Objective:To classify the symptom characteristics of young and middle-aged peritoneal dialysis patients and to explore the differences of demographic functional status and social function of patients with different symptom categories.Methods:A total of 179 peritoneal dialysis patients from 3 peritoneal dialysis centers in Shanghai were investigated from December 2019 to August 2020 by General Information Questionnaire, Peritoneal Dialysis Symptom Distress Scale. Latent class analysis was used to classify young and middle-aged peritoneal dialysis patients according to symptom characteristics. Multiple Logistic regression was used to explore the differences of demographic and disease characteristics of different categories of patients.Results:Peritoneal dialysis patients could be divided into three potential categories according to symptom characteristics ( P<0.05). According to the conditional probability of each category, they were named "low symptom group" (111 cases,62.0%), "high psychological-moderate physical symptom group" (22 cases, 12.3%), "high symptom group" (46 cases,25.7%). There were differences in working status ( OR=0.029, P<0.01), education level ( OR=152.799, P<0.01), duration ( OR=81.307, P<0.05), diabetic nephropathy ( OR=80.619, P<0.01) and CCI score ( OR=91.188, P<0.01) distribution among different potential categories of young and middle-aged peritoneal dialysis patients. Conclusions:There are three types of potential symptoms in young and middle-aged patients undergoing peritoneal dialysis. In clinical practice, medical staff should focus on the psychological status of young and middle-aged patients with low educational background and early stage of dialysis, and encourage them to return to work; at the same time, they should regularly evaluate the symptom burden of patients with diabetic nephropathy and high complication index peritoneal dialysis patients, in order to provide targeted intervention measures to prevent the progression of the disease.

OBJECTIVETo illustrate the significance of expression of phosphatase and tensin homologue derived from chromosome ten (PTEN) encoding product in normal mucosa, intestinal metaplasia (IM), dysplasia and carcinoma of the stomach, and to evaluate its clinical implication in tumorigenesis and progression of gastric carcinoma.

METHODSFormalin-fixed and paraffin-embedded tissues from 184 cases of gastric carcinoma, its adjacent normal mucosa, IM and dysplasia were evaluated for the expression of PTEN by SABC immunohistochemistry. PTEN expression was assessed as to tumor stage, lymph node metastasis, Lauren's classification and WHO histological classification of gastric carcinoma. Expression of VEGF protein was also studied in 60 cases of gastric carcinoma, with its correlation with PTEN concerned.

RESULTSThe positive rates of PTEN protein were 100% (102/102), 98.5% (65/66), 66.7% (4/6) and 47.8% (88/184) in normal mucosa, IM, dysplasia and carcinoma of stomach, respectively. The positive rates in the last two groups were lower than the first two (P < 0.01). PTEN was less expressed in advanced gastric carcinoma than in early ones (42.9% vs 67.6%, P < 0.01). The positive rate of PTEN protein was lower in gastric carcinoma with lymph node metastasis than without (40.3% vs 63.3%, P < 0.01). PTEN was less expressed in diffuse-type gastric carcinoma than in intestinal-type (41.5% vs 57.8%, P < 0.05). Signet ring cell carcinoma expressed PTEN stood the lowest (25.0%, 7/28), which was less than well and moderately differentiated ones (61.8%, 21/34) (P < 0.01). Expression of PTEN was inversely correlated with expression of VEGF though without any significance (P > 0.05).

CONCLUSIONLoss or reduced expression of PTEN protein is common in carcinogenesis and progression of gastric cancer. Altered expression of PTEN may contribute to carcinogenesis and progression of gastric cancer by increasing angiogenesis, cellular adhesion and mobility and so on. PTEN may be an objective marker for pathologically biological behavior of gastric carcinoma.

Adult ; Aged ; Carcinogenicity Tests ; Cell Adhesion ; Cell Movement ; Disease Progression ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Neovascularization, Pathologic ; PTEN Phosphohydrolase ; Phosphoric Monoester Hydrolases ; biosynthesis ; genetics ; Stomach Neoplasms ; metabolism ; pathology ; Tumor Suppressor Proteins ; biosynthesis ; genetics

BACKGROUNDOff-label application of drug-eluting stents (DES) during percutaneous coronary intervention (PCI) was not uncommon in daily practice, however DES in treating Chinese patients with complex lesion subset was under-investigated. The primary objective of the FIREMAN registry was to evaluate the long term efficacy and safety of the Firebird sirolimus-eluting stent (SES) in treating patients with complex coronary lesions. Here we report the mid-term of one-year clinical outcomes and eight-month angiographic follow-up results of FIREMAN registry.

METHODSThe FIREMAN registry was a prospective multi-center registry, which included 1029 consecutive patients undergoing PCI with Firebird SES implantation between September 2006 and July 2007 in 45 centers in China. The clinical follow-up was designed to be performed at 1, 6, 12, 18, 24, 30 and 36 months post index procedure, and non-mandatory angiographic follow-up at 8 months was planned. One hundred percent site monitoring was conducted.

