TROP-2, a tumor-associated antigen, has been implicated in the progression of various epithelial tumors. Due to its favorable expression profile, TROP-2 has emerged as a promising target for antibody-drug conjugates (ADCs) based anti-tumor therapies. Although ADCs have shown efficacy in cancer treatment, their application in solid tumors is hindered by their high molecular weight, poor tumor penetration, and release of cytotoxic molecules. Therefore, a recombinant immunotoxin was developed based on a shark-derived variable domain of immunoglobulin new antigen receptor (VNAR) antibody. VNARs are only one-tenth the size of IgG antibodies and possess remarkable tissue penetration capabilities and high stability. In this study, a shark VNAR phage display library was created, leading to the identification of shark VNAR-5G8 that targets TROP-2. VNAR-5G8 exhibited a high affinity and cellular internalization ability towards cells expressing high levels of TROP-2. Epitope analysis revealed that VNAR-5G8 recognizes a hidden epitope consisting of CRD and TY-1 on TROP-2. Subsequently, VNAR-5G8 was fused with a truncated form of Pseudomonas exotoxin (PE38) to create the recombinant immunotoxin (5G8-PE38), which exhibited significant anti-tumor activity in vitro and in vivo. Overall, this study highlights the promise of 5G8-PE38 as a valuable candidate for cancer therapy.

Objective:To investigate the therapeutic effect of comprehensive geriatric assessment(CGA) in elderly patients with chronic heart failure(CHF) complicated with sarcopenia, and to provide a theoretical reference for clinical application.Methods:This study was a prospective randomized controlled study. 110 elderly CHF patients with myopenia admitted to the Third People's Hospital of Hefei from January 2019 to February 2022 were selected. Using the random number table method, 56 cases were divided into an observation group and 54 cases into a control group. Before treatment, the control group of patients underwent a selective single assessment based on the hospital's requirements and the patient's actual situation, including a fall risk assessment, nutritional risk screening checklist assessment, and routine medication to improve cardiac function and prognosis; Before treatment, the patients in the observation group were assessed with CGA, including the assessment of physical function, mental and psychological status, multiple drug management, pain, Sleep disorder, and social environment. According to the assessment results, individual diagnosis and treatment plans were formulated, implemented, and dynamically adjusted. The two groups were treated for 12 weeks. The general information, treatment compliance, B-type brain natriuretic peptide (BNP) level, left ventricular Ejection fraction (LVEF), 6 min walking distance (6MWD), arm strength of upper limbs and 6 m walking speed, clinical efficacy and prognosis of the two groups were compared before and after treatment. The measurement data is represented by xˉ± s, group t-tests are used for inter group comparison, and paired t-tests are used for intra group comparison before and after treatment; Counting data is represented as an example (%), and inter group comparisons are made using χ 2 test, non parametric rank sum test was used for inter group comparison of hierarchical data. Results:There was no statistically significant difference in gender, age, course of CHF, smoking, alcohol consumption, number of comorbidities, cardiac function grading, and treatment compliance between the two groups of patients (all P>0.05), indicating comparability. Before treatment, there was no statistically significant difference in plasma BNP, LVEF, 6MWD, upper limb grip strength, and 6-meter walking speed between the two groups of patients (all P>0.05); After treatment, the BNP of both groups of patients was lower than before treatment and the observation group was lower than the control group. LVEF, 6MWD, upper limb grip strength, and 6-meter walking speed were all higher than before treatment and the observation group was higher than the control group [(343.45±34.95) ng/L vs (387.09±46.96) ng/L, (49.61±7.11)% vs (42.94±5.72)%, (348.92±37.73) m vs (297.74±43.48) m, (22.64±3.82) kg vs (19.48±3.88) kg, (0.97±0.10) m/s vs (0.83±0.12) m/s], The differences were statistically significant ( t-values were 5.51, -5.40, -6.60, -4.31, -6.60, all P<0.001). After 12 weeks of treatment, there was no statistically significant difference in clinical efficacy between the two groups of patients ( P=0.216), but the overall poor prognosis rate in the follow-up observation group was lower than that in the control group [7.14%(4/56) vs 22.22% (12/54)], and the difference was statistically significant (χ 2=5.03, P=0.025). Conclusions:Developing, implementing, and dynamically adjusting the individualized treatment plan involving CGA can improve the prognosis of elderly CHF patients with sarcopenia, help improve cardiac function, increase grip strength and somatic function, and reduce the risk of major adverse cardiovascular events ,all-cause mortality in elderly patients with CHF combined with sarcopeni and has certain clinical application value.

