to enhance the proliferation and migration of hUC-MSCs compared to apheresis Plt-Exos (P<0.05). These differences provide critical comparative data for their application in various clinical contexts. Conclusion: This study establishes a theoretical foundation for developing precise therapeutic strategies based on hiPSC-Plt-Exos. Furthermore, it underscores the necessity of selecting the appropriate type of exosomes according to the specific disease microenvironment to achieve optimal therapeutic outcomes.

BACKGROUND:Nano-zirconium dioxide has good application potential in the field of bone tissue repair.Studying the effect of nano-zirconium dioxide on osteogenic differentiation will help to promote the clinical application of nano-zirconium dioxide in the treatment of bone defects. OBJECTIVE:To explore the effect of nano-zirconium dioxide on the osteogenic differentiation of ectomesenchymal stem cells in the nasal mucosa. METHODS:Ectomesenchymal stem cells derived from rat nasal mucosa were isolated and cultured,and the biotoxicity of nano-zirconium dioxide to the cells was detected by CCK-8 assay.The biosafety concentration was selected according to the cytotoxicity,and the cells were randomly divided into a control group,a nano-zirconium dioxide group,and a nano-hydroxyapatite group.Osteogenic differentiation of cells was directionally induced in each group.On day 7 of induced differentiation,alkaline phosphatase staining was performed.qRT-PCR and western blot assay were used to detect the expression of early osteogenic markers(Runx2 and Osx).On day 21 of induced differentiation,alizarin red staining was conducted.qRT-PCR and western blot assay were utilized to determine the expression levels of late osteogenic markers(OPN and OCN). RESULTS AND CONCLUSION:(1)The median lethal concentration of nano-zirconium dioxide on ectomesenchymal stem cells in nasal mucosa was 0.6 mg/mL.In the experiment,the mass concentration of 200 μg/mL was selected for intervention.Zirconium dioxide had no significant effect on the proliferation of the cells.(2)Compared with the control group,the alkaline phosphatase staining of the cells in the nano-zirconium dioxide group was more obvious and the level of cell mineralization was higher,but there was no significant difference compared with the nano-hydroxyapatite.(3)Compared with the control group,the expression of bone-related genes and proteins increased significantly,but there was no significant difference compared with nano-hydroxyapatite.(4)The results show that nano-zirconium dioxide has good biological safety and can promote the osteogenic differentiation of ectomesenchymal stem cells in the nasal mucosa.This promoting effect is equivalent to that of nano-hydroxyapatite.

Objective To analyze the influencing factors of delayed postoperative bleeding(DPPB)after endoscopic submucosal dissection(ESD)for early gastric cancer and construct a Nomogram model.Methods The clinical information of 234 patients who underwent ESD treatment at our hospital and pathologically diagnosed with early gastric cancer from April 2021 to April 2023 were collected.The patients were grouped based on the presence or absence of DPPB.Logistic regression analysis was applied to screen for risk factors affecting DPPB after ESD in early gastric cancer patients.R software was applied to construct a Nomogram model for predicting the risk of DPPB in early gastric cancer patients after ESD.Receiver operator characteristic(ROC)curve,calibration curve,and Hosmer-Lemeshow goodness of fit test were plotted to evaluate the Nomogram model.Results A total of 23(9.8%)of 234 early gastric cancer patients who underwent ESD treatment developed DPPB.Multivariate Logistic regression analysis showed that the number of biopsies≥3(95%CI:2.482-20.424,P=0.000),the maximum diameter of lesions≥3 cm(95%CI:1.620-13.244,P=0.004),the depth of invasion to submucosa(95%CI:1.421-10.536,P=0.008),and intraoperative bleeding(95%CI:1.160-11.300,P=0.027)were independent risk factors for DPPB after ESD in early gastric cancer patients.The area under ROC curve(AUC)was 0.838(95%CI:0.743-0.932).The slope of the calibration curve was close to 1.Hosmer-Lemeshow goodness of fit test showed χ2=3.328,P=0.505.Conclusions The number of biopsies≥3,the maximum diameter of lesion≥3 cm,the depth of invasion to submucosa,and intraoperative bleeding are independent risk factors for DPPB after ESD in early gastric cancer patients.The Nomogram model based on these four independent risk factors can effectively predict the risk of DPPB after ESD in early gastric cancer patients.

