Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Heterotypic cell-in-cell structures (heCICs) are closely related to tumor development and progression, and have become a new frontier in life science research. Ras-related C3 botulinum toxin substrate 1 (Rac1) belongs to the classic Rho GTPase, which plays a key role in regulating the cytoskeleton and cell movement. To investigate the role and mechanism of Rac1 in the formation of heCICs, tumor cells and immune killer cells were labeled with cell-tracker, respectively, to establish the heCICs model. Upon treatment with the Rac1 inhibitor NSC23766, the formation of heCICs between tumor and immune cells was significantly reduced. The plasmid pQCXIP-Rac1-EGFP constructed by gene cloning was packaged into pseudoviruses that subsequently infect tumor cells to make cell lines stably expressing Rac1. As a result, the formation of heCICs was significantly increased upon Rac1 overexpression. These results demonstrated a promotive role of Rac1 in heCICs formation, which may facilitate treating cell-in-cell related diseases, such as tumors, by targeting Rac1.

Objective:To summarize the surgical technique and clinical experience of robotic-assisted laparoscopic radical nephrectomy (RN) + venous tumor thrombectomy (VTTE) approach for renal tumor with Mayo grade 0-Ⅲ tumor thrombus, and to discuss its safety and efficacy.Methods:A retrospective analysis of the clinical data of 26 patients with renal tumor associated with Mayo 0-Ⅲ thrombus admitted to Peking University Third Hospital from October 2020 to September 2021. There were 17 male cases and 9 female cases. The mean age was (56.9±13.9) years. The mean body mass index (BMI) was (25.8±3.5) kg/m 2. The renal tumors were located on the left side in 12 cases and on the right side in 14 cases, with a mean tumor diameter of (7.8±2.9) cm. The tumors were graded by Mayo: Mayo 0 in 10 cases, Mayo Ⅰ in 3 cases, Mayo Ⅱ in 11 cases and Mayo Ⅲ in 2 cases. The American Society of Anesthesiology (ASA) graded 23 cases as grade 2 and 3 cases as grade 3. All 26 patients were treated by robotic-assisted laparoscopic approach with RN+ VTTE. Mayo 0 tumor thrombus was treated in the same way as radical nephrectomy. For Mayo Ⅰ tumor thrombus, the lateral wall of the IVC at the inferior vena cava (IVC) where the renal vein joins was clamped to partially block the IVC flow and then the thrombus was removed. For Mayo Ⅱ tumor thrombus, after blocking the flow in the IVC with three blocking bands, the wall of the IVC was dissected and the thrombus was removed. For Mayo Ⅲ tumor thrombus: cut the short hepatic vein, free the liver, expose the posterior IVC and follow the same procedure as for Mayo Ⅱ tumor thrombus. Results:All 26 patients in this group were successfully operated on, 1 of which was converted to open surgery. The median operative time was 148.5 (77.0-399.0) min, and the median intraoperative estimated bleeding volume was 300 (10-2000) ml. Postoperative pathological diagnosis: 18 cases of renal clear cell carcinoma, 2 cases of papillary renal cell carcinoma type Ⅱ, 2 cases of TEF gene fusion-related renal carcinoma, 1 case of unclassified renal cell carcinoma, 1 case of uroepithelial carcinoma and 2 cases of AML. In 2 of the 26 cases, segmental resection of the IVC was performed because the right renal VTT had extensively invaded the wall of the IVC. Due to the residual wall thrombus at the head of the tumour thrombus, 1 case underwent inferior vena cava dissection and the inferior vena cava was cut obliquely to preserve the left renal venous return. 6 patients underwent intraoperative lymph node dissection of the hilum, three of which had pathology suggestive of lymph node metastasis. 1 patient underwent adrenalectomy for tumor invasion of the ipsilateral adrenal gland. The median postoperative hospital stay was 7.2(4.0-22.0)d. According to the modified Clavien classification, there were 18 grade Ⅰ and 8 grade Ⅱ postoperative complications. 26 patients were followed up for 1-11 months, with a median follow-up time of 5.5 months. 3 cases developed distant metastases, including 1 case with tumour-specific death due to multiple metastases in the liver and retroperitoneum at 4 months of follow-up.Conclusions:Robotic-assisted laparoscopic RN+ VTTE is a safe and effective procedure for the treatment of renal tumours with Mayo 0 to Ⅲ tumour thrombus, with the advantages of delicate operation, minimal trauma and low incidence of serious postoperative complications.

