Volume 103 ·  Issue 20 ·  2023

The "Expert Recommendations on the Diagnosis and Treatment of Alport Syndrome" published in 2018 have greatly promoted the standardized management of Alport syndrome in China. In recent years, the rapid advances in researches related to this disorder have provided new insights into the clinical practice of Alport syndrome. To this end, based on the latest research progress at home and abroad, the Alport Syndrome Collaborative Group, the National Clinical Research Center of Kidney Diseases of Jinling Hospital and the Rare Diseases Branch of Beijing Medical Association have jointly organized the experts in relevant fields to revise the 2018 version of the recommendations. The updated version adds new contents related to genetic testing and variant interpretation, and refines the strategies for diagnosis, treatment and follow-up management, thereby providing guidance for the clinical diagnosis and treatment of Alport syndrome.

To establish correction model of the sampling time error on the blood trough concentration of tacrolimus in non-sustained-release dosage form for renal transplant recipient and improve the accuracy of drug dose assessment and clinical adjustment in renal transplant recipients.

Visit records of 206 outpatients in the Department of Transplantation, Nanfang Hospital, Southern Medical University were retrospectively collected from October 15, 2022 to October 30, 2022. The distribution of sampling time of tacrolimus blood drug concentration was described and the time range of correction was determined. Twenty inpatients after renal transplantation in the Department of Transplantation, Nanfang Hospital, Southern Medical University from October 1, 2022 to November 30, 2022 were prospectively included, and their demography data, laboratory test results during follow-ups, and CYP3A5 genotype were collected. The patients took tacrolimus in non-sustained-release dosage form every 12 h starting from 19∶30 on the day of admission. Peripheral blood samples were collected from the patients on the second day of admission at 7∶30 and on the third day at 6∶00-10∶00 every 30 minutes to test the blood concentration of tacrolimus. Using the collection time as the independent variable and the blood tacrolimus concentration as the dependent variable, a simple linear regression was performed to fitting a linear model of tacrolimus blood concentration-sampling time. Multiple linear regression was performed to analyze the influencing factors of the tacrolimus metabolic rate within a specific period and generate the regression equation.

The 206 outpatients aged (46±13) years, including 131 males (63.6%). The time gap [M (Q₁, Q₃)] between the sampling time of the follow-up outpatients and standard C₁₂ was 24 (13.0, 46.5) min, and the maximum time gap was 135 min. The 20 enrolled inpatients aged (45±12) years, including 15 males (75.0%). There was no significant difference in the blood concentration of tacrolimus collected at 7∶30 on the second (7.87±2.21)ng/ml and third days (7.84±2.33)ng/ml after admission of the enrolled inpatients (P=0.917), and the blood tacrolimus concentration rhythm was stable in the trial. The plasma concentration of C_10.5-C_14.5 was linearly related to the time, with R² [M (Q₁, Q₃)] 0.88 (0.85, 0.92) and all P<0.05. The metabolic rate of tacrolimus during C_10.5-C_14.5=0.984+0.090×basic concentration of tacrolimus (ng/ml)-0.036×body mass index+0.489×CYP3A5 genotype-0.007×hemolobin(g/L)-0.035×alanine aminotransferase (U/L)+0.143×total cholesterol (mmol/L)+0.027×total bilirubin (μmol/L), with R²=0.85.

This study propose a correction model for tacrolimus (non-sustained-release dosage form) trough concentration around C₁₂, which is helpful for clinicians to easily and accurately assess renal transplant recipients′ tacrolimus exposure.

To investigate the prevalence of frailty among kidney transplant recipients and to analyze the influential factors of frailty after kidney transplantation.

We retrospectively included 201 kidney transplant recipients who were followed up in the Department of Urology, Beijing Chao-yang Hospital, Capital Medical University from November 2020 to May 2022. We investigated the prevalence of frailty based on the Fried Frailty Scale (including unexpected shrinking, slow walking speed, poor grip strength, low physical activity, and exhaustion). Then the logistic regression model and CART decision tree model were established separately to explore the influential factors of frailty after kidney transplantation.

