New insights from trio whole-exome sequencing in the children with kidney disease: A single-center retrospective cohort study.

BACKGROUND: Kidney disease of children markedly affects their health and development. Limited clinical data of early-stage kidney disease render a tremendous challenge for the accurate diagnosis. Trio whole-exome sequencing (Trio-WES) is emerging as a first-line diagnostic strategy in pediatric kidney disease, and shows important implications for the precision medicine strategies of children with kidney disease. METHODS: Trio-WES was performed in 133 Chinese children with kidney disease and their parents. The results for casual variants in genes known to cause kidney disease were analyzed. We further assessed the genetic diagnostic yield and the clinical implications of genetic testing. RESULTS: An overall diagnostic yield of 52.63% (70/133) was found, and the diagnostic rates ranged from 44.74% to 59.62% in different clinical phenotypes. The diagnostic yield of the three groups of simple proteinuria, renal insufficiency, and "other" was 50%, 50%, and 54.55%, respectively. Eight-seven diagnostic variants were identified in 70 probands with variants spanning 30 genes. The top 7 genes with diagnostic variants were COL4A5 (23, 26.44%), COL4A4 (13, 14.94%), ADCK4 (7, 8.05%), CLCN5 (3, 3.45%), ACE (3, 3.45%), PKD1 (3, 3.45%), and SLC12A3 (3, 3.45%), accounting for 63.22% of all variations in the cohort. CONCLUSIONS: The retrospective cohort study summarized the clinical utility of genetic testing in 133 probands, and expanded the phenotypic and genetic profiles of kidney disease in children. Trio-WES is an efficient diagnostic tool for children with kidney disease, which facilitates the clinical diagnosis and treatment. Our findings have important implications for the precise diagnosis of childhood nephropathy and may provide clinical guideline for disease management.

Brain Network Changes in Lumbar Disc Herniation Induced Chronic Nerve Roots Compression Syndromes.

Lumbar disc herniation (LDH) induced nerve compression syndromes have been a prevalent problem with complex neural mechanisms. Changes in distributed brain areas are involved in the occurrence and persistence of syndromes. The present study aimed to investigate the changes of brain functional network in LDH patients with chronic sciatica using graph theory analysis. A total of thirty LDH adults presenting L4 and/or L5 root (s) compression syndromes (LDH group) and thirty age-, sex-, BMI- and education-matched healthy control (HC group) were recruited for functional MRI scan. Whole-brain functional network was constructed for each participant using Pearson's correlation. Global and nodal properties were calculated and compared between two groups, including small-worldness index, clustering coefficient, characteristic path length, degree centrality (DC), betweenness centrality (BC) and nodal efficiency. Both LDH and HC groups showed small-world architecture in the functional network of brain. However, LDH group showed that nodal centralities (DC, BC and nodal efficiency) increased in opercular part of inferior frontal gyrus; and decreased in orbital part of inferior frontal gyrus, lingual cortex and inferior occipital gyrus. The DC and efficiency in the right inferior occipital gyrus were negatively related with the Oswestry Disability Index in LDH group. In conclusion, the LDH-related chronic sciatica syndromes may induce regional brain alterations involving self-referential, emotional responses and pain regulation functions. But the whole-brain small-world architecture was not significantly disturbed. It may provide new insights into LDH patients with radicular symptoms from new perspectives.

Regional Crustal Vertical Deformation Driven by Terrestrial Water Load Depending on CORS Network and Environmental Loading Data: A Case Study of Southeast Zhejiang.

