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There is currently a huge worldwide demand for donor kidneys for organ transplantation. Consequently, numerous marginal donor kidneys, such as kidneys with microthrombi, are used to save patients' lives. While some studies have shown an association between the presence of microthrombi in donor kidneys and an increased risk for delayed graft function (DGF) (McCall et al., 2003; Gao et al., 2019), other studies have demonstrated that microthrombi negatively impact the rate of DGF (Batra et al., 2016; Hansen et al., 2018), but not graft survival rate (McCall et al., 2003; Batra et al., 2016; Gao et al., 2019). In contrast, Hansen et al. (2018) concluded that fibrin thrombi were not only associated with reduced graft function six months post-transplantation but also with increased graft loss within the first year of transplantation. On the other hand, Batra et al. (2016) found no significant differences in the DGF rate or one-year graft function between recipients in diffuse and focal microthrombi groups. To date, however, the overall influence of donor kidney microthrombi and the degree of influence on prognosis remain controversial, necessitating further research.
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Humans , Thrombotic Microangiopathies , Transplantation, Homologous , Tissue Donors , Kidney , AllograftsABSTRACT
In recent years， with the increasing understanding of the genetic mechanisms of hypertrophic cardiomyopathy， novel molecular-targeted drugs Mavacamten and Aficamten are two cardiac myosin inhibitors currently approved by the FDA for the treatment of hypertrophic obstructive cardiomyopathy. Both of them have a similar mechanism of action and can selectively bind to different variable sites of cardiac myosin to inhibit cardiac myosin， thus reducing myocardial hypercontractility. Relevant clinical studies have also shown that both drugs can reduce patients’ left ventricular outflow tract pressure gradient， the levels of N-terminal pro-B-type natriuretic peptide and cardiac troponin I as cardiac markers， and improve New York Heart Association （NYHA） cardiac function class. They are safe， have mild adverse reactions， and can be tolerated by patients. Compared to Mavacamten， Aficamten， as a structurally optimized product， has a shorter half-life and fewer drug-drug interactions， which is more conducive to drug- targeted dose titration.
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Objective:By retrospectively analyzing 6 cases of IgG4-related membranous nephropathy (IgG4-MN), combined with literature review, to explore the clinical and renal pathological characteristics of the disease, and improve clinicians' understanding of the disease.Methods:The data of six patients with biopsy-proven IgG4-MN in the nephrology center of our hospital during April 2017 to January 2021 were collected. At the same time, we reviewed the literature systematically and summarized the clinicopathological characteristics.Results:Six male patients with the age ranged fom 55 to 75 years old were described. Urine protein level was (3.1±2.1) g/24 h, 3 cases (50%) showed nephrotic syndrome and 4 cases (67%) had elevated serum creatinine. The median creatinine level was (103±24) μmol/L. Six cases (100%) had elevated serum immunoglobulin (Ig)E level, and 4 cases (67%) had elevated IgG4. M-type phospholipase A2 receptor (PLA2R) was positive in 1 case (17%) and tubulointerstitial nephritis (TIN) was present in 6 cases. The review of the literature suggested that a total of 49 cases with IgG4-MN were reported, including 6 cases in this report. There were 40 males (40/46, 87%), with a age range of (61±12) years old, 32 cases (32/49, 65%) showed nephrotic syndrome range proteinuria, and the proportion of serum IgG and IgG4 increase was 61%(20/33) and 88% (36/41), respectively, 13 cases (13/15, 87%) had elevated serum IgE level, 47% (14/30) had low-complement C3 and 44%(12/27) had low-complement C4 level. The main organs involved were pancreas (15/37) and lymph nodes (16/37). Renal pathology showed TIN in 74%(36/49). Electron dense deposition was mainly subepithelial deposits. 7%(2/28) were positive for anti-PLA2R antibody in serum, 17%(3/18) were positive for PLA2R in kidney tissue, 6%(1/18) were suspected positive for PLA2R in kidney tissue, and 8%(1/12) were dual positive in blood and kidney tissue.Conclusion:IgG4-MN usually presents with nephrotic range proteinuria or nephrotic syndrome in middle-aged and elderly patients. Most of them are complicated with TIN and other organ involvement. A certain proportion of patients are PLA2R positive in IgG4-MN, and whether it is primary or secondary MN needs further study.
