OBJECTIVE: To explore the construction of a canine model of vascularized allogeneic spinal cord transplantation (vASCT) and preliminarily evaluate its therapeutic efficacy for spinal cord injury (SCI). METHODS: Sixteen female Beagle dogs aged 8-12 months were randomly selected, with 8 dogs serving as donors for the harvesting of spinal cord tissue with a vascular pedicle [dorsal intercostal artery (DIA) at the T₁₀ level and accompanying vein]. The remaining 8 dogs underwent a 1.5-cm-length spinal cord defect at the T₁₀ level, followed by transplantation of the donor spinal cord tissue for repair. Polyethylene glycol (PEG) was applied to both ends to spinal cord graft; then, using a random number table method, the dogs were divided into an experimental group (n=4) and a control group (n=4). The experimental group received immunosuppressive intervention with oral tacrolimus [0.1 mg/(kg∙d)] postoperatively, while the control group received no treatment. The operation time and ischemia-reperfusion time of two groups were recorded. The recovery of hind limb function was estimated by Olby score within 2 months after operation; the motor evoked potentials (MEP) was measured through neuroelectrophysiological examination, and the spinal cord integrity was observed through MRI. RESULTS: There was no significant difference in the operation time and ischemia-reperfusion time between the two groups (P>0.05). All dogs survived until the completion of the experiment. Within 2 months after operation, all dogs in the control group failed to regain the movement function of hind limbs, and Olby scores were all 0. In the experimental group, the movement and weight-bearing, as well as walking abilities of the hind limbs gradually recovered, and the Olby scores also showed a gradually increasing trend. There was a significant difference between the two groups from 3 to 8 weeks after operation (P<0.05). Neuroelectrophysiological examination indicated that the electrical signals of the experimental group passed through the transplanted area, and the latency was shortened compared to that at 1 month after operation (P<0.05), showing continuous improvement, but the amplitude did not show significant improvement (P>0.05). The control group was unable to detect any MEP changes after operation. MRI examination showed that the transplanted spinal cord in the experimental group survived and had good continuity with normal spinal cord tissue, while no relevant change was observed in the control group. CONCLUSION The vASCT model of dogs was successfully constructed. This surgical procedure can restore the continuity of the spinal cord. The combination of tacrolimus anti-immunity is a key factor for the success of transplantation.
Animals ; Dogs ; Female ; Spinal Cord/blood supply* ; Spinal Cord Injuries/surgery* ; Transplantation, Homologous ; Disease Models, Animal ; Recovery of Function ; Plastic Surgery Procedures/methods* ; Tacrolimus ; Immunosuppressive Agents

Objective:To explore the efficacy and safety of mitotane in adrenal cortical carcinoma (ACC) at high risk of recurrence.Methods:A prospective observational study was designed from September 2022 to November 2023. ACC patients undergoing surgery with high recurrence risk (positive margin or Ki-67 index >10% or capsule rupture or large size or high-grade ACC) in Peking Union Medical College Hospital were enrolled in this study. All patients started mitotane treatment within 3 months after surgery, with a dose of 1.5 g/d, increased by 0.5 g per week. Once the dose reached 3 g/day, adjustments were made based on blood concentration levels. All patients received mitotane therapy for at least 1 year, and CT was performed every 12 weeks to evaluate the efficacy. The primary endpoint was 1-year progression-free survival (PFS) and safety. The efficacy was analyzed by Kaplan-Meier method for survival, and the occurrence of treatment-related adverse events was summarized.Results:A total of 12 ACC patients at high risk of recurrence were screened, comprising 6 males and 6 females. Tumors were located on the left side in 8 patients, on the right in 3, and bilaterally in 1. Five patients were classified as ENSAT stageⅡ, while 7 were classified as ENSAT stage Ⅲ. The maximum diameter of tumor was (9.07 ± 2.86) cm; the median age at diagnosis was 48 (35, 51) years, and the median Ki-67 index was (28.9 ± 16.1)%. The median time from surgery to initiation of mitotane therapy was 31 (23.0, 43.2) days, and 9 patients had blood drug concentrations of 14-20 mg/L. The median follow-up time was 16.7 (12.4, 25.2) months. At 1 year after mitotane therapy, 10 (83.8%) patients were still in disease-free survival state, with a median mitotane PFS of 27.6 months (95% CI 16.4-not reached). All ACC patients experienced 1-2 grade adverse events after taking mitotane. One patient (8.3%) experienced grade 3 adverse event, including the increasing of alanine aminotransferase and aspartate aminotransferase, as well as anorexia. No grade 4-5 adverse events occurred. The most common adverse events were gastrointestinal symptoms (10 cases), including nausea, vomiting, anorexia, and diarrhea, followed by liver function damage(9 cases) and neurotoxicity(4 cases). Conclusions:Mitotane has shown the prospect of improving the prognosis of ACC patients at high risk of recurrence after surgery. Because of its serious toxic and side effects, it is necessary to monitor its blood concentration to adjust the dosage, and take measures for adverse reactions to ensure the safety of patients.