RESULTSLong lesions (59.2%), multi-vessel disease (50.4%), and small vessel disease (31.6%) were mostly found in angiography. Major adverse cardiac events (MACE) occurred in 51 (5.1%) patients at 1 year clinical follow-up, including cardiac mortality in 6 (0.6%), non-fatal myocardial infarction in 11 (1.1%), and target lesion revascularization in 36 (3.5%) of the patients. Definite and probable stent thrombosis (ST) by Academic Research Consortium (ARC) definition occurred in 12 (1.36%) patients at one-year clinical follow-up. The 8-month binary restenosis rate was 5.7% in-segment and 4.3% in-stent, respectively. Late lumen loss was (0.21 ± 0.40) mm in-segment and (0.23 ± 0.36) mm in-stent, respectively. Furthermore, Cox regression analysis revealed that diabetes, small vessel diameter, and chronic total occlusion were independent predictors of ST.

CONCLUSIONSThe results showed that the Firebird SES was effective and safe in treating Chinese patients with complex coronary lesions and occurrence of ST rate at one-year clinical follow-up was acceptable, however further long-term follow-up was still necessary. (NCT00552656)

Aged ; Angioplasty, Balloon, Coronary ; adverse effects ; methods ; Asian Continental Ancestry Group ; Coronary Angiography ; Coronary Disease ; diagnostic imaging ; therapy ; Drug-Eluting Stents ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Sirolimus ; therapeutic use ; Treatment Outcome

Objective To assess the prognosis and effect on renal function of pediatric urolithiasis caused by melamine-contaminated milk powder (PUMMP) in a long-term follow-up.Methods One hundred and two of 8335 children (≤ 6-year-old) with history of consuming melamine-contaminated milk powder screened in our hospital were followed up for eighteen months after diagnosis. Urinary system ultrasonography, urinalysis, urinary microprotein profiles [microalbumin (ALBU), immunoglobulin G (IgG), and N-acetyl-β-D-glucosidase (NAG)], urinary melamine and cyanuric acid were examined in the first visit and at the end of follow-up. Results Follow-up was completed in 91 children and the stone was excreted in 82 children (90.1%).Stones less than 5 mm in diameter were most vulnerable to discharge, and stones larger than 10 mm could not be expelled without interventions. At the end of follow-up, no melamine or cyanuric acid was found in the urine samples of 74 patients. Urinalysis showed that incidences of proteinuria, microscopic hematuria and leukocyturia were 0%, 5.1% and 2.0%, which were significant different from those in the first visit (Pproteinutria=0.123, Phemnatuna=0.038 and Pleukocyhuris=0.005).Urinary microprotein profiles revealed that some children whose urinalysis was normal still presented glomerular and renal tubular injury and the abnormal rates were 8.8% and 12.1%respectively. The glomerular injury was mainly related to persistent stone, male and younger.Conclusions 90.1% of children with PUMMP passes urinary stones at the end of follow-up.Stone size is the major risk factor of discharge. No melamine or cyanuric acid is found in the urine of children. After eighteen months, glomerular and renal tubular injury is still found in some patients. Further follow-up is necessary.

This study investigated the drug delivery performance of oral co-loaded puerarin(PUE) and daidzein(DAZ) mixed micelles(PUE/DAZ-FS/PMMs) from the perspectives of pharmacokinetics, pharmacodynamics, and tissue distribution. The changes in PUE plasma concentration in rats were evaluated based on PUE suspension, single drug-loaded micelles(PUE-FS/PMMs), and co-loaded micelles(PUE/DAZ-FS/PMMs). Spontaneously hypertensive rats(SHR) were used to monitor systolic blood pressure, diastolic blood pressure, and mean arterial pressure for 10 weeks after administration by tail volume manometry. The content of PUE in the heart, liver, spleen, lung, kidney, brain, and testes was determined using LC-MS/MS. The results showed that compared with PUE suspension and PUE-FS/PMMs, PUE/DAZ-FS/PMMs significantly increased C_(max) in rats(P<0.01) and had a relative bioavailability of 122%. The C_(max), AUC_(0-t), AUC_(0-∞), t_(1/2), and MRT of PUE/DAZ-FS/PMMs were 1.77, 1.22, 1.22, 1.17, and 1.13 times higher than those of PUE suspension, and 1.76, 1.16, 1.08, 0.84, and 0.78 times higher than those of PUE-FS/PMMs, respectively. Compared with the model control group, PUE/DAZ-FS/PMMs significantly reduced systolic blood pressure, diastolic blood pressure, and mean arterial pressure in SHR rats(P<0.05). The antihypertensive effect of PUE/DAZ-FS/PMMs was greater than that of PUE suspension, and even greater than that of PUE-FS/PMMs at high doses. Additionally, the distribution of PMMs in various tissues showed dose dependency. The distribution of PMMs in the kidney and liver, which are metabolically related tissues, was lower than that in the suspension group, while the distribution in the brain was higher than that in the conventional dose group. In conclusion, PUE/DAZ-FS/PMMs not only improved the bioavailability of PUE and synergistically enhanced its therapeutic effect but also prolonged the elimination of the drug to some extent. Furthermore, the micelles facilitated drug penetration through the blood-brain barrier. This study provides a foundation for the development of co-loaded mixed micelles containing homologous components.
Rats ; Animals ; Micelles ; Tissue Distribution ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Rats, Inbred SHR ; Isoflavones/pharmacology*

Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis, followed by glycometabolic disorder, lipid deposition, increased inflammation, and markedly promotes NASH development. Conversely, transgenic mice with Usp13 overexpression, lentivirus (LV)- or adeno-associated virus (AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent. Mechanistically, in response to metabolic stresses, USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N (UBC13), a ubiquitin E2 conjugating enzyme, and thus prevents its activation of downstream cascade pathway. USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.