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Extracorporeal membrane oxygenation (ECMO), a kind of life support technology that can replace lung and heart function, is widely used in critical respiratory and circulatory exhaustion. Because of the serious diseases and the use of interventional catheters, patients receiving ECMO life support are often administrated with broad-spectrum antimicrobial agents, which increase the risk of fungal infection. Fungal infection during ECMO can increase mortality. How to effectively control fungal infection is a thorny problem faced by clinicians. During the treatment of ECMO, the patient's physiological status, ECMO oxygenation membrane, circulation pipeline and other factors may change the pharmacokinetic profiles of antifungal drugs, thereby affect the clinical efficacy of drugs. This artical reviews the pharmacokinetic characteristics of antifungal drugs during ECMO support, in order to provide references for clinical antifungal treatment.
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Objective To investigate the clinical characteristics,efficacy and prognostic factors of primary bone lymphoma(PBL).Methods The clinicopathologic characteristics and prognostic factors of 19 PBL patients from January 2012 to February 2016 were retrospectively analyzed.Results Nineteen PBL patients included 11 males,8 females,and the median age was 51 years old.It occurred mainly in cuboid(5 cases)and spine(5 cases).8 patients received chemoradiotherapy and 11 patients received chemoradiotherapy only.The overall response rate was 89.5%,including 12 cases with complete remission(CR)and 5 cases with partial remission.The 2-year overall survival(OS)and the 2-year progression-free survival(PFS)rates of 19 patients with completed follow-up were 61.0% and 48.3%,respectively.Further analysis of 15 patients with primary bone diffuse large B-cell lymphoma(PB-DLBCL)subgroup showed that their 2-year OS and PFS rates were 59.2% and 45.5% respectively.Univariate analysis indicated that the international prognostic index(IPI)score(≤2),no soft tissue invasion and CR in initial treatment could be treated as the favorable prognostic factors of both OS and PFS; Eastern Cooperative Oncology Group(ECOG)score(≤2)could improve OS; the addition of rituximab could improve PFS.Multivariate analysis indicated that the IPI score was the only independent factor of OS and soft tissue invasion was the only independent factor of PFS.Conclusions For PB-DLBCL patients,low IPI score(≤2)and local soft tissue without invasion indicate better prognosis,furthermore,a more appropriate IPI model should be explored based on local soft tissue invasion.
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Objective To investigate the clinical characteristics,efficacy and prognostic factors of primary bone lymphoma(PBL).Methods The clinicopathologic characteristics and prognostic factors of 19 PBL patients from January 2012 to February 2016 were retrospectively analyzed.Results Nineteen PBL patients included 11 males,8 females,and the median age was 51 years old.It occurred mainly in cuboid(5 cases)and spine(5 cases).8 patients received chemoradiotherapy and 11 patients received chemoradiotherapy only.The overall response rate was 89.5%,including 12 cases with complete remission(CR)and 5 cases with partial remission.The 2-year overall survival(OS)and the 2-year progression-free survival(PFS)rates of 19 patients with completed follow-up were 61.0% and 48.3%,respectively.Further analysis of 15 patients with primary bone diffuse large B-cell lymphoma(PB-DLBCL)subgroup showed that their 2-year OS and PFS rates were 59.2% and 45.5% respectively.Univariate analysis indicated that the international prognostic index(IPI)score(≤2),no soft tissue invasion and CR in initial treatment could be treated as the favorable prognostic factors of both OS and PFS; Eastern Cooperative Oncology Group(ECOG)score(≤2)could improve OS; the addition of rituximab could improve PFS.Multivariate analysis indicated that the IPI score was the only independent factor of OS and soft tissue invasion was the only independent factor of PFS.Conclusions For PB-DLBCL patients,low IPI score(≤2)and local soft tissue without invasion indicate better prognosis,furthermore,a more appropriate IPI model should be explored based on local soft tissue invasion.
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Objective To confirm the interference effect of heparin lithium on turbidimetry method for detecting total protein , and to conduct performance evaluation of it .Methods Eight different concentrations of total protein urine specimen with and with ‐out heparin lithium were detected respectively ,to confirm the interference of heparin lithium on the experiment .Adding different concentration of heparin lithium solution to the prepared total protein samples with concentration of 0 .172 ,0 .427 g/L(a series of interference experiment samples ,with heparin lithium concentrations of 0 .000 ,0 .025 ,0 .030 ,0 .035 ,0 .040 ,0 .045 ,0 .050 mg/L ) , repeat four times detection ,and then conduct the dose‐effect experiment of interference .Results The biggest bias of the testing re‐sults in the two paired samples was 159 .37% ,the mini‐bias was 11 .37% ,the difference of the results in two groups was statistical significant(t= 17 .24 ,P< 0 .05) .95% confidence interval of the interference effect in the total protein samples with concentration of 0 .172 g/L was 0 .034 ~ 0 .062 ,while in the total protein samples with concentration of 0 .427 g/L was 0 .043 - 0 .053 .When the heparin lithium were 0 .025 mg/mL and 0 .050 mg/mL respectively ,the results of bias of the total protein samples with concentra‐tion of 0 .172 g/L were 27 .33% ,58 .14% respectively .But in the 0 .427 g/L total protein samples ,the results of bias were 11 .24% 、18 .74% respectively .Dose effect of interference both showed a linear relationship in the series concentration of the hepa ‐rin lithium and interference of sample of 0 .172 g/L and 0 .427 g/L ,and the linear equations were Y = 1 .974X - 0 .001 03 ,Y = 1 .599 X - 0 .000 5 respectively .Conclusion Heparin lithium is the exogenous interfering substance to the detection of total protein in tur ‐bidimetry method ,it is the positive interference to the determination results of total proteins ,especially for the low level of total pro‐tein detection ,and as heparin lithium concentration increases ,the stronger the interference effect .