Frail kidney transplant recipients accounted for 25.9% (n=52) of all participants. The age [M (Q₁, Q₃)] of the frailty group was higher than that of the non-frailty group, and the median ages of the two groups were 57(49, 62) and 46(38, 56) (P<0.001); the males accounted for 51.9% (n=27) and 62.4% (n=93), respectively. There was no significant difference in gender composition (P=0.244). Among the five components of Fried Frailty Scale, the incidence of unexpected shrinking was the lowest (19.4%, 39/201). In the frailty group, the frailty combination with the highest incidence was slow walking speed+low physical activity+exhaustion, which was 19.2% (10/52). The logistic regression model showed that advanced age (OR=1.062, 95%CI: 1.005-1.123), history of acute rejection (OR=16.776, 95%CI: 2.288-123.028), increased neutrophil/lymphocyte ratio (NLR) (OR=2.096, 95%CI: 1.158-3.792), and comorbidity (OR=10.600, 95%CI: 1.828-61.482) were risk factors for frailty among kidney transplant recipients, and high serum albumin level (OR=0.623, 95%CI: 0.488-0.795) was a protective factor. The CART decision tree grew in three layers with four terminal nodes, and three explanatory variables were screened out: serum albumin, NLR, and age. The accuracy, sensitivity, and specificity of the logistic regression model were 87.1% (95%CI: 82.5%-91.7%), 69.2% (95%CI: 54.7%-80.9%), and 93.3% (95%CI: 87.7%-96.6%), respectively. The area under the ROC curve (AUC) of the logistic regression model was 0.951 (95%CI: 0.923-0.978). The accuracy, sensitivity, and specificity of the CART decision tree model were 91.0% (95%CI: 87.0%-95.0%), 82.7% (95%CI: 69.2%-91.3%), and 94.0% (95%CI: 88.5%-97.0%), respectively. The AUC of the CART decision tree model was 0.883 (95%CI: 0.819-0.948).

The prevalence of frailty among kidney transplant recipients in this study is 25.9%. Advanced age, history of acute rejection, low serum albumin level, increased NLR, and comorbidity are likely to be associated with the long-term frailty among kidney transplant recipients.

To analyze high-risk factors affecting BK polyomavirus (BKPyV) infection and to construct a prediction model for BKPyV infection in children after renal transplantation.

The clinical data of 332 children who received allogeneic kidney transplantation in the First Affiliated Hospital of Zhengzhou University from January 2014 to March 2022 were retrospectively collected. According to the BKPyV load level, the dynamic change process of lymphocytes at different time points were analyzed. The factors that have potential influence on BKPyV infection were screened by Cox regression analysis, and the receiver operating characteristic curve (ROC) was used to evaluate the sensitivity and specificity of the predictive model of infection.

