Objective:To evaluate the efficacy of individualized removal therapeutic regimen for donor-specific antibodies (DSA) and examine its related influencing factors.Method:From January 2016 to January 2021, 34 recipients of kidney transplant (KT) underwent regular DSA testing and the results were positive. DSA removal therapy based upon rituximab (RTX) plus intravenous immune globulin (IVIG) was offered. Correlation between DSA negative conversion rate and DSA types, time from start of treatment to transplantation, HLA loci targeted by DSA and DSA mean fluorescent intensity (MFI) were analyzed retrospectively. Changes of immunedominant DSA (iDSA) and serum creatinine in individuals with de novo DSA (dnDSA) before and after treatment were also examined.Results:At Month 3 post-treatment, antibodies turned negative in 17/34(50.0%) patients and DSA became negative in 19/34(55.9%) at the last follow-up. Then we identified 78 DSA from all patients. No significant difference existed in negative conversion rate of pfDSA and dnDSA at Month 3 post-treatment [62.9%(39/62) vs 37.5%(6/16)] and at the last follow-up [4.2%(46/62) vs 56.3%(9/16)]( P=0.067, 0.219). For pfDSA, negative conversion rate of pfDSA with different MFIs after 3-month treatment varied significantly [negative conversion rate of weak positive DSA was 78.6%(33/42) and positive and above DSA 30%(6/20), P<0.001]. It was an independent related factor of whether or not pfDSA could turn negative (48.6%, 95% CI: 22.3%-66.8%, P=0.001). At the last follow-up, negative conversion rate of pfDSA differed markedly at different timepoints from start of treatment to transplantation [treated within 30 days post-operation was 79.2%(42/53) and over 30 days post-operation was 44.4%(4/9), P=0.042] and among different DSA MFI [88.1%(37/42) of weakly positive DSA and 45%(9/20) of positive and above DSA, P<0.001] and they were independent related factors for negative conversion of pfDSA (34.8%, 95% CI: 3.2%-61.8%, P=0.008; 43.1%, 95% CI: 18.5%-63.4%, P=0.001). Mean decline rate in iDSA was 66.67% at Month 3 post-treatment and 77.90% at the last follow-up. The difference was statistically significant ( P=0.035). Serum level of creatinine of 9 patients with dnDSA was (110.2±26.9) μmol/L pre-treatment, (178.8±90.5) μmol/L during treatment, (153.9±72.8) μmol/L at Month 3 post-treatment and (213.6±185.8) μmol/L at the last follow-up. Serum creatinine rose during treatment ( t=-2.794, P=0.023), declined at Month 3 post-treatment ( t=3.430, P=0.009) and spiked again at the last follow-up ( P=0.028). Conclusion:After DSA removal therapy based upon RTX plus IVIG, negative conversion rate of pfDSA is correlated with its MFI and time from start of treatment to transplantation. There is no significant rebound in DSA MFI and graft function of dnDSA patients improves immediately after treatment.

IgA nephropathy (IgAN) is one common type of glomerulonephritis caused by a deposition of immune complexes in mesangium and partial capillary loops. It is also an important risk factor for end-stage renal disease (ESRD). Kidney transplantation (KT) has been an ultimate treatment for IgAN patients progressing into ESRD. However, there is still a high risk of recurrence after transplantation. Currently no effective treatment is available for recurrent IgAN. This review summarized the latest researches of managing IgAN recurrence after KT, such as optimal treatment, immunosuppression, complement therapy and surgery.