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<p><b>OBJECTIVE</b>To assess the association of genetic polymorphisms of CYP2C19*2,*3,*17 with the recurrence risk of ischemic stroke during clopidogrel prevention in ethnic Han Chinese from Fujian Province.</p><p><b>METHODS</b>Clinical data of 985 patients with acute ischemic stroke was collected. After 1 year postdischarge follow-up evaluations, only 114 patients with persistence of clopidogrel were enrolled. CYP2C19 genetic polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)and direct sequencing ,then we analysis the correlation between polymorphisms and the recurrence of stroke.</p><p><b>RESULTS</b>Among the 114 patients, 23 had a second onset whilst receiving clopidogrel treatment. During the antiplatelet therapy with clopidogrel, carriers of CYP2C19 poor metabolizer (CYP2C19*2/*2 or *2/*3) had a higher rate of recurrent stroke compared with extensive metabolizers (CYP2C19*1/*1) (OR=4.71, 95%CI: 1.18-18.80, P<0.05). Carriers of CYP2C19 *2 mutant allele had increased recurrence compared with those carrying none loss-of-function allele (OR=2.31, 95%CI: 1.20-4.46, P<0.05). The rate of recurrent stroke in those carrying homozygous mutant *2 allele (CYP2C19*2/*2) was 6.14 times greater than the rate of wild-type homozygotes (CYP2C19*1/*1) (95%CI: 1.54-24.54, P<0.05). Patients with previous stroke history had increased risk of recurrence (OR= 4.146, 95%CI: 1.259-13.655, P<0.05). However, CYP2C19*17 was not detected in the group.</p><p><b>CONCLUSION</b>For ethnic Han Chinese patients receiving clopidogrel treatment, carriers of poor metabolizer or homozygous mutant *2 allele (CYP2C19*2/*2) have a higher risk of recurrent stroke. The CYP2C19 *2 allele is an independent risk factor for recurrent stroke. Those with previous history of stroke are more prone to the recurrence.</p>
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Aged , Female , Humans , Male , Middle Aged , Alleles , Asian People , Genetics , Brain Ischemia , Ethnology , China , Cytochrome P-450 CYP2C19 , Genetics , Gene Frequency , Genetic Predisposition to Disease , Ethnology , Genetics , Genotype , Linkage Disequilibrium , Logistic Models , Platelet Aggregation Inhibitors , Therapeutic Uses , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Polymorphism, Single Nucleotide , Recurrence , Risk Factors , Sequence Analysis, DNA , Stroke , Ethnology , Genetics , Ticlopidine , Therapeutic Uses , Time FactorsABSTRACT
Objective To explore the serum levels of cytokines in patients with depression and their correlations with sex,age,depression severity and anxiety severity.Methods After enrolling subjects into the corresponding patient group and control group,the same trained researcher should continue to collect general information of the enrolled subjects as well as the HAMA and HAMD scoring results collection and assessment;And the serum levels of interlukin-1β (IL-1β),interlukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected with the method of enzyme-linked Immuno-sorbent assay (ELISA) in two groups.Results ① The serum levels of IL-1β,IL-6 and TNF-α of depression group were significantly higher than these in control group (P＜0.05),which were ((5.45±3.60) pg/ml vs(2.63± 1.92) pg/ml,(5.09±3.74) pg/ml vs (3.83±2.71) pg/ml,(5.77±3.94) pg/ml vs (4.05±3.25) pg/ml) respectively.②There was no significant difference in serum levels of IL-1 β,IL-6 and TNF-α between male and female patients with depression (P＞0.05).③ No conspicuous differences were found between the young group and the middle-aged group in serum levels of IL-1β,IL-6,TNF-α (P＞0.05).④ Serum level of IL-6 in major depressive disorder group((6.24±4.68) pg/ml) was more higher than that in mild to moderate depression group((3.95± 1.97)pg/ml),and the difference was statistically significant (t=2.467,P＜0.05).⑤There was significant differences in serum level of IL-6 between two groups,which were depression patients with and without anxiety (separately(5.80±4.37) pg/ml vs(3.87±1.80) pg/ml) (t=2.397,P＜0.05).Conclusions ①There is a phenomenon of immune activation,and levels of blood cytokines are raised in patients with depression.②Age and gender have no impact on depression in the level of cytokines.③IL-6 may be an important biological index that reflected the severity of depression and anxiety.
