[Efficacy of plasma exchange in severe crescentic IgA nephropathy: A multicentered, cohort study].

OBJECTIVE: To evaluate the efficacy of plasma exchange therapy on crescentic IgA nephropathy (IgAN). METHODS: A retrospective analysis was performed in a cohort of patients with crescentic IgAN from January 2012 to September 2020 at 9 sites across China. Clinical and pathological data, as well as therapeutic regimens, were collected. In order to minimize the effect of potential confounders in baseline characteristics, propensity score matching using a 1 ∶1 ratio nearest neighbor algorithm was performed between the adjunctive plasma exchange therapy group and the intensive immunosuppressive therapy group. The primary outcome was end-stage of kidney disease (ESKD). Kaplan-Meier method was used to compare the difference in renal survival between the two groups. RESULTS: A total of 95 crescentic IgAN patients with acute kidney disease were included in this study, including 37 (38.9%) patients receiving adjunctive plasma exchange therapy, and 58 (61.1%) patients receiving intensive immunosuppressive therapy. In the whole cohort, the baseline eGFR was 12.77 (7.28, 21.29) mL/(min·1.73 m2), 24-hour urinary protein quantification was 5.9 (4.0, 8.9) g, and crescent percentage was 64.71% (54.55%, 73.68%). In the study, 23 patients in each group were matched after propensity score matching The median follow-up time was 7 (1, 26) months. As a whole, 29 patients (63.0%) reached ESKD, including 16 patients (69.6%) in the adjunctive plasma exchange therapy group and 13 (56.5%) patients in the intensive immunosuppressive therapy group.. There were no stastical difference between the two groups in terms of baseline eGFR [14.30 (9.31, 17.58) mL/(min·1.73 m2) vs. 11.45 (5.59, 20.79) mL/(min·1.73 m2)], 24-hour urinary protein (7.4±3.4) g vs. (6.6±3.8) g, crescent percentage 64.49%±13.23% vs. 66.41%±12.65% and the proportion of patients received steroid therapy[23 (100.0%) vs. 21 (91.3%)] (All P>0.05). Kaplan-Meier survival analysis demonstrated that there was no significant difference in renal survival rate between the two groups (Log-rank test, P=0.933). CONCLUSION: The adjunctive plasma exchange therapy in addition to conventional intense immunosuppressive therapy did not additionally improve the prognosis of crescentic IgA nephropathy.

[Radiofrequency ablation combined with systemic chemotherapy in the management of nasopharyngeal carcinoma with liver metastasis].

Objective: To determine the treatment efficacy of systemic chemotherapy combined with sequential CT-guided radiofrequency ablation (chemo-RFA) in the management of nasopharyngeal carcinoma (NPC) with liver metastasis. Methods: A total of 427 NPC patients diagnosed with liver metastasis at Sun Yat-sen University Cancer Center between January 2000 and December 2013 were enrolled. Of the patients, 340 cases were male, 87 cases were female, the median age was 45 years (range 18-80 years), all patients received systemic chemotherapy and part of them also received RFA treatment. Patients were evaluated for response every two cycles during systemic chemotherapy and then every three months until death. One-to-one matched pairs between chemo-RFA group with chemo-only group were generated using propensity score matching; survival analysis was further conducted. Results: Of all the enrolled patients, 56 patients (13.1%) received combined treatment, 371 patients (86.9%)received chemotherapy alone. After propensity score matching, 56 pairs of well-matched liver metastatic NPC patients were selected from different treatment groups. The 1-, 3-, 5- year overall survival (OS) rates for chemo-RFA group were 89.2%, 45.5% and 32.5% and chemo-only group were 77.1%, 27.5% and 4.8% respectively; the 1-, 3-, 5- year progression-free survival (PFS) rates for chemo-RFA group were 64.0%, 25.4% and 10.7% and chemo-only group were 44.1%, 5.5% and 5.5% respectively.The adjusted hazard ratio in OS and PFS of the choice for chemo-RFA approach to chemo-only was HR 0.43, 95% CI 0.25-0.73 and HR 0.44, 95% CI 0.28-0.71 respectively. Conclusion: CT-guided RFA combined with chemotherapy approach could improve the survival rate for NPC patients with liver metastasis.

Effect of TIMP1 transfection on PTEN expression in human kidney proximal tubular cells.