Objective:To explore the risk factors related to acute rejection (AR) after pediatric kidney transplantation (KT).Methods:Retrospective analysis was performed for 189 pediatric KT recipients from September 2011 to August 2022.They were divided into two groups of AR (n=33) and non-AR (n=156).Univariate and multivariate Logistic regression analyses were performed for identifying potential risk factors of AR.And the effects of AR on graft function and survival were also examined.Results:During follow-ups, a total of 33(17.5%) patients developed AR with a 1-year cumulative incidence of AR of 16.9%(32/189).Univariate analysis revealed that median time on dialysis was longer in AR group than that in non-AR group (19 vs. 11 months, P=0.034).Median age of donors (12 vs. 24 months, P=0.033), median weight of donors (9.5 vs. 12 kg, P=0.025) and median donor/recipient body weight ratio (0.36 vs. 0.50, P=0.005) were lower in AR group than those in non-AR group.And the proportion of subtherapeutic tacrolimus (TAC) trough level was higher in AR group than that in non-AR group (45.5% vs. 21.2%, P=0.004).Multivariate regression analysis indicated that subtherapeutic TAC trough level was an independent risk factor for AR ( OR=2.977, 95% CI: 1.314-6.743, P=0.009).At the last follow-up, serum creatinine and eGFR were (78.4±24.3) vs. (74.6±24.7) μmol/L and (85.3±26.3) vs. (89.5±24.2) ml·min -1·1.73 m -2 in AR and non-AR groups respectively.There were no significant differences.1/5-year patient survival rate was both 97% in AR group and both 99.4% in non-AR group; 1/5-year graft survival rate both 90.9% in AR group and was 98.1% and 97.4% in non-AR group.No significant inter-group differences existed in patient and graft survival. Conclusions:Although an occurrence of early AR does not negatively impact graft outcomes, the incidence of AR remains high after pediatric KT.Therefore prompt diagnosis and treatment of AR should be strengthened.

As a ligand-dependent transcription factor,retinoid-associated orphan receptor γt(RORyt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the pro-gression of several inflammatory and autoimmune conditions.An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORyt to decrease Th17 cell development and IL-17 production.Several RORyt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORyt by binding to orthosteric-or allosteric-binding sites in the ligand-binding domain.Some of small-molecule inhibitors have entered clinical evaluations.Therefore,in current review,the role of RORyt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted.Notably,the recently developed RORyt inhibitors were summarized,with an emphasis on their optimization from lead compounds,ef-ficacy,toxicity,mechanisms of action,and clinical trials.The limitations of current development in this area were also discussed to facilitate future research.

Ulcerative colitis (UC) is one of types of inflammatory bowel disease with high recurrence. Recent studies have highlighted that microbial dysbiosis as well as abnormal gut immunity are crucial factors that initiate a series of inflammatory responses in the UC. Modulating the gut microbiota-intestinal immunity loop has been suggested as one of key strategies for relieving UC. Many Chinese herbal medicines including some of single herb, herbal formulas and the derived constituents have been reported with protective effect against UC through modulating gut microbiome and intestinal immunity. Some clinical trials have shown promising results. This review thus focused on the current knowledge on using Chinese herbal medicines for treating UC from the mechanism aspects of regulating intestinal homeostasis involving microbiota and gut immunity. The existing clinical trials are also summarized.

Interference with quorum sensing(QS)represents an antivirulence strategy with a significant promise for the treatment of bacterial infections and a new approach to restoring antibiotic tolerance.Over the past two decades,a novel series of studies have reported that quorum quenching approaches and the discovery of quorum sensing inhibitors(QSIs)have a strong impact on the discovery of anti-infective drugs against various types of bacteria.The discovery of QSI was demonstrated to be an appropriate strategy to expand the anti-infective therapeutic approaches to complement classical antibiotics and antimicrobial agents.For the discovery of QSIs,diverse approaches exist and develop in-step with the scale of screening as well as specific QS systems.This review highlights the latest findings in strategies and methodologies for QSI screening,involving activity-based screening with bioassays,chemical methods to seek bacterial QS pathways for QSI discovery,virtual screening for QSI screening,and other potential tools for interpreting QS signaling,which are innovative routes for future efforts to discover additional QSIs to combat bacterial infections.

