[Current status and prospects of genetic research on membranous nephropathy].

Primary membranous nephropathy (PMN) is one of the most frequent pathological subtypes of nephrotic syndrome in adults. The use of genome-wide association study (GWAS) technology has propelled the transition from conventional medicine to precision medicine, offering a fresh perspective for comprehending the pathogenesis of PMN and individual variations in greater detail. Furthermore, GWAS will aid in clinical translation, laying a firm foundation for the precise diagnosis and treatment of PMN.

[Exploration of the high-risk factors of catheter-related thrombosis in breast cancer].

Objective: To explore the high risk factors of catheter-related thrombosis (CRT) in breast cancer patients, and provide the basis for the development of appropriate prevention and treatment strategies. Methods: A total of 1 432 breast cancer patients scheduled to receive central venous catheterization in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 1, 2015 to August 31, 2019 were selected. Baseline information and catheterization information of patients were collected. The occurrence of CRT was confirmed by vascular ultrasound examination, and the influencing factors of CRT were analyzed. Results: The total number of catheter days were 121, 980 days in 1 432 patients with breast cancer, and the average number of catheter days in each patient was 85.2 days. The incidence of CRT was 6.8% (97/1 432), which was 0.79 cases/1 000 catheter days. Among 815 patients with centrally inserted central venous catheters (CICC), 43 (5.3%) had CRT, which was 0.70 cases/1 000 catheter days. Among 617 patients with peripherally inserted central venous catheters (PICC), 54 (8.8%) developed CRT, which was 0.90 cases/1 000 catheter days. CRT was most common in subclavian vein (63.9%). Multivariate regression analysis showed that age ≥ 60 years old (OR=1.712, 95% CI: 1.056-2.775, P=0.029), PICC (OR=1.732, 95% CI: 1.130-2.656, P=0.012), the catheter position except subclavian vein (OR=10.420, 95% CI: 1.207-89.991), secondary adjustment of catheter position (OR=3.985, 95% CI: 1.510-10.521, P=0.005) and high D-Dimer level (OR=1.129, 95% CI: 1.026-1.241, P=0.012)were independent risk factors for CRT. Conclusions: The CRT problem can't be ignored in the clinical treatment of breast cancer patients with central venous catheterization. Screening the appropriate age of patients and the type of central venous catheters, reducing the secondary adjustment of catheter position, and timely monitoring the level of D-dimer are helpful to the prevention and treatment of CRT.

Relationship between inflammatory factors and arrhythmia and heart rate variability in OSAS patients.