【Objective】 To evaluate the clinical efficacy and safety of one kind of human prothrombin complex concentrate in treatment of patients with hemophilia B. 【Methods】 The clinical data of 36 patients with hemophilia B treated with human prothrombin complex concentrate produced by Shenzhen Weiguang Biological Products Co. Ltd. from May 2018 to April 2019 were retrospectively analyzed, and its clinical efficacy and safety were analyzed. 【Results】 A total of 35 subjects entered the full analysis set (FAS)and safety set (SS), 33 subjects entered the per protocol Set (PPS). Thirty minutes after the first infusion of FAS subjects, the activity of coagulation factor Ⅸ increased from (3.93±0.975) IU/dL to (25.61±9.337) IU/dL, and the infusion efficiency was (96.43±22.007)%. The increased value of coagulation factor Ⅱ activity was (73.25±14.874) IU/dL. The activity of coagulation factor Ⅶ was (42.79±16.847) IU/dL. The increased value of coagulation factor Ⅹ activity was (65.29±17.042) IU/dL. The increased value of coagulation factor Ⅸ activity was (21.68±9.434%) IU/dL. Twenty-four hours after the first infusion of FAS subjects, the improvement of bleeding symptoms and signs was excellent in 21 cases (60%), improved in 14 cases (40.0%), and the effective rate was 100%. The incidence of adverse reactions was 2.9%(1/35), and there was no antibody to human coagulation factor Ⅸ and new virus infection. 【Conclusion】 Infusion of human prothrombin complex concentrate produced by Shenzhen Weiguang Biological Products Co. Ltd. in the treatment of hemophilia B has significant clinical efficacy and good safety.

Objective:To explore the diagnosis and treatment of pure red cell aplastic anemia (PRCA) caused by parvovirus B19 (HPV-B19)infection after liver transplantation (LT).Methods:Three adult PRCA patients caused by parvovirus B19 infection after LT were reviewed retrospectively.The relevant literatures were collected to sort out the detection methods and treatment of parvovirus B19 infection after LT.Results:All three patients received liver transplantation due to end-stage liver disease with massive intraoperative blood transfusion and smooth postoperative recovery.Severe anemia occurred at 1-2 Months after discharge.Hemorrhagic anemia was excluded after re-admission and PRCA was diagnosed by bone marrow aspiration and next generation sequencing (NGS). After tapering the intensity of immunosuppressive therapy, intravenous immunoglobulin (IVIG) was administered for 7-10 days and hemoglobin soon normalized.A review of 15 recent literatures on HPV-B19 infection after LT revealed that the diagnosis and treatment of parvovirus B19 infection after LT gradually were became same.Conclusions:HPV-B19 infection causes PRCA after LT in adults.Diagnosing with NGS, intravenous injection of immunoglobulin and modification of immunosuppressant regimen may achieve excellent therapeutic efficacies.

