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 clinical efficacy of transfer of a free segment of the proximal second toe interphalangeal joint composite tissue flap in reconstruction of defects of interphalangeal joint of fingers, and simultaneously reconstruct the donor site defect left with the second toe by a transfer of a pedicled bone flap of the fibular proximal great toe.Methods:From December 2020 to April 2023, a total of 9 patients with interphalangeal joint defects of fingers were treated in the Department of Hand Microsurgery of Shunde Heping Surgery Hospital. The patients were 7 males and 2 females, aged 18-55 years old, with an average age of 31 years old. Firstly, transfers of a free segment of the proximal second toe interphalangeal joint composite tissue flap were performed to reconstruct the defects of finger joints. Simultaneously in the surgery, transfers of the fibular pedicled bone flap of the proximal great toe were conducted to reconstruct the donor site defects left in the second toe. Patients were instructed with appropriate postoperative functional exercises. K-wires were removed at 8-12 weeks after surgery. Outpatient visits, telephone and WeChat follow-ups were conducted to evaluate the appearance and functional recovery of the reconstructed interphalangeal joints and donor feet. Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, Vancouver Scar Scale (VSS) and American Orthopedic Foot and Ankle Society (AOFAS) foot function scoring standards were employed in the evaluation.Results:Postoperative follow-up lasted for 6 to 30 months. All of the 9 interphalangeal joint composite tissue flaps in the fingers survived with complete and good appearance. Function of the reconstructed interphalangeal joints of the fingers recovered well. According to the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, the average score achieved 12 points, with 6 patients of excellent, 2 of good and 1 of fair. After surgery, the appearance and function of the donor great toes and second toes all recovered well. The average score of the scars in donor second toe evaluated by VSS was 4 points. All the donor feet were kept with 5 toes, with full, intact and good in appearance. According to the AOFAS foot function scoring standard, the average score achieved 95 points, and were excellent.Conclusion:Application of transfer of free proximal segment of interphalangeal joint composite tissue flap of the second toe in reconstruction of the interphalangeal joint defect of a finger, and simultaneously reconstruct the defect left with the donor second toe with a fibular proximal great toe flap pedicled with bone tissue can achieve good clinical efficacy in reconstruction of the defects of interphalangeal joint of fingers, restore the function of the interphalangeal joint of fingers and the appearance and function of the donor foot.

Objective:To explore the clinical effect of free fibular great toe flap in reconstruction of digit-tip defect with only anastomosis of artery.Methods:From February 2022 to January 2023, a total of 8 patients with digit-tip defects received reconstruction surgery using free flap of fibular great toe with anastomosis of artery only in the Department of Hand Surgery, Shunde Heping Surgical Hospital. The patients were 5 males and 3 females, with an average age of 33 (14-55) years old. Two defected digit-tips were of thumbs, 3 of index fingers, 2 of middle fingers and 1 of little finger. The digit-tip defects were 1.5 cm×0.5 cm-2.0 cm×1.2 cm in size. During the surgery, a perforator flap of fibular great toe with fibular plantar digital artery and a branch of digital nerve was harvested. And the artery and nerve carried by the flap were anastomosed to the digital artery arch and nerve of the recipient site. No reflux vein was included in the free flap due to the small size of flap. The donor sites were directly closed. Postoperative anti-infection, anti-coagulation, and anti-vasospasm were offered. Scheduled postoperative follow-ups were conducted at outpatient clinics after surgery.Results:All flaps survived smoothly without any vascular compromise. All patients were included in the follow-up with an average of 7.1 (5-13) months. At the final follow-up, the appearances of the digit-tips were full and beautiful, with recovered finger print and good stability of flaps, as well as normal sweating. All flaps had good sensation recovery, with TPD at 6.0 mm to 7.5 mm and at 6.7 mm in average. There was no significant difference in skin temperature between the donor sites and the healthy sides. According to the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, 7 patients were rated as excellent and 1 as good.Conclusion:The clinical effect is excellent for the free flap of fibular great toe with anastomosis of artery only in the reconstruction of digit-tip defect. It not only has satisfactory reconstruction but also restores the appearance and function of the flap donor site. Worth promoting and applying in clinical practice.

