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 explore the application value of a special fence in percutaneous transhepatic cholangial drainage(PTCD)under the guidance of C-arm CT.Methods A total of 43 patients who underwent PTCD were randomly divided into observation group and control group.The intervention operation in the observation group was guided by C-arm CT and located by special fence;in the control group,the intervention operation was only performed under digital subtraction angiography(DSA)fluoroscopy.Respectively,the differences in operation time,number of puncture needles and number of complications between the two groups were compared.Results The operation time,puncture times and complications in the observation group were(39.33±12.96)min,(1.67±0.80)times and 3 cases respectively;in the control group were(86.77±22.70)min,(3.41±1.26)times and 13 cases respectively;There were significant differences between the two groups(P<0.05).Conclusion The application of special fence in PTCD under the guidance of C-arm CT can short the operation time,reduce the number of punctures and reduce complications,which has important clinical application value.

Sesquiterpenoids are natural compounds composed of 15 carbon atoms， which can be divided into sesquiterpene alcohols， ketones， lactones， aldehydes， and carboxylic acids according to oxygen groups. These compounds are widely distributed in nature， and their physiological activities are diverse. For example， many sesquiterpenes with potential anticancer effects have been found for anti-tumor effects， including cytotoxicity， antioxidant， immune regulation， cell proliferation， and so on. In addition， some sesquiterpenoids have good application prospects in antibacterial， anti-inflammatory， and anti-cardiovascular diseases. Malignant tumors， inflammation， bacterial diseases， and cardiovascular diseases are the main diseases that cause human death， and natural products have unique advantages in the treatment of these diseases. Therefore， the development of new drugs that are easy to promote has become a new research hotspot. In this paper， the sesquiterpenes extracted from the natural components of Chinese herbs and plants with anti-tumor， anti-inflammatory， antibacterial， and anti-cardiovascular activities， such as Xanthium， Atractylodes， Convolvulus， Acanthium， Ligularia， Artemisia， Ligularia， Ligularia， Labiaceae Mint， Acanthophyllum， Turmeria， Ginger， and other Chinese herbs and plants， were discussed. The biological activities and related mechanisms of this compound were reviewed， which provided a reference for further research and clinical application of sesquiterpenes.

OBJECTIVE To extract the-SH active fractions(SHF)from Bubali Cornu(water buffalo horn)and evaluate its an-tipyretic activity.METHODS SHF was extracted from Bubali Cornu by SDS-DTT,and the content of native thiols(-SH)was deter-mined by Ellman reagent method.SHF was identified based on nano LC-MS/MS technology.Evaluation of antipyretic activity of SHF was based on LPS-induced fever rat model.The levels of PGE2,IL-1β,and TNF-α in plasma as well as the levels of cAMP,PGE2,and TNF-α in the hypothalamus were measured by ELISA kits.An untargeted metabolomics approach was used to further investigate the intervention of SHF on plasma metabolites in febrile rats.RESULTS SDS-DTT could effectively extract SHF from Bubali Cornu,in which the main components were type Ⅰ,type Ⅱ keratins and keratin-associated proteins,which were rich in Cys,and the ratio of-SH to protein in SHF was increased about 20 times more than that of traditional decoction.SHF could significantly decrease(P＜0.01)the body temperature which lasted for 4.5 hours.SHF could also significantly decrease the levels of PGE2,IL-1β,TNF-α and cAMP in plasma and hypothalamic.A total of 137 potentially differential metabolites were identified from plasma samples of the control and model groups,of which 31 metabolites could be dialed back after SHF administration,including lysophosphatidic acid,phosphatidyli-nositol,phosphatidic acid,triglycerides,phosphatidylcholine and so on,which were mainly involved in the glycerophospholipid meta-bolic pathway.CONCLUSION SHF has precise antipyretic effect,and the dosage of 1/10 of the aqueous extract can show its com-parable antipyretic effect,which provides the direction and basis for the basic research on the antipyretic efficacy of Bubali Cornu.

