Objective To investigate the impact of two different surgical methods, orthotopic kidney transplantation and abdominal heterotopic kidney transplantation, on the surgical outcomes of pig-to-pig kidney transplantation and the short-term survival of recipient pigs after surgery. Methods Twenty-four Bama miniature pigs were divided into two groups, with 12 pigs in each group, and underwent orthotopic kidney transplantation and abdominal heterotopic kidney transplantation, respectively. The perioperative indicators of the recipient pigs, renal blood perfusion, the overall incidence rate of complications and survival rate were compared between the two surgical methods. Results The total surgical time, renal artery anastomosis time, renal vein anastomosis time, cold ischemia time and total ischemia time were all shorter in the abdominal heterotopic kidney transplantation group than in the orthotopic kidney transplantation group, with statistically significant differences (all P<0.05). The number of satisfactory renal perfusion cases was higher in the abdominal heterotopic kidney transplantation group than in the orthotopic kidney transplantation group (83% vs. 75%), but the difference was not statistically significant (P>0.05). The total incidence of postoperative complications was 33% in the heterotopic kidney transplantation group, with a survival rate of 92%, and the cause of death was rupture of the vascular anastomosis. The total incidence of postoperative complications was 50% in the orthotopic kidney transplantation group, with a survival rate of 83%, and the causes of death were renal vein thrombosis and renal artery thrombosis. There were no statistically significant differences in the total incidence of postoperative complications and survival rates between the two groups (all P>0.05). Conclusions Compared with orthotopic kidney transplantation, abdominal heterotopic kidney transplantation showes better surgical outcomes in pig-to-pig kidney transplantation and is more beneficial for the short-term survival of recipient pigs after surgery. This provides experience for improving the stability of pig-to-non-human primate kidney xenotransplantation models in the future.

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

Organ shortage has become one of the major challenges hindering the development of organ transplantation. Xenotransplantation is one of the most valuable methods to resolve global organ shortage. In recent years, the development of genetic engineering technique and research and development of new immunosuppressant have provided novel theoretical basis for xenotransplantation. International scholars have successively carried out researches on xenotransplantation in genetically modified pigs to non-human primates or brain death recipients, making certain substantial progresses. However, most of the researches are still in the preclinical stage, far from clinical application. Therefore, according to the latest preclinical experimental research progress at home and abroad, the history of xenotransplantation, the development of gene modification technology, xenotransplantation rejection and immunosuppression regimens were reviewed, aiming to provide reference for subsequent research of xenotransplantation, promote clinical application of xenotransplantation and bring benefits to more patients with end-stage diseases.

Objective:To investigate the alterations in soft tissue morphology and thickness in the mid-face region of patients with cleft lip and palate (UCLP) secondary to maxillofacial deformity following Le Fort I osteotomy.Methods:A total of 22 patients (16 males and 6 females aged from 17 to 28 years with an average of 20 years) diagnosed with cleft lip and palate secondary to maxillofacial deformity were collected from the Wuhan University Hospital of Stomatology from July 2012 to August 2020. All patients underwent Le Fort I osteotomy. CBCT scans were obtained at T0 (3 days before surgery), T1 (7 days after surgery), and T2 (1 year after surgery). The Dolphin11.95 software and 3D Slicer software were utilized to measure and analyze the soft tissue near the mid-face osteotomy line. Differences in soft tissue thickness before and after surgery were compared.Results:Before and after the operation, the soft tissue thickness at P3, P5, P6, and P8 on the affected side was thicker than that on the healthy side, and the difference was statistically significant, with a P-value of <0.05. At P5, P6, P7, P8, and P9 below the osteotomy line at T2-T0, the degree of postoperative thinning on the affected side was more apparent than that on the healthy side, and there was statistical significance at P6 ( P<0.05). The postoperative soft tissue asymmetry in the Ck region was improved compared with the preoperative one. The preoperative average protruding of the affected side was 0.63 compared with the healthy side, and the postoperative value was 0.17. The preoperative and postoperative Mann-Whitney U tests showed significantly statistical difference. Conclusions:After Le Fort I osteotomy, the facial asymmetry of patients with unilateral cleft lip and palate secondary to maxillofacial deformity is improved. However, there is still a difference in the soft tissue thickness between the healthy side and the affected side, and the change in soft tissue thickness on the affected side is more significant than that on the healthy side.