Objective:To evaluated the options in selection of surgical procedures for treatment of the patients suffering from diabetic feet with chronic refractory wounds.Methods:From January 2020 to June 2021, 23 patients with diabetic feet complicated with refractory wounds were treated in Department of Hand Surgery, Shunde Heping Surgical Hospital. The patients were 15 males and 8 females, aged 51-86 years old and with an average age of 65 years old. All the patients had Type-II diabetes for over 5 - 22 years. Average blood glucose of the patients was found at 15.6 mmol/L on admission. Free anterolateral thigh perforator flaps (ALTPF) were used for reconstruction of the wound of diabetic feet in 19 patients, 2 patients received vascular bypass surgery and 2 had amputations. Regular outpatient follow-up were conduct on all patients after surgery.Results:Follow-up time lasted for 8 to 30 months, 12 months in average. At the last follow-up, the donor and recipient sites healed well in the 19 patients who received flap reconstruction, without an infection, necrosis and wound recurrence. Pains were significantly relieved after the surgery in the 2 patients who received vascular bypass surgery, and wounds all healed well after symptomatic treatment and dressing change without recurrence of wounds at the last follow-up. Average Maryland score of foot function was 84 for the patients who had limb salvage, and 2 patients were in excellent and 19 in good at the last follow-up. The 2 patients who had amputation successfully survived through the perioperative period, and the wounds healed well at the last follow-up.Conclusion:The treatment is complicated in the patient suffering from diabetic foot with chronic refractory wounds due to factors such as advanced age, co-existing and complicated underlying diseases together with the complex wounds. Most patients can achieve good prognosis in wound treatment of free flap transfer or vascular bypass surgery. However, a limb salvage is recommended with caution for the patients who have severe infections and dry gangrene.

Objective:To investigate the changes in gray matter volume (GMV) and abnormalities in structural covariant network (SCN) patterns in patients with chronic pontine infarction (PI).Methods:Patients with unilateral chronic PI (case group) with the first onset admitted to the First Affiliated Hospital of Zhengzhou University and Tianjin Medical University General Hospital from October 2014 to June 2021 were prospectively included. At the same time, healthy subjects matched with age, gender and education years (normal control group) were included. High-resolution three-dimensional T 1 structural MRI images and behavioral scores of the subjects were collected. The voxel-based morphometry and two-sample t test were used to explore the differences in GMV between the groups. Using GMV differential brain regions as seed points, SCN was constructed to explore the abnormality of structural covariant patterns in patients with PI. Spearman rank correlation analysis was used to analyze the correlation between GMV in differential brain regions and behavioral scores. Results:A total of 60 patients with PI were enrolled, including 33 left PI and 27 right PI, while 34 healthy controls were also enrolled. Compared with the normal control group, the GMV in bilateral posterior cerebellar lobe decreased significantly in the left PI group, and the GMV in left anterior and posterior cerebellar lobes and the right posterior cerebellar lobe decreased significantly in the right PI group (Gaussian random field correction with voxel level P<0.001 and cluster level P<0.05, cluster voxel >20), and there was a significant correlation between GMV values in the left anterior and posterior cerebellar lobes and the right posterior cerebellar lobe and the motor function score ( P<0.05). In addition, compared with the normal control group, the right PI group had broader covariate brain regions and a significant increase in the number of structural connections between covariate brain regions (family-wise error correction with voxel level P<0.05, cluster voxel >20). Conclusions:The GMV in bilateral posterior cerebellar lobe decreases significantly in patients with chronic PI, and were secondary to broader covariate brain regions and structural connections. This may be the neural mechanism of impaired behavioral function in patients with PI.

