Objective To analyze the clinical and therapeutic characteristics of Epstein-Barr virus (EBV)-negative posttransplant lymphoproliferative disease (PTLD) with diffuse large B-cell lymphoma (DLBCL) in the context of specific cases and literature. Methods A case of EBV-negative DLBCL (GCB type) after kidney transplantation is reported. The patient was a 45-year-old male who underwent living-related kidney transplantation in 2016 and has been receiving triple immunosuppressive therapy with tacrolimus, mycophenolate mofetil and methylprednisolone since then. In 2024, the patient presented with intermittent fever, night sweats and gastrointestinal symptoms. The diagnosis was confirmed by endoscopic pathology, immunohistochemical staining and positron emission tomography/computed tomography. The R-CDOP regimen (rituximab + cyclophosphamide + liposomal doxorubicin + vincristine + dexamethasone) was used for treatment. Results The patient was diagnosed with EBV-negative DLBCL (GCB type, Ann Arbor stage Ⅳ B). After 4 cycles of R-CDOP chemotherapy, the efficacy assessment was partial remission, and the transplant kidney function remained stable. Conclusions For EBV-negative PTLD after kidney transplantation, it is necessary to break through the "virus-dependent" diagnostic thinking. In clinical practice, the focus should be on protecting the transplant kidney, and individualized treatment plans should be developed for patients.

BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

Clinically,the incidence of portal vein thrombosis(PVT)in patients with cirrhosis can be up to 10％-23％.When PVT is not treated promptly,it may develop to cavernous transformation of the portal vein(CTPV).CTPV can aggravate portal hypertension,accelerate the progression of esophagogastric varices bleeding,refractory ascites,refractory peritonitis,biliary tract diseases,and hepatic insufficiency.At present,noninvasive imaging techniques such as portal vein reconstruction,enhanced CT and ultrasound are mostly used to make the diagnosis and evaluation of CTPV.It is rather difficult to perform portosystemic shunt surgery in patients with CTPV complicated by portal hypertension,which was once regarded as a contraindication for interventional portosystemic shunt procedures.With the improvement of related technologies and surgical instruments,the transjugular intrahepatic portosystemic shunt(TIPS)has become an important treatment for CTPV.This paper aims to make a comprehensive review about the relevant researches concerning the portosystemic shunt surgery in patients with CTPV so as to clarify the importance of TIPS in the treatment of CTPV.

Objective To investigate the correlation between muscle strength level and bone mineral density and bone metabolism indexes in postmenopausal women in Beijing.Methods Postmenopausal women who were investi-gated by on-site questionnaires and followed by bone mineral density examination in Beijing from September 2017 to May 2018 were recruited as study subjects.They were divided into early menopausal group,middle menopausal group,late menopausal group,and twilight menopausal group according to the years of menopause.Changes in grip strength,5 times sit-to-stand test(FTSST)with bone mineral density(BMD)and bone metabolism indexes were observed in the four groups and their correlations were analyzed.Results A total of 815 cases of postmenopausal women were included.At different menopausal stages,muscle strength was all found to decrease with the increase of menopausal years(P＜0.05),there was non-significance of different bone metabolism indexes among the four groups(P＞0.05);Femoral neck and lumbar spine BMD decreased with the increase of menopausal years(P＜0.05).Maximum grip strength was positively correlated with both femoral neck and lumbar spine BMD(R=0.158,P＜0.05;R=0.130,P＜0.05).There was no correlation between muscle strength and bone metabo-lism indexes(P＜0.05).Conclusions Different bone metabolism indexes are not associated with muscle strength in menopausal women.Maximum grip strength is positively correlated with bone mineral density,which can be used as an auxiliary screening tool for osteoporosis(OP)in women.The FTSST suggests that the lower limb muscle strength of menopausal women decreases with age,which can be used as one of the indicators for predicting the risk of falls in menopausal women.