Objective:To assess the efficacy and safety of 100 units of botulinum toxin A (BTX-A) intradetrusor injection in patients with overactive bladder.Methods:From April 2016 to December 2018, 17 tertiary hospitals were selected to participate in this prospective, multicenter, randomized, double-blind, placebo-controlled study. Two phases of study were conducted: the primary phase and the extended phase. This study enrolled patients aged 18 to 75 years who had been inadequately managed by anticholinergic therapy (insufficient efficacy or intolerable side effects) and had spontaneous voiding with overactive bladder. Exclusion criteria included patients with severe cardiac, renal and hepatic disorders, patients with previous botulinum toxin treatment for 6 months or allergic to BTX-A, patients with urinary tract infections, patients with urinary stones, urinary tract tumors, diabetes mellitus, and bleeding tendency. Eligible patients were randomly assigned to BTX-A group and placebo control group in a ratio of 2∶1. Two groups of patients received 20 intradetrusor injections of BTX-A 100U or placebo at the depth of the submucosal muscle layer respectively under cystoscope, including 5 injections at the base of the bladder, 3 injections to the bladder triangle, 5 injections each to the left and right walls and 2 injections to the top, sparing the bladder neck. As a placebo control group, patients received same volume of placebo containing no BTX-A and only adjuvant freeze-dried preparations for injection with the same method. A combination of gelatin, sucrose, and dextran served as adjuvants. Average micturition times per 24 hours, urinary incontinence (UI) episodes per day, average micturition volume per day, OAB symptom score(OABSS), and quality of life (QOL) score were recorded at baseline and the 2nd, 6th and 12th week after treatment. The primary efficacy endpoint was the change from baseline in the average micturition times per 24 hours at the 6th week after treatment. The secondary efficacy endpoints included the change from baseline in the average micturition times per 24 hours at 2nd and 12th week, as well as the change from baseline in the OABSS, QOL score, average frequency of urgency and UI episodes per day, urgency score, average micturition volume per day at 2nd, 6th and 12th week after treatment. Patients were followed for 12 weeks to assess adverse events (AEs). After assessed at week 12, if the micturition times has decreased less than 50% compared to baseline and the patient is willing to receive retreatment, then patients could enter the extended trial phase. In that phase, patients in both groups were injected with 100 units BTX-A from 12th week onwards and then followed up the same indicators for 12 weeks.Results:216 patients were enrolled in this trial (144 cases in the BTX-A group and 72 cases in the placebo control group). Baseline characteristics such as age (47.75±14.20 in the BTX-A group and 46.39±15.55 in the control group), sex (25 male/117 female in the BTX-A group and 10/61 in the control group), and disease duration (0.51 years in the BTX-A group and 0.60 years in the control group) were balanced between the two groups( P>0.05). A marked reduction from baseline in average micturition times per 24 hours was observed in all treatment groups at the 6th week and the reduction of the two groups was statistically different ( P<0.001 and P=0.008 respectively). Compared with the baseline, the average micturition times per 24 hours at the 6th week decreased from baseline by 2.40(0.70, 4.60)times for the BTX-A group and 0.70(-1.00, 3.30) times for the placebo control group respectively, and the difference between the two groups was considered to be statistically significant ( P=0.003). The change rates of average micturition times per 24 hours from baseline at the 6th week of the two groups were (16±22)% and (8±25)% respectively, and the difference between the two groups was statistically significant ( P=0.014). Compared with the baseline, the average micturition times per 24 hours at 2nd and 12th week decreased by 2.00(0.00, 4.00)and 3.30(0.60, 5.03)for the BTX-A group, 1.00(-1.00, 3.00)and 1.70(-1.45, 3.85)for the placebo control group respectively. The difference between two groups was considered to be statistically significant ( P=0.038 and P=0.012); the changes of average urgency times per day for the BTX-A group and the control group at the 2nd, 6th and 12th week were 2.00(0.00, 4.30)and 2.40(0.30, 5.00), 3.00(0.30, 5.70)and 0.70(-1.30, 2.70), 0.70(-1.30, 3.00) and 1.35(-1.15, 3.50), respectively. There were significant differences between two groups at the 2nd, 6th and 12th week, ( P=0.010, P=0.003 and P=0.025, respectively). The OABSS of the BTX-A group and the control group at the 6th week decreased by 1.00(0.00, 4.00)and 0.50(-1.00, 2.00) compared with the baseline, and the difference between the two groups was statistically significant ( P=0.003). 47 cases of BTX-A group and 34 cases of placebo control group entered the extended trial phase, and 40 and 28 cases completed the extended trial phase, respectively. The average micturition volume per 24 hours changed by -16.60(-41.60, -0.60)ml and -6.40(-22.40, 13.30)ml, (-35.67±54.41)ml and(-1.76±48.69)ml, (-36.14±41.51)ml and (-9.28±44.59)ml, (-35.85±43.35)ml and(-10.41±40.29)ml for two groups at the 12th, 14th, 18th and 24th week, and the difference between two groups was statistically significant at each follow-up time ( P=0.01, 0.006, 0.012 and 0.016, respectively). There was no significant difference in other parameters( P>0.05). However, adverse reactions after intradetrusor injection included increased residual urine volume (27 in the BTX-A group and 3 in the control group), dysuria (21 in the BTX-A group and 6 in the control group), urinary infection (19 in the BTX-A group and 6 in the control group), bladder neck obstruction (3 in the BTX-A group and 0 in the control group), hematuria (3 in the BTX-A group and 1 in the control group), elevated alanine aminotransferase (3 in the BTX-A group and 0 in the control group), etc. During the follow-up period, there was no significant difference in the other adverse events between two groups except the increase of residual urine volume( P<0.05). In the primary trial phase, among the 27 cases with increased residual urine volume in BTA group, only 1 case (3.70%) with PVR more than 300 ml; the PVR of 3 patients in the placebo group was less than 100 ml. The increase of residual urine volume caused by the injection could be improved or disappeared with the passage of time. Conclusions:Intradetrusor injection of Chinese BTX-A improved the average micturition times per 24 hours, the average daily urgent micturition times, OABSS, and average micturition volume per time, and reduced the adverse effects in patients with overactive bladder.Chinese BTX-A at dose of 100U demonstrated durable efficacy and safety in the management of overactive bladder.

