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

Objectives: This study explored the relationship between weight control and atrial fibrillation (AF) recurrence after catheter ablation in overweight and obese patients. Methods: We prospectively enrolled consecutive 333 overweight and obese patients aged 28 to 87 years old, who underwent catheter ablation for AF in Beijing Anzhen Hospital between October 2015 and February 2016. Data of patients′ characteristics, laboratory examination and treatment were collected at baseline. Each patient was followed up at 3, 6 and 12 months after ablation to collect information on weight, AF recurrence, stroke, major bleeding, hospitalization for cardiovascular reasons and death, etc. Patients were divided into weight controlled group (ΔBMI<-1 kg/m²) and weight uncontrolled group (ΔBMI≥-1 kg/m²), according to the changes in the most recent exposure BMI before AF recurrence in patients with recurrence or the BMI at 12 months′ follow-up in patients without recurrence and the BMI at baseline. Multivariate logistic regression was performed to adjust other known risk factors of AF recurrence and to explore the association between weight control and AF recurrence after catheter ablation. Results: There were 54 patients in weight controlled group and 279 patients in weight uncontrolled group. There were no significant differences in age, gender, education level, left atrial size and history of hypertension between the two groups (all P>0.05). The proportion of patients using angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was higher in the weight controlled group (50.0%(27/54) vs. 34.8%(97/279), P=0.034). However, there was no significant difference in the proportion of patients with obesity (33.3% (18/54) vs. 29.7% (83/279)), paroxysmal AF (59.3% (32/54) vs. 56.6% (158/279)) and AF duration less than 5 years (76.9% (40/52) vs. 65.4% (178/272)) between the weight controlled group and the uncontrolled group. During 1-year follow-up after ablation, the recurrence rate of AF was significantly lower in the weight controlled group than that in the weight uncontrolled group (14.8% (8/54) vs. 32.6%(91/279), P=0.009). Multivariable logistic regression analysis shows that weight control is independently associated with a lower postoperative AF recurrence rate (OR=0.40, 95%CI 0.18-0.90, P=0.026). Conclusion Weight control is strongly associated with a lower AF recurrence rate after catheter ablation in overweight and obese patients.

OBJECTIVE： To analyze the formulation regularity of Chinese patent medicine for knee osteoarthritis （KOA）， and to provide reference for the clinical standard use of Chinese patent medicine for KOA and the research and development of new drugs. METHODS： Chinese Pharmacopoeia （2015 edition， part Ⅰ），National Drug Reimbursement List （2017 edition）， National Essential Drug List （2017 edition）， Chinese Materia Medica Preparation （1992 version）， Compilation of National Standard for Chinese Patent Medicines （2002 edition）， Handbook of Rational Application of Chinese Patent Medicines in Surgery and Orthopedics （2010 edition） were searched to collect the type and formulation of Chinese patent medicines for “KOA”， “osteoarthritis”， “Bi syndrome”， “promoting blood circulation and removing blood stasis， dispelling wind and removing dampness， tonifying liver and kidney”. Supplementary the type and formulations of Chinese patent medicines for KOA by questionaire survey of clinial experts. The types， properties， meridian tropism， frequency and combination of medicinal materials used in Chinese patent medicine formulations were counted by using TCM inheritance auxiliary platform software V 2.5. The association rules and entropy clustering method were used to analyze the formulation regularity. RESULTS： A total of 190 Chinese patent medicines were collected， involving 289 TCM. With the top 10 used frequency being Angelica sinensis （75 times）， Boswellia carterii （55 times）， Carthamus tinctorius （53 times）， Commiphora myrrha （51 times）， Achyranthes bidentata （49 times）， Notopterygium incisum （47 times）， Angelica pubescens （45 times）， Saposhnikovia divaricata （45 times）， Angelica dahurica （39 times）， Ligusticum chuanxiong （39 times）. Medicinal material were mainly Xinwen in properties field and mainly liver meridian and spleen meridian in meridian entry field. Top 5 frequency of medicinal material combinations were C. myrrha-B. carterii， B. carterii-A. sinensis， A. sinensis-N. incisum， A. bidentata-A. sinensis， L. chuanxiong-A. sinensis. 14 core medicinal material combinations and 7 new developed formulations were concluded. CONCLUSIONS： This study analyzed the formulation regularity of Chinese patent medicines for KOA with the help of TCM inheritance auxiliary platform software V 2.5， which can provide reference for clinical differentiation of symptoms and signs and research and development of related new medicines related to KOA.