Objective To investigate the clinical,imaging,pathological and molecular biological features of mitochondrial encephalomyopathy with lactic acidosis and stroke -like episodes(MELAS)in children.Methods The clinical,imaging,pathological and molecular biological features of 1 2 children with MELAS diagnosed through muscle biopsy or gene sequencing in the Fifth Affiliated Hospital of Zhengzhou University from January 201 1 to December 201 5 were retrospectively analyzed.Results (1 )Clinical features:the main manifestations included headache and vomiting in 1 1 cases,epileptic seizures in 9 cases,short stature in 8 cases,hairy in 7 cases,intolerance fatigue in 7 cases,cogni-tive decline in 7 cases,visual disturbance in 6 cases,hearing disturbance in 6 cases,and 5 cases had positive family history.In addition,7 cases had the serum lactic acid level increase in a rest for 1 0 min after exercise.(2)Imaging fea-tures:4 cases showed bilateral basal ganglia calcification symmetry in 8 patients who underwent head CT scan.The most frequently involved parts of the lesion were occipital in 1 0 cases,temporal in 9 cases and parietal lobe in 7 cases in stroke -like episodes.The lesions were lamellar necrosis.The abnormal areas by MRI showed low signal intensity on T1 weighted imaging,high signal intensity on T2 weighted imaging and fluid attenuated inversion recovery,high or equal signal intensity on diffusion weighted imaging,high or low signal intensity on apparent diffusion coefficient;the lactate peak significantly increased on magnetic resonance spectroscopy.The distribution was not in accordance with the control region of the cerebral vessels.Dynamic observation revealed that the lesions were reversible and migratory.(3)Myo-pathological features:muscle biopsy was performed in all children,and ragged -red fibers were found in 1 0 cases by im-proved Gomori staining,strongly succinate dehydrogenase -reactive were found in 9 cases,and the lipid droplets slight-ly increased in 8 cases by oil red O staining.Besides,the crystalline inclusion bodies in mitochondria were arranged in a parking lotpattern in 9 cases by electromicroscope.(4)Molecular biological characteristics:the mitochondrial gene mutations were analyzed in peripheral blood of 9 children and their parents,including 8 cases with A3243G muta-tion and 1 case with G13513A mutation.Five mothers had the same A3243G mutation site in 8 cases.Conclusions Children with MELAS have complex and varied clinical manifestations and certain characteristic of neuroimaging.More-over,muscle pathology and gene sequencing have important diagnostic value.Fully understanding the clinical,muscle pathology,imaging and molecular biological characteristics of children with MELAS can be helpful to the early diagnosis and treatment,also reduce misdiagnosis.

[ ABSTRACT] AIM:To observe the treatment effect and its immune regulation of human amnion epithelial cells ( hAECs) on Alzheimer’ s disease ( AD)-like pathology rat model.METHODS: The hAECs were isolated from amnion with trypsin digestion, and the phenotype of hAECs was analyzed by flow cytometry.SD rats ( n=48) were randomly divid-ed into sham control group, model group, medium group and hAECs group.AD-like pathology rat model was induced by bilateral intraventricular injection of lipopolysaccharide (LPS).hAECs (5 ×105) were injected into the hippocampus of the AD-like pathology rats.At 2 weeks after transplantation, the animals were tested by Morris water maze to observe the function of learning and memory.The pathological change of the brain was observed by HE staining.The expression of am-yloid β-protein 42 (Aβ42) and Tau protein and the level of acetylcholine (ACh) in the injury brain were determined by immunohistochemistry.The survival and differentiation of hAECs in the hippocampus were measured by immunofluorescent technique.The percentages of lymphocyte subsets in the peripheral blood mononuclear cells were analyzed by flow cytome-try.The contents of serum cytokines were detected by cytometric bead array.RESULTS:Compared with model group and medium group, hAECs group showed shortened escape latency ( P<0.01) , increased frequency of going through the plat-form (P<0.05), reduced loss of hippocampal neurons, decreased expression of Tau protein and Aβ42 in the hippocampus (P<0.05), increased ACh level in the hippocampus (P<0.05), decreased percentages of Th1 and Th17 subsets, in-creased percentages of Th2 and Treg cells ( P<0.05) , decreased concentrations of IFN-γand IL-2 in the serum, and in-creased concentration of IL-4 ( P<0.05 ) .CONCLUSION: hAECs improve the cognitive learning and memory function and alleviate pathologic damage of hippocampus through immune regulation in AD-like pathology rats.

The authors explained in the first place the challenges facing hospitals in the new century. These include: impact of the reform of the social security system on hospitals; impact of China's accession to the WTO on domestic hospitals; and impact of people's diversified needs on the construction of hospitals. Then the authors set forth some development strategies for hospitals in the new century. These include: ①establishment of new concepts; ②reinforcement of awareness in four aspects, viz. management awareness, competition awareness, service awareness, and innovation awareness; ③stress on the systematic nature of hospital construction, viz. market-and battlefield-oriented adjustment of the layout of disciplines, construction of the contingent of talents in accordance with the needs of the market, and enhancement of medical quality in light of new quality concepts; ④establishment of a flexible and highly efficient management mechanism, viz. setting up a speedy and highly efficient decision-making procedure and an individual-centered management mechanism, reforming the distribution mechanism in line with the rules of the market economy, and finding ways for the government to solve the problem of funds compensation for non-profit hospitals.

This paper introduces a virtual ECG sampling system based on LabVIEW. The system, utilizing self-developed ECG sampling card, fulfils ECG measurement and A/D conversion safely and realizes ECG data processing and display under Labview developing environment.