Objective:To explore the clinical characteristics of bilateral nodular adrenal cortical disease（BmacAD）and primary pigmentary nodular adrenal cortical disease（PPNAD）.Methods:A retrospective analysis was conducted on the clinical records of 58 patients with BmacAD and 26 patients with PPNAD who were treated at Peking Union Medical College Hospital from January 2005 to December 2024. The clinical manifestations，endocrine examination，and surgical results between BmacAD patients and PPNAD patients were compared. Endocrine related examinations were reexamined 1 to 7 days and 15 to 30 days after the operation，and the recovery of cortisol within 30 days after the operation was recorded.Results:The male to female ratios of BmacAD patients and PPNAD patients were 31/27 and 11/15，with no statistically significant difference（ P > 0.05）. The age of BmacAD patients and PPNAD patients were 53.5（45.0，61.0）years and 19.0（15.8，24.0）years，respectively，with a statistically significant difference（ P < 0.001）. In terms of clinical manifestations，the proportion of BmacAD patients and PPNAD patients with Cushing syndrome appearance were 50.00%（29/58）and 96.15%（25/26），respectively，with a statistically significant difference（ P < 0.001）. There were no statistically significant differences between BmacAD and PPNAD patients in hypertension［87.93%（51/58）and 80.77%（21/26）］，abnormal glucose tolerance/diabetes［39.66%（23/58）and 34.62%（9/26）］and hypokalemia［18.97%（11/58）and 15.38%（4/26）］（ P > 0.05）. The difference in the proportion of osteopenia/osteoporosis /fracture between the two group was statistically significant［13.79%（8/58）and 53.85%（14/26）， P < 0.001］. In terms of hormone secretion，the median levels of 24-hour urinary free cortisol in BmacAD and PPNAD patients before surgery were 174.00（85.35，531.43）μg/24 h and 408.35（334.28，800.78）μg/24h（ P < 0.001），respectively. The proportion of preoperative plasma adrenocorticotropic hormone（ACTH）levels less than 5 pg/ml were 60.34%（35/58）and 84.62%（22/26）（ P < 0.05），respectively. Among the BmacAD patients 32 underwent unilateral total adrenalectomy，23 underwent unilateral partial adrenalectomy，and 3 underwent unilateral total adrenalectomy+contralateral partial adrenalectomy；the proportion of patients with increased preoperative cortisol secretion who recovered to normal within 30 days after surgery was 79.17%（38/48）. All 26 PPNAD patients underwent unilateral adrenalectomy. Within 30 days after surgery，68.00%（17/25）of the PPNAD patients had normal 24-hour urinary free cortisol levels. Conclusions:The cortisol secretion level in PPNAD patients is significantly higher than that in BmacAD patients，and the proportion of abnormal bone metabolism is higher. The short-term therapeutic efficacy of unilateral adrenalectomy or unilateral partial adrenalectomy is significant for both BmacAD and PPNAD.

Osteoporosis and cardiovascular calcification,two major age-related chronic diseases that China is confronting today,pose serious threats to public health.Previous studies have reported overlapping connections in the pathological processes and molecular mechanisms of these two diseases,particularly concerning inflammation,oxidative stress,and dysregulation of mineral metabolism,and that these two diseases tend to share common pathogenic factors.However,research exploring the comorbidity mechanisms of the two diseases remains limited in both depth and scope,largely due to the lack of widely accepted comorbidity animal models.Herein,we analyzed the latest research findings on the comorbidity mechanisms of vascular calcification and osteoporosis,focusing on summarizing the animal disease models currently in extensive use and the relevant evaluation criteria.We aim to provide new references for comorbidity research models and offer scientific evidence for future studies on pathological mechanisms and the development of new therapeutic strategies.