Among the 332 children, there were 215 males and 117 females; the age of transplantation was (12.2±3.9) years old; 37 cases were preschool (1-5 years old), and 295 cases were post-school age (6-18 years old). BKPyV load in 224 urine samples and 30 blood samples of children were detected. There were 9 cases of BKPyV-associated viruria and 3 cases of BKPyV associated viremia in pre-school children, 76 cases BKPyV associated viruria and 14 cases of BKPyV associated viremia in post-school children. Multivariate Cox regression analysis showed that higher body mass index (BMI) (HR=1.105, 95%CI: 1.020-1.197), antithyroglobulin (ATG) application (HR=2.196, 95%CI: 1.335-3.613), and higher tacrolimus concentration (HR=2.484, 95%CI: 1.298-4.753), higher natural killer (NK) lymphocyte count (HR=1.193, 95%CI: 1.009-1.411), higher CD14⁺⁺CD16^-cell count (HR=1.096, 95%CI: 1.024-1.173) were independent risk factors for BKPyV associated viruria in post-school children. Delayed graft function (DGF) (HR=4.993, 95%CI: 1.555-16.038), Acute rejection (AR) (HR=6.021, 95%CI: 1.930-18.787), higher CD14⁺⁺CD16^-cell count (HR=1.227, 95%CI: 1.081-1.392) were independent risk factors for BKPyV associated viremia in post-school children. The results of ROC curve analysis showed that combined BMI, immune induction drugs, tacrolimus concentration, NK cell count, and CD14⁺⁺CD16^-cell count predicted the occurrence of BKPyV associated viruria in post-school children after kidney transplantation at 0.5, 1, 2, and 5 years with area under curve (AUC) of 0.712 (95%CI: 0.626-0.798), 0.708 (95%CI: 0.612-0.804), 0.754 (95%CI: 0.668-0.840) and 0.767 (95%CI: 0.685-0.849). The sensitivity and specificity of the model were 64.9%, 61.4%, 61.6%, 55.8% and 70.9%, 72.4%, 76.0%, 84.0%, respectively. Combined with DGF, AR, and CD14⁺⁺CD16^-cell counts predicted the occurrence of BKPyV-associated viremia at 0.5, 1, 2, and 5 years after renal transplantation in post-school children with AUC of 0.791 (95%CI: 0.631-0.951), 0.744 (95%CI: 0.547-0.936), 0.786 (95%CI: 0.629-0.946) and 0.812 (95%CI: 0.672-0.948). The sensitivity and specificity of the model were 76.1%, 67.1%, 75.0%, 77.9% and 88.9%, 89.0%, 89.9%, 88.0%, respectively.

The postoperative CD14⁺⁺CD16^-cell level can be used as an independent predictor of BKPyV infection in post-school children after renal transplantation. Combined BMI, immune induction drugs, tacrolimus concentration, NK cell count, CD14⁺⁺CD16^-cell count and combined DGF, AR, CD14⁺⁺CD16^-cell count show good fitting effect in predicting the occurrence of BKPyV-associated viruria and viremia after transplantation in post-school children respectively.

To analyze the clinicopathological factors affecting long-term disease-free survival and the characteristics of local recurrence or distance metastasis of rectal cancer patients with complete pathological response after neoadjuvant chemoradiotherapy.

The clinicopathological data and follow-up information of patients with a complete pathological response of rectal cancer after neoadjuvant chemoradiotherapy in the Cancer Hospital of Chinese Academy of Medical Sciences from June 2004 to December 2019 were retrospectively collected. The clinicopathological factors affecting the long-term disease-free survival of patients were analyzed to build a prediction model of local recurrence and distant metastasis and to evaluate the benefits of postoperative chemotherapy.

The age of 108 patients was(56.3±11.6) years, of which 68 were males (63.0%); The median follow-up time was 79.9 (61.8, 112.6) months. There were 12 patients (11.1%) who had a local recurrence or distant metastasis. The 5-year disease-free survival rate was 91.1% with 9 patients who experienced recurrence. Multivariate Cox proportional hazards regression analysis showed that the maximum diameter of the residual tumor or scar (HR=8.41, 95%CI: 1.08-65.22, P=0.042) and the distance from the lower edge of the tumor to the anal margin before treatment (HR=4.54, 95%CI: 1.23-16.81, P=0.023) were independent risk factors affecting the prognosis. The prognosis of patients was stratified based on relevant factors. The 5-year cumulative disease-free survival rate of those patients receiving postoperative standardized chemotherapy was 92.0%, while for patients who did not receive or complete standardized chemotherapy, the 5-year cumulative disease-free survival rate was 82.3%.

The maximum diameter of the residual tumor or scar and the distance from the lower edge of the tumor to the anal margin before treatment were independent risk factors affecting the prognosis of patients with a complete pathological response. Patients with independent risk factors could benefit from the standardized postoperative chemotherapy.