Objective:To investigate the risk factors for biochemical recurrence after radical prostatectomy.Methods:The clinical data of 558 radical prostatectomy patients admitted to the First Affiliated Hospital of Air Force Military Medical University from January 2010 to December 2020 were retrospectively analyzed. The average age was 67.9 (40-87) years old, and the average body mass index was 24.56 (15.12-35.94) kg/m 2. The average PSA was 41.07 ng/ml, including 48 cases<10 ng/ml, 98 cases 10-20 ng/ml, and 412 cases>20 ng/ml. There were 123, 214, 118, 89, and 14 cases with biopsy Gleason 6-10 score, respectively. The clinical stage : 90 cases in ≤T 2b, 273 cases in T 2c, and 195 cases in ≥T 3 . 558 cases underwent radical prostatectomy, including 528 robotic-assisted laparoscopic surgery, 25 laparoscopic surgery, and 5 open-surgery. The risk factors for postoperative biochemical recurrence were analyzed by Cox regression. Results:A total of 63 patients had postoperative pathological stage pT 2a, 32 patients had pT 2b, 241 patients had pT 2c, and 222 patients had ≥pT 3. A total of 210 cases developed biochemical recurrence after surgery, and the mean time to biochemical recurrence was 33.3 (3-127) months after the radical prostatectomy. The biochemical recurrence rates at 1, 3, and 5 years were 9.7% (54/558), 21.5% (120/558), and 31.7% (177/558), respectively. Among pT 2a and pT 2b patients, 7 (11.1%) and 4 (12.5%) cases developed biochemical recurrence, respectively. Among pT 2c stage patients, 145 (60.17%) cases had positive cut margins, treated with androgen-deprivation therapy (ADT) after surgery. 68 (28.21%) cases of pT 2c stage patients had biochemical recurrence at mean 36.1 (3-106)months after the radical prostatectomy. Among ≥pT 3 patients, 147 patients with positive margins, perineural invasion, seminal vesicle invasion and positive pelvic lymph nodes were treated with postoperative androgen deprivation therapy (ADT) + radiotherapy. 98 of 147 patients (66.67%) had biochemical recurrence, and the average time to biochemical recurrence was 30.6 (24-98) months.75 patients of ≥pT 3 without positive margins, perineural invasion, seminal vesicle invasion or positive pelvic lymph nodes, were treated with postoperative ADT. 33 of them (44%) had biochemical recurrence, and the average time to biochemical recurrence was 32.5 (21-106) months. 5-and 10-year survival rates of 210 patients with biochemical recurrence were 89.05% (187/210) and 78.09% (164/210) respectively, 5- and 10-year tumor-specific survival rates were 92.57% and 87.69%, respectively. 46 of 210 cases died, of which 31 (67.39%) died from prostate cancer, and 15 cases (32.61%) died from cardiovascular and cerebrovascular diseases. Multifactorial Cox regression analysis showed that patient's age ≥70 years, initial PSA > 20ng/ml, ≥pT 3 and Gleason score ≥7 were independent risk factors for biochemical recurrence. Conclusions:After radical prostatectomy, patients were treated according to their pathological stage and surgical margins. Patients with positive margins have a higher risk of biochemical recurrence. The independent risk factors for biochemical recurrence included age ≥70 years, initial PSA > 20ng/ml, ≥pT 3 and Gleason score ≥7.

Shenling Baizhusan is a traditional Chinese medicine compound prescription formulated on the basis of Si Junzitang （Ginseng Radix et Rhizoma， Atractylodis Macrocephalae Rhizoma， Poria， Glycyrrhizae Radix et Rhizoma）. It has excellent functions of replenishing Qi， invigorating spleen， draining dampness， and checking diarrhea， and is one of the classical prescriptions of ''reinforcing earth to generate metal''. This prescription is primarily used in clinical practice to treat malnutrition in children， chronic diarrhea， gastrointestinal dysfunction， and other disorders. In addition， it has a good effect on gastrointestinal adverse reactions associated with radiotherapy and chemotherapy. With the booming of molecular biology， researchers have revealed the role of Shenling Baizhusan in the treatment of diseases， especially the mechanism of regulating different signaling pathways. We retrieved 26 relevant papers （4 written in English and 22 in Chinese） published in recent 5 years from 6 databases including China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， PubMed， Cochrance Library， and Excerpta Medica Database （Embase）. On the basis of these papers， we summarized the mechanisms of Shenling Baizhusan in disease treatment. In the animal model of inflammatory bowel disease， Shenling Baizhusan can protect gastrointestinal mucosa by regulating the activation of nuclear factor kappa-B （NF-κB）， mitogen-activated protein kinase （MAPK）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， and myosin light chain kinase-myosin light chain （MLCK-MLC） signaling pathways. In the animal model of non-alcoholic fatty liver disease， Shenling Baizhusan regulates the activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway and Kelch-like ECH-associating protein 1/NF-E₂-related factor 2/advanced glycation end-products （KEAP1/NRF2/AREs） signaling pathway， thus alleviating the lipid metabolism disorder induced by high-fat diet and reducing liver lipid accumulation and inflammatory response. In the animal model of lung cancer with bone metastasis， Shenling Baizhusan regulates the activation of PI3K/Akt/mTOR signaling pathway， thus playing an analgesic role. By summarizing the mechanisms of Shenling Baizhusan in treatment of different disease models from signaling pathways， we aim to provide clues for the in-depth study of this prescription.

Objective    To further understand the anatomical characteristics and rules of left upper lingual pulmonary artery. Methods    CT data of 120 patients (82 males, 38 females, median age of 65 years ranging 36-78 years) with pulmonary nodules from December 2018 to August 2020 in our hospital were retrospectively analyzed. The anatomic characteristics of the lingual segment of the upper left lung were analyzed by three-dimensional reconstruction. Results    Mediastinal lingual artery appeared in 34 of the 120 patients, accounting for 28.4%. There were 26 patients of mixed mediastinal/interlobar type, 8 patients of pure mediastinal lingual artery, and 92.3% (24/26) mixed mediastinal/interlobar type blood vessel contained A4b. Fifty-eight (58/120, 48.3%) patients had interlobar type A4+5 type, the rest were two-branches type. And 22 patients of A4 and A5 type accounted for the most two-branches type (22/28, 78.6%). The single-branch type was located at the distal end of A6 in 54 (54/58, 93.1%) patients, originated from the proximal end of A6 in 4 patients, and originated from the basilar artery in 6 patients. The two-branches type was at the distal end of A6 accounting for 50.0% (14/28). Conclusion    Mediastinal lingual artery is more common than expected, accounting for 28.4%, among which mixed lingual artery is more prevalent, usually located in the first pulmonary trunk, and mostly follows the principle of proximity to supply relevant lung tissues. The location of the interlobar branches in the pulmonary trunk can be at the distal or proximal end of A6, care should be taken to avoid damaging adjacent structures.