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.

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.

【Objective】 To analyze the data of clinical blood transfusion quality control supervision in Shanghai, so as to provide reference for the improvement of clinical blood transfusion quality management in hospitals at all levels. 【Methods】 The data of clinical blood transfusion quality control supervision in hospitals at all levels from 2016 to 2021 were retrospectively analyzed to obtain the characteristics and indicators in the quality management. 【Results】 The overall level of clinical blood transfusion quality management in Shanghai steadily improved from 2016 to 2021 (F=3.82, P<0.01), and the management level of different hospitals varied significantly (F=9.00, P<0.01). In 2021, the full compliance rates of housing facilities, instruments and equipment, diagnostic reports and medical record writing among the third-level indicators of clinical blood transfusion quality management in hospitals at all levels were as follows: 86.49%(32/37), 100% (37/37)and 43.24%(16/37) for tertiary comprehensive hospitals; 61.11%(11/18), 88.89%(16/18) and 50.00% (9/18)for tertiary specialized hospitals; 60.87%(14/23), 78.26%(18/23)and 47.83%(11/23) for secondary comprehensive hospitals, ; 60.00%(9/15), 66.67%(10/15), 40.00%(6/15) for secondary specialized hospitals; 52.38%(11/21), 38.10%(8/21), 42.86%(9/21) for private hospitals. 【Conclusion】 The characteristics of clinical blood transfusion quality management in hospitals at all levels in Shanghai differed significantly, with different strengths and weaknesses. Hospitals should improve blood transfusion management in terms of housing facilities, personnel management, system process as well as diagnostic reports and medical record writing, in order to enhance the clinical blood transfusion quality management.

【Objective:】 To summarize the research status, problems and countermeasures of ethical issues related to volunteer action in public health emergencies by reviewing relevant literature. 【Methods:】 Using four keywords: public health emergencies, volunteers, ethics, and research, this paper searched the Chinese and English databases for the literature published from December 2006 to December 2021 (15 years in total) on "ethical research on volunteer action in public health emergencies". After searching, it was found that there were not many related papers. A total of 31 papers were retrieved, and only 23 papers were selected. 【Results:】 The ethical problems faced by volunteers in public health emergencies were complex and diverse, and the individual ethical behavior of volunteers was affected by many factors. The strategies to solve the relevant ethical issues were not yet perfect. 【Conclusions:】 The ethical issues related to volunteer actions in public health emergencies needed to be further studied.

Objective:To evaluate clinical efficacy and safety of topical compound oleum lithospermi in the treatment of mild to moderate diaper dermatitis.Methods:A multicenter, randomized, positive-drug parallel-controlled clinical trial was conducted in 19 hospitals from July 2019 to August 2020. Children aged 0 - 12 months with mild to moderate diaper dermatitis were enrolled and randomly divided into 2 groups using a random number table: test group topically treated with compound oleum lithospermi, and control group topically treated with zinc oxide cream. The treatment was carried out 6 - 8 times a day for 7 days. Visits were scheduled on days 0 and 7, and total response rate and clinical healing time were evaluated. Changes in the dermatitis family impact (DFI) score were compared between the test group and control group, and adverse events were recorded. Statistical analysis was carried out by using independent-sample t test for normally distributed continuous data, Wilcoxon rank sum test for non-normally distributed continuous data, and chi-square test or Fisher′s exact test for unordered categorical data; survival curves were drawn, and log-rank test was used for comparisons between two groups. Results:A total of 343 children with diaper dermatitis were enrolled in this study. Among them, 31 children violated the protocol, so 312 were included in the per protocol set, including 157 in the test group and 155 in the control group, and all completed the visits on days 0 and 7. The total response rate was significantly higher in the test group (87.26%, 137/157) than in the control group (78.71%, 122/155; χ2 = 4.04, P = 0.044) . The clinical healing time was significantly shorter in the test group (5.33 days) than in the control group (6.13 days; χ2 = 4.67, P = 0.025) . After 7-day treatment, the DFI score significantly decreased in both the 2 groups compared with that before the treatment, but there was no significant difference in the DFI score between the 2 groups (test group: 4.02 ± 6.96, control group: 3.58 ± 5.90, Z = -0.39, P = 0.686) . The incidence of adverse events was 2.92% (5/171) and 5.45% (9/165) in the test group and control group respectively, and there was no significant difference between the 2 groups ( χ2 = 0.03, P = 0.865) . Conclusion:Compound oleum lithospermi can markedly reduce the clinical severity of diaper dermatitis, improve the total response rate, shorten the clinical treatment period, and improve the quality of life of children′s families with a favorable safety profile.

