ObjectiveTo investigate the therapeutic effect of Qinggongtang in regulating Glu/GABA metabolic balance and the mechanism of its anxiolytic effect on rat models of anxiety. MethodFifty-four rats were randomly divided into normal， model， diazepam （0.225 mg·kg^-1）， and low-dose， medium-dose， and high-dose groups of Qinggongtang （5.085， 10.17， 20.34 g·kg^-1）， with nine rats in each group. Except for the normal group， the other groups were subjected to indeterminate vacutainer stress and chronic restraint stress for 12 days to prepare the anxiety model. On the 3^rd day of the stress， 10 days of corresponding drug intervention was started. At the end of the drug treatment， the anxiety level of rats in each group was evaluated by the elevated cross maze experiment （EPM） and the light and dark box experiment （LDB）， and the effect of Qinggongtang on the anxiety behavior of rats was preliminarily analyzed. The levels of Glu and GABA in the amygdala tissue of the rats were detected by enzyme linked immunosorbent assay （ELISA）， and the changes in the synaptic ultrastructure of the amygdala of the rats in each group were observed by electron microscopy. The mRNA expression of glutamic acid decarboxylase （GAD65 and GAD67）， glutamine synthetase （GS）， and glutamate transporter-1 （GLT-1） in the amygdala were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and their protein expression was detected by Western blot. ResultCompared with those in the normal group， rats in the model group showed an obvious anxiety state and dull yellow and lusterless fur. They were irritable， easy to anger， and preferred to curl up in the corner. The number of times the EPM entered the open arm and the residence time in the open arm were significantly reduced （P<0.01）， and the residence time in the open box and the number of times the LDB went through the box were significantly reduced （P<0.01）. The content of Glu in the amygdala was increased （P<0.01）， and the content of GABA was reduced （P<0.01）. The value of Glu/GAB was elevated （P<0.01）， and the number of synaptic and pre-synaptic membrane vesicles in the amygdala was decreased. Sparse dense material in the post-synaptic membrane， increased synaptic gap， slightly disrupted internal structure， and decreased mRNA and protein expressions of GAD65， GAD67， GS， and GLT-1 in the amygdala were observed （P<0.01）. Compared with those in the model group， rats in the medium-dose and high-dose groups of Qinggongtang and the diazepam group had bright fur， sensitive reactions， and more active behavior. The number of times EPM entered the open arm and the residence time in the open arm increased significantly （P<0.01）， and the residence time in the open box and the number of times the LDB went through the box increased significantly （P<0.01）. The content of Glu in all-dose groups of Qinggongtang and the diazepam group decreased （P<0.05， P<0.01）， while GABA content increased （P<0.05， P<0.01）. The value of Glu/GABA decreased （P<0.01）， and the internal and external synaptic structure of each groups of Qinggongtang and the diazepam group was more complete. Synapses and vesicles were numerous， and the synaptic gap was more clearly defined. The efficacy of the high-dose group of Qinggongtang and the diazepam group was the best， and the mRNA and protein expressions of GAD65， GAD67， GS， and GLT-1 in the amygdala were increased in the high-dose group of Qinggongtang and diazepam group （P<0.05， P<0.01）. ConclusionQinggongtang can improve synaptic plasticity and affect the expression of GAD65， GAD67， GS， and GLT-1 in the amygdala of rats to regulate Glu/GABA metabolic balance and thus exert anxiolytic effects.