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Objective To evaluate the triage value of high-risk human papillomavirus (HR-HPV)detection in women with atypical squamous cells of undetermined significance (ASCUS).Methods Two huandred women with atypical squamous cells of undetermined significance (ASCUS) were selected by thinprep cell test(TCT) simultaneously using HPV DNA testing by hybrid capture Ⅱ (HC) and biopsy under the colposcopy,compared the HR-HPV DNA testing with final pathological diagnosis.CIN (cervical intraepithelial neoplasia) means cervical biopsy positive.Results The positive rate of cervical biopsy in HPV positive patients was 60.38％(96/159),and in HPV negative patients was 21.95％(9/41),the difference was obviously (P ＜ 0.05).Conclusion HR-HPV detection is a good triage approach for the patients with ASCUS.
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ObjectiveTo explore clinical,histopathological and genetic features in a case of fatal familial insomnia (FFI) and related literatures were reviewed. Methods The clinical features in one patient with FFI were analyzed,and the dead patient was examined at autopsy and histopathological studies were performed on the brain tissues; and the blood samples from the patient and some of her familial members were collected for the sequencing of prion protein gene (PRNP). Results The main clinical features included intractable insomnia,psychiatric symptoms and abnormal night sleep behavior,unsteady gait,difficulty swallowing,sudden death,and positive family history. The pathological studies showed multiple neuronal loss and gliosis of brain tissues from the proband,predominated in thalamus; and analysis of PRNP revealed gene D178N mutation,and linkage with 129 methionine (Met) allele in the proband and a relative.ConclusionsFFI patients may manifest as sudden death,and may have prominent psychiatric symptoms; the corresponding gene mutation could occur in the asymptomatic carriers; the data of autopsy and brain tissue pathology is helpful for further understanding of this disease.
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To prepare rivastigmine liposome, rivastigmine was loaded into liposome via ammonium sulfate gradient method. Its pharmacokinetic profile in rats was evaluated after intranasal administration. The size, zeta potential, entrapped efficiency and release of rivastigmine from the liposome in vitro were determined. Plasma concentration of rivastigmine was determined by high performance liquid chromatography-tandem mass spectrometry (HPLC/MS) using antipyrine as internal standard. The pharmacokinetic parameters were calculated by DAS 2.0. The entrapped efficiency of rivastigmine liposome was (33.41 +/- 6.58) %, with the mean diameter of 154-236 nm and zeta potential of (-10.47 +/- 2.41) mV. The release behavior of rivastigmine was fitting the first order equation in vitro. The pharmacokinetic studies indicated that the C(max), T(max) and AUC(0-infinity), of rivastigmine liposome were (1.50 +/- 0.15) mg x L(-1), 15 min and (89.06 +/- 8.30) mg x L(-') x min, respectively. Rivastimine liposome was absorbed rapidly, and could reach a certain concentration in rat plasma after intranasal delivery.
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Objective To assess the role of dynamic contrast-enhanced MRI for diagnosis and differential diagnosis of prostatic cancer. Methods Six volunteers, 32 patients with benign prostatic hyperplasia and 13 patients with biopsy-proven prostatic cancer underwent MR imaging. Dynamic MR with Gd-DTPA (gadolinium-diethylene triamine pentaacetic acid) bolus enhancement was performed followed by post-contrast T 1-weighed imaging. The signal intensive value in dynamic MRI was measured and calculated to draw the time-signal intensity curve of normal peripheral zone, prostatic cancer and benign hyperplasia. Results In dynamic MRI, the normal peripheral zone were enhanced mildly and slowly. The lesion enhancement of benign prostatic hyperplasia in 32 patients were obvious in early phase (60 s) and strengthened gradually, and then went to decrease in late phase (240 s) after peak value. The lesions in 9 of 13 cases with prostate cancer were enhanced obviously in early phase (60 s) and washed out rapidly in late phase, and the peak value was located on early phase. Conclusions In dynamic MRI, the enhancement of normal peripheral zone, prostate cancer and benign hyperplasia were different significantly. Dynamic MRI was very useful in the diagnosis and differentiation of prostate cance.