Objective To observe the effects of electroacupuncture on intestinal flora and serum inflammatory factors in rabbit model with rheumatoid arthritis(RA);To explore the mechanism of its therapeutic effect on RA.Methods RA model rabbits were established by ovalbumin induction combined with Freund's complete adjuvant,and the rabbits after successful modeling were randomly divided into model group,probiotic group and electroacupuncture group,with 6 rabbits in each group.Another 6 rabbits were set as the normal group.The electroacupuncture group received electroacupuncture at the bilateral"Zusanli"and"Dubi"for 30 minutes,the probiotic group was given probiotic capsules solution(14.5 mg/kg)by gavage,once a day,for two consecutive weeks.The knee joint circumference and pain threshold of rabbits were measured,histopathological morphological changes of colonic tissue and synovial tissue ws observed by HE staining,16S rDNA sequencing was used to analyze structural changes of intestinal flora,the contents of TNF-α,IL-1β and IL-6 in serum were detected by ELISA.Results Compared with the normal group,the circumference of knee joint of rabbits in the model group increased significantly,the pain threshold was significantly decreased(P<0.01);the colonic mucosal damage was serious,the goblet cells were missing,a large number of inflammatory cells were infiltrate;the joint capsule synovial surface was rough,the synovial cell layer was hyperplasia and thickening,the synovial tissue inflammatory cell infiltration was obvious;the number and evenness of gut microbiota species decreased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes decreased(P<0.05,P<0.01),the relative abundance of Desulfobacteria increased(P<0.01),while the relative abundance of Campylobacter,Lawsonella,and Pseudomonas increased(P<0.01),while the relative abundance of Heshanomonas and Herbaspirillum decreased(P<0.01);the contents of serum TNF-α,IL-1β and IL-6 increased(P<0.01).Compared with the model group,the knee joint circumference of the probiotic group and the electroacupuncture group decreased,the pain threshold increased(P<0.01,P<0.05);the degree of intestinal mucosal damage was reduced,the goblet cells were basically arranged neatly,the inflammatory cell infiltration was reduced;synovial cells proliferation and thickening decreased,with a small amount of inflammatory cell infiltration;the number and evenness of gut microbiota species increased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes increased(P<0.05,P<0.01),the relative abundance of Desulfobacteria decreased(P<0.01),while the relative abundance of Campylobacter,Lawsonella and Pseudomonas decreased(P<0.01),the relative abundance of Heshanomonas and Herbaspirillum increased(P<0.05,P<0.01);the contents of serum TNF-α,IL-1β and IL-6 significantly decreased(P<0.01).Conclusion Electroacupuncture can significantly improve the symptoms of RA rabbits and reduce the inflammatory reaction in synovial tissue of joint,and the mechanism may be related to the regulation of intestinal flora structure.

Objective:Based on the pathological model of acceptance and commitment therapy(ACT), to explore the correlation between cognitive fusion and resting-state spontaneous brain activity amplitude of low frequency fluctuation in patients with major depressive disorder(MDD).Methods:Patients with MDD ( n=19) and healthy controls (HCs, n=19)matched with gender, age, and years of education were enrolled from August 2022 to May 2023 in Hangzhou Seventh People's Hospital. 17-item Hamilton depression rating scale(HAMD-17) and cognitive fusion questionnaire(CFQ) were used to estimate the depressive symptoms and cognitive fusion of the participants. The amplitude of low frequency fluctuation(ALFF) data were collected on a 1.5 T-GE scanner. Based on DPABI v7.0 software of MATLAB 7.11.0 (R2018b), two independent sample t-test was used to compare the ALFF of the MDD group and HC group. ALFF values and the cognitive fusion scale scores were investigated by Pearson correlation analysis. Results:Compared with HCs, ALFF in patients with MDD was decreased relatively in the left triangular part of the inferior frontal gyrus(MNI: x, y, z=-36, 24, 21; t=-2.107, P=0.042), the right cuneus(CUN; MNI: x, y, z=12, -87, 24; t=-8.635, P<0.001) as well as the left calcarine fissure and surrounding cortex(MNI: x, y, z=-18, -57, 6; t=-14.188, P<0.001), while increased relatively in left superior occipital gyrus(MNI: x, y, z=-21, -72, 33; t=-7.253, P<0.001). There was a significant negative correlation between cognitive fusion and ALFF values of abnormal activity in left IFGtriang (belonging to ECN)( r=-0.57, P<0.05). Conclusion:There is a correlation between cognitive fusion and resting-state spontaneous brain activity ALFF in patients with MDD. Both cognitive fusion and depressive symptoms may affect patients' cognitive control deficits through multiple sources.