Clinically,the incidence of portal vein thrombosis(PVT)in patients with cirrhosis can be up to 10％-23％.When PVT is not treated promptly,it may develop to cavernous transformation of the portal vein(CTPV).CTPV can aggravate portal hypertension,accelerate the progression of esophagogastric varices bleeding,refractory ascites,refractory peritonitis,biliary tract diseases,and hepatic insufficiency.At present,noninvasive imaging techniques such as portal vein reconstruction,enhanced CT and ultrasound are mostly used to make the diagnosis and evaluation of CTPV.It is rather difficult to perform portosystemic shunt surgery in patients with CTPV complicated by portal hypertension,which was once regarded as a contraindication for interventional portosystemic shunt procedures.With the improvement of related technologies and surgical instruments,the transjugular intrahepatic portosystemic shunt(TIPS)has become an important treatment for CTPV.This paper aims to make a comprehensive review about the relevant researches concerning the portosystemic shunt surgery in patients with CTPV so as to clarify the importance of TIPS in the treatment of CTPV.

ObjectiveTo explore the impact of exogenous chitosan on the growth and metabolism of Glycyrrhiza uralensis Fisch. (G. uralensis) and to improve the quality of cultivated G. uralensis for both medicine and food and aid in the increase in the content of effective components in G. uralensis.MethodsIn this study, whole G. uralensis plants were treated with exogenous chitosan, and comprehensive analyses of secondary metabolites and proteins were conducted using liquid chromatography with tandem mass spectrometry and isobaric tag for relative and absolute quantitation, respectively. Effects of chitosan induction on endogenous hormones of G. uralensis were analyzed using an enzyme-linked immunosorbent assay. Gene ontology function annotation and Kyoto Encyclopedia of Genes and Genomes pathway annotation were conducted to study the effect of chitosan induction on the proteome.ResultsChitosan induction significantly increased the levels of flavonoids in G. uralensis; however, the variation in triterpenoids was not substantial. Biological processes, including photosynthesis, secondary metabolism, and abiotic stress responses, were significantly enriched. Additionally, the photosynthetic pathway, photosynthesis-antenna protein pathway, and plant hormone signal transduction pathway were significantly enriched. In the flavonoid biosynthesis pathway, the upstream-related enzyme phenylalanine ammonia-lyase (PAL) and the downstream-related enzymes chalcone synthase (CHS), polyketide reductase (PKR), chalcone isomerase (CHI), and vestitone reductase (VR) were significantly upregulated.ConclusionsOur findings suggest that chitosan induction may promote the tricarboxylic acid (TCA) cycle, and the TCA cycle enhancement significantly upregulated PAL, CHS, PKR, CHI, and VR, the five key enzymes involved in flavonoid synthesis of G. uralensis, indicating that chitosan induction activated the entire metabolic pathway associated with flavonoids in G. uralensis. Our findings provide a reference for improving the quality of cultivated G. uralensis from the perspective of pharmacodynamic components.

