ABSTRACT
Diets rich in taurine can increase the production of taurine-conjugated bile acids, which are known to exert antihypertensive effects. Despite their benefits to the heart, kidney and arteries, their role in the central nervous system during the antihypertensive process remains unclear. Since hypothalamic paraventricular nucleus (PVN) plays a key role in blood pressure regulation, we aimed to investigate the function of bile acids in the PVN. The concentration of bile acids in the PVN of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKY) fed with normal chow was measured using LC-MS/MS, which identified taurocholic acid (TCA) as the most down-regulated bile acid. To fully understand the mechanism of TCA's functions in the PVN, bi-lateral PVN micro-infusion of TCA was carried out. TCA treatment in the PVN led to a significant reduction in the blood pressure of SHRs, with decreased plasma levels of norepinephrine and improved morphology of cardiomyocytes. It also decreased the number of c-fos+ neurons, reduced the inflammatory response, and suppressed oxidative stress in the PVN of the SHRs. Most importantly, the TGR5 receptors in neurons and microglia were activated. PVN infusion of SBI-115, a TGR5 specific antagonist, was able to counteract with TCA in the blood pressure regulation of SHRs. In conclusion, TCA supplementation in the PVN of SHRs can activate TGR5 in neurons and microglia, reduce the inflammatory response and oxidative stress, suppress activated neurons, and attenuate hypertension.
Subject(s)
Hypertension , Paraventricular Hypothalamic Nucleus , Receptors, G-Protein-Coupled , Taurocholic Acid , Animals , Male , Rats , Antihypertensive Agents/pharmacology , Blood Pressure/drug effects , Hypertension/drug therapy , Hypertension/metabolism , Neurons/drug effects , Neurons/metabolism , Paraventricular Hypothalamic Nucleus/metabolism , Paraventricular Hypothalamic Nucleus/drug effects , Rats, Inbred SHR , Rats, Inbred WKY , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/geneticsABSTRACT
A 37-year-old female patient was diagnosed with intrahepatic cholangiocarcinoma (ICC), with the lesion located in the right lobe of the liver. Despite radical resection, postoperative adjuvant chemotherapy and a combination of adjuvant chemotherapy and immunotherapy, the patient continued to experience multiple instances of intrahepatic tumor metastases. Furthermore, the patient exhibited significant adverse reactions to systemic chemotherapy and had poor treatment tolerance. Guidance from paraffin section fluorescence in situ hybridization gene sequencing was used to select a combination of immunotherapy and targeted therapy treatments with programmed cell death 1 (PD-1)/PD-1 ligand 1 antibody durvalumab and the targeted drug pemigatinib. The patient tolerated the treatment and has continued to survive for 28 months. According to imaging evaluations, the lesions continued to decrease, with some disappearing completely. The tumor marker carbohydrate antigen 19-9 remained normal for >9 weeks during the treatment. This report described the patient's treatment process in detail and briefly reviewed relevant literature on the treatment progress of postoperative patients with ICC.
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The enzymatic activities of Furin, Transmembrane serine proteinase 2 (TMPRSS2), Cathepsin L (CTSL), and Angiotensin-converting enzyme 2 (ACE2) receptor binding are necessary for the entry of coronaviruses into host cells. Precise inhibition of these key proteases in ACE2+ lung cells during a viral infection cycle shall prevent viral Spike (S) protein activation and its fusion with a host cell membrane, consequently averting virus entry to the cells. In this study, dual-drug-combined (TMPRSS2 inhibitor Camostat and CTSL inhibitor E-64d) nanocarriers (NCs) are constructed conjugated with an anti-human ACE2 (hACE2) antibody and employ Red Blood Cell (RBC)-hitchhiking, termed "Nanoengineered RBCs," for targeting lung cells. The significant therapeutic efficacy of the dual-drug-loaded nanoengineered RBCs in pseudovirus-infected K18-hACE2 transgenic mice is reported. Notably, the modular nanoengineered RBCs (anti-receptor antibody+NCs+RBCs) precisely target key proteases of host cells in the lungs to block the entry of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), regardless of virus variations. These findings are anticipated to benefit the development of a series of novel and safe host-cell-protecting antiviral therapies.