Monitoring regional terrestrial water load deformation is of great significance to the dynamic maintenance and hydrodynamic study of the regional benchmark framework. In view of the lack of a spatial interpolation method based on the GNSS (Global Navigation Satellite System) elevation time series for obtaining terrestrial water load deformation information, this paper proposes to employ a CORS (Continuously Operating Reference Stations) network combined with environmental loading data, such as ECMWF (European Centre for Medium-Range Weather Forecasts) atmospheric data, the GLDAS (Global Land Data Assimilation System) hydrological model, and MSLA (Mean Sea Level Anomaly) data. Based on the load deformation theory and spherical harmonic analysis method, we took 38 CORS stations in southeast Zhejiang province as an example and comprehensively determined the vertical deformation of the crust as caused by regional terrestrial water load changes from January 2015 to December 2017, and then compared these data with the GRACE (Gravity Recovery and Climate Experiment) satellite. The results show that the vertical deformation value of the terrestrial water load in southeast Zhejiang, as monitored by the CORS network, can reach a centimeter, and the amplitude changes from -1.8 cm to 2.4 cm. The seasonal change is obvious, and the spatial distribution takes a ladder form from inland to coastal regions. The surface vertical deformation caused by groundwater load changes in the east-west-south-north-central sub-regions show obvious fluctuations from 2015 to 2017, and the trends of the five sub-regions are consistent. The amplitude of surface vertical deformation caused by groundwater load change in the west is higher than that in the east. We tested the use of GRACE for the verification of CORS network monitoring results and found a relatively consistent temporal distribution between both data sets after phase delay correction on GRACE, except for in three months-November in 2015, and January and February in 2016. The results show that the comprehensive solution based on the CORS network can effectively improve the monitoring of crustal vertical deformation during regional terrestrial water load change.

Differences in Manifestations and Gut Microbiota Composition Between Patients With Different Henoch-Schonlein Purpura Phenotypes.

Background: Gut microbiota plays an important role in the pathogenesis of immune-mediated diseases. However, the complex pathogenesis of Henoch-Schonlein Purpura (HSP) remains elusive. This study aimed to characterize the gut microbiota in HSP patients and explore the potential association between gut microbiota composition and phenotypic changes in HSP. Methods: 16SrRNA gene sequencing and bioinformatic analyses were performed using total DNA extracted from the fecal microbiota of 34 children with HSP, including 18 primary cases, 16 recurrent cases, and 23 healthy children. Results: The diversity indexes showed significant differences in the microbial community among the primary HSP groups, the recurrent HSP group and healthy controls. The abundance of Escherichia-Shigella in the recurrent HSP group was significantly higher than that in the primary HSP group, and the constructed ROC curve had an AUC value of 0.750. According to the Spearman correlation analysis, the abundance of Bacteroides was positively associated with the serum IgG level in children with HSP, while the abundance of Lachnoclostridium was negatively correlated with the complement component 3 (C3). The diversity indexes of gut microbiota in the HSP group with abdominal symptoms were higher than those in the HSP group without GI involvement, and also higher than those in the healthy control group. In the HSP group with GI involvement, the abundance of Faecalibacterium was decreased, while the abundance of Streptococcus and Fusobacteria was increased, compared to the HSP group without GI involvement. Conclusions: The gut microbiota of children with HSP was different from that of healthy children. The genus Escherichia-Shigella has a diagnostic value for HSP recurrence. Bacteroides and Lachnoclostridium may affect IgG and complement C3 levels in children with HSP. Abdominal symptoms in HSP children were related to gut microbiota (Streptococcus and butyric acid-producing bacteria).

Health-related quality of life in pilots of a Chinese commercial airline.

Health-related quality of life (HRQOL) is currently an important issue in the medical industry. However, data on HRQOL in commercial airline pilots are lacking. This study aimed to investigate HRQOL and its related factors in a sample of commercial pilots. A purposive sample of 373 participants was recruited from a Chinese Commercial Airline. The median (IQR) score for physical health, psychological health and social relationship were 64.3 (75-53.6), 62.5 (70.8-54.2) and 75 (75-58.3), respectively. The mean (SD) score for Environment was 62.2 (16). After controlling for demographics, the multiple linear regression analyses showed that physical activity, fruit intake and vegetable intake were positively correlated with HRQOL score (p < .05), while time-zone flights, smoking, alcohol drinking and being dyslipidemic showed a negative correlation with HRQOL score (p < .05). Healthcare providers should consider time-zone flights, behavioral factors and dyslipidemia when planning related health promotion and disease prevention programs for commercial pilots in the future.

Rhabdomyolysis in a Civil Aviation Pilot.

