The individual variability should be considered in precision medicine-prevention and treatment strategies.Medical research using genomics, proteomics, metabolomics, systems analyses, and other modern tools has made big progress.In 2002, the members of the Complex-Trait Consortium proposed to develop a new mouse genetics resource called the Collaborative Cross (CC).The CC is a genetic reference panel of recombinant inbred lines of mice, designed for the dissection of complex traits and gene networks.It will provide a powerful measure for functional studies of biological networks, which will be essential to understand the intricacies of disease processes.

Objective To investigate the establishment of a six-gene-edited pig-to-non-human primate kidney xenotransplantation model. Methods The kidney of humanized genetically-edited pig (GTKO/β4GalNT2KO/CMAHKO/hCD55/hCD46/hTBM) was transplanted into a cynomolgus monkey. The survival of the recipient and kidney condition after blood perfusion were observed. The parenchymal echo, blood flow changes, and size of the kidney were monitored on a regular basis. Routine blood test, kidney function test and electrolyte assessment were carried out. Dynamic changes of urine, feces and body mass were monitored. At the end of life, the transplant kidney, heart, liver, spleen, lung, and cecum were collected for pathological examination. Results The recipient died at postoperative 7 d. After blood flow was restored, the kidney was properly perfused, the organ was soft and the color was normal. At the end of the recipient's life, a slight amount of purulent secretion was attached to the ventral side of the kidney, with evident congestion and swelling, showing the appearance of "red kidney". Postoperatively, the echo of renal parenchyma was increased, blood flow was decreased, the cortex was gradually thickened, and a slight amount of effusion surrounded the kidney and abdominal cavity over time. In the recipient, the amount of peripheral red blood cells, hemoglobin, albumin, and platelets was progressively decreased, and serum creatinine level was increased to 308 μmol/L at postoperative 7 d, whereas the K⁺ concentration did not significantly change. Light yellow urine was discharged immediately after surgery, diet and drinking water were resumed within postoperative 3 h, and light yellow and normal-shape stool was discharged. The reddish urine was gradually restored to normal color within postoperative 1 d, which were consistent with the results of the routine urine test. A large amount of brown bloody stool was discharged twice in the morning of 2 d after surgery. Omeprazole was given for acid suppression, and the stool returned to normal at postoperative 4 d. The β₂-microglobulin level was increased to 0.75 mg/L at postoperative 7 d. The body mass was increased by 1.7 kg. Autopsy pathological examination showed interstitial edema and bleeding of the transplant kidney, a large amount of infiltration of lymphocytes and macrophages, infiltration of lymphocytes in the arteriole wall and arterial cavity, accompanied by arteritis changes, lymphocyte infiltration in the cecal stroma and congestion in the spleen tissues. No significant abnormal changes were observed in other organs. Conclusions The humanized genetically-edited pig-to-non-human primate kidney xenotransplantation model is successfully established, and postoperative survival of the recipient is 1 week.

Objective:To explore the incidence, clinical and microbiological characteristics and risk factors of infection in patients with acute lymphoblastic (ALL) , non-Hodgkin lymphoma (NHL) , and multiple myeloma (MM) within 28 days after CAR-T cell infusion. It provides data support for early identification of infection and the rational use of antibacterial drugs in these patients.Methods:We retrospectively analyzed the baseline data of 170 patients with ALL, NHL and MM who received chimeric antigen receptor-modified T (CAR-T) -cell treatment in the Department of Hematology of Wuhan Union Hospital from January 2016 to December 2020, and the clinical characteristics of infection within 28 days after infusion, including 72 patients with ALL, 56 patients with NHL, and 42 patients with MM; we used Poisson regression and Cox proportional hazard regression models to assess high-risk factors for infection before and after infusion, respectively.Results:Among 170 patients, 119 infections occurred in 99 patients within 28 days, with a cumulative infection rate of 58.2%. Seventy-eight patients had 98 bacterial infections and the cumulative incidence of bacterial infection was 45.9%. The infection density was 2.01, and the median time for the first infection was about 12 days after infusion. The adjusted baseline characteristic model showed that ALL patients, previous 30 days of infection history, refractory disease, absolute neutrophil count (ANC) <0.5×10 9/L before infusion and ≥4 prior antitumor treatment regimens had a higher infection density within 28 days; grade 3 or 4 CRS was the only high-risk factor related to infection after infusion in the multivariate analysis. Conclusion:Infection is a common complication of CAR-T cell therapy in patients with hematologic malignancy. Bacterial infections occur in most patients regardless of the type of disease. ALL patients, previous 30 days of infection history, refractory disease, ANC<0.5×10 9/L before infusion and grade 3 or 4 CRS are risk factors for infection. Chinese Clinical Trial Register::ChiCTR-OIC-17011180, ChiCTR1800018143

Objective To investigate the differences and the immunocompatibility of wild-type (WT), four-gene modified (TKO/hCD55) and six-gene modified (TKO/hCD55/hCD46/hTBM) pig erythrocytes with human serum. Methods The blood samples were collected from 20 volunteers with different blood groups. WT, TKO/hCD55, TKO/hCD55/hCD46/hTBM pig erythrocytes, ABO-compatible (ABO-C) and ABO-incompatible (ABO-I) human erythrocytes were exposed to human serum of different blood groups, respectively. The blood agglutination and antigen-antibody binding levels (IgG, IgM) and complement-dependent cytotoxicity were detected. The immunocompatibility of two types of genetically modified pig erythrocytes with human serum was evaluated. Results No significant blood agglutination was observed in the ABO-C group. The blood agglutination levels in the WT and ABO-I groups were higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (all P<0.001). The level of erythrocyte lysis in the WT group was higher than those in the ABO-C, TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups. The level of erythrocyte lysis in the ABO-I group was higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (both P<0.01). The pig erythrocyte binding level with IgM and IgG in the TKO/hCD55 group was lower than those in the WT and ABO-I groups. The pig erythrocyte binding level with IgG and IgM in the TKO/hCD55/hCD46/hTBM group was lower than that in the WT group and pig erythrocyte binding level with IgG was lower than that in the ABO-I group (all P<0.05). Conclusions The immunocompatibility of genetically modified pig erythrocytes is better than that of wild-type pigs and close to that of ABO-C pigs. Humanized pig erythrocytes may be considered as a blood source when blood sources are extremely scarce.