Fusobacterium nucleatum is an opportunistic pathogenic bacterium that can be enriched in colorectal cancer tissues, affecting multiple stages of colorectal cancer development. The two-component system plays an important role in the regulation and expression of genes related to pathogenic resistance and pathogenicity. In this paper, we focused on the CarRS two-component system of F. nucleatum, and the histidine kinase protein CarS was recombinantly expressed and characterized. Several online software such as SMART, CCTOP and AlphaFold2 were used to predict the secondary and tertiary structure of the CarS protein. The results showed that CarS is a membrane protein with two transmembrane helices and contains 9 α-helices and 12 β-folds. CarS protein is composed of two domains, one is the N-terminal transmembrane domain (amino acids 1-170), the other is the C-terminal intracellular domain. The latter is composed of a signal receiving domain (histidine kinases, adenylyl cyclases, methyl-accepting proteins, prokaryotic signaling proteins, HAMP), a phosphate receptor domain (histidine kinase domain, HisKA), and a histidine kinase catalytic domain (histidine kinase-like ATPase catalytic domain, HATPase_c). Since the full-length CarS protein could not be expressed in host cells, a fusion expression vector pET-28a(+)-MBP-TEV-CarS_cyto was constructed based on the characteristics of secondary and tertiary structures, and overexpressed in Escherichia coli BL21-Codonplus(DE3)RIL. CarS_cyto-MBP protein was purified by affinity chromatography, ion-exchange chromatography, and gel filtration chromatography with a final concentration of 20 mg/ml. CarS_cyto-MBP protein showed both protein kinase and phosphotransferase activities, and the MBP tag had no effect on the function of CarS_cyto protein. The above results provide a basis for in-depth analysis of the biological function of the CarRS two-component system in F. nucleatum.
Humans ; Histidine Kinase/metabolism* ; Fusobacterium nucleatum/metabolism* ; Automobiles ; Protein Kinases/genetics* ; Escherichia coli/metabolism* ; Colorectal Neoplasms

Objective : To analyze the length of hospital stay of patients with heart failure in a multicenter cohort in order to explore the influencing factors of length of stay and provide data support for further intervention. Methods: A total of 2 794 patients enrolled in the multicenter prospective heart failure cohort were divided into two groups: long hospital stay group (≥9 days) and short hospital stay group ( < 9 days) . The general data of the two groups were compared, and the factors with statistical difference in univariate analysis were included in Logistic multifactor regression analysis to explore the difference in length of hospital stay between the two groups. According to left ventricular ejection fraction(LVEF), patients were divided into heart failure with preserved reduced ejection fraction (HFpEF)group, heart failure with mildly reduced ejection fraction(HFmrEF)group and heart failure with reduced ejection fraction(HFrEF) group, and Logistic multifactor regression analysis was performed to find influencing factors. Results : Logistic multifactor regression analysis showed that LVEF, pneumonia, N⁃terminal pro⁃B⁃type natriuretic peptide(NT⁃proBNP), serum sodium, cardiac resynchronization therapy( CRT) or implantable cardioverter defibrillator(ICD)implantation, β blockers, aldosterone receptor antagonists, positive inotropic drugs and vasodilators were all factors influencing the hospitalization of HF patients. In the HFpEF, HFmrEF, and HFrEF groupsCRT/ICD implantation, positive inotonic drugs, and vasodilator use were suggested to be common factors affecting length of hospital stay in all three groups. Conclusion LVEF, pneumonia, NT⁃proBNP, serum sodium, CRT or ICD implantation, β blockers, aldosterone receptor antagonists, positive inotropic drugs and vasodilators are the influencing factors of hospitalization time in HF patients.

【Objective】 To investigate the effects of neutrophil-derived exosomes on skin wound healing. 【Method】 ① The venous blood was taken from 10 healthy volunteers to separate and purify neutrophils, and exosomes were prepared from neutrophil supernatants using differential centrifugation on Sepharose columns. ② The rat trauma model with full-thickness skin defect was prepared and randomly divided into three groups: control group, 50 μg/mL exosomes group, and 100 μg/mL exosomes group. The CCK8 test and the scratch test were used to determine the proliferation and migration of vascular endothelial cells, respectively, which was used to investigate the effects of neutrophil-derived exosomes on the formation of endothelial cell tubular structures in vitro. On day 7 and day 14 after surgery, the skin wound healing was observed and the wound healing rate in different treatment groups was compared. On day 14 after surgery, the wound tissues of each group were stained with HE and Masson to observe the arrangement of collagen fibers. 【Results】 ① Neutrophil-derived exosomes were round or oval vesicles with diameter about 100 nm. ② On post injury hour (PIH) 12, the scratch test suggested that wound healing rates in the three groups were close (P>0.05 ), while wound healing rate of 100 μg/mL neutrophil-derived exosomes in the treatment group was higher than that in the control group (P<0.01) and 50 μg/mL exosomes group (P<0.05) on PIH 24. On PIH 12, the result of CCK8 assay showed that 50 and 100 μg/mL exosomes groups had enhanced proliferative activity of vascular endothelial cells (P<0.01) and the results were still higher in both groups than in the control group on PID 24. The results of tube formation assay showed that neutrophil-derived exosomes could promote the formation of tubular structures of endothelial cells in vitro (P<0.01). ③ On day 7 and 14 after surgery, compared with the control group, the wound healing rates of the 50 and 100 μg/mL exosomes groups were higher (P<0.01). The wound healing rate of 100 μg/mL exosomes group was higher than that of 50 μg/mL exosomes group (P<0.01). Compared with the control group, the newly formed epidermis and dermis on the wound surface of the 100 μg/mL exosomes group were longer, the number of collagen fibers increased, and the arrangement direction was highly consistent on the 14 th day after surgery. 【Conclusions】 Neutrophil-derived exosomes can promote full-thickness wound healing in rats by promoting the proliferation and migration of new vascular endothelial cells and the formation of collagen fibrous.