ObjectiveTo establish an ischemia-reperfusion model in cynomolgus macaques and to analyse the effects of edaravone intervention. MethodsA total of fifteen adult male cynomolgus macaques were randomly divided into three groups: sham operation (Sham group, n=3), ischemia-reperfusion model (Model group, n=6) and edaravone treatment (Edaravone group, n=6). Ischemic-reperfusion model of cynomolgus macaques was established by clamping the M1 branch of the left cerebral artery for 1 h. After 2 h of reperfusion, the animals in Edaravone group were injected with 0.5 mg/kg edaravone intravenously for intervention treatment, while the animals in Sham and Model groups were injected with an equal volume of normal saline intravenously, twice a day, from the 2nd to 7th day. The behavioral video recordings, clinical observations and neurological deficit scores of cynomolgus macaques were obtained, and brain edema volume and cerebral ischemia volume were statistically analyzed. ResultsCompared with the Sham group, the animals in Model group showed typical symptoms of ischemic stroke, with a significant increase in the neurological deficit score， the volumes of edema and infarct of brain tissue (all P＜0.01). Compared with Model group, the neurological deficit score, the volumes of edema and infarct of brain tissue were significantly reduced in Edaravone group (all P＜0.05). ConclusionAn animal model of ischemia-reperfusion in cynomolgus macaques was successfully established, and edaravone was confirmed to alleviate the damage caused by ischemia-reperfusion.

BACKGROUND: Although ABO-incompatible (ABOi) kidney transplantation (KT) has been performed successfully, a standard preconditioning regimen has not been established. Based on the initial antidonor ABO antibody titers, an individualized preconditioning regimen is developed, and this study explored the efficacy and safety of the regimen. METHODS: From September 1, 2014, to September 1, 2020, we performed 1668 consecutive living-donor KTs, including 100 ABOi and 1568 ABO-compatible (ABOc) KTs. ABOi KT recipients (KTRs) with a lower antibody titer (≤1:8) were administered oral immunosuppressive drugs (OIs) before KT, while patients with a medium titer (1:16) received OIs plus antibody-removal therapy (plasma exchange/double-filtration plasmapheresis), patients with a higher titer (≥1:32) were in addition received rituximab (Rit). Competing risk analyses were conducted to estimate the cumulative incidence of infection, acute rejection (AR), graft loss, and patient death. RESULTS: After propensity score analyses, 100 ABOi KTRs and 200 matched ABOc KTRs were selected. There were no significant differences in graft and patient survival between the ABOi and ABOc groups (P  = 0.787, P  = 0.386, respectively). After using the individualized preconditioning regimen, ABOi KTRs showed a similar cumulative incidence of AR (10.0% υs . 10.5%, P  = 0.346). Among the ABOi KTRs, the Rit-free group had a similar cumulative incidence of AR ( P  = 0.714) compared to that of the Rit-treated group. Multivariate competing risk analyses revealed that a Rit-free regimen reduced the risk of infection (HR: 0.31; 95% CI: 0.12-0.78, P  = 0.013). Notably, antibody titer rebound was more common in ABOi KTRs receiving a Rit-free preconditioning regimen ( P  = 0.013) than those receiving Rit. ABOi KTRs with antibody titer rebound had a 2.72-fold risk of AR (HR: 2.72, 95% CI: 1.01-7.31, P  = 0.048). ABOi KTRs had similar serum creatinine and estimated glomerular filtration rate compared to those of ABOc KTRs after the first year. CONCLUSIONS An individualized preconditioning regimen can achieve comparable graft and patient survival rates in ABOi KT with ABOc KT. Rit-free preconditioning effectively prevented AR without increasing the risk of infectious events in those with lower initial titers; however, antibody titer rebound should be monitored.
Humans ; Kidney Transplantation/adverse effects* ; Living Donors ; Kidney ; Immunosuppressive Agents/therapeutic use* ; Rituximab/therapeutic use* ; ABO Blood-Group System ; Graft Rejection ; Graft Survival