Objective: To explore the relationship between weight change and the changes in blood pressure, blood glucose and blood lipid profiles in middle-aged and elderly Chinese people. Methods: All participants were from the Dongfeng-Tongji cohort study. The study included 16 606 middle-aged and elderly Chinese people with complete information in the baseline survey in 2008 and the first follow-up survey in 2013. We collected the data on demographic characteristics, lifestyle, history of diseases and medication, and the results of medical health examinations, including height, weight, blood pressure, fasting blood glucose and lipid profiles. We divided the weight change into five groups, moderate or above weight loss (<-8.0%), slight weight loss (-8.0%, -3.1%), weight maintenance (-3.0%, 3.0%), slight weight increased (3.1%, 8.0%), and moderate or above weight increased (>8.0%). Generalized linear regression model was used to analyze the relationship between weight change and the changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride (TG). Subgroup analyses were used to explore the influences of gender, age and baseline BMI level on the relationship between weight change and the above-mentioned metabolic indicators. Results: The average age of participants in baseline survey was (62.19±7.28) years with a range of 45 to 89 years. During the five-year period, there were 18.86% (2 633), 28.03% (4 655), 35.87% (5 956), 13.96% (2 319), 6.28% (1 043) people with moderate or above weight loss, slight weight loss, weight maintenance, slight weight increased, and moderate or above weight increased, respectively. Regression analyses showed that body weight change were positively correlated with changes in SBP, DBP, FBG, TC, LDL-C and TG, and negatively correlated with change in HDL-C (all linear trend P values were<0.05); As every 10% of weight changed, the β (95%CI) of changes in SBP (mmHg) (1 mmHg=0.133 kPa), DBP (mmHg), FBG (mmol/L), TC (mmol/L), LDL-C (mmol/L), HDL-C (mmol/L) and TG (mmol/L) were 4.94 (4.32, 5.55), 2.50 (2.11, 2.88), 0.05 (0.02, 0.08), 0.13 (0.11, 0.16), 0.14 (0.12, 0.16), -0.05 (-0.07, -0.04) and 0.16 (0.14, 0.18), respectively. Furthermore, subgroup analyses showed that weight change can lead to greater changes in blood pressure in older and overweight or obesity elderly people (all P for interaction<0.05). Conclusion Weight loss was beneficial for middle-aged and elderly people to improve the blood pressure, blood glucose and blood lipid profiles, regardless of the weight at the baseline, while weight gain was not.