Objective:To retrospectively summarize the clinical experiences of managing renal artery stenosis after donor kidney transplantation in children.Methods:From January 2018 to October 2021, 114 pediatric kidney transplants(donor/recipient aged <18 years)were performed.According to the findings of color Doppler ultrasonography, they were divided into two groups of normal( n=80)and rapid flow( n=34). Rapid flow group were assigned into symptomatic( n=13)and asymptomatic( n=21)sub-groups based upon clinical features of hypertension and renal instability. Results:Among them, there were 65 males and 49 females.A significant inter-gender difference existed in the proportion of higher arterial flow rate of transplanted kidney(38.5% and 18.4%, P=0.02). No significant difference existed in age or body weight of transplant recipients among all groups( P>0.05). The mean age(10.4 months)and body weight(9 kg)of donors were significantly lower in symptomatic group than those in normal group(65.3 months, 21 kg)and asymptomatic group(64.4 months, 21.2 kg). The mean velocity of symptomatic group was significantly higher than that of asymptomatic group(363.5 vs 228.8 cm/s)( P<0.001). In symptomatic group, 6 cases received medications and their clinical manifestations were completely relieved.Among 7 patients invasively treated, one percutaneous transluminal angioplasty(PTA)was offer once( n=2), twice( n=2)and triple( n=1)with clinical relief and stable renal function.One case of bleeding at puncture site during PTA had treatment failure with a gradual loss of graft function.One ineffective case of PTA was subsequently placed with an endovascular stent.However, repeated stent dilation failed due to restenosis.After surgical exploration, vascular stent removal and transplantation of renal artery clipping, clinical symptoms were relieved. Conclusions:Male recipient, low body weight or young donor may be risk factors for transplant renal artery stenosis(TRAS)during pediatric donor renal transplantation.A higher flow rate of transplanted renal artery on ultrasonography could not confirm the diagnosis of TRAS.Greater arterial flow and associated clinical manifestations often hint at a strong possibility of TRAS, requiring drug or invasive treatment interventions.If PTA efficacy is not satisfactory, multiple treatments should be performed.Nevertheless, stenting should be avoided as far as possible to prevent in-stent restenosis.

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

Objective:To explore the feasibility and efficacy of kidney transplantation with pediatric donors to pediatric recipients (PTP) according to the quality control parameters of kidney transplantation in China.Methods:From September 2011 to September 2019, the clinical data were reviewed for 147 children undergoing kidney transplantation. The general status of donors and recipients, survival rate and complications of transplantation were analyzed.The median age was 130(21-270) month and the median weight 26.0(8.5-71.5) kg. The median age of 120 donors was 12 month (4 day-180 month) and the median weight 9.3(2.5-50.0) kg.Results:After a follow-up period of 10 days to 9 years, the cumulative survival rates of patients and grafts were 97.3% and 88.8%. The cumulative survival rates of patients and grafts were 95.7% and 60.9% in en bloc kidney transplant recipients versus 96.8% and 94.2% in single kidney transplant recipients. The major complications of en bloc kidney transplantation were graft thrombosis (47.8%) and ureteral complications (17.4%). Single kidney transplantation was characterized by delayed graft function recovery (DGF, 18.6%) and acute rejection reaction (10.5%). Two cases died from donor-derived infection after transplantation, one from cytomegalovirus infection and one from epileptic seizure.Conclusions:PTP kidney transplantation is effective. Organ matching and optimal operative mode selection are essential. Preventing postoperative thrombosis for avoiding an early graft loss has remained a high priority during PTP kidney transplantation.

Objective:To explore the application of high-throughput second-generation gene sequencing technology based upon metagenomics in the diagnosis of pulmonary infection after organ transplantation.Methods:From June 2016 to January 2020, clinical records were retrospectively reviewed for 34 renal and liver transplant recipients hospitalized for pulmonary infection. From June 2016 to December 2018, they were assigned as group A (n=20) of traditional pathogen detections. From January 2019 to January 2020, 14 cases in group B were sequenced by high-throughput second-generation technology. The detection rate, sensitivity and specificity, the return time of detection results, the average length of stay and the mortality of 28 days between two groups were analyzed.Results:No significant inter-group difference existed in clinical data (age, gender, antibody induction method, immunosuppressant use, etc.). As compared with group A, the positive detection rate of etiology and the the sensitivity were higher in group B and the differences in specificity were statistically insignificant. The return time of test results in group B was significantly shorter than that in group A. And the difference was statistically significant. The average hospitalization stay and 28-day mortality of group B were lower than those of group A. And the differences were statistically significant.Conclusions:High-throughput second-generation gene sequencing technology can improve the detection rate of pulmonary infection after organ transplantation. Providing a " precise and accurate" direction for disease treatment, it is a useful supplement to traditional diagnostic methods.