Objective:To explore the safety and early prognosis of robot assisted living donor kidney transplantation(KT)and plot the learning curve of mastering the operation.Methods:From July 2020 to March 2021, 30 cases of living robot assisted KT were completed.The follow-up period was 3 months.Cumulative sum analysis was performed for plotting the learning curve.According to the learning curve, they were divided into two groups of practice period(the first 17 cases)and proficiency period(the last 13 cases). Time of each operative stage and early prognosis were compared.Kidney function and perioperative complications of two groups were compared for evaluating the safety and effectiveness of robot assisted KT.Results:The average operative duration was (221.4±36.1)min.No intestinal obstruction, delayed graft function, urinary leakage and incision infection occurred during perioperative period.The average anal exhaust time was(1.9±0.2)days.During follow-ups, both pulmonary infection(2 cases)and acute rejection(1 case)improved after treatment.According to the learning curve, venous anastomosis(10 cases), arterial anastomosis(12 cases), warm ischemic time(12 cases)and ureteral anastomosis(17 cases)should be performed for reaching a proficiency level.An average of 15 operations was required for achieving proficiency throughout operations.Significant inter-group differences existed in operative duration [(235.5±31.6)vs(203.0±34.3)min, P=0.012] and warm ischemic time [(63.7±24.9)vs(47.0±11.3)min, P=0.033]. At some postoperative timepoints, creatinine of proficiency group was lower than that of practice group, such as Day 7 post-operation [(192.7±135.2)vs(107.8±27.9)μmol/L, P=0.022] and Day 30 post-operation [(147.8±46.3)vs(112.3±28.0)μmol/L, P=0.021]. However, no significant difference existed in estimated glomerular filtration rate at Day 7 post-operation [(56.1±34.1)ml/(min·1.73m 2)vs(72.0±18.5)ml/(min·1.73m 2), P=0.14] and Day 30 post-operation [(56.2±18.9)ml/(min·1.73m 2)vs(68.7±15.3)ml/(min·1.73m 2), P=0.14]. Conclusions:Robot assisted KT is both safe and feasible.And the learning curve requires 17 cases for reaching a proficiency level.

Objective:To evaluate the safety of pregnancy after kidney transplantation and summarize the optimal timing of pregnancy and the experience in the management during pregnancy and peripartum.Methods:A total of 25 kidney transplant recipients were pregnant during March 2013 to February 2020. A matched cohort of 75 general pregnant women wasincluded as control.Results:Twenty-five women successfully delivered healthy babies in the transplant group. The mean age at kidney transplantationwas (25.6 ±3.2) years old, and the mean interval between transplantation and conception was (54.0±23.1) months. 92% (23 / 25) of recipients had cesarean surgery and all infants were singletons.During pregnancy, the incidence of preeclampsia was significantly higher in the transplant group(20.0%VS. 1.3%, P=0.001)compared with matched control. Compared with pre-pregnancy, the serum creatinine levels of the recipients decreased in the second trimester( P<0.001)and increased in the third trimester( P=0.019), which was similar with the control group. In the third trimester, 40%(10/25)of recipients in the transplant group had proteinuria, which decreased to negative(5/10) or 1+ (4/10) within 6 months after delivery. No rejection occurred in all patients during pregnancy and 6 months after delivery. A higher dose of tacrolimus was needed to maintain the normal trough level after pregnancy, which returned to routine dose postpartum. Conclusions:Although the risk of pregnancy was higher in kidney transplant recipients than that in non-transplant women, the overall risk was acceptable. Strict screening of patients preparing for pregnancy, adjustment of immunosuppressive drugs, and multi-disciplinary collaboration are important for safe pregnancy and delivery.

Objective:To explore the efficacy and safety of pretreating with oral immunosuppressants alone for ABO-incompatible (ABOi) renal transplant recipients with an initial isoagglutinin titer <1: 8.Methods:From September 2014 to October 2019, 16 cases of ABOi renal transplantation pretreated with oral immunosuppressants alone and 32 cases of ABO-compatible (ABOc) renal transplantation were recruited for comparing the inter-group incidence of graft function, acute rejection, infection and recipient and allograft survival.Results:The 16 ABOi renal transplantations were AB-to-A(n=4), AB-to-B(n=3), A-to-B(n=1), B-to-A(n=4), A-to-O(n=2) and B-to-O(n=2). The initial isoagglutinin titer (IgM & IgG) and that on the date of transplantation were both ≤1∶8. The median follow-up period was 495(90-1696) days. One patient in ABOi group underwent allograft nephrectomy due to hyperacute rejection. The graft survival rates were 93.75%(15/16) and 100%(32/32) in ABOi and ABOc groups respectively. No recipient died. No significant inter-group difference existed in postoperative renal function after 6 months (serum creatinine μmol/L: 114.30±28.13 vs. 106.08±23.80, P=0.38; eGFR ml/min/1.73 m 2: 64.93±19.60 vs. 82.34±22.58, P=0.13). In ABOi group, there were 3 episodes of postoperative infection, 2 episodes of acute rejection within 2 weeks (including 1 episode of hyperacute rejection) and 1 episode of acute rejection after 2 weeks; 5 episodes of postoperative infection, no acute rejection within 2 weeks and 5 episodes of acute rejection after 2 weeks in ABOc group. No significant inter-group difference existed in the incidence of infection or rejection ( P>0.05). Conclusions:Using oral immunosuppressant alone is both safe and feasible for ABOi renal transplantation recipients with an initial isoagglutinin titer ≤1∶8. It may greatly simplify the pretreatment scheme for those with a low initial isoagglutinin titer and lower the incidence of complications.