OBJECTIVE: Obstructive Sleep Apnea Syndrome (OSAS) is a disorder characterized by recurrent upper airway obstruction, apnea, and hypopnea, associated with decreased oxygen saturation and disturbed sleep structure during sleep. It was found that OSAS was associated with a variety of arrhythmia and conduction disorders, but the relationship between multiple types of arrhythmia and the severity of OSAS, and its possible mechanism remain unclear. The purpose of this study was to observe the main types of arrhythmia and the condition of heart rate variability (HRV) in patients with OSAS, to detect the levels of multiple inflammatory factors in serum of OSAS patients, and to observe the correlation between polysomnographic parameters or inflammatory factors, and arrhythmia or HRV, as well as its possible mechanisms. PATIENTS AND METHODS: 141 patients with suspected OSAS were collected in the Second Affiliated Hospital of Soochow University and Xinghua People's Hospital from February 2016 to February 2018. According to the sleep apnea hypopnea index (AHI), they were divided into control group (AHI <5, n = 34), mild-moderate OSAS group (5≤ AHI <30, n = 48), and severe OSAS group (AHI ≥30, n = 59). Clinical data such as gender and age were collected. All patients completed polysomnography (PSG), 24-hour Holter monitoring and blood routine, biochemical indexes and serum hs-CRP, TNF-α, IL-6, and IL-1ß testing. The indicators in the three groups were compared, and the correlation between PSG parameters, HRV and inflammatory biomarkers was investigated. RESULTS: Compared with control group, there were significant differences in age, sex ratio, BMI, uric acid, TC, and TG in the mild-moderate OSAS group (p<0.05), and in age, sex ratio, BMI, red blood cell count, hemoglobin, hematocrit, uric acid, FBS, TC, TG, LDL, and HDL in severe OSAS group (p<0.05). There were significant differences in gender ratio, BMI, red blood cell count, hemoglobin, hematocrit, uric acid, FBS, TC, TG, LDL, and HDL between mild-moderate OSAS group and severe OSAS group (p<0.05). Heart rate variability (HRV) parameters include SDNN, SDNN index, RMSSD, PNN50, LF, HF, and LF/HF. SDNN, PNN50, and HF in severe OSAS group and mild-moderate OSAS group were significantly lower than those in control group (p<0.05). LF/HF was significantly higher than that of control group (p<0.05). There was a significant difference in PNN50, HF, and LF/HF between severe OSAS group and mild-moderate OSAS group (p<0.05). In terms of inflammation, serum hs-CRP was significantly higher in mild-moderate OSAS group and severe OSAS group than that in control group (p<0.05). Serum IL-1ß was significantly higher in mild-moderate OSAS group than that in severe OSAS group (p<0.05). There was no significant difference in other indicators (p>0.05). There was a significant positive correlation between hs-CRP and oxygen reduction index (ODI) (r=0.209, p=0.013) and a significant negative correlation with PNN50 (r=-0.188, p=0.025). There is no significant correlation between other indicators. CONCLUSIONS: Systemic inflammatory reactions existed in patients with OSAS. With the increase of OSAS, inflammation was aggravated, especially serum hs-CRP. Hs-CRP was significantly and negatively correlated with PNN50 and positively correlated with ODI. The results suggested that the inflammatory response was involved in the occurrence of heart rate variability in OSAS patients.

Detection of Hole Pockets in the Candidate Type-II Weyl Semimetal MoTe_{2} from Shubnikov-de Haas Quantum Oscillations.

The bulk electronic structure of T_{d}-MoTe_{2} features large hole Fermi pockets at the Brillouin zone center (Γ) and two electron Fermi surfaces along the Γ-X direction. However, the large hole pockets, whose existence has important implications for the Weyl physics of T_{d}-MoTe_{2}, has never been conclusively detected in quantum oscillations. This raises doubt about the realizability of Majorana states in T_{d}-MoTe_{2}, because these exotic states rely on the existence of Weyl points, which originated from the same band structure predicted by density functional theory (DFT). Here, we report an unambiguous detection of these elusive hole pockets via Shubnikov-de Haas (SdH) quantum oscillations. At ambient pressure, the quantum oscillation frequencies for these pockets are 988 and 1513 T, when the magnetic field is applied along the c axis. The quasiparticle effective masses m^{*} associated with these frequencies are 1.50 and 2.77 m_{e}, respectively, indicating the importance of Coulomb interactions in this system. We further measure the SdH oscillations under pressure. At 13 kbar, we detected a peak at 1798 T with m^{*}=2.86m_{e}. Relative to the oscillation data at a lower pressure, the amplitude of this peak experienced an enhancement, which can be attributed to the reduced curvature of the hole pockets under pressure. Combining our experimental data with DFT+U calculations, where U is the Hubbard parameter, our results shed light on why these important hole pockets have not been detected until now.

[Recurrent syncope related to catecholaminergic polymorphic ventricular tachycardia due to de novo RyR2-R2401H mutation].

