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

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

AIM:To compare the differences of ocular biometric parameters of age-related cataract between Tibetan and Han ethnic groups, and to analyze the distribution characteristics of ocular biometric parameters in Tibetan cataract patients.METHODS:Retrospective cohort study. A total of 661 patients(1 030 eyes)with age-related cataract confirmed in the hospital between January 2019 and December 2020 were enrolled. The parameters of axial length, anterior chamber depth, keratometry, corneal astigmatism and astigmatic axis were measured by IOL Master 500 in 483 cases(739 eyes)of Tibetan age-related cataract patients and 178 cases(291 eyes)of Han patients.RESULTS:The axial length, anterior chamber depth and corneal astigmatism of the Tibetan patients with age-related cataract were 23.33(22.81, 23.86)mm, 3.04(2.79, 3.30)mm and 0.73(0.47, 1.07)D. The mean keratometry was 43.89±1.35 D. The results indicated that Tibetan cataract patients had shorter axial lengths and smaller keratometry compared to Han patients(all P<0.05). Age in Tibetan patients was negatively correlated with axial length and anterior chamber depth, and positively correlated with keratometry(all P<0.05). Tibetan male patients had longer axial lengths, deeper anterior chambers, and flatter corneas compared to female patients(all P<0.05).CONCLUSION:There were differences in ocular biometric parameters between age-related cataract patients of Tibetan and Han ethnicities. The distribution of ocular biometric parameters in Tibetan cataract patients varied across different age groups and gender groups.

Objective To investigate the distribution of traditional Chinese medicine(TCM)syndromes in patients with type 2 diabetic retinopathy(T2DR)and to explore the correlation of TCM syndromes with serum inflammatory factors and adiponectin(APN)levels,so as to provide evidence for TCM syndrome differentiation of T2DR.Methods A cross-sectional case-control study was conducted in 42 patients(involving 84 eyes)diagnosed as T2DR in the Department of Ophthalmology,Ganzhou People's Hospital from September 2022 to March 2023.The correlation between fundus fluorescein angiography(FFA)staging and TCM syndrome differentiation in patients with T2DR was explored.The relationship between TCM syndrome types and serum levels of inflammatory factors and APN,as well as the differences in serum inflammatory factors and APN levels of the patients with various FFA stages were analyzed.The correlation between each variable and TCM syndrome types in patients with T2DR was investigated.Results(1)Among the 42 patients with T2DR,27 cases were male and 15 cases were female,and their age averaged(54.0±12.0)years old.Among them,14 cases(33.3％)were differentiated as liver-kidney deficiency with malnutrition of eye collateral syndrome,15 cases(35.7％)were differentiated as yin-essence deficiency with internal dry-heat syndrome,9 cases(21.4％)were differentiated as qi-yin deficiency with collateral stasis and obstruction syndrome,4 cases(9.5％)were differentiated as yin-yang deficiency with blood stasis and phlegm coagulation syndrome,and none case(0.0％)was differentiated as spleen dysfunction and water-damp obstruction syndrome.(2)FFA staging showed that FFA staging ≥ 4[i.e.,having proliferative diabetic retinopathy(PDR)]was found in 78.6％(11/14)of the patients with liver-kidney deficiency with malnutrition of eye collaterals syndrome,73.3％(11/15)of the patients with yin-essence deficiency with internal dry-heat syndrome,100％(9/9)of the patients with qi-yin deficiency with collateral stasis and obstruction syndrome,and 100％(4/4)of the patients with yin-yang deficiency with blood stasis and phlegm coagulation syndrome.But the intergroup comparison showed no significant differences among various syndrome types(P=0.272).(3)Among the 42 patients with T2DR,35 patients(83.3％)had higher level of tumor necrosis factor-α(TNF-α),28 patients(68.3％)had higher level of C-reactive protein(CRP)and 38 patients(90.5％)had higher level of glycosylated hemoglobin(HbA1c)than the normal.However,there was no significant difference in the levels of serum inflammatory factors of TNF-α,CRP,interleukin-6(IL-6)and vascular endothelial growth factor(VEGF),APN and HbA1c among the patients with different FFA stages(P＞0.05),neither did the difference in serum APN,TNF-α,CRP,IL-6 and VEGF levels among the patients with different TCM syndrome types(P＞0.05).(4)The correlation analysis showed that the patients with yin-yang deficiency with blood stasis and phlegm coagulation syndrome had a shorter course of eye diseases than the patients with liver-kidney deficiency with malnutrition of eye collaterals syndrome(r=-0.467,P=0.051),had higher CRP level than the patients with yin-essence deficiency with internal dry-heat syndrome(r=0.592,P=0.010),and had higher CRP level(r=0.668,P=0.013)and a longer course of diabetes(r=0.629,P=0.021)than the patients with qi-yin deficiency with collateral stasis and obstruction syndrome.Conclusion Increased serum TNF-α and CRP expressions are presented in the patients with T2DR.Liver-kidney deficiency with malnutrition of eye collaterals syndrome and yin-essence deficiency with internal dry-heat syndrome are the common syndromes in T2DR.Yin-yang deficiency with blood stasis and phlegm coagulation syndrome is closely correlated with CRP level,and the patients with yin-yang deficiency with blood stasis and phlegm coagulation syndrome have a longer course of diabetes.