Objective:To explore the effect of critical nursing combined with early warning nursing in patients with chronic obstructive pulmonary disease (COPD) complicated with respiratory failure.Methods:From October 2019 to October 2021, 92 COPD patients with respiratory failure who received non-invasive ventilator treatment in the First Affiliated Hospital of Zhengzhou University were selected as the research object by convenience sampling. According to the method of random number table, the patients were divided into the observation group and the control group, 46 cases in each. The patients in the control group received routine nursing during treatment, while the patients in the observation group received critical nursing combined with early warning nursing. Before and after intervention, the quality of life and resilience of patients were evaluated with the Generic Quality of Life Inventory-74 (GQOLI-74) and the Connor-Davidson Resilience Scale (CD-RISC) , and the complications of patients were compared.Results:Before intervention, there were no statistical differences in GQOLI-74 score and CD-RISC score between the two groups ( P>0.05) . After intervention, the GQOLI-74 scores, the total score and dimension scores of CD-RISC in the observation group were statistically higher than those in the control group ( P<0.05) . The total incidence of complications in the observation group (8.70%) was lower than that in the control group (26.09%) , with a statistically significant difference ( P<0.05) . Conclusions:Critical nursing combined with early warning nursing can improve the quality of life and psychological resilience of COPD patients complicated with respiratory failure, and reduce the incidence of complications during treatment.

Objective : To analyze the status and influencing factors of the intention of people aged 18 to 25 years to primary medical institutions and their satisfaction for health services in Zhejiang Province, so as to provide basis for the improvement of health services in primary medical institutions. Methods: During November and December in 2019,the 18-25 year-old people in Zhejiang Province were recruited to investigate the general information, intention to seek medical advice and satisfaction for health services in primary medical institutions through WeChat. Logistic regression was performed to analyze the influencing factors of the intention and the satisfaction. Importance matrix was used to analyze the key drivers of the satisfaction. Results: Among the 620 people surveyed, with a response rate of 93.37%, 142 (22.90%) chose primary medical institutions for advice. Actually 516 (83.23%) people went to primary medical institutions last year, and 384 ( 74.42% ) of them were satisfied with the health services. The results of multivariate logistic regression analysis showed that the people aged 18-25 years who were under the new rural cooperative medical care system ( OR=3.062, 95%CI: 1.745-5.373 ) and who had records in community health centers ( OR=0.547, 95%CI: 0.308-0.970 ) were more likely to go to primary medical institutions for medical advice; the ability of doctors ( OR=1.478, 95%CI:1.168-1.871 ) ,the drug notification by medical staff ( OR=1.308, 95%CI: 1.065-1.606 ) , routine examination items ( OR=1.523, 95%CI: 1.227-1.889 ) , the ways of payment ( OR=1.168, 95%CI: 1.017-1.340 ) , the comfort of environment ( OR=1.785, 95%CI: 1.437-2.219 ) and the bulletin boards of health knowledge ( OR=1.302, 95%CI: 1.086-1.561 ) were associated with the satisfaction. The results of importance matrix analysis showed that the ability of doctors and routine examination items were the priorities to improve, followed by the drug notification by medical staff; the comfort of environment had competitive advantages; the ways of payment and the bulletin boards of health knowledge needed to be further analyzed. Conclusions The 18-25-year-old people in Zhejiang Province were less intended to seek medical advice in primary medical institutions, which was associated with the type of medical insurance and records in community health centers. They were satisfied with the health services, the ability of doctors and routine examination items were the key drivers.

In December 2019, novel coronavirus pneumonia epidemic occurred in Wuhan, Hubei Province, and spread rapidly across the country. In the early stages of the epidemic, China adopted the containment strategy and implemented a series of core measures around this strategic point, including social mobilization, strengthening case isolation and close contacts tracking management, blocking epidemic areas and traffic control to reduce personnel movements and increase social distance, environmental measures and personal protection, with a view to controlling the epidemic as soon as possible in limited areas such as Wuhan. This article summarizes the background, key points and core measures in the country and provinces. It sent prospects for future prevention and control strategies.