Objectives This study explored the relationship between weight control and atrial fibrillation (AF) recurrence after catheter ablation in overweight and obese patients. Methods We prospectively enrolled consecutive 333 overweight and obese patients aged 28 to 87 years old, who underwent catheter ablation for AF in Beijing Anzhen Hospital between October 2015 and February 2016. Data of patients′ characteristics, laboratory examination and treatment were collected at baseline. Each patient was followed up at 3, 6 and 12 months after ablation to collect information on weight, AF recurrence, stroke, major bleeding, hospitalization for cardiovascular reasons and death, etc. Patients were divided into weight controlled group (ΔBMI<-1 kg/m2) and weight uncontrolled group (ΔBMI≥-1 kg/m2), according to the changes in the most recent exposure BMI before AF recurrence in patients with recurrence or the BMI at 12 months′ follow?up in patients without recurrence and the BMI at baseline. Multivariate logistic regression was performed to adjust other known risk factors of AF recurrence and to explore the association between weight control and AF recurrence after catheter ablation. Results There were 54 patients in weight controlled group and 279 patients in weight uncontrolled group. There were no significant differences in age, gender, education level, left atrial size and history of hypertension between the two groups (all P>0.05). The proportion of patients using angiotensin?converting enzyme inhibitors/angiotensin receptor blockers was higher in the weight controlled group (50.0%(27/54) vs. 34.8%(97/279), P=0.034). However, there was no significant difference in the proportion of patients with obesity (33.3% (18/54) vs. 29.7% (83/279)), paroxysmal AF (59.3% (32/54) vs. 56.6% (158/279)) and AF duration less than 5 years (76.9% (40/52) vs. 65.4% (178/272)) between the weight controlled group and the uncontrolled group. During 1?year follow?up after ablation, the recurrence rate of AF was significantly lower in the weight controlled group than that in the weight uncontrolled group (14.8% (8/54) vs. 32.6%(91/279), P=0.009). Multivariable logistic regression analysis shows that weight control is independently associated with a lower postoperative AF recurrence rate ( OR=0.40, 95%CI 0.18-0.90, P=0.026). Conclusion Weight control is strongly associated with a lower AF recurrence rate after catheter ablation in overweight and obese patients.

BACKGROUNDElderly multiple organ dysfunction syndrome (MODS) patients receiving invasive mechanical ventilation have poor prognosis in intensive care units (ICUs). We studied the usefulness of four commonly used severity scores and extrapulmonary factors that affected weaning to predict outcome of such patients.

METHODSClinical data of 197 patients on admission to ICUs (from January 2009 to June 2012) were used retrospectively. The Acute Physiology and Chronic Health Evaluation (APACHE) II, APACHE III, Sample Acute Physiological Score (SAPS) II and MODS scores were calculated. All the patients were grouped into survivors and nonsurvivors according to the prognosis. Patients, who weaned from ventilator (n = 154), were subdivided into a successful weaning group and a failed weaning group. The receiver operating characteristic (ROC) curves and Logistic regression was used for prognostic and weaning assessment.

RESULTSBased on the outcomes, the areas under the ROC of APACHE II, APACHE III, SAPS II, and MODS were 0.837, 0.833, 0.824, and 0.837, respectively. The Logistic regression analysis revealed that the odds ratio (OR) of underlying lung diseases, serum albumin and creatinine, and the number of organ failures was 2.374, 0.920, 1.003, and 1.547. APACHE II scores on admission performed excellent (ROC: 0.921) on the weaning assessments.

CONCLUSIONSAPACHE II and MODS systems were marginally better for evaluating the prognosis of elderly MODS patients who received invasive mechanical ventilation. Underlying lung diseases, serum albumin, serum creatinine and the number of organ failures were independent prognostic factors. Using the APACHE II scores on admission before weaning may increase the likelihood of successful weaning. (ClinicalTrial.gov identifier NCT01802983).

Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Multiple Organ Failure ; pathology ; therapy ; Prognosis ; Respiration, Artificial ; methods ; Retrospective Studies