ObjectiveAlthough expression of the TEAD1 protein in preadipocytes has been established, its function remains unclear. In this study, we sought to detect transcripts of TEAD1 in chicken and to examine the effects of this protein on the proliferation, migration, apoptosis, and differentiation of immortalized chicken preadipocyte cell lines (ICP1). MethodsThe full-length sequence of the TEAD1 gene was cloned and the two transcripts were subjected to bioinformatics analysis. The subcellsular localization of TEAD1 transcripts was determined based on indirect immunofluorescence. The effects of TEAD1 transcripts overexpression on the proliferation of ICP1 cells were examined by RT-qPCR, CCK-8, and EdU assays; the effects of TEAD1 transcripts on ICP1 cells migration were examined based on the scratch test; and the effects of TEAD1 transcripts overexpression on ICP1 cells apoptosis were analyzed using apoptosis-Hoechst staining and RT-qPCR. The expression of TEAD1 transcripts in different tissues, cells lines, and ICP1 at different periods of differentiation was analyzed by RT-qPCR. The effects of TEAD1 transcripts overexpression on lipid droplet accumulation and adipogenic-related gene expression in ICP1 cells were analyzed based on Oil Red O and BODIPY staining, RT-qPCR, Western blot, and dual-luciferase reporter gene assays. Finally, the content of triglyceride (TG) was measured in TEAD1 overexpressed ICP1 cells. ResultsThe full-length TEAD1 was cloned and two TEAD1 transcripts were identified. The TEAD1-V1 protein was found to be localized primarily in the cell nucleus, whereas the TEAD1-V2 protein is localized in the cell cytoplasm and nucleus. The overexpression of both TEAD1-V1 and TEAD1-V2 significantly inhibited the proliferation of ICP1 cells. Whereas the overexpression of TEAD1-V1 promoted ICP1 cell migration, the overexpression of TEAD1-V2 had no significant effects on ICP1 migration; the overexpression of both TEAD1-V1 and TEAD1-V2 significantly promoted the apoptosis of ICP1 cells. We found that the different transcripts of TEAD1 have similar expression pattern in different tissues and cells lines. During induced preadipocyte differentiation, the expression of these genes initially declined, although subsequently increased. Overexpression of TEAD1-V1 promoted a significant reduction in lipid droplet formation and inhibited C/EBPα expression during the differentiation of ICP1 cells (P<0.05). However, the overexpression of TEAD1-V2 had no significant effect on lipid droplet accumulation or the expression of adipogenic-related proteins (P>0.05). Overexpression of TEAD1-V1 significantly decreased triglyceride content in ICP1 cells (P<0.05), while overexpression of TEAD1-V2 had no effect on triglyceride content in ICP1 cells (P>0.05). ConclusionIn this study, for the first time, identified two TEAD1 transcripts. Overexpressed transcripts TEAD1-V1 and TEAD1-V2 both inhibited the proliferation of chicken preadipocytes and promoted apoptosis of chicken preadipocytes. TEAD1-V1 inhibited the differentiation of preadipocytes and promoted the migration of preadipocytes, while TEAD1-V2 had no effect on the differentiation and migration of preadipocytes.