Background Arsenic is a well-known environmental toxicant. Hepatic fibrosis could occur dueto excessive or long-term exposure to arsenic, while associated molecular mechanisms remain undefined. Mitogen-inducible gene 6 (Mig-6) exhibits a protective effect on numerous diseases or cancers. However, the specific role of Mig-6 in the mechanisms of arsenite-induced hepatic fibrosis remains indistinct. Objective To investigate the specific role of Mig-6 in the activation of hepatic stellate cells (HSC) and the deposition of extracellular matrix (ECM) induced by sodium arsenite (NaAsO₂). Methods Human hepatic stellate cells (Lx-2) were treated with 0, 1.875, 3.75, 7.5, and 15 μmol·L⁻¹ of NaAsO₂ for 24 h, or with 7.5 μmol·L⁻¹ NaAsO₂ for 0, 12, 24, 48, and 72 h. Additionally, Lx-2 cells were transfected by pcDNA3.1(+)/Mig-6, then treated with 7.5 μmol·L⁻¹ NaAsO₂ for 24 h; a blank control group, a pcDNA3.1(+)-control group, a pcDNA3.1(+)/Mig-6 group, and an arsenic (7.5 μmol·L⁻¹ NaAsO₂) group were also set up. After transfection, the cells and culture supernatants were collected, and the protein levels of Mig-6, α-smooth muscle actin (α-SMA), and transforming growth factor-β1 (TGF-β1) in Lx-2 cells were identified by Western blotting analysis; moreover, the secretion levels of main ECM components in supernatants such as hyaluronic acid (HA), laminin (LN), collagens IV (COL-IV), and procollagen-III (PIIINP) were tested by ELISA. Results The Mig-6 expression decreased in the 3.75, 7.5, and 15 μmol·L⁻¹ NaAsO₂ groups (0.561±0.095, 0.695±0.048, and 0.401±0.030) compared to the control group (1.000±0.000) in Lx-2 cells (P<0.05). After administration with 7.5 μmol·L⁻¹ of NaAsO₂ for 24, 48, and 72 h, the Mig-6 expression (0.856±0.036, 0.515±0.077, 0.491±0.060) decreased compared with the 0 h group (1.000±0.000) (P<0.05). After over-expression of Mig-6, the results of Lx-2 activation related protein levels showed that compared to the control group, the α-SMA and TGF-β1 expression were up-regulated in the arsenic group (P<0.05); meanwhile, the α-SMA and TGF-β1 in the Mig-6 over-expression combined arsenic exposure group reduced compared to the arsenic (7.5 μmol·L⁻¹) group (P<0.05). The results of ELISA showed that compared with the control group, the HA, LN, PIIINP, COL-IV in the arsenic group were up-regulated (P<0.05); while compared to the arsenic group, the HA, LN, PIIINP, and COL-IV in the Mig-6 over-expression combined with arsenic exposure group were decreased (P<0.05). Conclusion Arsenic down-regulates Mig-6 expression in HSC, and over-expression of Mig-6 can reverse the activation of HSC and ECM deposition induced by arsenic exposure. It suggests that Mig-6 plays a protective role in arsenic-induced HSC activation and ECM deposition.

New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
Angiotensin-Converting Enzyme 2 ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Epitopes ; Humans ; SARS-CoV-2/genetics* ; Spike Glycoprotein, Coronavirus/genetics*