BACKGROUND: Rhabdomyolysis is a potentially fatal disease caused by trauma, infections, and toxins. Rhabdomyolysis has not been reported in Chinese civil aircrew, but in our case report a male civil copilot contracted rhabdomyolysis after excessive exercise, showing potential for morbidity in pilots.CASE REPORT: After excessive exercise, a 29-yr-old male civil aviation copilot complained of serious myalgia and weakness in lower limb muscles and gross hematuria, whose values of alanine transaminase (ALT), aspartate transaminase (AST), myohemoglobin (Mb), creatine kinase (CK), CK-MB, lactate dehydrogenase (LDH), and -hydroxybutyrate dehydrogenase (-HBDH) were conspicuously increased. Magnetic resonance imaging showed abnormal signal intensities in the lower limbs. The patient was diagnosed with rhabdomyolysis. He was treated with hydration and urine alkalinization. When his condition was stabilized, the patient was discharged. After remaining asymptomatic for 3 mo and getting documentation of normalized lab results, he was granted a first-class medical certificate and returned to work.DISCUSSION: This was the first case of rhabdomyolysis reported in Chinese civil aircrew. Excessive exercise in an overweight pilot may induce rhabdomyolysis. This condition can be controlled and cured by early and effective treatment. Rhabdomyolysis could occur in a population suffering from overweight, obesity, or hyperlipidemia. This case fits in with several other cases of military pilots exercising excessively. The progression could lead to acute kidney injury without prompt and effective intervention. And common symptoms like muscular weakness or myalgia may induce sudden in-flight incapacitation, so early medical intervention should be adopted. Moreover, recurrence of rhabdomyolysis should be considered when resuming flying duties.Liu X, Meng X, Zhang C, Chen J, Li P, Wu X, Fan H. Rhabdomyolysis in a civil aviation pilot. Aerosp Med Hum Res. 2020; 91(11):901903.

Bridging Terrestrial Water Storage Anomaly During GRACE/GRACE-FO Gap Using SSA Method: A Case Study in China.

The terrestrial water storage anomaly (TWSA) gap between the Gravity Recovery and Climate Experiment (GRACE) and its follow-on mission (GRACE-FO) is now a significant issue for scientific research in high-resolution time-variable gravity fields. This paper proposes the use of singular spectrum analysis (SSA) to predict the TWSA derived from GRACE. We designed a case study in six regions in China (North China Plain (NCP), Southwest China (SWC), Three-River Headwaters Region (TRHR), Tianshan Mountains Region (TSMR), Heihe River Basin (HRB), and Lishui and Wenzhou area (LSWZ)) using GRACE RL06 data from January 2003 to August 2016 for inversion, which were compared with Center for Space Research (CSR), Helmholtz-Centre Potsdam-German Research Centre for Geosciences (GFZ), Jet Propulsion Laboratory (JPL)'s Mascon (Mass Concentration) RL05, and JPL's Mascon RL06. We evaluated the accuracy of SSA prediction on different temporal scales based on the correlation coefficient (R), Nash-Sutcliffe efficiency (NSE), and root mean square error (RMSE), which were compared with that of an auto-regressive and moving average (ARMA) model. The TWSA from September 2016 to May 2019 were predicted using SSA, which was verified using Mascon RL06, the Global Land Data Assimilation System model, and GRACE-FO results. The results show that: (1) TWSA derived from GRACE agreed well with Mascon in most regions, with the highest consistency with Mascon RL06 and (2) prediction accuracy of GRACE in TRHR and SWC was higher. SSA reconstruction improved R, NSE, and RMSE compared with those of ARMA. The R values for predicting TWS in the six regions using the SSA method were 0.34-0.98, which was better than those for ARMA (0.26-0.97), and the RMSE values were 0.03-5.55 cm, which were better than the 2.29-5.11 cm RMSE for ARMA as a whole. (3) The SSA method produced better predictions for obvious periodic and trending characteristics in the TWSA in most regions, whereas the detailed signal could not be effectively predicted. (4) The predicted TWSA from September 2016 to May 2019 were basically consistent with Global Land Data Assimilation System (GLDAS) results, and the predicted TWSA during June 2018 to May 2019 agreed well with GRACE-FO results. The research method in this paper provides a reference for bridging the gap in the TWSA between GRACE and GRACE-FO.

Palliative treatment of pelvic bone tumors using radioiodine (125I) brachytherapy.