To explore the role of metalloproteinase-1 (TIMP-1) tissue inhibitor in the mechanisms of kidney aging, we observed the effects of sense and antisense transfection of TIMP-1 and of metalloproteinase (MMP) inhibitors on phosphatase and tensin homolog (PTEN), vascular endothelial growth factor (VEGF), and Flk-1 expression in TIMP-1 transgenic human proximal tubular epithelial cells (HKCs). Transfected HKCs were co-incubated with 100 µM MMP-2 and MMP-9 inhibitor III for 24 h to affect enzyme inhibition. TIMP-1, MMP-2, MMP-9, PTEN, VEGF, and Flk-1 mRNA expression was detected by reverse transcription-polymerase chain reaction. PTEN, VEGF, and Flk-1 protein expression in cells of each experimental group was measured by indirect immunofluorescence. We found that PTEN expression was up-regulated (P < 0.05) in the sense TIMP-1-transfected group (P < 0.05) compared with the non-transfected and empty vector groups, and that expression of VEGF and Flk-1 was down-regulated (P < 0.05). In contrast, the antisense TIMP-1 transgenic group showed the opposite results (P < 0.05). No significant differences in expression of PTEN, VEGF, or Flk-1 were observed among the MMP- 2/MMP-9 inhibitor III, non-transfected, and empty vector groups (P > 0.05). These results suggest that in the progression of renal aging, high expression of TIMP-1 up-regulates PTEN expression through an MMP-independent pathway, and subsequently down-regulates the expression of VEGF and Flk-1, indicating that PTEN and TIMP-1 are involved in the aging-associated impairment of renal angiogenesis. Our study provides a theoretical basis for further exploration of the mechanism underlying TIMP- 1 participation in renal aging progression.

Peripheral Blood Leukocyte Telomere Length Is Associated with Age but Not Renal Function: A Cross-Sectional Follow-Up Study.

OBJECTIVES: We aimed to evaluate the relationship between baseline renal function and changes in telomere length in Han Chinese. METHODS: The telomere restriction fragment (TRF) length of leukocytes in the peripheral blood was measured in healthy volunteers recruited in 2014. The estimated glomerular filtration rate (eGFR) was calculated based on serum creatinine (Scr) and serum cystatin C (CysC)-eGFRcys and eGFRScr-cys through the Cockcroft-Gault formula (eGFRC-G) or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI / eGFRCKD-EPI) equation. The correlation between telomere length changes over time and renal function was analyzed. RESULTS: Leukocyte TRF lengths were negatively correlated to age (r = -0.393, p < 0.001) and serum CysC (r = -0.180, p < 0.01), while positively associated with eGFRCKD-EPI, eGFRC-G, eGFRcys, and eGFRScr-cys (r = 0.182, 0.122, 0.290, and 0.254 respectively, p < 0.01). The 3-year change of telomere length was 46 bp/years. When adjusted for age, the associations between telomere length changes and baseline, subsequent TRF lengths, and serum CysC were no longer present. No association was observed between TRF length changes and renal function. CONCLUSION: The rate of telomere length changes was affected by age and baseline telomere length. The telomere length changes might be important markers for aging.

Coronavirus JHM OMP1 pathogenesis in owl monkey CNS and coronavirus infection of owl monkey CNS via peripheral routes.

Two separate studies are described in this report. First, 5 Owl monkeys were inoculated intracerebrally (IC) with coronavirus JHM OMP1; this virus isolate was cultured from the brain of an animal inoculated with uncloned MHV JHM. Two of the animals became neurological impaired and were sacrificed; these animals had developed severe encephalomyelitis as previously described. Two of the remaining 3 healthy animals were inoculated IC again at 90 days post-inoculation (DPI) and all 3 were sacrificed approximately 5 months after the first virus inoculation. Despite the lack of detectable infectious virus, viral RNA and antigen, all 3 animals had significant white matter inflammation and areas of demyelination in the spinal cord. In the second study 4 Owl monkeys were inoculated intranasally (IN) and ocularly and 4 inoculated intravenously (i.v.) with JHM OMP1. The animals were sacrificed between 16 and 215 DPI with 2 IN and 2 i.v. animals receiving a second i.v. inoculum at 152 DPI. Viral RNA and/or antigen was detected in the brains of all animals and the distribution corresponded to areas of inflammation and edema. One of the animals that received the second inoculum developed neurological impairment and subsequent analysis of tissues showed viral antigen in both brain and spinal cord. Viral products were predominantly found in blood vessels suggesting hematogenous spread with entry into the central nervous system (CNS) through endothelium.

Construction of an integral formula of biological age for a healthy Chinese population using principle component analysis.