Here we investigate the physical and chemical properties of chiral self-assembling peptides and the role of uterine trauma regeneration. The circular dichroism was used to analyze secondary structure of chiral self-assembled peptide, and Congo red staining was used to observe the macroscopic process of peptide self-assembling. Erythrocyte lysis assay was used to examine the cleavage of peptide on cell membrane. The nanofiber scaffolds self-assembled by Chiral self-assembling peptides were used as the three-dimensional culture material to observe the growth effect of Hela cell. CCK-8 (cell counting kit-8) was used to study cell viability level between 2D (2-dimensional) and 3D (3-dimensional) culture environment. Rats endometrium curettage model was founded to evaluate the changes by immunohistochemistry staining and and HE staining. The secondary structure of chiral self-assembling peptides was stable β-sheet, and peptide could form dense membrane structure after 24 hours self-assembling cultured in salt ions. There was no harmful for the cell membrane of the peptide before and after self-assembling. Animal experiments show that chiral self-assembling peptide can significantly reduce the inflammatory response, promote the production of neovascularization, and accelerate the repair process. Chiral self-assembling peptide, as a new type of scaffold material, can construct a three-dimensional cell culture environment and used to repair uterine trauma.
Animals ; Endometrium ; Female ; HeLa Cells ; Humans ; Nanofibers ; Peptides ; Rats ; Regeneration

Objective To evaluate the safety of super-minimal incision kidney transplantation (SMIKT).Methods We included the clinical data and outcomes of 40 cases of SMIKT and 56 cases of conventional Gibson incision kidney transplantation (CIKT),and compared the operation time,post operative pain,analgesic requirements,1 month renal function and 1 month Vancouver scar scale between the two groups.Results As compared with CIKT,operation time was significantly shortened (100 ± 10 versus 127.5 ± 34.3 min,P =0.044),incision length was significantly shortened (5.2 ± 0.2 versus 13.0 ± 2.0 cm,P＜0.001),and post-operative pain at day 1 was significantly reduced in SMIKT (1.31 ± 1.15 versus 4.02 ± 1.83,P =0.004).However,there was no significant difference in post-operative pain at day 2 and day 3 between CIKT and SMIKT.SMIKT required less analgesic medications than CIKT (3.13 ± 1.74 versus 11.69 ± 2.89,P =0.002).No significant difference in 1 month renal function was observed between two groups.SMIKT had fewer Vancouver scar scale score than CIKT (6.50 ± 0.58 versus 8.67 ± 0.58,P =0.004).Conclusion SMIKT is a safe novel surgery,which can significantly reduce operation time,post-operative pain,had fewer analgesic requirements and better 1-month cosmetic effect.

