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

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

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 explore the efficacy and safety of subretinal injection of conbercept in treating refractory neovascular age-related macular degeneration(nAMD).Methods In this prospective clinical study,17 eyes of 17 pa-tients diagnosed with refractory nAMD at the Department of Fundus Disease,the Affiliated Eye Hospital of Nanchang Uni-versity from March 2022 to September 2023 were enrolled.The 10 g·L-1 conbercept was injected into the subretinal area of the macular area using a 41G ultra-fine microneedle.If retinal exudation was found in the macular area by optical coherence tomography during the follow-up,the intravitreal injection of 10 g·L-1 conbercept was performed.The best corrected vis-ual acuity(BCVA),central macular retinal thickness(CMT),number of injections and complications were recorded before and 1,3,6,and 12 months after the operation.Results Compared with the preoperative values,the BCVA of patients significantly improved(all P＜0.001)1,3,6 and 12 months postoperatively.There was no significant change in BCVA at each time point after operation(all P＞0.05).Compared with pre-operation,CMT of patients significantly decreased at 1,3,6 and 12 months after operation(all P＜0.001).From 1 month to 12 months after the operation,the CMT of patients gradually decreased(all P＜0.001).Pearson correlation analysis showed that there were positive correlations between pre-operative BCVA and preoperative CMT,preoperative BCVA and 12-month postoperative BCVA(r=0.643,P=0.005;r=0.634,P=0.006).During the treatment,the number of anti-vascular endothelial growth factor injections in 17 eyes was(1.35±0.61)times,with 1 time in 12 eyes,2 times in 4 eyes,and 3 times in 1 eye.Correlation analysis showed that the number of injections was positively correlated with preoperative CMT(r=0.664,P=0.004).No intraoperative or postop-erative complications related to the operation occurred in 17 eyes.Conclusion Subretinal injection of conbercept,which can reduce CMT and improve visual prognosis,is a safe and effective treatment method for refractory nAMD.

ObjectiveThe hygroscopic properties of Mume Flos decoction pieces were studied from the perspectives of macroscopic［water activity（A_w）］ and microscopic（water molecular mobility）， which provided a theoretical basis for the determination of the safe storage moisture content. MethodAdsorption isotherm of Mume Flos decoction pieces was obtained by static weighing method， and seven common hygroscopic models were fitted and estimated. The best model was selected according to the principle that determination coefficient（R²） was closer to 1， residual sum of squares（RSS） was closer to 0 and Akaike information criterion（AIC） was smaller. According to the optimal model， the absolute and relative safe moisture contents of Mume Flos decoction pieces at 25， 35， 45 ℃ was calculated. Low-field nuclear magnetic resonance（LF-NMR） was used to measure the water molecular mobility in the hygroscopic process of Mume Flos decoction pieces. ResultThe best model to describe the adsorption isotherm of Mume Flos decoction pieces was the Peleg model. According to the model expression， the absolute safe moisture contents of Mume Flos decoction pieces at 25， 35， 45 ℃ were 9.59%， 7.96% and 7.68%， and the relative safe moisture contents were 13.05%， 11.99%， 11.77%， respectively. Mume Flos decoction pieces all contained two water states during the process of hygroscopic absorption at different temperatures， namely bound water T₂₁ and free water T₂₂. During the process of hygroscopic absorption， bound water had the largest increase in peak area. The sum of peak areas of the bound water and free water had a good linear relationship with the moisture contents， and the R² were 0.959 9， 0.911 8 and 0.974 7 at 25， 35， 45 ℃， respectively. When A_w<0.57， T₂₁ did not change， and the water molecular mobility remained unchanged. When A_w>0.57， T₂₁ showed an increasing trend， and the water molecular mobility increased. The moisture contents of Mume Flos decoction pieces were 8.44%， 6.81% and 6.25% when the water molecular mobility increased at 25， 35， 45 ℃， respectively. ConclusionCombined with the theory of water activity and water molecular mobility， 6.25% is recommended as the safe storage moisture content of Mume Flos decoction pieces， this study can provide reference for determining the safe storage moisture content of other decoction pieces.

Background/Aims: The aim of this study was to analyze the chronological changes in postoperative complications in surgical ulcerative colitis patients over the past decade in China and to investigate the potential parameters that contributed to the changes. Methods: Ulcerative colitis patients who underwent surgery during 2008–2017 were retrospectively enrolled from 13 hospitals in China. Postoperative complications were compared among different operation years. Risk factors for complications were identified by logistic regression analysis. Results: A total of 446 surgical ulcerative colitis patients were analyzed. Fewer short-term complications (24.8% vs. 41.0%, P=0.001) and more laparoscopic surgeries (66.4% vs. 25.0%, P<0.001) were found among patients who received surgery during 2014–2017 than 2008–2013. Logistic regression suggested that independent protective factors against short-term complications were a higher preoperative body mass index (odds ratio [OR], 0.870; 95% confidence interval [CI], 0.785–0.964; P=0.008), laparoscopic surgery (OR, 0.391; 95% CI, 0.217–0.705; P=0.002) and elective surgery (OR, 0.213; 95% CI, 0.067–0.675; P=0.009). The chronological decrease in short-term complications was associated with an increase in laparoscopic surgery. Conclusions Our data revealed a downward trend of short-term postoperative complications among surgical ulcerative colitis patients in China during the past decade, which may be due to the promotion of minimally invasive techniques among Chinese surgeons.