OBJECTIVETo clone human CD45 gene PTPRC and establish Hela cells overexpressing recombinant human CD45 protein.

METHODSThe intact cDNA encoding human CD45 amplified using RT-PCR from the total RNA extracted from peripheral blood mononuclear cells (PBMCs) of a healthy donor was cloned into pMD-18T vector. The CD45 cDNA fragment amplified from the pMD-18T-CD45 by PCR was inserted to the coding region of the PcDNA3.1-3xflag vector, and the resultant recombinant expression vector PcDNA3.1-3xflag-CD45 was transfected into Hela cells. The expression of CD45 in Hela cells was detected by flow cytometry and Western blotting, and the phosphastase activity of CD45 was quantified using an alkaline phosphatase assay kit.

RESULTSThe cDNA fragment of about 3 900 bp was amplified from human PBMCs and cloned into pMD-18T vector. The recombinant expression vector PcDNA3.1-3xflag-CD45 was constructed, whose restriction maps and sequence were consistent with those expected. The expression of CD45 in transfected Hela cells was detected by flow cytometry and Western blotting, and the expressed recombinant CD45 protein in Hela cells showed a phosphastase activity.

CONCLUSIONThe cDNA of human CD45 was successfully cloned and effectively expressed in Hela cells, which provides a basis for further exploration of the functions of CD45.

Blotting, Western ; Cloning, Molecular ; DNA, Complementary ; Genetic Vectors ; HeLa Cells ; Humans ; Leukocyte Common Antigens ; genetics ; Leukocytes, Mononuclear ; Polymerase Chain Reaction ; Recombinant Proteins ; genetics ; Transfection

OBJECTIVETo investigate the diagnosis, treatment and surgical outcomes of ureteropelvic junction obstruction (UPJO) caused by renal crossing vessels.

METHODSThe case records of 24 patients discharged from Peking University Third Hospital between June 2001 and September 2011 with the diagnosis of UPJO caused by renal crossing vessels were reviewed .Of the 24 patients, 17 were male and 7 were female patients. The mean age was 28 years (range, 2-63 years). The mean disease duration was 22.3 months (range, 7 days to 180 months). Of which, 4 patients underwent open surgery, and the other 20 patients were treated with laparoscopic surgery. Surgical approach was decided by operative conditions: adhesion release technique, dismembered pyeloplasty or Y-V anastomosisor, with or without cut off the crossing vessels. The kind of crossing vessels was recorded, and the effect of surgery was evaluated by follow-up.

RESULTSFifteen cases were caused by oppressed renal crossing artery, 8 cases by renal crossing vein, and 1 case by 2 renal crossing arteries and 1 renal crossing vein. Among them, 11 cases were followed up successfully. Average follow-up time was 48.2 months (range, 13-120 months). Eight cases (8/11) were relieved, and 1 case (1/11) had no obvious improvement, another 2 cases (2/11) were aggravating. Among those 6 cases underwent adhesion release technique, 3 cases were relieved, 1 case had no obvious improvement, and 2 cases were aggravating. Five cases who underwent dismembered pyeloplasty was relieved significantly.

CONCLUSIONSRenal crossing artery is one of the main causes of UPJO, the crossing artery should be retained as far as possible. Crossing vessel oppression is not the only pathological cause of UPJO, so the treatment of UPJ constriction is also very important. Dismembered pyeloplasty seems to be the most efficacies treatment procedure for UPJO caused by repressed vessels, and the remission rate of adhesion release technique seems limited.

