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

OBJECTIVE: To investigate the predictive value of sphinor kinase 1 (sphk1), D-lactic acid, and intestinal fatty acid binding protein (I-FABP) for gastrointestinal injury in patients with sepsis. METHODS: A prospective observational study was conducted. Sixty-eight patients with sepsis and gastrointestinal dysfunction admitted to the department of critical care medicine of the First Affiliated Hospital of Baotou Medical College Inner Mongolia University of Science and Technology from May 2024 to March 2025 were enrolled (sepsis group), and they were divided into acute gastrointestinal injury (AGI) I-IV groups according to the definition and grading criteria of AGI proposed by the European Society of Intensive Care Medicine in 2012. Twenty non-sepsis patients without AGI admitted to the intensive care unit during the same period were enrolled as the control group (non-sepsis group). Within 30 minutes of patient enrollment, plasma sphk1, D-lactic acid, and I-FABP levels were determined by enzyme linked immunosorbent assay (ELISA). General data such as gender, age were recorded, and levels of procalcitonin (PCT), high-sensitivity C-reactive protein (hs-CRP), lactic acid (Lac), and acute physiology and chronic health evaluation II (APACHEII), sequential organ failure assessment (SOFA) were measured. Spearman method was used to analyze the correlation between sphk1, I-FABP, D-lactic acid and other indicators. The receiver operator characteristic curve (ROC curve) was used to evaluate the predictive value of sphk1, D-lactic acid, I-FABP, APACHEII score, and SOFA score for gastrointestinal injury in patients with sepsis. RESULTS: Among the 68 sepsis patients, 13 were classified as AGI grade I, 16 as AGI grade II, 23 as AGI grade III, and 16 had AGI grade IV. There were no statistically significant differences in gender, age, and abdominal infection rate among the groups. The SOFA score and APACHEII score of the sepsis group were significantly higher than those of the non-sepsis group; and the APACHEII score of the AGI IV group was significantly higher than that of the AGI I and AGI II groups. The levels of sphk1, D-lactic acid, I-FABP, PCT, Lac and hs-CRP in the sepsis group were significantly higher than those in the non-sepsis group, and each indicator gradually increased with the increase of AGI grade. Correlation analysis showed that plasma sphk1, D-lactic acid, and I-FABP in patients with sepsis-induced gastrointestinal injury were positively correlated with PCT, Lac, APACHEII score, and AGI grade (all P < 0.05), and sphk1 was positively correlated with I-FABP and D-lactic acid (r values were 0.773 and 0.782, respectively, both P < 0.05). ROC curve analysis showed that sphk1, D-lactic acid, I-FABP, APACHEII score, and SOFA score had high predictive value for gastrointestinal injury in patients with sepsis, with area under the curve (AUC) of 0.996, 0.987, 0.976, 0.901, and 0.934 (all P < 0.05). When the optimal cut-off value of sphk1 was 60.46 ng/L, the sensitivity and specificity were 95.6% and 100%, respectively; when the optimal cut-off value of D-lactic acid was 1 454.3 μg/L, the sensitivity and specificity were 95.6% and 100%, respectively; when the optimal cut-off value of I-FABP was 0.91 ng/L, the sensitivity and specificity were 95.6% and 100%, respectively; when the optimal cut-off value of APACHEII score was 14.5, the sensitivity and specificity were 80.9% and 85.0%, respectively; when the optimal cut-off value of SOFA score was 3.5, the sensitivity and specificity were 85.3% and 95.0%, respectively. CONCLUSIONS The levels of plasma sphk1, I-FABP, and D-lactic acid were significantly elevated in patients with sepsis and gastrointestinal injury. These indicators can serve as sensitive and relatively specific serological markers for early prediction of intestinal mucosal damage.
Humans ; Lactic Acid/blood* ; Fatty Acid-Binding Proteins/blood* ; Sepsis/complications* ; Prospective Studies ; Male ; Female ; Middle Aged ; Predictive Value of Tests ; Adult ; Aged ; Gastrointestinal Diseases/blood* ; Prognosis