Subject(s)
COVID-19 , Cathepsin L , SARS-CoV-2 , Serine Proteinase Inhibitors , Animals , Mice , Angiotensin-Converting Enzyme 2/metabolism , Cathepsin L/antagonists & inhibitors , Cathepsin L/metabolism , COVID-19/prevention & control , COVID-19/virology , Erythrocytes , Lung/metabolism , Peptide Hydrolases/metabolism , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Serine Endopeptidases/metabolism , Serine Proteinase Inhibitors/pharmacology , Serine Proteinase Inhibitors/therapeutic useABSTRACT
Chemical investigation of the deep-sea-derived fungus Hypocrea sp. ZEN14 afforded a new 3α-hydroxy steroidal lactone, hyposterolactone A (1) and 25 known secondary metabolites (2-26). The structure of the new compound was established by detailed spectroscopic analysis, electronic circular dichroism (ECD) calculation as well as a J-based configuration analysis. Compound 10 showed potent cytotoxicity against Huh7 and Jurkat cells with IC50 values of 1.4â µM and 6.7â µM, respectively.
Subject(s)
Hypocrea , Trichoderma , Humans , Lactones/pharmacology , Steroids/pharmacology , Molecular Structure , Circular DichroismABSTRACT
OBJECTIVE@#To observe the effect of modified acupuncture at sphenopalatine ganglion for allergic rhinitis (AR).@*METHODS@#A total of 80 patients with AR were randomly divided into an observation group and a control group, 40 cases in each group. In the observation group, modified acupuncture at sphenopalatine ganglion was given, 30 min each time, 2 times a week and with an interval of 3-4 days. In the control group, budesonide nasal spray was given. Both groups were treated for 4 weeks. The total nasal symptom score (TNSS) and total non-nasal symptom score (TNNSS) were observed before treatment, after first treatment, after last treatment and 4 weeks after treatment; the scores of visual analogue scale (VAS) and rhinoconjunctivitis quality of life questionnaire (RQLQ) were observed before treatment, after last treatment and 4 weeks after treatment; the recurrence condition was evaluated 4 weeks after treatment; the clinical efficacy was evaluated after last treatment in the two groups.@*RESULTS@#Compared with before treatment, the total scores and each score of TNSS, TNNSS scores after first treatment, after last treatment and 4 weeks after treatment were decreased in both groups (P<0.01, P<0.05). After first treatment, the total score, stuffy nose score, itchy nose score of TNSS and TNNSS score in the observation group were lower than the control group (P<0.01, P<0.05). After last treatment, the total score, stuffy nose score, itchy nose score of TNSS in the observation group were lower than the control group (P<0.01). Four weeks after treatment, the total score and each score of TNSS, TNNSS score in the observation group were lower than the control group (P<0.01, P<0.05). Compared with before treatment, the scores of VAS and RQLQ after last treatment and 4 weeks after treatment were decreased in both groups (P<0.01), and those in the observation group were lower than the control group (P<0.01). The recurrence rate was 13.5% (5/37) in the observation group, which was lower than 44.8% (13/29) in the control group (P<0.01). The total effective rate was 92.5% (37/40) in the observation group, which was higher than 72.5% (29/40) in the control group (P<0.05).@*CONCLUSION@#Modified acupuncture at sphenopalatine ganglion could effectively improve symptoms and quality of life in patients with AR, and the recurrence rate is lower.
Subject(s)
Humans , Quality of Life , Acupuncture Therapy , Rhinitis, Allergic/therapy , Pain MeasurementABSTRACT
The present paper focuses on the controllability of the aviation supply chain network and establishes the judgment criterion for structural controllability of the aviation supply chain network. We determine the control effect by applying the control input to different nodes in the aviation supply chain network. These control nodes include the core enterprises of the aviation supply chain network, the upstream suppliers, and the downstream distributors. It is observed that the control effect is better when the control input is applied to the upstream suppliers of the aviation supply chain network than to the core enterprises of the aviation supply chain network. It is also more desirable to apply the control input to the core enterprises than to the distributors. That is, the control effect is the weakest when the control input is applied to the distributors, whereas the effect is best on application of the control to the upstream suppliers in the supply chain (that is, by choosing the upstream suppliers as the controlled nodes in the aviation supply chain network).