To discuss the value of amplified in breast cancer 1(AIB1) and androgen receptor (AR) for the resistance of adjuvant tamoxifen in estradiol receptor (ER) positive breast cancer.

A total of 188 cases with breast cancer after receiving tamoxifen treatment in the Tianjin Medical University Cancer Institute and Hospital from June 2008 to July 2013 were enrolled in this study.Using immunohistochemical SP method to detect AIB1and AR expression in breast cancer tissue, analyzing the relationship of AIB1 and AR expression and the effect of tamoxifen.And verify the results of the experiment through the GEPIA database.

The response of tamoxifen was 80.3%. The response rate in AR positive group and AR negative group was 79.6% and 82.4%, with no significant difference (P=0.669). The response rate in AIB1 High expression group and AIB1 Low expression group was 68.4% and 93.3%, respectively, with a significant difference (P<0.001).The response rate in AR negative and AIB1 Low expression group, AR negative and AIB1 High expression group, AR positive and AIB1 Low expression group, AR positive and AIB1High expression group was 89.7%, 71.4%, 96.7%, 66.2%respectively, with a significant difference (P<0.001).

The expression level of AIB1 is correlated with the therapeutic effect of tamoxifen in breast cancer. Its high expression can cause tamoxifen resistance, while AR positive and High expression of AIB1 are more likely to cause tamoxifen resistance, and AIB1 can be used as an independent influencing factor for breast cancer tamoxifentreatment.

To analyze the clinical, endoscopic and pathological feature of gastric adenocarcinoma of fundic gland type (GA-FG) (18 cases) collected from Sir Run Run Shaw Hospital, affiliated with Zhejiang University School of Medicine and Taizhou Hospital of Zhejiang Province from January 2019 to July 2022. There were 18 cases of patient of GA-FG, including male 12 cases, female 6 cases, aged from 38 to 78 years old, with average age of 60.5 years old. Gastroscopy showed that bulging or flat lesions of gastric fundus were 0.2-5.5 cm in size, and the mucosal surface was smooth, redness or rough. Histologic examination showed that tumor cells were dominated by chief cells and scattered with a few oxyntic cells, formed a complex gland that anastomoses each other, and infiltrated to the submucosa. The results of immunohistochemistry showed that tumor cells were positive for the expression of mucin-6 (MUC6) and Pepsinogen 1, and partial expression of synaptophysin (Syn). GA-FG is a rare type of gastric adenocarcinoma with good differentiation, and currently only a few cases have been reported, and often easily been misdiagnosed or missed. Therefore, to master the characteristics of clinic and pathology is helpful to improve the ability of clinical pathologists in differential diagnosis.

To evaluate the learning curve of the "Double Grooves-Double Rings" (DGDR) technique of transurethral Thulium laser enucleation of the prostate (ThuLEP) for benign prostatic hyperplasia (BPH) by a single surgeon. From June 2021 to July 2022, 84 patients mean age (69.0±8.0) years,preoperative prostate volume (90.9±40.3)ml with BPH underwent ThuLEP in the Department of Urology, Peking University First Hospital.Performed by a single surgeon who had no experience of transurethral resection of prostate (TURP) and any laser surgeries. The case scatter plots with the best fitting line were drawn to analyze the learning curve. According to the date of the surgeries, the patients were equally divided into three learning stages (28 patients for each group). The T-PSA,prostate volume,operative time,enucleation time, enucleation efficiency,catheter indwelling time, hemoglobin drop and perioperative complications (including re-TURP, blood transfusion, stress incontinence≥3 months and urethral stricture) were compared among the groups. The learning curve was divided into three stages, and the cutting point was shown on the 14^th case. Except the prostate volume [stage1 (75.7±30.7) ml, stage2 (93.40±39.6)ml, stage3 (103.5±46.2) ml, P<0.05], there was no significant difference of the baseline data between three groups (P>0.05). Compared with those of stage 1(100.6±24.7) min,(0.55±0.22) g/min, a statistically significant improvement was observed in both of the operative time and the enucleation efficiency among stage 2[(84.5±36.6) min, (0.87±0.33) g/min and stage 3 (71.2±26.3) min, (1.27±0.45) g/min, P<0.05]. The learning curve of the DGDR technique for ThuLEP can be divided into three stages. A ThuLEP beginner can preliminarily master this technique after completing 14 cases.