Objective To investigate the clinical efficacy and safety of individualized preconditioning in ABO-incompatible living donor kidney transplantation.Methods A series of 36 living donor kidney transplants across a wide range of ABO blood group incompatibilities using individualized preconditioning protocols were performed from September 2014 to June 2017.Preconditioning included oral immunosuppressants with or without the administration of rituximab,PE or DFPP.Medical records and electronic databases were reviewed for isoagglutinin titers,patient and graft survivals,graft function,rejections,infections as well as surgical complications.Results Of 30 ABO blood group incompatibilities,there were 6 cases of AB to A,2 cases of AB to B,4 cases of A to B,3 cases of B to A,13 cases of A to O (13),and 8 cases of B to O.Median initial ABO antibody titers were 1∶32 (1∶2-1∶256) (IgM) and 1 ∶ 8 (0-1∶64) (IgG),respectively.Individualized preconditioning included oral immunosuppressants alone (10 cases),oral immunosuppressants + PE (4 cases),oral immunosuppressants + PE + DFPP (1 case),oral immunosuppressants + rituximab + PE (16 cases),oral immunosuppressants + rituximab + DFPP (2 cases),and oral immunosuppressants + rituximab + PE+ DFPP (3 cases).After individualized preconditioning,an acceptable ABO antibody titer (≤1 ∶ 16) was obtained on the day of transplantation.Median follow-up duration was 12 months (1-33).Graft and patient survival rate was 94.4％ (34/36) and 100％ (36/36) respectively.Median value of serum creatinine at one year posttransplantation was 89 μmol/L,and eGFR was (81.07 mL/min/1.73 m2).In total,there was one episode of urinary tract infection and upper gastrointestinal tract hemorrhage,two cases of hyperacute rejection (leading to graft loss),acutecelluar-mediated rejection,delayed graft function,bone marrow suppression and pneumonia,and 3 cases of acute antibody-mediated rejection and wound fat liquefaction,respectively.Conclusion Our initial experience indicates that individualized preconditioning protocol based on initial ABO antibody titers is safe and technically feasible,and leads to excellent short-term survival of ABOi living donor kidney transplantation.

Objective To investigate the safety and efficacy of conversion from calcineurin inhibitors (CNI) to mammalian target of rapamycin (mTORi) in liver transplant recipients.Methods Such databases as MEDLINE (PUBMED),EMBASE,Cochrane Library and clinical trial registries (ClinicalTrials.gov,WHO International Trial Registry Network,Australian & New Zealand Clinical Trials Registry) were searched from the inception of each resource up to April 2015 for collecting the randomized controlled trials (RCTs) about liver transplant recipients after conversion from CNIs to mTORi,and the references of those trials were also searched by hand.After study selection,assessment and data extraction conducted by two reviewers independently,meta-analyses were performed by using the RevMan5.3 software.The quality of those trials was assessed by using the Jadad Score.Then,the safety and efficacy of conversion from CNI to mTORi were systematically assessed as a strategy for eliminating CNI exposure in liver transplant recipients.Results Ten RCTs (1917 patients) were included in this meta-analysis.The follow-up duration post-randomization was 6 to 36 months.The mean mTORi conversion time after transplantation was ≤6 months in 4 trials,and ＞6 months in 6.The meta-analysis revealed that the estimated glomerular filtration rate was significantly increased,and the incidence of renal failure and hyperglycemia was significantly reduced in mTORi conversion group as compared with those in CNI treatment group (P＜0.05 for all).The incidence of acute rejection in mRORi conversion group and CNI treatment group was 11.3％ and 6.3％ respectively (P＜0.01),and that confirmed by biopsy was 14.0％ and 8.4％ respectively (P＜0.01).The percentage of recipients discontinuing the medication in mRORi conversion group and CNI treatment group was 41.6％ and 21.5％ respectively (P＜0.01).The main reasons for drug withdrawal were drug-related adverse events (Aes),including acute rejection,bone marrow depression,anemia,leucopenia,thrombocytopenia,mouth sores/stomatitis,hyperlipidemia,hypercholesterolemia,rash,edema,and pyrexia.There was no significant difference between the two groups with regard to death,graft loss,loss to follow-up,infection,gastrointestinal symptoms,malignancy,and hypertension.Conclusion Conversion from CNI to mTORi therapy results in a significant improvement in renal function.However,this conversion strategy may lead to the high discontinuation rate due to mTORi-associated Aes,indicating that conversion may only be a treatment option in selected patients.