Adolescent ; Adult ; Arteries ; surgery ; Child ; Child, Preschool ; Female ; Humans ; Hydronephrosis ; congenital ; etiology ; surgery ; Kidney ; blood supply ; Kidney Pelvis ; blood supply ; Laparoscopy ; methods ; Male ; Middle Aged ; Multicystic Dysplastic Kidney ; etiology ; surgery ; Renal Artery ; abnormalities ; Treatment Outcome ; Ureteral Obstruction ; etiology ; surgery ; Young Adult

Objective To report a retroperitoneal laparoscopic surgery for ureteropelvic junction obstruction (UPJO) by double renal veins.Methods A 28-year-old male patient with left low back pain for 6 months was diagnosed as left hydronephrosis and UPJO.A ureteral stent had been placed 3 months before and failed to improve hydronephrosis,so the ureteral stent was pulled out.CT scan showed that left UPJ went through the two renal veins,suggesting UPJO.Nephrogram showed that left GFR and right GFR were 35 ml/min and 34 ml/min,respectively.These results indicated mechanical obstruction of left upper urinary tract.The patient underwent retroperitoneal laparoscopic Anderson-Hynes dismembered pyeloplasty.Results The surgical procedure was successful.Two left renal veins were found,and the ventral one was in front of ureter,compressing the ureter.An aberrant renal artery went into left kidney with the ureter.0.5 cm stenosis of ureteropelvic junction was excised,and pyeloplasty was performed.A ureteral stent was placed into the ureter,then the pelvis and the ureter were sew up in front of the ventral renal vein.The surgical time was 240 min,and blood loss was 50 ml.Postoperative hospital stay time was 4 d.During 4 months' follow up,hydronephrosis was attenuated significantly.Conclusion Retroperitoneal laparoscopic surgery for UPJO with aberrant two renal vein might be a minimally-invasive and effective procedure.

Objective To review the clinical characteristics of paraganglioma of the urinary bladder with 5 cases reprt.Methods The clinical data of 5 patients (2 males and 3 females,age 23-68 years)with paraganglioma of the urinary bladder were reported.Two cases were diagnosed by ultrasonography during health examination,1 case was found by hematuria,1 had difficulty of voiding,and 1 presented with palpitation,chest discomfort while urination.Two cases were clinical diagnosed as bladder paraganglioma,1case urachal carcinoma,and 2 cases bladder tumor.Cystoscopy showed a protruding tumor within the bladder or bladder had compressed changes.One case of tumor located in the triangle,1 in the posterior wall,1in the top,2 in the anterior wall.Three cases of biopsy were negative.Three cases of preoperative endocrine examinations showed norepinephrine significantly higher.Results Laparoscopic partial cystectomy was performed in 3 cases,open partial cystectomy in 1 case,and transurethral resection of bladder tumor (TURBT) in 1 case.One case had the complication of stress cardiomyopathy during TURBT,3 cases found intraoperative hypertensive crisis.The bleeding volume was 20-800 ml (average 126 ml),and I case received blood transfusion.During the follow-up period for 3-48 months,the blood pressure was normal,and no recurrence was found.Conclusions Bladder paraganglioma is uncommon and easily misdiagnosed.For the patients with bladder tumor,accompanied by changes in blood pressure,palpitations during urination should be highly suspicious of bladder paraganglioma.Partial cystectomy is the main treatment method.

Objective　To evaluate the diagnosis and surgical treatment of hilar cholangiocarcinoma(H-CC). Methods　Retrospective analysis was made on the clinical feature, surgical treatment and the effect on 73 patients with H-CC. Results　Diagnosis was made in all of the patients preoperatively and the correct diagnostic rate of BUS was 69.9%. In the treatment, radical resection was performed on 15 patients with good results in a short-term period. Of the 43 patients who underwent biliary tract internal drainage or exterrnal drainage, 37 patients had good results in a short-term period, while 6 died after operation. Laparotomy or hepatic artery cannulization with chemotherapy was performed on 15 patients and no change occurred in a short-term period after operation. In 15 cases subjected to radical resection, 11 cases were followed up. The 1,3-year survival rates was 90.9%, 20.0% respectively, but none of the patients survived for over 5 years. In patients undergoing other operations, none survived more than 9 months. Conclusions　It's still difficult to mak early diagnosis of H-CC, which mainly depends on imaging technics. The BUS should be choiced first. Radical resection rate is still low nowadays. The lobus quadratus resection is helpful to select the operation.