OBJECTIVE: To explore the clinical and genetic characteristics of a child with intellectual development disorder and seizures due to a variant of AP2M1 gene. METHODS: Clinical data of a child with intellectual development disorder and epilepsy who was admitted to the Department of Pediatric Neurology of the Third Affiliated Hospital of Zhengzhou University in January 2021 were retrospectively analyzed. Peripheral blood samples of the child and his parents were collected for whole exome sequencing. Candidate variant was verified by Sanger sequencing and pathogenicity analysis. The three-dimensional structure of the AP2M1 protein was visualized using Chimera v1.10.1 software. Pathogenicity of candidate variant was classified according to the Standards and Guidelines for the Interpretation of Sequence Variants from the American College of Medical Genetics and Genomics American College of Medical Genetics (ACMG). With "AP2M1 gene" "epilepsy" "intellectual disability" as the keywords, relevant cases were searched from CNKI, Wanfang Data knowledge service platform and PubMed databases with the search time spanning from the establishment of the database to September 2024. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2020-57). RESULTS: The child was a 8-years-and-6-months-old boy, who could raise his head at 3 months and sit alone at 8 months old. He could not walk alone at 1 year old and underwent 2 months' rehabilitation treatment, and could walk alone and call his parents at 1-and-a-half-years-old. At 4-years-and-10-months-old, he started to have frequent seizures, manifesting as low level of consciousness, body shaking, accompanied by blinking, lasting about a few seconds several times a day and could be relieved. With the treatment of sodium valproate combined with lamotrigine, the convulsions were controlled, but his movement and cognition were lagged behind. DNA sequencing revealed that he has harbored a novel variant of the AP2M1 gene (NM_004068.3) c.508C>T (p.Arg170Trp). Sanger sequencing confirmed that both of his parents were of the wild-type. According to the guidelines from the American College for Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PS2+PS4+PM1+PM2+PP2+PP3). The difference between the wild-type and mutant AP2M1 proteins can be clearly viewed through its three-dimensional structure. Two previous reports have included 5 cases due to the same variant. Common manifestations have included seizures (100%, 5/5), motor retardation (100%, 5/5), intellectual impairment (100%, 5/5), autism spectrum disorder (60%, 3/5), ataxia (100%, 5/5), and special facial features (20%, 1/5). CONCLUSION The c.508C>T (p.Arg170Trp) variant of the AP2M1 gene may underlie the intellectual retardation and seizure in this child.
Humans ; Male ; Child ; Intellectual Disability/genetics* ; Seizures/genetics* ; Exome Sequencing ; Mutation

Objective:To explore the efficacy and safety of mitotane in adrenal cortical carcinoma (ACC) at high risk of recurrence.Methods:A prospective observational study was designed from September 2022 to November 2023. ACC patients undergoing surgery with high recurrence risk (positive margin or Ki-67 index >10% or capsule rupture or large size or high-grade ACC) in Peking Union Medical College Hospital were enrolled in this study. All patients started mitotane treatment within 3 months after surgery, with a dose of 1.5 g/d, increased by 0.5 g per week. Once the dose reached 3 g/day, adjustments were made based on blood concentration levels. All patients received mitotane therapy for at least 1 year, and CT was performed every 12 weeks to evaluate the efficacy. The primary endpoint was 1-year progression-free survival (PFS) and safety. The efficacy was analyzed by Kaplan-Meier method for survival, and the occurrence of treatment-related adverse events was summarized.Results:A total of 12 ACC patients at high risk of recurrence were screened, comprising 6 males and 6 females. Tumors were located on the left side in 8 patients, on the right in 3, and bilaterally in 1. Five patients were classified as ENSAT stageⅡ, while 7 were classified as ENSAT stage Ⅲ. The maximum diameter of tumor was (9.07 ± 2.86) cm; the median age at diagnosis was 48 (35, 51) years, and the median Ki-67 index was (28.9 ± 16.1)%. The median time from surgery to initiation of mitotane therapy was 31 (23.0, 43.2) days, and 9 patients had blood drug concentrations of 14-20 mg/L. The median follow-up time was 16.7 (12.4, 25.2) months. At 1 year after mitotane therapy, 10 (83.8%) patients were still in disease-free survival state, with a median mitotane PFS of 27.6 months (95% CI 16.4-not reached). All ACC patients experienced 1-2 grade adverse events after taking mitotane. One patient (8.3%) experienced grade 3 adverse event, including the increasing of alanine aminotransferase and aspartate aminotransferase, as well as anorexia. No grade 4-5 adverse events occurred. The most common adverse events were gastrointestinal symptoms (10 cases), including nausea, vomiting, anorexia, and diarrhea, followed by liver function damage(9 cases) and neurotoxicity(4 cases). Conclusions:Mitotane has shown the prospect of improving the prognosis of ACC patients at high risk of recurrence after surgery. Because of its serious toxic and side effects, it is necessary to monitor its blood concentration to adjust the dosage, and take measures for adverse reactions to ensure the safety of patients.