Objective: To explore the clinical and molecular genetic features of a Chinese patient with catecholaminergic polymorphic ventricular tachycardia (CPVT). Methods: Clinical data including resting electrocardiography, echocardiography and treadmill exercise testing of a patient with CPVT admitted to our department in March 2013 were analyzed, and the peripheral venous blood samples of the patient and his family members and 400 ethnicity-matched healthy controls were obtained. All exons and exon-intron boundaries of the six CPVT-related genes including RYR2, CASQ2, TRDN, CALM1, KCNJ2 and ANKB were sequenced to detect the variants related to CPVT. The relationship between the genotypes and phenotypes was analyzed to direct the target therapy. Results: Recurrent syncope induced either by exercise or extreme frightened fear was observed in this patient. There was no positive family history of syncope or sudden death. The resting electrocardiography and echocardiography of the patient were normal, while the exercise testing revealed bidirectional and polymorphic ventricular tachycardia. A cardiac ryanodine receptor gene mutation (R2401H) was identified in this patient, while this mutation was absent in his parents and sister and 400 controls. No variant was detected in the remaining five candidate genes. Treatment with high dose of metoprolol succinate (118.75 mg/d) was effective and patient was free of syncopal attack during the 2 years follow-up. Conclusion: This is the first report on RyR2-R2401H mutation in Chinese patient with CPVT, and high dose of metoptolol is the effective therapy option for CPVT related to RyR2 mutation.

Nonuniform allocation of hippocampal neurons to place fields across all hippocampal subfields.

The mechanisms governing how the hippocampus selects neurons to exhibit place fields are not well understood. A default assumption in some previous studies was the uniform random draw with replacement (URDWR) model, which, theoretically, maximizes spatial "pattern separation", and predicts a Poisson distribution of the numbers of place fields expressed by a given cell per unit area. The actual distribution of mean firing rates exhibited by a population of hippocampal neurons, however, is approximately exponential or log-normal in a given environment and these rates are somewhat correlated across multiple places, at least under some conditions. The advantage of neural activity-dependent immediate-early gene (IEG) analysis, as a proxy for electrophysiological recording, is the ability to obtain much larger samples of cells, even those whose activity is so sparse that they are overlooked in recording studies. Thus, a more accurate representation of the activation statistics can potentially be achieved. Some previous IEG studies that examined behavior-driven IEG expression in CA1 appear to support URDWR. There was, however, in some of the same studies, an under-recruitment of dentate gyrus granule cells, indicating a highly skewed excitability distribution, which is inconsistent with URDWR. Although it was suggested that this skewness might be related to increased excitability of recently generated granule cells, we show here that CA1, CA3, and subiculum also exhibit cumulative under-recruitment of neurons. Thus, a highly skewed excitability distribution is a general principle common to all major hippocampal subfields. Finally, a more detailed analysis of the frequency distributions of IEG intranuclear transcription foci suggests that a large fraction of hippocampal neurons is virtually silent, even during sleep. Whether the skewing of the excitability distribution is cell-intrinsic or a network phenomenon, and the degree to which this excitability is fixed or possibly time-varying are open questions for future studies. © 2016 Wiley Periodicals, Inc.

Genetic and morphological variation of three freshwater lake populations of Coilia ectenes (Engraulidae).

Population structure of the important commercial fish, Coilia ectenes, was investigated in samples from three freshwater lakes in the Eastern China using a multivariate approach of morphometrics and mitochondrial DNA control region sequencing. A total of eighteen morphological distances of truss method and eight morphometric variables were taken from each fish. Multivariate analyses of the morphometric data revealed significant morphological differences among the three lake populations, especially for those samples from Taihu Lake. Discriminant functions were used to compare sites, and these permitted an 83% success rate in distinguishing fish from the three sites. However, no obviously geographical differentiation was found among those populations of C. ectenes based on the genetic data. In the AMOVA analysis, only 2.2% genetic variability came from different populations, and most of them were present within the sub-populations. Experience a recent population expansion and some movement of fish among those areas, quite possibly enough to bring about relative genetic homogeneity, but there is insufficient to prevent the three populations from differing phenotypically. The diversified environmental factors may be playing an important role in shaping morphological variations among those populations.

Impact of rapamycin on peritoneal fibrosis and transport function.