Objective To establish a differential model of phlegm and blood stasis pattern and qi deficiency and blood stasis pattern in stable angina pectoris using radiomics.Methods A total of 91 patients with stable angina pectoris who underwent coronary artery CT angiography in Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from January 2021 to January 2022 were collected,including 47 cases of phlegm and blood stasis pattern and 44 cases of qi deficiency and blood stasis pattern.The patients were divided into train set(64 cases)and test set(27 cases)according to the ratio of 7∶3 by stratified random sampling method.3D-slicer software was used to extract the radiomics features of pericoronary adipose tissue(PCAT)images.Principal component analysis was used to visualize the distribution of radiomics features of pattern of phlegm and blood stasis and pattern of qi deficiency and blood stasis.The least absolute shrinkage and selection operator regression analysis and support vector machine decreasing feature elimination were used for feature selection.The multinomial logistics regression was used for model construction.The receiver operating characteristic(ROC)curve was used to verify the model in the train set and the test set to evaluate the effectiveness of the radiomics features in differentiating phlegm and blood stasis pattern and qi deficiency and blood stasis pattern.Finally,Spearman coefficient was used to analyze the correlation between the differential features and clinical physicochemical data.Results A total of 837 radiomics features were extracted from PCAT images by 3D-slicer software.In the principal component analysis,PC1 and PC2 explained 77.9%and 8.1%of the total variance,respectively,and there was a relatively obvious separation trend between the two pattern groups.After feature screening,7 radiomics features were used to construct the differential model of phlegm and blood stasis pattern and qi deficiency and blood stasis pattern.The area under the ROC curve(AUC)of the differential model was 0.844 in the train set and 0.834 in the test set.Spearman correlation analysis showed that the differential features were significantly correlated with cTnI,neutrophil,triglyceride,total cholesterol,and leukocyte.Conclusion The CT radiomics model based on PCAT has a high discrimination efficiency for stable angina pectoris with phlegm and blood stasis pattern and qi deficiency and blood stasis pattern.

Objective To observe the curative effect of comprehensive traditional Chinese medicine(TCM)therapy for the treatment of refractory sudden hearing loss(i.e.,suffering sudden hearing loss more than 2 weeks),and to analyze the factors that may affect the prognosis.Methods A retrospective analysis was carried out in 405 hospitalized patients with refractory sudden hearing loss who were treated in the Department of Otorhinolaryngology,the First Affiliated Hospital of Guangzhou University of Chinese Medicine from 2005 to 2022.The patients were all treated by comprehensive TCM therapy including oral administration of Chinese medicine,acupuncture,acupoint seed-pressing application after individualized syndrome differentiation.The overall clinical efficacy was evaluated,and the difference of efficacy in the patients with various courses of disease,degrees of deafness,types of hearing curve,concomitant symptoms and TCM syndrome types,having or not having previous treatment history was analyzed.Results For the 405 patients with refractory sudden hearing loss,the cure rate was 5.7％and the total effective rate was 28.1％.Among the 405 patients,the best efficacy was achieved in the patients with mild hearing loss,low-frequency decline type of hearing curve,and having no previous treatment history,and the differences were statistically significant(P＜0.05 or P＜0.01).There was no significant difference in the efficacy of patients with different courses of disease,with or without concomitant symptoms,or with various syndrome types(P＞0.05).Conclusion The comprehensive TCM therapy has a certain effect on refractory sudden hearing loss.Patients with poor efficacy after conventional western medicine can still benefit from the comprehensive TCM therapy.