OBJECTIVE To systematically evaluate the efficacy and safety of oral Janus kinase （JAK） inhibitor in the treatment of alopecia areata （AA）in order to provide evidence -based reference for clinical use . METHODS PubMed，Embase， Web of Science ，the Cochrane Library ，CNKI，Wanfang and CBM were searched from the inception to March 29，2022. Randomized controlled trials （RCTs）of oral JAK inhibitors （trial group ）versus placebo （control group ）in the treatment of AA were collected . Two researchers independently screened the literature ，extracted the data ，and evaluated the quality of the included studies. RevMan 5.4 software was used for meta -analysis and analysis of publication bias . RESULTS A total of 2 170 patients were enrolled in 5 RCTs，including 1 619 in the trial group and 551 in the control group . Meta-analysis results showed that ：compared with control group ，the ratio of the patients with the Severity Alopecia Tool （SALT）score ≤20 at 24th week [RR＝6.10，95%CI （3.86，9.63），P＜0.000 01] and 36th week [RR＝6.59，95%CI（4.16，10.43），P＜0.000 01] were both higher ；Hospital Anxiety and Depression Scale -Anxiety （HADS-A） score [RR＝0.35， 95%CI （0.07，0.64），P＝0.02] and Hospital Anxiety and 1009） Depression Scale -Depression （HADS-D） score [RR＝0.50， 95%CI（0.22，0.77），P＝0.000 4] were more decreased at 24th week . HADS-A score [RR＝0.55，95%CI（0.21，0.89）， 话：0371-66913047。 P＝0.001] and HADS -D score [RR＝0.50， 95%CI （0.16，0.84），P＝0.004] were also significantly decreased at 36th week . The incidence of acne [RR＝4.07，95%CI（1.83，9.08），P＝0.000 6] and low density lipoprotein （LDL）elevation [RR＝1.66，95%CI（1.21，2.28），P＝0.002] in trial group were incr eased significantly （P＜0.05）. There were no significant differences in the incidence of urinary tract infection，upper respiratory tract infection ， headache，nasopharyngitis and creatine phosphokinase elevation between 2 groups （P＞0.05）. There was little possibility of publication bias in this study based on the publication bias analysis . CONCLUSIONS Oral JAK inhibitor can significantly improve AA patients ’hair regrowth ，anxiety and depression . Acne and LDL elevation are the main adverse events .

Objective: To investigate the association between mental sub-health and physical fitness of Chinese adolescents, to provide a reference for promoting the physical and mental health of Chinese adolescents. Methods: A total of 16 545 adolescents (13-22 years) were selected by random cluster sampling in six major administrative regions in China. The psychological part of the Multidimensional Sub-health Questionnaire of Adolescents (MSQA) and the physical fitness index test were used to assess mental sub-health and physical fitness, respectively. The chi-square test and Logistic regression analysis were used to analyze and compare the relationships between different levels of physical fitness and mental sub-health. Results: The overall detection rate of mental sub-health status among high-grade physical fitness index adolescents was 11.9%, and the detection rate among low-grade physical fitness index youths was 26.0%, and the difference was statistically significant (χ2=970.73，P<0.05). The overall detection rate among high-grade physical fitness index boys was 11.1%, and that of low-grade physical fitness index boys was 24.4%. The difference was statistically significant (χ2=566.12，P<0.05). The overall detection rate of mental sub-health status among high-level physical fitness index girls was 12.8%, and that among low-level physical fitness index girls was 27.6%, and the difference was statistically significant (χ2=412.25，P<0.05). After adjusting for gender, age, BMI, and region in the Logistic regression model, the detection rate of mental sub-health status of adolescents with low-grade physical fitness index was 2.35 times higher than that of high-grade physical fitness index adolescents(95%CI=2.12-2.61). Conclusion Adolescents with poor physical fitness have a higher risk of mental sub-health.Attention should be paid to adolescent physical fitness development to comprehensively improve physical and mental health development.

Objective: To understand the relationships between video time, exercise time and the mental sub-health of Chinese adolescents, and to assist the development of Chinese adolescents’ mental health. Methods: In this study, 16 545 adolescents aged 13-22 years in six administrative regions of China were surveyed using an adolescent sub-health multi-dimensional assessment questionnaire (MSQA), and daily physical exercise time, video screen time and other indicators were recorded. Binary Logistic regression analysis was used to understand adolescents’ mental sub-health and the correlation between video time and exercise time. Results: Detection rate of mental sub-health status in adolescents with video time ≤2 h/d was lower than that of adolescents with video time >2 h/d(19.1%，22.1%), and the detection rate of adolescents with exercise time ≤60 min/d(22.1%，17.7%) was higher than that of adolescents with exercise time >60 min/d. These differences were statistically significant (χ2=14.47, 6.97, P<0.05). Binary Logistic regression analysis showed that the risk of mental sub-health status for Chinese adolescents whose screen time was more than 2 h/d was 1.20 times that of those with screen time ≤2 h/d, and the difference was statistically significant (P<0.01). The risk of mental sub-health for students whose exercise time was > 60 min/d was 0.86 times that of students who exercised ≤ 60 min/d, and the difference was statistically significant (P<0.05). Conclusion Screen time >2 h/d and exercise time <60 min/d were negative factors leading to mental sub-health symptoms in Chinese adolescents.It is proposed to jointly promote the healthy adolescent development through health education,as well as positive family and social environment.