BACKGROUND: Whereas chronological age (CA) cannot distinguish functional differences among individuals of the same age, the biological age (BA) may be used to reflect the functional state of the body. The purpose of this study was to construct an integral formula of the BA, by using principle component analysis (PCA). METHODS: The vital organ function of 505 healthy individuals of Han origin (age 35-91 years) was examined. A total of 114 indicators of cardiovascular, pulmonary, and brain functions, and clinical, inflammatory, genetic, psychological, and life habit factors were assessed as candidate indicators of aging. Candidate indicators were submitted with CA to correlation and redundancy analyses. The PCA method was used to build an integral formula of the BA for the population. RESULTS: Seven biomarkers were selected in accordance with a certain load standard. These biomarkers included the trail making test (TMT), pulse pressure (PP), mitral valve annulus ventricular septum of the peak velocity of early filling (MVES), minimum carotid artery intimal-medial thickness (IMTmin), maximum internal diameter of the carotid artery (Dmax), maximal midexpiratory flow rate 75/25 (MMEF75/25), and Cystatin C (CysC). The formula for the BA was: BA = 0.0685 (TMT) + 0.267 (PP) - 1.375 (MVES) + 22.443 (IMTmin) + 2.962 (Dmax) - 2.332 (MMEF75/25) + 16.104 (CysC) + 0.137 (CA) + 0.492. CONCLUSION: Several genetic and lifestyle indicators were considered as candidate markers of aging. However, ultimately, only markers reflecting the function of the vital organs were included in the BA formula. This study represents a useful attempt to employ multiple indicators to build a comprehensive BA evaluation formula of aging populations.

Association of Klotho and interleukin 6 gene polymorphisms with aging in Han Chinese population.

Certain gene polymorphisms are associated with human aging. This study investigated polymorphisms of a metabolism-related gene, Klotho, and an inflammatory gene, IL6, for association with the aging process in a healthy Han Chinese population. A total of 482 healthy subjects were recruited and divided into aging and young groups according to chronological age and biological age. Snapshots were used to detect a Klotho gene tag SNP (rs571118) and the F-SNPs rs9536314 (F352V) and rs9527025 (C370S), and an interleukin 6 (IL-6) gene tag SNP (rs1524107) and the F-SNPs rs1800795 (-174G/C) and rs1800796 (-572G/C). Klotho F352V and IL-6-174G/C was G homozygous, C370S was T homozygous while IL-6-572G/C MAF less than 5%. There was a statistically significant difference in the Klotho rs571118 SNP between chronological age groups, but not biological age groups. However, other SNPs, including IL-6 gene SNPs, didn't correlate with age in the Han Chinese population. Human aging is a complex process that includes chronological and biological aging. Our current data showed that Klotho gene rs571118 SNP was associated with chronological aging, but not biological aging, in a Han Chinese population. Further study will investigate genetic build up for the difference between chronological and biological aging.

Induction treatment of proliferative lupus nephritis with leflunomide combined with prednisone: a prospective multi-centre observational study.

To evaluate the efficacy and safety of leflunomide in the treatment of proliferative lupus nephritis, a prospective multi-centre observational study was conducted. Patients with biopsy proven proliferative lupus nephritis were assigned to receive either leflunomide or cyclophosphamide with concomitant prednisone. Leflunomide was given orally with a loading dose of 1 mg/kg/day for 3 days followed by 30 mg/day. Intravenous cyclophosphamide was administered monthly at a dose of 0.5 g/m2 of body-surface area. A total of 110 patients were enrolled, 70 in the leflunomide group and 40 in the cyclophosphamide group. The complete remission rate in the leflunomide group was 21% and partial remission rate 52%, as compared with 18% and 55%, respectively, in the cyclophosphamide group. Renal parameters and systemic lupus erythematosus disease activity index improved significantly and similarly in both groups. Serum creatinine decreased or stabilized in both treatment groups. No significant difference was noted with respect to clinical outcome between groups. Repeat biopsy also showed a significant reduction of active lesions in kidney pathology after 6 months of leflunomide treatment. Major adverse events, similar in both treatment groups, included infection, alopecia and hypertension. Leflunomide, compared with cyclophosphamide, in combination with prednisone was effective in the induction therapy of proliferative lupus nephritis and was generally well-tolerated.

[Study on identification of liver isoferritin by isoelectrofocusing in thin-layer polyacrylamide gels].

