Objective:To construct a safety intelligent early warning system,and to explore its application effect in the management of medical equipment in laminar flow room of hematology department.Methods:The safety intelligent early warning system was constructed by using the browser and server(B/S)mode.The system was consisted of three layers:client layer,application server layer and database server layer,as well as four core modules:data acquisition,data transmission,data processing and data application.A total of 45 equipment in clinical use in the laminar flow room of the Department of Hematology,Tangdu Hospital,Air Force Medical University from November 2021 to October 2023 were selected.Routine management was implemented during the use period of the equipment from November 2021 to October 2022,and the safety intelligent early warning system management(hereinafter referred to as the intelligent management)was applied during the equipment use period from November 2022 to October 2023.The equipment safety risk evaluation index,the potential safety risk rate of the equipment sampled randomly and the average accuracy rate of the equipment use in 600 checks(300 times for each method)under the two management methods were compared.Results:The safety risk assessments of 45 equipment adopted the intelligent management method were poor,fair,good,and excellent with risk indices of 0.02±0.01,0.06±0.02,0.18±0.04 and 0.39±0.07,respectively,the poor,fair,and good risk indices were lower than those of routine management method,and the safety risk index assessed as excellent was higher than that of routine management method,the difference was statistically significant(t=19.092,12.457,6.751,15.809,P＜0.05).Among the 137 cases of 45 equipment randomly sampled using intelligent management method,4,5 and 1 cases of mechanical injury,cross-infection and electric shock injury occurred,with the incidence rates of 2.92％,3.65％and 0.73％,respectively,which were lower than those of routine management methods,the difference was statistically significant(x2=9.336,16.286,17.328,P＜0.05).The average accuracy rates(％)of the 45 equipment adopted the intelligent management method in terms of correct placement,correct connection sequence,correct parameter setting and organization and standard use of the equipment were 99.52±3.51,98.63±4.05,99.74±4.18 and 97.37±5.36,respectively,which were higher than those of the routine management method,the difference was statistically significant(Z=12.231,9.075,13.584,8.933,P＜0.05).Conclusion:The application of safety intelligent warning system for the equipment management of laminar flow room in the department of hematology can effectively prevent potential safety risks of the equipment and improve the accuracy of equipment use.

Objective To investigate the clinical characteristics of vestibular paroxysmia （VP）： age distribution，triggers，accompanying symptoms，maximum frequency per day，nystagmus features during attacks，and neurovascular compression. Methods The clinical data of 70 patients with VP were collected to analyze their age distribution，triggers，accompanying symptoms，maximum frequency per day，nystagmus features during attacks，and neurovascular compression by using descriptive statistical methods. Results Among the 70 patients with VP，30 （42.86%） were elderly，23 （32.86%） were young，and 17 （24.29%） were middle-aged patients. The maximum frequency per day was 2-5 in 53 cases （75.71%），6-10 in 9 cases （12.86%），and >10 in 8 cases （11.43%）. Thirty-six patients （51.43%） had triggers，including rapid walking，emotional excitement，driving，cycling，sexual intercourse，coughing or wheezing，speaking or chatting，bathing，defecation，drinking alcohol，and sound stimulation. Thirty-three patients （47.14%） had unilateral tinnitus，bilateral tinnitus，and tinnitus with facial spasms； nystagmus during VP episodes met the characteristics of the head coordinate system，which was horizontal-torsional towards the affected side. Among 57 patients examined for the relationship between the vestibulocochlear nerve and vessels using magnetic resonance angiography，37 patients （64.91%） had contact between the vestibulocochlear nerve and the right anterior inferior cerebellar artery，15 patients （26.32%） had contact between the vestibulocochlear nerve and the left anterior inferior cerebellar artery，and 5 patients （8.77%） had contact between the vestibulocochlear nerve and the basilar artery. Conclusion VP is most prevalent in the elderly，then young and middle-aged people. Most patients with VP have a maximum frequency of 2-5 per day. VP can be triggered by anger，excitement，exercise，and various stimuli. VP attacks can be accompanied by tinnitus and facial spasms. Its nystagmus is horizontal-torsional towards the affected side. The percentage of contact between the vestibulocochlear nerve and the right anterior inferior cerebellar artery is highest in patients with VP.