Objective To investigate the seroprevalence of Toxoplasma gondii infections among patients with hematological diseases, so as to provide insights into improving the prognosis and quality of life among patients with hematological diseases. Methods A total of 240 patients with hematological diseases (including 170 patients with hematological tumors and 70 patients with non-tumor hematological diseases) admitted to The Affiliated Hospital of Putian University during the period from January 1, 2021 through October 10, 2023 and 500 healthy volunteers in the hospital during the same period were enrolled. Subjects’ demographics and serum samples were collected, and serum specific IgG and IgM antibodies against T. gondii were detected using the chemiluminescence assay, with any of a positive IgG or IgM antibody defined as a positive T. gondii infection. The seroprevalence of specific IgG and IgM antibodies against T. gondii was compared between patients with hematological diseases and healthy volunteers. Results The mean age (F = 2.034, P > 0.05) and gender distribution (χ² = 0.462, P > 0.05) were comparable among patients with hematological tumors, patients with non-tumor hematological diseases and healthy volunteers, and there was no significant difference in the proportion of history of cat or dog contacts between patients with hematological diseases and healthy volunteers (χ² = 0, P > 0.05). The seroprevalence of anti-T. gondii antibody was significantly higher among patients with hematological diseases than among healthy volunteers (15.8% vs. 0.6%; χ² = 71.902, P < 0.01), and there was a significant difference in the seroprevalence of anti-T. gondii antibody among patients with hematological tumors (18.2%), patients with non-tumor hematological diseases (10.0%) and healthy volunteers (χ² = 78.327, P < 0.01). The seroprevalence of anti-T. gondii antibody was significantly higher among patients with hematological tumors and non-tumor hematological diseases than among healthy volunteers (both P values < 0.05), while no significant difference was seen in the seroprevalence of anti-T. gondii antibody between patients with hematological tumors and non-tumor hematological diseases (P > 0.05). In addition, the proportion of history of cat or dog contacts was significantly higher among patients with hematological diseases that were positive for serum anti-T. gondii anti-body than among those negative for serum anti-T. gondii antibody (21.1% vs. 5.4%; χ² = 8.653, P < 0.05). Conclusions There is a high seroprevalene rate of T. gondii infections among hematological diseases, which is significantly greater than that among healthy volunteers.

Objective:To discuss and analyze the clinical efficacy and application value of transperineal ultrasound dynamic monitoring for the contraction function of pelvic floor muscle to guide training based on its feedback in the treatment of stress incontinence of female.Methods: 169 female patients with stress incontinence were enrolled this study. And all of them were treated by using the Koegel physical training of pelvic floor muscle under the guidance of doctor, at the same time, the relative contraction function indicators of pelvic floor muscle before and after treatment were observed and compared by applied transperineal ultrasound dynamic monitoring.Results: The differences between before and after treatment of physical training on pelvic floor muscle about the length of the levator hiatus, the acreage of pelvic diaphragm hiatus, and the perimeter of pelvic diaphragm hiatus in contraction and silent period were significant (t=-2.858,t=-2.949,t=-4.899,P<0.05), and that of after treatment was higher than that of before treatment. The horizontal distance of pubis combined with margo inferior, vertical distance and thickness of viscera on pubis of after treatment were significant higher than that of before treatment (t=3.674, t=-4.899,t=4.230,P<0.05). The posterior urethra intersection angle and the intersection angle of left and right levator after treatment were significantly higher than that of before treatment (t=-4.087,t=6.584, P<0.05).Conclusion: Transperineal ultrasound dynamic monitoring can correctly evaluate the clinical efficacy of the contraction function of pelvic floor muscle to guide training based on its feedback in the treatment of stress incontinence of female. And this method has important clinical value.

Melioidosis is a endemic infectious disease caused by Burkholderia pseudomallei, and is considered one of the major causes of fatal pneumonia and sepsis.This paper reports diagnosis and treatment course of one case pulmonary melioidosis, and reviews the related literatures, so to improve clinical workers'' understanding towards melioidosis, avoid misdiagnosis and missed diagnosis.

Artificial liver support system (ALSS),as a means of bridging patients with liver failure to transplantation,has been widely used at home and abroad.However,clinical trails show that different ALSS may have different therapeutic effects.This review briefly introduces the widely-used non-biological liver support technologies and extensively-studied biological liver support technologies,and tries to give an overview on their impact on biochemical markers and survival.

Objective To investigate serum nesfatin-1 levels in type 2 diabetes (T2DM)patients with or without nonalcohol-ic fatty liver(NAFLD).Methods The hight,weight,serum GLU,lipid profiles,INS,HbA1c,ALT,nesfatin-1 levels were measured in 21 1 T2DM patients[98 without NAFLD(TD2M without NAFLD group)and 1 13 with NAFLD(TD2M with NAFLD group)] and 75 normal subjects(NGT group).BMI、HOMA-IR were also calculated.Results The serum nesfatin-1 level was significantly higher in T2DM group than those in NGT group(P <0.05),and T2DM with NAFLD group had higher nesfatin-1 level than T2DM without NAFLD group (P < 0.05 ).There was a close relation between nefastin-1 of T2DM group and course of disease (r=-0.447,P <0.05).NAFLD existed a significant correlation with BMI、TG and nesfatin-1 (P <0.05).Conclusion nesfatin-1 may partially contribute to the pathogenesis of T2DM and NAFLD.