OBJECTIVE To explore the effects of posaconazole combined with proton pump inhibitors （PPI） on the blood concentration and the risk of invasive fungal disease （IFD） in patients with malignant hematological disorder. METHODS In accordance with the random number table method， 40 patients with malignant hematological disorders who were admitted to the hematology department of our hospital between December 2020 and December 2021 were chosen and divided into control group （20 cases） and observation group （20 cases）. The control group received Posaconazole oral suspension alone， while the observation group received Posaconazole oral suspension combined with PPI. The incidence of IFD， attainment rate of blood concentration， the time from the start of prophylaxis to IFD onset， the fatality associated with IFD， treatment of infected patients， and blood concentrations of posaconazole on 7th， 14th， 21st， and 28th day after posaconazole application were compared between 2 groups； the occurrence of adverse events during drug administration in the two groups was recorded. RESULTS The study was stopped because 2 patients in the observation group and 9 patients in the control group received hospital departures after taking posaconazole for fewer than 7 days. The incidence of IFD in the observation group was significantly higher than control group， and the attainment rate of blood concentration in the observation group was significantly lower than control group （P＜0.05）. There was no significant difference in the time from the start of prophylaxis to IFD onset， the fatality associated with IFD， treatment of infected patients and the incidence of adverse events （P＞ 0.05）. The blood concentration of posaconazole in the observation group was significantly lower than control group on 7th day of medication （P＜0.05）； there was no significant in blood concentration of posaconazole between 2 groups on the 14th day of medication （P＞0.05）. CONCLUSIONS Posaconazole combined with PPI can reduce the blood concentration of patients with malignant hematological disorders， increase the risk of IFD. Clinical practice should try to avoid the combination of the two or use them under the guidance of therapeutic drug monitoring.

【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 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 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.

OBJECTIVETo study the clinicopathological features, immunophenotype, differential diagnosis and prognosis of low-grade nasopharyngeal papillary adenocarcinoma (LGNPPA).

METHODSThe histopathological features and clinical and pathological data of nine cases of LGNPPA were retrospectively analyzed. Immunohistochemistry (Two-step EnVision methods) was used to evaluate the expression of CKpan, vimentin, CK7, CK19, TTF-1 and TG; in situ hybridization was used to detect Epstein-Barr virus mRNA (EBER); and flow-through hybridization was used to evaluate the presence of human papilloma virus (HPV).

RESULTSThe mean age for the nine patients (eight males, one female) was 45.3 years (range 23 to 62 years). Microscopically the tumors were characterized by lobulated, papillary and glandular structures with patchy distribution of spindle cells. The papillary interstitial tissue was edematous, myxoid or hyalinized. The tumors were unencapsulated and infiltrated into the surrounding stroma. Four cases displayed transition between normal nasopharyngeal epithelium to neoplastic cells; and one case contained psammoma bodies. Five cases were strongly positive for CKpan, vimentin, CK7, CK19, TTF-1, and were focally positive for EMA and CD117. These five cases were all negative for TG, CK5/6, CK20, S-100 protein, p63, Calponin and SMA. In situ hybridization for EBER and flow-through hybridization for HPV were negative in all five cases. Follow-up data showed no post-operative recurrence of the LGNPPA.

CONCLUSIONSLGNPPA is a rare low-grade neoplasm with distinct morphological characteristics. Its diagnosis is primarily based on the site of lesions and the histological features. The diagnosis and differential diagnosis of LGNPPA could be aided by immunohistochemical staining. LGNPPA may originate from nasopharyngeal epithelium; and the prognosis is good with simple and complete resection.

Adenocarcinoma, Papillary ; metabolism ; pathology ; Adult ; Carcinoma ; Diagnosis, Differential ; Female ; Herpesvirus 4, Human ; genetics ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Male ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Neoplasm Proteins ; metabolism ; Nuclear Proteins ; metabolism ; Prognosis ; RNA, Messenger ; metabolism ; Retrospective Studies ; S100 Proteins ; metabolism ; Thyroid Nuclear Factor 1 ; Transcription Factors ; metabolism ; Vimentin ; metabolism

Objective To study the clinicopathological features , immunophenotype , differential diagnosis and prognosis of low-grade nasopharyngeal papillary adenocarcinoma ( LGNPPA).Methods The histopathological features and clinical and pathological data of nine cases of LGNPPA were retrospectively analyzed.Immunohistochemistry ( Two-step EnVision methods ) was used to evaluate the expression of CKpan, vimentin, CK7, CK19, TTF-1 and TG;in situ hybridization was used to detect Epstein-Barr virus mRNA ( EBER);and flow-through hybridization was used to evaluate the presence of human papilloma virus (HPV).Results The mean age for the nine patients (eight males, one female) was 45.3 years (range 23 to 62 years).Microscopically the tumors were characterized by lobulated , papillary and glandular structures with patchy distribution of spindle cells.The papillary interstitial tissue was edematous , myxoid or hyalinized.The tumors were unencapsulated and infiltrated into the surrounding stroma.Four cases displayed transition between normal nasopharyngeal epithelium to neoplastic cells ;and one case contained psammoma bodies.Five cases were strongly positive for CKpan , vimentin, CK7, CK19, TTF-1, and were focally positive for EMA and CD117.These five cases were all negative for TG , CK5/6, CK20, S-100 protein, p63, Calponin and SMA.In situ hybridization for EBER and flow-through hybridization for HPV were negative in all five cases.Follow-up data showed no post-operative recurrence of the LGNPPA.Conclusions LGNPPA is a rare low-grade neoplasm with distinct morphological characteristics.Its diagnosis is primarily based on the site of lesions and the histological features.The diagnosis and differential diagnosis of LGNPPA could be aided by immunohistochemical staining.LGNPPA may originate from nasopharyngeal epithelium;and the prognosis is good with simple and complete resection.