Objective To observe the effects of needle-knife tendon-sparing and knot-dissolving technique on NF-κB/Bcl-2 pathway activity and the expression of TNF-α,IL-1β,IL-6,Bax and caspase-3 in synovial tissue of knee joints of rabbits with rheumatoid arthritis(RA)model;To explore the mechanism of its inhibitory effect on RA synovial inflammation.Methods Totally 24 New Zealand white rabbits were randomly divided into normal group,model group,drug group and needle-knife group,with 6 rabbits in each group.Except for the normal group,the other groups were injected with ovalbumin and Freund's complete adjuvant into the knee joint cavity to replicate the RA model,and corresponding interventions were given for 18 consecutive days.The knee pain threshold and knee circumference were measured,ultrasound was used to observe the joint cavity effusion,synovial thickness and internal blood flow signals,the synovial tissue morphology were observed by HE staining,the apoptosis of fibroblast-like synoviocytes(FLS)in synovial tissue was observed by TUNEL staining,the expression of TNF-α,IL-1β and IL-6 in synovial tissue were detected by immunohistochemistry,RT-PCR was used to detect NF-κBp65 and Bcl-2 mRNA expression in synovial tissue,Western blot was used to detect the protein expression of NF-κBp65,p-NF-κBp65,Bcl-2,Bax and caspase-3 in synovial tissue.Results Compared with the normal group,the knee pain threshold decreased,knee circumference increased,ultrasonic score and pathological score of synovial tissue increased in the model group;FLS apoptosis rate decreased,the expression of TNF-α,IL-1β and IL-6 in synovial tissue increased,the expressions of NF-κBp65,Bcl-2 mRNA and protein,and p-NF-κBp65 protein increased,while the expression of Bax,caspase-3 protein decreased,with statistical significance(P<0.05).Compared with the model group,the knee pain threshold increased in the drug group and the needle knife group,the circumference of the knee joint decreased,the ultrasonic score and pathological score of synovial tissue were significantly decreased;the apoptosis rate of FLS increased,the expression of TNF-α,IL-1β and IL-6 in synovial tissue decreased,the expressions of NF-κBp65,Bcl-2 mRNA and protein,and p-NF-κBp65 protein decreased,and the expression of Bax and caspase-3 protein increased,with statistical significance(P<0.05).Conclusion Needle-knife tendon-sparing and knot-dissolving technique may promote FLS apoptosis and reduce TNF-α,IL-1β and IL-6 production,inhibit synovial inflammation in RA,reduce knee joint swelling,and raise pain threshold by reducing the activity of synovial tissue NF-κB/Bcl-2 pathway.

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.

Objective:To investigate the possible role of long non-coding RNA (LncRNA) 00602 in promoting browning in adipocytes induced by adenovirus type 36 (Ad36).Methods:According to Ad36 infection, adipose tissue samples of obese patients were divided into Ad36-negative group and Ad36-infected group. Realtime fluorescent quantitative PCR (qRT-PCR) was used to detect the changes in the expression of LncRNA00602 mRNA in omental adipose tissue of the two groups, and analyze the differences between the two groups. The correlation between waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, fasting blood glucose, triacylglyceride and other indicators of the patients in the group with LncRNA00602 mRNA expression were analyzed. HE staining was used to detect the size of adipocytes in the omental adipose tissue of the Ad36 negative group and the Ad36 infection group. qRT-PCR and Western blotting were used to detect the mRNA and protein expression levels of uncoupling protein 1 (UCP1) and PR domain containing 16 (PRDM16) in omental adipose tissue of two groups of patients. Human adipose-derived stem cells (hADSC) were isolated and cultured, using Ad36 to induce differentiation, and divided into control group and LncRNA00602 knockdown group. On 0, 2, and 4 days after LncRNA00602 knockdown, fluoroboron dipyrrole (BODIPY) and mitochondrial red fluorescence (Mito-Tracker Red) were used to stain intracellular lipid droplets and mitochondria. At the same time, qRT-PCR and Western blotting were used to detect changes in the expression of UCP1 and PRDM16.Results:The expression of LncRNA00602 gene in the Ad36 infection group was higher than that in the Ad36 negative group (all P<0.05). The expression of LncRNA00602 in the Ad36 negative group was not significantly different from the above clinical indicators, while the expression of LncRNA00602 was negatively correlated with serum fasting blood glucose and triacylglyceride ( r=-0.522, -0.486, P<0.05) in the Ad36 infection group; HE staining showed that the average adipocyte area of the Ad36 infection group was smaller than that of the Ad36 negative group. At the same time, UCP1 and PRDM16 gene expression were higher than the negative group (all P<0.05). At the cellular level, on the 2nd and 4th days after knockdown of LncRNA00602, the lipid droplet area of adipocytes in the LncRNA00602 knockdown group was larger than that of the control group, the number of mitochondria decreased compared with the control group, and difference was statistically significant ( P<0.05 or P<0.01); Compared with the control group, there was significantly lower expression of the browning marker genes UCP1, PRDM16, and protein in the adipocytes in the LncRNA00602 knockdown group (all P<0.05). Conclusion:In Ad36-induced adipocyte differentiation, LncRNA00602 may positively regulate the expression of UCP1, PRDM16 and lipid droplet metabolism, and promote the browning of adipocytes.