OBJECTIVES: To observe the impact of rapamycin on peritoneal fibrosis and peritoneal transport function in a rat model of peritoneal fibrosis. METHODS: A total of 40 male SD rats were randomly divided into five groups, with 8 rats in each group. Group N was the normal control. In group NS, the rats were injected daily with 20 ml of saline intraperitoneally. In groups GLU, L-RAPA and H-RAPA, rats were injected daily with 20 ml of 4.25% peritoneal dialysis solution intraperitoneally, together with 150 µg of lipopolysaccharide on days 1, 3, 5 and 7. Rapamycin was administered to groups L-RAPA (250 µg/day) and H-RAPA (500 µg/day) intragastrically. On days 21 and 35, 4 rats from each group were selected to evaluate their peritoneal transport function (ultrafiltration volume, D(2)/D(0) ratio). The parietal peritoneal membrane from the rats was used for pathological study. Light microscopy (HE staining and VG staining) was used to assess the morphological changes. The expression levels of Col I, α-SMA, TGF-ß(1), Reca and Ki67 in the parietal peritoneal membrane were observed by immunohistochemistry. RESULTS: The ultrafiltration volume and D(2)/D(0) ratio decreased in group GLU compared with group N on day 21 (p < 0.05) and further decreased on day 35 (p < 0.01), whereas such a significant change was not observed in group L-RAPA or H-RAPA. Furthermore, severe loss of the peritoneal mesothelial cells, exposure of the collagen matrix under the mesothelial cells, and infiltration of fibroblasts and various inflammatory cells were detected in group GLU on days 21 and 35. The thickness of the submesothelial compact zone significantly increased in group GLU compared with group N (p < 0.01). However, in groups L-RAPA and H-RAPA, the morphological changes were clearly alleviated, and the submesothelial compact zone was thinner than in group GLU (p < 0.01). The expression levels of Col I, α-SMA, TGF-ß(1), Ki67 and Reca in the peritoneal membrane were significantly increased in group GLU compared with group N on days 21 and 35 (p < 0.01), whereas these changes were significantly attenuated in groups L-RAPA and H-RAPA compared with group GLU (p < 0.01). CONCLUSIONS: Rapamycin had an obvious effect in inhibiting peritoneal fibrosis and improving peritoneal membrane transport function.

UV-induced grafting processes with in situ formed photomask for micropatterning of two-component biomolecules.

We report a photolithographic process for micropatterning of two-component biomolecules on a transparent organic film via lateral functional polymer brushes of poly(sodium acrylate) (P(AA)) and poly(glycidyl methacrylate) (P(GMA)). The pattern of binary polymer brushes were prepared via consecutive UV-initiated grafting processes, under the assistance of the in situ formed poly (4,4'-bi[N-(4-vinylbenzyl) pyridinium]) (P(BVV)) photomask. The epoxy groups of the P(GMA) microdomains can be aminated for covalently coupling biotin, while the P(AA) microdomains were used for immobilizing immunoglobulin (IgG). The resulting biotin- and IgG-coupled microdomains interact specifically with their corresponding target proteins, avidin and anti-IgG, respectively.

Computed tomographic peritoneography in the investigation of patent processus vaginalis in CAPD patients.

Continuous ambulatory peritoneal dialysis (CAPD) is a useful and practical modality for the treatment of end-stage renal disease (ESRD). In the properly selected patient this method is well-tolerated with minimal complications. We report a case of intermittent massive genital edema secondary to patent processus vaginalis in a patient receiving CAPD. The diagnosis of patent processus vaginalis, which was strongly suggested by the intermittent nature of the symptoms, was confirmed by computerized tomography (CT) peritoneography.

Prospective studies on applications of a two-cuff Swan neck catheter and a Tenckhoff catheter to Chinese CAPD patients.