Thin-layer IEF, an analytical technique of high resolution for protein, was used to identify the liver isoferritin in Wistar rat, normal human and patients with hepatocellular carcinoma (HCC) respectively. The focusing conditions were 2000 V, 25W, 10 degrees C, 2h. The results showed that the IEF bands of the liver isoferritin in Wistar rat, normal human and patients with HCC were 7, 6, 3 and the pI of the liver isoferritin were 5.76-4.75, 5.80-4.85, 4.50-4.43 respectively. The method and data in this paper might be good reference for in-depth study of the structure and function of ferritin and its applications in clinical medicine.

The hemopexin gene maps to the same location as the beta-globin gene cluster on human chromosome 11.

Using human hemopexin cDNA clones isolated from lambda gt11 cDNA library as probes, we have carried out Southern blot analysis of a series of human-Chinese hamster somatic cell hybrids containing different combinations of human chromosomes. Synteny analysis revealed 100% concordance between the hemopexin gene and human chromosome 11. In situ hybridization of 3H-labeled hemopexin cDNA to metaphase chromosomes prepared from human lymphocytes further localized the gene to the region p15.4-p15.5, the same location as the beta-globin gene cluster.

Further observations on coronavirus infection of primate CNS.

Previously, we demonstrated that intracerebral (IC) inoculation of a murine coronavirus, MHV-JHM, into two species of primates can result in acute encephalomyelitis (Murray et al., 1992a). Infectious virus isolated from acutely infected animals, designated JHM-OMp1, was inoculated IC into a second group of monkeys. In this report we describe observations on the acutely infected animals and those surviving the acute infection were sacrificed at later times post-infection. Results from dual in situ hybridization/immunohistochemistry screening of tissues show that astrocytes are target cells in white matter lesions during acute infection. In animals sacrificed 150 days post-infection, areas of demyelinated gliotic lesions, prominent in the spinal cord, were seen throughout the neuraxis. No virus products were detected in these late-infection lesions.

Evaluation of a commercial PCR kit for diagnosis of cytomegalovirus infection of the central nervous system.

We evaluated the AMPLICOR cytomegalovirus (CMV) PCR kit for the diagnosis of neurologic CMV infections on 43 positive and 112 negative archived cerebrospinal fluid specimens originally tested by an in-house PCR method. The AMPLICOR kit showed sensitivity and specificity of 95 and 100%, respectively, versus the home-grown assay, indicating its utility in this clinical setting.

Frequency of acyclovir-resistant herpes simplex virus in clinical specimens and laboratory isolates.

The proportion of acyclovir (ACV)-resistant herpes simplex virus (HSV) isolates in clinical specimens and laboratory isolates was determined. HSV isolates in clinical specimens and laboratory isolates were cultured in the absence or presence of 5 microg of ACV per ml. The frequency of ACV-resistant HSV was calculated as (average virus titer in the wells with ACV)/(average virus titer in the wells without ACV). The mutation frequency of HSV type 1 isolates in clinical samples (directly from patient lesions) was 7.5 x 10(-4) +/- 2.5 x 10(-4) (mean +/- standard error), and that of HSV type 2 isolates was 15.0 x 10(-4) +/- 4.6 x 10(-4). The mutation frequencies of isolates derived in the laboratory from these clinical samples were very similar. Similarly, the 50% inhibitory concentrations for isolates in clinical samples and laboratory isolates were identical. The frequencies of ACV-resistant HSV types 1 and 2 were in a narrow range of 7.5 x 10(-4) to 15.0 x 10(-4) among isolates in clinical specimens and did not change for laboratory-derived pools of viral isolates.

Coronavirus infects and causes demyelination in primate central nervous system.

Two species of primates, Owl and African green monkeys, were inoculated intracerebrally with either the neurotropic mouse hepatitis virus JHM or the putative multiple sclerosis brain coronavirus isolate SD. These viruses caused an acute to subacute panencephalitis and/or demyelination in the infected animals. The course of pathogenesis and sites of detected viral RNA and antigen was dependent both on animal species and virus strain but the results clearly showed that these viruses replicated and disseminated in the central nervous system (CNS) of these primates. This study suggests that human CNS may be susceptible to coronavirus infection.

Interstrain variation in the human cytomegalovirus DNA polymerase sequence and its effect on genotypic diagnosis of antiviral drug resistance. Adult AIDS Clinical Trials Group CMV Laboratories.

The polymerase (pol) coding sequence was determined for 40 independent clinical cytomegalovirus isolates sensitive to ganciclovir and foscarnet. Sequence alignments showed >98% interstrain homology and amino acid variation in only 4% of the 1, 237 codons. Almost all variation occurred outside of conserved functional domains where resistance mutations have been identified.