Objective:To explore the clinical efficacy of single-center infant kidney donor adult dual kidney transplantation to explore the difference of different operation methods and the operation options of different donor kidney conditions so as to improve the success rate of children kidney donor adult dual kidney transplantation and reduce complications.Methods:A total of 42 cases of infant and adult dual kidney transplantations at Department of Kidney Transplantation in The Second Xiangya Hospital of Central South University from December 2012 to May 2019 were divided into two groups according to whether or not donor kidney fulfilled the criteria of three " 5" . According to different surgical approaches, they were divided into three groups of A (classical En-Bloc operation), B (separated dual kidney transplantation) and C (modified operation). The clinical data and prognoses were analyzed.Results:The median follow-up period was 55(11-92) months. The estimated glomerular filtration rate was 123.4(92.2-156.6) ml/min for operation A, 97.2(81.3-116.6) ml/min for operation B and 133.9(133.9-133.9) ml/min for operation C. In donor group not fulfilling the " 5" principle, no thrombotic event occurred for operation A/C and 3 cases of transplantation for operation B. There were single renal embolism ( n=2) and dual renal embolism ( n=1)(3/5, 60%)( P<0.05). Urinary protein was positive in the last follow-up: operation A (1/2, 50%) and operation B (3/5, 60%) ( P<0.05). The estimated glomerular filtration rate at the last follow-up was 82.4(80.9-83.9) ml/min for operation A, 71.8(46.1-114.2) ml/min for operation B and 122(83.3-142.4) ml/min for operation C. The 1-year graft survival rate was 100% and 89.5% in three " 5" donor group and 3-year graft survival rate was 100% and 84.2% respectively. Conclusions:Satisfactory outcomes might be obtained during dual kidney transplantation for infants and adults. The incidence of thrombosis, urine leakage and urinary protein is lower in improved kidney transplantation group than that in previously operated group. The problem of graft hyperperfusion injury is well solved. And the long-term follow-up outcome is excellent.

Objective:To investigate the abnormalities of gray matter volume (GMV) and the synergistic changes in different cerebral regions in the first-episode and early-onset depression (EOD) patients.Methods:A total of 60 patients with untreated EOD (EOD group) and 64 healthy controls (control group) matched for age, gender, and education underwent high-resolution T 1WI MR scans. Voxel-based morphometry was used to calculate the cerebral GMV. The difference in GMV between the two groups was compared with the t-test. Different brain regions were selected as seeds for structural covariation network (SCN) analysis. Spearman correlation model was used to analyze the correlation between the GMV in different cerebral regions and illness duration as well as the scores of Hamilton rating scale for depression (HAMD) 17 items in EOD group. Results:Compared to control group, the EOD group had significantly increased GMV in the right orbitofrontal cortex, right dorsolateral prefrontal cortex, right inferior parietal lobule, right superior parietal lobule and bilateral precuneus ( P<0.05, corrected by FDR). Based on the right orbitofrontal cortex and dorsolateral prefrontal cortex as seed regions, structural covariance analysis revealed that abnormal cooperative brain regions in EOD group, mainly distributed in the bilateral frontal lobe, parietal lobe, occipital lobe, temporal lobe, paralimbic system and cerebellum ( P<0.05, corrected by FDR). In EOD group, significant negative correlations were observed between the GMV in the right orbitofrontal cortex ( r=-0.314, P=0.015), the left precuneus ( r=-0.283, P=0.029), and illness duration. Significant positive correlations were observed between the GMV in the right dorsolateral prefrontal cortex and the scores of anxiety/somatization factor of HAMD17 ( r=0.331, P=0.010), the left precuneus and weight factor of HAMD17 ( r=0.255, P=0.049), respectively. Conclusions:Abnormal GMV changes are observed in some regions of the prefrontal and parietal lobule in patients with untreated EOD, accompanied by extensive covariant brain regions and additional structural connectivity. In addition, the abnormal GMV changes in some regions are associated with clinical features. Part of the prefrontal and parietal lobule may be the biomarkers to objectively evaluate abnormal brain structure in depression patients in the early stage.