AIM: To compare the difference of clinical curative effects of continuous ambulant peritoneal dialysis (CAPD) patients in China by using a two-cuff Swan neck catheter and a Tenckhoff catheter. METHODS: 110 patients with end-stage renal disease (ESRD) were enrolled. They were divided into Group A (Swan neck catheter group, n = 55) and Group B (Tenckhoff catheter group, n = 55). One-year follow-up visits were made and information was recorded. Survival analysis was made by adopting the Kaplan-Meier method. RESULTS: After 12 month follow-up visits, 17 patients had died, 3 had been transferred to renal transplantation, 8 had been transferred to hemodialysis, 3 were transferred to other hospitals, and the remaining 79 patients (71.8%) continued their peritoneal dialysis therapy in our hospital. 26 patients in both groups had peritonitis, with a total of 35 occurrences taking place. The total incidence of peritonitis was 0.32 times/patient year, with the detailed figure of 0.35 times/patient year for Group A and 0.29 times/patient year for Group B respectively (p > 0.05). Regarding mechanical complications of the 2 groups concerned, including catheter tip migration, Omental enwrapment, peritoneal dialysate leakage, skid of outer cuff, incidence of inguinal hernia and bellyache, etc, no significant difference existed between two groups (p > 0.05). The two groups had the same 12-month technical survival rate of 92.73%. The 12-month survival rate for Group A was 86.34% while the corresponding figure for Group B was 80.68% (p > 0.05). CONCLUSIONS: Infections, mechanical complications, technical survival rate and patients' survival rate were quite similar, when a Swan neck catheter and a Tenckhoff catheter were used in Chinese CAPD patients.

Chimeric adenoviral vector Ad5/F35-mediated APE1 siRNA enhances sensitivity of human colorectal cancer cells to radiotherapy in vitro and in vivo.

Apurinic/apyrimidinic endonuclease (APE1), a bifunctional AP endonuclease/redox factor, is important in DNA repair and redox signaling, may be associated with radioresistance. Here we investigate whether targeted inhibition of APE1 can sensitize tumor cells to irradiation in vitro and in vivo. We first constructed chimeric adenoviral vector Ad5/F35 carrying human APE1 siRNA (Ad5/F35-APE1 siRNA). The infectivity of chimeric Ad5/F35 to LOVO colon cancer cells was greater than that of Ad5. APE1 was strongly expressed and nuclear factor kappaB (NF-kappaB), a downstream molecule of APE1, known as a radioresistance factor, was constitutively active in LOVO cells. Infection of LOVO cells with Ad5/F35-APE1 siRNA resulted in a dose-dependent decrease of APE1 protein and AP endonuclease activity in vitro. Ad5/F35-APE1 siRNA significantly enhanced sensitivity of LOVO cells to irradiation in clonogenic survival assays, associated with increased cell apoptosis. The APE1 expression in LOVO cells was induced by irradiation in a dose-dependent manner, accompanied with the enhancement of DNA-binding activity of NF-kappaB and Ad5/F35-APE1 siRNA effectively inhibited constitutive and irradiation-induced APE1 expression and NF-kappaB activation. In a subcutaneous nude mouse colon cancer model, Ad5/F35-APE1 siRNA (5 x 10(8) IU, intratumoral injection) inhibited the expression of APE1 protein in LOVO xenografts, and significantly enhanced inhibition of tumor growth by irradiation. In conclusion, APE1 may be involved as one of the radioresistance factors, and targeted inhibition of APE1 shows an effective means of enhancing tumor sensitivity to radiotherapy.

Over-expression of the potassium channel Kir2.3 using the dopamine-1 receptor promoter selectively inhibits striatal neurons.

Dysfunction of basal ganglia circuits underlies a variety of movement disorders and neuropsychiatric conditions. Selective control of the electrical activity of striatal outflow pathways by manipulation of ion channel function presents a novel therapeutic approach. Toward this end, we have constructed and studied in vitro an adenoviral gene transfer vector that employs the promoter region of the dopamine-1 receptor to drive expression of the inward rectifier K(+) channel Kir2.3. The use of this neuronal promoter confers cell-type specificity and a physiological level of trans-gene expression in rat primary striatal cultures. The electrophysiological properties were confirmed in transfected human embryonic kidney cells, in which an inwardly-rectifying, Cs(+)-sensitive current was measured by voltage clamp. Current clamp studies of transduced striatal neurons demonstrated an increase in the firing threshold, latency to first action potential and decrease in neuronal excitability. Neurotoxin-induced activation of c-Fos, a marker of neuronal activity, was blocked in transduced neurons indicating that the decrease in electrical excitability was physiologically significant. When used in vivo, this strategy may have the potential to positively impact movement disorders by selectively changing activity of neurons belonging to the direct striatal pathway, characterized by the expression of dopamine-1 receptors.