Objective To investigate the correlation between the level of N-terminal pro-Brain natriuretic peptide(NT-proBNP)and cardiorespiratory fitness following acute exposure to high altitude.Methods Forty-six subjects were recruited from the Second Affiliated Hospital of Army Medical University in June 2022,including 19 males and 27 females.After completing cardiopulmonary exercise test(CPET),serological detection of myocardial cell-related markers,and multiple metabolites at a plain altitude(300 meters above sea level),all subjects flew to a high-altitude location(3900 meters above sea level).Biomarker testing and CPET were repeated on the second and third days after arrival at high altitude.Changes in serum biomarker and key CPET indicators before and after rapid ascent to high altitude were compared,and the correlation between serum levels of various myocardial cell-related markers and metabolites and high altitude cardiorespiratory fitness was analyzed.Results Compared with the plain altitude,there was a significant decrease in maximal oxygen uptake after rapid ascent to high altitude[(25.41±6.20)ml/(kg.min)vs.(30.17±5.01)ml/(kg.min),P<0.001].Serum levels of NT-proBNP,Epinephrine(E),plasma renin activity(PRA),angiotensin Ⅱ(Ang Ⅱ),angiotensin-converting enzyme 2(ACE2)and leptin(LEP)significantly increased,with all differences being statistically significant(P<0.05)after acute high altitude exposure.In contrast,no statistically significant differences were observed for creatine kinase MB(CK-MB),cardiac troponin I(cTnI),myoglobin(Myo)and norepinephrine(NE)(P>0.05).Correlation analysis showed a significant negative correlation between NT-proBNP at plain altitude(r=-0.768,P<0.001)and at high altitude(r=-0.791,P<0.001)with maximal oxygen uptake at high altitude.Multivariate linear regression analysis indicated that maximal oxygen uptake at plain altitude(t=2.069,P=0.045),NT-proBNP at plain altitude(t=-2.436,P=0.020)and at high altitude(t=-3.578,P=0.001)were independent influencing factors of cardiorespiratory fitness at high altitude.Conclusion Cardiorespiratory fitness significantly decreases after rapid ascent to high altitude,and the baseline NT-proBNP level at plain altitude is closely related to cardiorespiratory fitness at high altitude,making it a potential predictor indicator for high altitude cardiorespiratory fitness.

Objective:To evaluate the screw placement assisted by robotic navigation in cannulated screw fixation for treatment of fracture of scapular coracoid process.Methods:A retrospective study was conducted to analyze the data of 24 patients with fracture of scapular coracoid process who had been treated by cannulated screw fixation at Department of Orthopaedics and Trauma, Red Cross Hospital Affiliated to Xi'an Jiaotong University from January 2020 to December 2023. According to whether the intraoperative screw placement was assisted by robotic navigation or not, the patients were divided into 2 groups. In group A of 11 cases, there were 6 males and 5 females with an age of (47.4±3.4) years whose screw placement was assisted by robotic navigation during the internal fixation with cannulated screws. In group B of 13 cases, there were 10 males and 3 females with an age of (43.5±4.9) years whose screw placement was assisted by conventional C-arm X-ray fluoroscopy during the internal fixation with cannulated screws. The operative time, intraoperative blood loss, fracture healing time, intraoperative fluoroscopy frequency, intraoperative adjustments of guide wire, Constant-Murley score of shoulder function at the last follow-up and postoperative complications were compared between the 2 groups.Results:There was no significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). The follow-up time was (25.3±9.1) months for group A and (27.6±10.8) months for group B, showing no statistically significant difference ( P>0.05). The intraoperative blood loss [(51.8±35.7) mL], intraoperative fluoroscopy frequency [(5.7±1.0) times] and intraoperative adjustments of guide wire [(1.6±0.7) times] in group A were significantly less than those in group B [(123.8±73.9) mL, (12.5±2.7) times, and (5.3±1.0) times] ( P<0.05). There were no significant differences in operative time [(88.2±21.3) min versus (80.4±31.1) min], fracture healing time [(10.0±1.3) weeks versus (11.5±2.7) weeks] or Constant Murley score of shoulder function at the last follow-up [(86.7±6.1) points versus (91.1±10.0) points] between group A and group B ( P>0.05). No patient reported such complications as wound infection, fracture nonunion, or failure of internal fixation during the follow-up period. Conclusions:In the treatment of fracture of scapular coracoid process by cannulated screw fixation, robotic navigation can be used to assist screw placemen to achieve good efficacy comparable to conventional C-arm X-ray fluoroscopy. Moreover, assistance by robotic navigation can help reduce intraoperative blood loss and radiation, and improve surgical accuracy.

The Elekta Synergy Linear Accelerator in some hospital from 2012 to 2022 were retrospectively analyzed in terms of operation,failure time distribution and failure of each system.Some countermeasures were put forward accordingly to decrease the failure rate and strengthen the training of relevant personnel's operation and maintenance.References were provided for effective management and operation of medical linear accelerators.