Objective To evaluate the relationship between resistin and hepatic fibrosis in nonalcoholic fatty liver disease (NAFLD) subjects.Methods Serum resitin and Interleukin (IL)-18's concentrations were measured in 144 subjects (70 NAFLD pa-tients and 74 healthy controls) with enzyme-linked immunosorbent assay (ELISA) and their serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting blood glucose (FBG), HbA1c, triglyceride (TG), total-cholesterol (TC), low density lip-oprotein ( LDL) , high density lipoprotein ( HDL) , homeostasis model assessment of insulin resistance ( HOMA-IR) , hyaluronic acid , IVcollagen, height, body weight, waist circumference, and hip circumference were also measured .Their waist-to-hip ratio (WHR) and body mass indes (BMI) were calculated.Results There were higher levels of systolic blood pressure (SBP), WHR, BMI, TG, ALT, AST, HOMA-IR, hyaluronic acid, IV collagen, resistin, and IL-18 in the NAFLD patients than those of the healthy controls ( P <0.05 ) .The serum resistin level was significantly and positively correlated with WHR , BMI, ALT, HOMA-IR, TG, IV collagen , and IL-18 ( r =0.231 , 0.341 , 0.223 , 0.264 , 0.213 , 0.315 , and 0.669 , P <0.05 ) .After adjustment for body fat and IL-18 , the serum resistin level was still significantly and positively correlated with ALT and IV collagen ( r =0.222 , 0.0.326 , P <0.05 ) . Conclusions Resistin might take part in the development of NAFLD insulin resistance and its pro -inflammation.

BACKGROUND: External preparations treatment of fractures in traditional Chinese medidne are mostly ordinary hard-paste, cream, ointment, which lack of modernized traditional Chinese medicine transdermal delivery systems, and the treatment has poor drug absorption and simple process. The treating procedure needs to be used repeatedly, which would affect fracture external fixation and lead to unsatisfactory therapeutic effect. In this Paler, the extemal treatment of traditional Chinese medidna was combined with advanced micro-nano-technology to develop a new medical complex functional materials-micron traditional Chinese medicine functional lining material, which is an organic combination of diaplasis, fixation and local drug remedy, which provides a better treatment for fractures. OBJECTIVE: To explore the effect of micron tradifional Chinese medicine functional lining material on the healing of fracture in rabbits, METHODS: After model preparation, rabbits were randomly divided into 4 groups: rabbits in the micron group were treated with micron traditional Chinese medicine functional lining material plus plaster external fixation; those in the traditional Chinese medidna control group were treated with ordinary Chinese medicine functional material plus plaster extemal fixation; those in the lining material control group were treated with ordinary lining material added plaster extemal fixation; those in the natural healing control group had no special treatments. The effect of fracture healing was evaluated by X-ray at 2, 4 and 6 weeks after modeling. The serum concentration of alkaline phosphatase, calcium and phosphorus was detected respectivaly before modeling and at 2, 4 and 6 weeks after modeling. RESULTS AND CONCLISION: ①X-rap examination:After 6 weeks the external was almost copletly absorbed and medullary cavity was completely recanalizad in the micron group, while fracture line disappeared and the external callus began to be absorbed and medullary cavity was not recanalized in the traditional Chinese medidne control group. Additionally, there were case of non-union stump hardening in natural healing group. ②Serum biochemistry:The activity of alkaline phosphatase reached a peak after 2 weeks in micron group, which was 2 weeks ahead of time compared with that in traditional Chinese medicine control group. And the peak concentration of alkaline phosphatase in micron group was higher than other groups. After 4 weeks serum calcium concentration started to fall significantly and phosphorus concentration started to rise significantly in micron group, as was statistically significant compared with other groups. After 6 weeks serum calcium concentration in micron group had fallen to normal level, while that in other groups was higher than normal. And phosphorus concentration in micron group increased significantly, which was statistically significant compared with natural healing group. The results demonstrated that micron feature traditional Chinese medicine lining matedat can enhance the activity of alkaline phosphatase, decrease the serum concentration of calcium and increase the serum concentration of phosphorus and the product of calcium and phosphorus, therefore, promote the healing of fracture, It shows that micron traditional Chinese medicine functional lining matedal plays a stronger effect on promoting the healing of fracture than that of ordinary Chinese medicine functional lining material.

Objective To study the expressions of the tumor suppressor gene TSH receptor( TSHR),P16, and RAS in papillary thyroid carcinoma ( PTC ) , and the correlation between the occurrence of tumor and the aberrant promoter hypermethylation of three tumor suppressor genes. Methods RT-PCR was used to detect the mRNA expression of three tumor suppressor genes in tissues of 50 cases of PTC ,20 cases of nodular goiter,and 12 cases of thyroid adenoma. The promoter methylation status of three tumor suppressor genes was examined by methylation-specific PCR technique( MSP). Gene sequencing was used to test if the hypermethylation existed in the promoter of three tumor suppressor genes. Results In 68.0% (34/50) TSHR gene, 54.0% (27/50) P16 gene, and 60.0% ( 30/50 ) RAS gene in PTCs, hypermethylation in promoter region was detected, the respective results 21.9% (7/32) , 15. 6% (5/32) ,and 31. 3% (10/32) were found in control tissues. The rates of the three genes with promoter hypermethylation in PTC were significantly higher than those in control tissues ( all P<0. 05). The mRNA expressions of TSHR,P16,and RAS were significantly lower in PTC than those in control tissues (0. 41 ± 0.11 vs 0.63±0. 08,0. 51±0. 17 vs 0. 72±0. 22,0. 56±0. 10 vs 0. 67±0. 16, all P<0. 05). The sequencing confirmed that there was CC to TC transmission in the promoters of three tumor suppressor genes. Conclusions The methylation of three tumor suppressor genes in promoter region is a common molecule event and may be involved in the genesis and development of human PTC.