BACKGROUND: Complete resection of pelvic bone tumors, especially recurrent and metastatic ones, is often impossible to achieve using conventional surgery. This study aimed to assess the benefits and adverse effects of computed tomography (CT)-guided radioiodine (125I) brachytherapy for inoperable recurrent and metastatic bone tumors of the pelvis. METHODS: This was a retrospective study of 22 patients with confirmed pelvic bone tumors (10 females and 12 males; 15-84 years; 21 with primary pelvic tumor and one with pelvic metastasis). CT-guided 125I brachytherapy was performed using 9-21 125I seeds (radioactivity of 0.5-0.7 mCi). Seed implantation was validated by postoperative CT scanning. Complications, pain, survival, and CT-estimated tumor size were carried out to evaluate the therapeutic benefits. RESULTS: Postoperative CT scans revealed satisfactory 125I seed implantation, and the radiation dose delivered to 90% of the target area (D90) was higher than the prescription dose (PD). No obvious complications were observed. Pain was reported by 19 of 22 patients, but 17 reported pain relief after implantation. Follow-up ranged 8-27 (median, 19) months. Tumor size was reduced in 11 patients within 1 month after surgery, nine patients showed no change, and tumor size increased in two patients. Finally, 1- and 2-year survival was 81.8 and 45.5%, respectively; 1- and 2-year local tumor control rates were 59.1 and 36.4%, respectively. CONCLUSIONS: 125I seed implantation significantly reduced bone tumor size and relieved pain, with a low complication rate. These findings suggest that 125I brachytherapy treatment could be a useful palliative approach for pelvic bone tumor treatment.

Shikonin extracted from medicinal Chinese herbs exerts anti-inflammatory effect via proteasome inhibition.

Shikonin, extracted from medicinal Chinese herb (Lithospermum erythrorhizo), was reported to exert anti-inflammatory and anti-cancer effects both in vitro and in vivo. We have found that proteasome was a molecular target of shikonin in tumor cells, but whether shikonin targets macrophage proteasome needs to be investigated. In the current study, we report that shikonin inhibited inflammation in mouse models as efficiently as dexamethasone. Shikonin at 4 µM reduced the Lipopolysaccharides (LPS)-mediated TNFα release in rat primary macrophage cultures, and blocked the translocation of p65-NF-κB from the cytoplasm to the nucleus, associated with decreased proteasomal activity. Consistently, shikonin accumulated IκB-α, an inhibitor of NF-κB, and ubiquitinated proteins in rat primary macrophage cultures, demonstrating that the proteasome is a target of shikonin under inflammatory conditions. Shikonin also induced macrophage cell apoptosis and cell death. These results demonstrate for the first time that proteasome inhibition by shikonin contributes to its anti-inflammatory effect. The novel finding about macrophage proteasome as a target of shikonin suggests that this medicinal compound has great potential to be developed into an anti-inflammatory agent.

Inhibition of tumor cellular proteasome activity by triptolide extracted from the Chinese medicinal plant 'thunder god vine'.

AIMS: The molecular mechanisms of triptolide responsible for its antitumor properties are not yet fully understood. The ubiquitin/proteasome system is an important pathway of protein degradation in cells. This study investigated whether triptolide may inhibit proteasomal activity and induce apoptosis in human cancer cells. MATERIALS AND METHODS: In vitro proteasome inhibition was measured by incubation of a purified 20S proteasome with triptolide. Human breast and prostate cancer cell lines were also treated with different doses of triptolide for different times, followed by measurement of proteasome inhibition (levels of the chymotrypsin-like activity, ubiquitinated proteins and three well-known proteasome target proteins, p27, IκB-α and Bax) and apoptosis induction (caspase-3 activity and PARP cleavage). RESULTS: Triptolide did not inhibit the chymotrypsin-like activity of purified 20S proteasome. However, treatment of triptolide was able to cause decreased levels of cellular proteasomal chymotrypsin-like activity and accumulation of ubiquitinated proteins and three well-known proteasome target proteins in human breast and prostate cancer cells, associated with apoptosis induction. CONCLUSION: It is possible that at least one of metabolites of triptolide has proteasome-inhibitory activity.