Objective:To evaluate the effect of dual-tube epidural segmental injection of lidocaine analgesia on the delivery outcome and maternal and infant complications of persistent posterior occipital position postpartum or lateral occipital position postpartum patients with protracted active phase.Methods:The full and single-term primiparas ( n=216, 37 to 42 weeks gestation, 22 to 35 years) diagnosed as persistent posterior or lateral occipital position during the active period were selected from the Department of Obstetrics of Qingdao Municipal Hospital from January 2015 to October 2019. The subjects were randomly assigned into two groups: double-tube epidural block group ( n=108) and single-tube epidural block group ( n=108), 1% lidocaine was used for epidural analgesia respectively under ultrasound guidance. Senior midwife or obstetricians implement new partogram, and guide women to perform position management, and push or rotate the fetal head in a timely manner. Observation indicators: general condition, the use of non-pharmacological analgesic measures, analgesia related conditions and pain visual analogue scale (VAS) score, delivery-related indicator, cesarean section indication, anesthesia-related indicator, maternal and child complications. Results:(1) General condition: the age, weight, height, gestational age, the ratio of persistent lateral or posterior occipital position, cephalic score, and neonatal birth weight between the two groups of women were not statistically significant (all P>0.05). (2) The use of non-pharmacological analgesic measures: the women’s Lamaze breathing method, Doula delivery companionship, percutaneous electrical stimulation, and other measures between two groups were compared, and there were not significant differences (all P>0.05). (3) Analgesia related conditions and VAS scores of women undergoing vaginal delivery: compared with the single-tube epidural block group ( n=40), the second-partum time of the women in the double-tube epidural block group ( n=59) was significantly shortened [(124±44) vs (86±33) minutes, P<0.01]; after 30 minutes of analgesia (4.4±0.5 vs 0.9±0.5, P<0.01), during forced labor in the second stage of labor (5.7±0.6 vs 1.3±0.4, P<0.01), the VAS scores of pain were also significantly reduced ( P<0.01). (4) Labor-related indicators: compared with the single-tube epidural block group, the natural delivery rate (21.3% vs 49.1%) and the delivery experience satisfaction rate (51.9% vs 98.1%) of women in the double-tube epidural block group were significantly increased (all P<0.01), cesarean section rate (63.0% vs 45.4%), instrument assisted rate (15.7% vs 5.6%) decreased significantly (all P<0.05). (5) Cesarean section indications: compared with the single-tube epidural block group, the cesarean section rate caused by prolonged labor or protracted active phase of women in the double-tube epidural block group was significantly reduced (38.0% vs 22.2%； P<0.05), and the fetal distress, intrauterine infection, and social factors caused by cesarean section between the two groups were compared, while the differences were not statistically significant (all P>0.05).(6) Anesthesia related indexes: the block planes of the maternal upper tube administration in the double-tube epidural block group were mostly T7, T8, T9-L2 and L3,While,the block planes in the single-tube epidural block group were mostly T10, T11-S1, S2, S3, and the modified Bromage score were all 0. (7) Maternal and child complications: compared with the single-tube epidural block group, the postpartum hemorrhage rate (18.5% vs 7.4%), the perineal lateral cut rate (20.4% vs 5.6%), the neonatal asphyxia rate (12.0% vs 3.7%), ICU rate of transferred neonates (13.9% vs 4.6%) in the double-tube epidural block group were significantly reduced (all P<0.05). Soft birth canal injury rate, puerperal disease rate and neonatal birth rate between two groups were compared, and there were not statistically significant differences (all P>0.05). Conclusion:Dual-tube epidural segmental injection of lidocaine analgesia could increase the natural delivery rate of women with posterior occipital or lateral occipital position with active stagnation, reduce the rate of cesarean section and the rate of transvaginal instruments, and reduce the complications of mother and child.