Objective:To explore the clinical characteristics of bilateral nodular adrenal cortical disease（BmacAD）and primary pigmentary nodular adrenal cortical disease（PPNAD）.Methods:A retrospective analysis was conducted on the clinical records of 58 patients with BmacAD and 26 patients with PPNAD who were treated at Peking Union Medical College Hospital from January 2005 to December 2024. The clinical manifestations，endocrine examination，and surgical results between BmacAD patients and PPNAD patients were compared. Endocrine related examinations were reexamined 1 to 7 days and 15 to 30 days after the operation，and the recovery of cortisol within 30 days after the operation was recorded.Results:The male to female ratios of BmacAD patients and PPNAD patients were 31/27 and 11/15，with no statistically significant difference（ P > 0.05）. The age of BmacAD patients and PPNAD patients were 53.5（45.0，61.0）years and 19.0（15.8，24.0）years，respectively，with a statistically significant difference（ P < 0.001）. In terms of clinical manifestations，the proportion of BmacAD patients and PPNAD patients with Cushing syndrome appearance were 50.00%（29/58）and 96.15%（25/26），respectively，with a statistically significant difference（ P < 0.001）. There were no statistically significant differences between BmacAD and PPNAD patients in hypertension［87.93%（51/58）and 80.77%（21/26）］，abnormal glucose tolerance/diabetes［39.66%（23/58）and 34.62%（9/26）］and hypokalemia［18.97%（11/58）and 15.38%（4/26）］（ P > 0.05）. The difference in the proportion of osteopenia/osteoporosis /fracture between the two group was statistically significant［13.79%（8/58）and 53.85%（14/26）， P < 0.001］. In terms of hormone secretion，the median levels of 24-hour urinary free cortisol in BmacAD and PPNAD patients before surgery were 174.00（85.35，531.43）μg/24 h and 408.35（334.28，800.78）μg/24h（ P < 0.001），respectively. The proportion of preoperative plasma adrenocorticotropic hormone（ACTH）levels less than 5 pg/ml were 60.34%（35/58）and 84.62%（22/26）（ P < 0.05），respectively. Among the BmacAD patients 32 underwent unilateral total adrenalectomy，23 underwent unilateral partial adrenalectomy，and 3 underwent unilateral total adrenalectomy+contralateral partial adrenalectomy；the proportion of patients with increased preoperative cortisol secretion who recovered to normal within 30 days after surgery was 79.17%（38/48）. All 26 PPNAD patients underwent unilateral adrenalectomy. Within 30 days after surgery，68.00%（17/25）of the PPNAD patients had normal 24-hour urinary free cortisol levels. Conclusions:The cortisol secretion level in PPNAD patients is significantly higher than that in BmacAD patients，and the proportion of abnormal bone metabolism is higher. The short-term therapeutic efficacy of unilateral adrenalectomy or unilateral partial adrenalectomy is significant for both BmacAD and PPNAD.

Objective:To explore the influence of points system management on the career development of medical staff in health management discipline.Methods:Using a cross-sectional study design, medical staff in the health management discipline of tertiary hospitals in China were selected as the research objects from February 1 to March 1, 2024 through questionnaire star convenience sampling and snowball sampling, and their general information, performance appraisal satisfaction, professional identity, burnout, professional benefit, professional career management and other information were collected, and the correlation and influencing factors among them were explored. A total of 423 questionnaires were distributed, and 402 (95.0%) valid questionnaires were collected.Results:A total of 207 (51.5%) medical staff had job burnout, and 257 (63.9%) of them had medium or below level of professional identity. There were positive correlations among performance appraisal satisfaction, professional identity, career benefit and professional career management. There was a negative correlation between burnout and performance appraisal satisfaction ( r=-0.439), professional identity ( r=-0.356), career benefit ( r=-0.584), and professional career management ( r=-0.185) (all P<0.05). Higher age, working time, monthly income level, title level, position level, understanding of performance appraisal system, satisfaction with feedback results and application satisfaction were the protective factors of burnout, and under the points-based system, the scores of performance appraisal satisfaction, professional identity, career benefit, and professional career management were higher, and the differences were statistically significant (all P<0.05). A total of 310 medical staff (77.1%) believed that performance appraisal had a motivating effect on them. Conclusion:The performance appraisal of the point system has a good motivating effect on the medical staff of the health management discipline, and is closely related to professional identity, burnout, professional benefit, and professional career planning.