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*

OBJECTIVE：To establish a method for concentration determination of anlotinib in human plasma and apply it in the clinic. METHODS ：The plasma samples were pretreated by salting-out assisted with liquid-liquid extraction with ammonium acetate as salting out assistant and acetonitrile as solvent. Using voriconazole as internal standard ，LC-MS/MS method was adopted. The separation was performed on Waters X Bridge C 18 column with mobile phase consisting of 0.2％ formic acid solution- acetonitrile（gradient elution ）at the flow rate of 1 mL/min. The column temperature was set at 40 ℃，and sample size was 10 μL. The split ratio was 3∶7. The electrospray ion source and multiple reaction monitoring mode were used for the analysis. The ion pair of anlotinib and internal standard under positive ion mode were m/z 408.3→339.3 and m/z 350.2→281.3，respectively. RESULTS ： Anlotinib showed a good linear relationship in the concentration range of 0.2-200 ng/mL（R2＞0.996 7）. The lowest limit of quantitation was 0.2 ng/mL. Intra-day and inter-day RSDs were no more than 12％ （n＝6 or n＝3）. Accuracies were 90.92％-108.00％（n＝6 or n＝3）. The average extraction recoveries were 87.51％-100.00％（RSD＜8％，n＝6）. The average matrix effects were 96.66％-99.93％（RSD＜5％，n＝6）. The plasma concentration of 3 patients with NSCLC treated with anlotinib was 8.74-65.60 ng/mL. CONCLUSIONS ：The method is simple ，accurate and specific ，and is suitable for the plasma concentration monitoring of anlotinib in NSCLC patients.

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.

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.

Ocular opsoclonus is a rare disorder of the saccadic system, in which fixation is continuously interrupted by involuntary, chaotic, rapid and multi-directional saccadic eye movements, interrupting the gaze-holding function, leading to“dancing eyes”. Ocular opsoclonus has rarely been reported in China. A case of ocular opsoclonus associated with anti-N-methyl-D-aspartate receptor encephalitis is reported to improve awareness about the ocular sign. The patient′s condition reached the peak at the 5th week. He developed ocular opsoclonus on the basis of nonconvulsive status epilepticus, accompanied by frequent involuntary movements of the mouth and limbs. The ocular opsoclonus gradually relieved on the 7th week with the active treatment.

Objective To investigate the efficacy and limitation of endoscopic ultrasonography (EUS) on the diagnosis of gastrointestinal submucosal tumor (SMT) prior to endoscopic resection.Methods Data of 211 patients,who were confirmed as gastrointestinal SMT before operation and received endoscopic resection for gastrointestinal submucosal tumor at Department of Gastroenterology,Shanghai Ruijin Hospital from January 2016 to December 2018 were analyzed.The value and limitation of EUS for SMT were investigated according to the final pathology.Results For the lesion distribution,66 were in esophagus,108 in stomach,2 in duodenum and 35 in rectum.The accuracy of tumor origin by EUS was 99.5％ (210/211).The accuracy of tumor nature by EUS was 75.8％ (160/211).For the lesions originated from different locations,the diagnostic accuracy for lesion originated from esophageal mucosa/submucosa,esophageal muscularis propria,gastric mucosa/submucosa,gastric muscularis propria,duodenal submucosa,rectal mucosa/submucosa by EUS were 90.0％ (54/60),83.3％ (5/6),31.0％ (13/42),89.4％ (59/66),50.0％(1/2),82.9％ (29/35),respectively.With respect to hypoechoic lesions,leiomyoma,leiomyoma/gastrointestinal stromal tumor,and neuroendocrine tumor were the predominant type of tumor originated from esophageal mucosa,gastrointestinal muscularis propria and rectal mucosa/submucosal,respectively.Conclusion Although EUS is indispensible for the diagnosis of gastrointestinal submucosal tumor,it plays a limited role in the differential diagnosis of various lesions originated from gastric mucosa and submucosa.Since part of the submucosal tumors may be potential for malignant development,an diagnosis made by EUS should be more careful.

Objective To explore the risk factors and interventional strategies of bleeding caused by brain arteriovenous malformations associated with aneurysms.Methods Clinical and imaging data of 42 cases of brain arteriovenous malformations associated with aneurysms were collected and analyzed.According to the results of intraoperative angiography and the architectural characteristics of vessels,the therapeutic schedule was formulated.Three months,6 months and 1 year after interventional management,all patients were followed with DSA to observe whether arteriovenous malformations recurred or not.Results The risk factors of hemorrhage caused by brain arteriovenous malformations associated with aneurysms included lesions located in subtentorium,deep vein or mixed venous drainage,Spetzler-Martin grade Ⅲ-Ⅳ,as well as type Ⅰ and type Ⅱ a aneurysms of Redekop classification.Glasgow outcome score of 38 postoperative patients were more than 4 points,visual impaired happened in 1 patient,whereas 2 patients had different degree of limb dysfunction and 1 patient died.DSA follow-up found no recurrence of arteriovenous malformation in 37 patients.Conclusion Understanding the vessel architectural characteristics and substantial hemorrhage risk factors before intervention,therefore formulating individualized therapeutic schedules are benefit to improving safety and efficacy for the treatment of brain arteriovenous malformations associated with aneurysms.