This research aims to explore the clinical characteristics and treatment of transplant ureteral strictures. We retrospectively analyzed the clinical data from fifteen patients diagnosed with transplant ureteral stricture. Of the fifteen patients, five underwent regular ureteral stent or nephrostomy tube exchanges, while ten underwent open surgery. There were no significant differences in basic clinical characteristics between the two groups. The median follow-up time for regular ureteral stent or nephrostomy tube exchanges and open surgery group was 36.8 (11.8-56.0) months and 25.0 (4.5-31.2) months, respectively. Among patients who underwent regular exchanges, one required regular dialysis. Nine patients in the open surgery group had successful removal of the ureteral stent. Our findings suggest that regular ureteral stent or nephrostomy tube exchanges, as well as open surgery, are effective treatment options for transplant ureteral strictures.

Antibody-mediated rejection (AMR) is a key factor affecting the long-term survival of renal allografts. Donor-specific antibody (DSA) is the etiology of AMR. So it is very important to accurately detect DSA. The single antigen bead (SAB) method, which is widely used in clinical practice, is prone to miss DSA detection and underestimate its mean fluorescence intensity (MFI). In this paper, the probability of missed detection of two SAB reagents was calculated by comparing common HLA alleles in China population, and the in vitro effect of antibody cross reaction on MFI value of DSA was revealed. The authors emphasized the clinical significance of the above two problems, tried to manage them by using functional epitope (eplet) analysis and give some clinical examples. Finally, the limitations of this correction method were analyzed.

The Dicer enzyme encoded by the DICER1 gene is a member of the ribonuclease (RNase) III family and plays a key role in post-transcriptional gene silencing. DICER1 gene mutation can lead to DICER1 syndrome, which makes the body susceptible to various benign and malignant tumors, mainly multinodular goiter, pleuropulmonary blastoma, cystic nephroma, ovarian sertoli-mesenchymal cell tumor, ciliary body medullary epithelioma, cervical embryonic rhabdomyosarcoma, differentiated thyroid cancer, etc. A variety of thyroid diseases are involved, including thyroid adenoma, papillary thyroid carcinoma, follicular thyroid carcinoma, poorly differentiated thyroid carcinoma, and thyroblastoma. By studying the characteristics of thyroid disorders in DICER1 syndrome. In order to clarify the potential harm of thyroid disease in DICER1 syndrome, and to assist in disease diagnosis and disease management, this paper reviews the clinical manifestations, diagnosis, monitoring and the relationship between thyroid disease in DICER1 syndrome.

About 30% of patients with endometrial cancer have DNA mismatch repair pathway defects. Such patients are significantly related to multiple adverse prognostic indicators (such as lymphatic vascular invasion, deep muscle invasion, etc.), and are more likely to need adjuvant therapy after surgery. Clinically, according to its pathogenesis, it can be divided into Lynch syndrome cases, Lynch-like syndrome cases and MutL homolog 1 (MLH1) promoter hypermethylation cases. Cases with Lynch syndrome and Lynch-like syndrome often have higher expression of programmed cell death ligand-1 (PD-L1) and respond well to immunotherapy, while cases with hypermethylated MLH1 promoter benefit from immunotherapy is limited. This difference may be related to the intensity of microsatellite instability and the resulting tumor mutation burden. This article reviews the clinicopathological features and treatment progress of patients with mismatch repair pathway-deficient endometrial cancer, in order to explore individualized treatment options for this type of patients.