Descending facilitation from the rostral ventromedial medulla maintains nerve injury-induced central sensitization.

Nerve injury can produce hypersensitivity to noxious and normally innocuous stimulation. Injury-induced central (i.e. spinal) sensitization is thought to arise from enhanced afferent input to the spinal cord and to be critical for expression of behavioral hypersensitivity. Descending facilitatory influences from the rostral ventromedial medulla have been suggested to also be critical for the maintenance, though not the initiation, of experimental neuropathic pain. The possibility that descending facilitation from the rostral ventromedial medulla is required for the maintenance of central sensitization was examined by determining whether ablation of mu-opioid receptor-expressing cells within the rostral ventromedial medulla prevented the enhanced expression of repetitive touch-evoked FOS within the spinal cord of animals with spinal nerve ligation injury as well as nerve injury-induced behavioral hypersensitivity. Rats received a single microinjection of vehicle, saporin, dermorphin or dermorphin-saporin into the rostral ventromedial medulla and 28 days later, underwent either sham or spinal nerve ligation procedures. Animals receiving rostral ventromedial medulla pretreatment with vehicle, dermorphin or saporin that were subjected to spinal nerve ligation demonstrated both thermal and tactile hypersensitivity, and showed significantly increased expression of touch-evoked FOS in the dorsal horn ipsilateral to nerve injury compared with sham-operated controls at days 3, 5 or 10 post-spinal nerve ligation. In contrast, nerve-injured animals pretreated with dermorphin-saporin showed enhanced behaviors and touch-evoked FOS expression in the spinal dorsal horn at day 3, but not days 5 and 10, post-spinal nerve ligation when compared with sham-operated controls. These results indicate the presence of nerve injury-induced behavioral hypersensitivity associated with nerve injury-induced central sensitization. Further, the results demonstrate the novel concept that once initiated, maintenance of nerve injury-induced central sensitization in the spinal dorsal horn requires descending pain facilitation mechanisms arising from the rostral ventromedial medulla.

[Experimental study on effect of kang ai-bao II to cancer cells with cell CT analysis in mice].

The result of the experiment indicated that Kang Ai-bao II ([symbol: see text] II) had a destructive effect on DNA and RNA of cancer cells. Our study provided the basis for the clinical practice. The effect of Kang Ai-bao II on U14 cancer cell in C57 BL mice was investigated with confocal laser scanning microscopy.

[Ultrastructural observation of intratumoral neutrophils and macrophages induced by garlic oil].

After injection of garlic oil in tumor focus a large amount of neutrophils, macrophages and lymphocytes appeared. Some neutrophils and macrophages located adjacent to the tumor cells, some processes of neutrophils and macrophages penetrated into intracellular body of tumor cells. This result showed that garlic oil could induce neutrophils and macrophages against tumor.

[Flow cytometric analysis of the garlic oil effect on DNA content of cancer cell cycle].

Flow cytometry (FCM) is a new technique developed in the recent decade. This technique may measure DNA content of 5000 cells per second and trace the dynamic changes in cell proliferation cycle and offer a hint for designing clinical treatment protocol, monitor prognosis and elucidate the mechanisms of antitumor drugs. The authors previous studies showed significant effect of garlic oil on prolongation of life expectancy and inhibition of tumor growth in mice. Using FCM the authors analysed the effect of garlic oil on cell cycle in S180 tumor cells, 2-6 hrs after single administration or multiple administration the cell number in S phase rapidly decreased, in G1 phase increased. This suggests garlic oil may blockade cells to progress from G1 phase to S phase and result in accumulation of cells in G1 phase and directly inhibit the synthesis of DNA and the cell cycle. Theoretical basis for clinical application was offered and some aspects of antitumor mechanism of garlic oil were elucidated.