Subject(s)
AviationABSTRACT
Expanded non-coding RNA repeats of CCUG are the underlying genetic causes for myotonic dystrophy type 2 (DM2). There is an urgent need for effective medications and potential drug targets that may alleviate the progression of the disease. In this study, 3140 small-molecule drugs from FDA-approved libraries were screened through lethality and locomotion phenotypes using a DM2 Drosophila model expressing 720 CCTG repeats in the muscle. We identified ten effective drugs that improved survival and locomotor activity of DM2 flies, including four that share the same predicted targets in the TGF-ß pathway. The pathway comprises two major branches, the Activin and BMP pathways, which play critical and complex roles in skeletal development, maintenance of homeostasis, and regeneration. The Drosophila model recapitulates pathological features of muscle degeneration in DM2, displaying shortened lifespan, a decline in climbing ability, and progressive muscle degeneration. Increased levels of p-smad3 in response to activin signaling were observed in DM2 flies. Decreased levels of activin signaling using additional specific inhibitors or genetic method ameliorated climbing defects, crushed thoraxes, structure, and organization of muscle fibers. Our results demonstrate that a decrease in activin signaling is sufficient to rescue muscle degeneration and is, therefore, a potential therapeutic target for DM2.
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Understanding the mechanisms, structuring microbial communities in oligotrophic ocean surface waters remains a major ecological endeavor. Functional redundancy and metabolic tuning are two mechanisms that have been proposed to shape microbial response to environmental forcing. However, little is known about their roles in the oligotrophic surface ocean due to less integrative characterization of community taxonomy and function. Here, we applied an integrated meta-omics-based approach, from genes to proteins, to investigate the microbial community of the oligotrophic northern Indian Ocean. Insignificant spatial variabilities of both genomic and proteomic compositions indicated a stable microbial community that was dominated by Prochlorococcus, Synechococcus, and SAR11. However, fine tuning of some metabolic functions that are mainly driven by salinity and temperature was observed. Intriguingly, a tuning divergence occurred between metabolic potential and activity in response to different environmental perturbations. Our results indicate that metabolic tuning is an important mechanism for sustaining the stability of microbial communities in oligotrophic oceans. In addition, integrated meta-omics provides a powerful tool to comprehensively understand microbial behavior and function in the ocean. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-021-00119-6.
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0bjective To analyze the clinical characteristics, pathological types, treatment and prognosis in children with steroid resistant nephrotic syndrome (SRNS) in Northwest China, in order to provide reference for the treatment of SRNS. Methods:The clinical data, renal pathological results, treatment plan and efficacy of 102 children diagnosed with SRNS in the Department of Nephrology, Xi'an Children's Hospital of Shaanxi Province from January 1st, 2018 to December thirty-first, 2020 were analyzed retrospectively. All children were divided into groups according to age, clinical classification, pathological type, treatment scheme and treatment outcome, and the risk factors affecting the prognosis of children with SRNS were discussed. The measurement datas conforming to normal distribution were expressed as xˉ± s, and t test was used for comparison between groups. Measurement datas that did not conform to normal distribution were represented by M ( Q1, Q3), and Kruskall-Wallis test was used for comparison between groups.Enumeration datas were compared by χ 2 test. Risk factors were analyzed by multiple factor Logistic regression analysis. Results:The median age of onset of 102 children with SRNS was 3.0 years. Focal segmental glomerulosclerosis (FSGS) accounted for 36.3% (37/102), minimal lesions accounted for 33.3% (34/102), and mesangial proliferative glomerulonephritis accounted for 23.5% (24/102). The prevalence rates of hypertension (35.1% (13/37)), 24-h urine protein quantification (130.5 (91.5, 159.6) mg/(kg·24 h) and renal insufficiency (21.6% (8/37)) in FSGS group were higher than those in non-FSGS group (13.8% (9/65), 65.8 (51.2,85.5) mg/(kg·24 h), 4.6% (3/65)). The differences between the two groups were statistically significant (statistical values were χ 2=6.32, Z=5.90, χ 2=7.09; P values were 0.012, <0.001, 0.008). Logistic multivariate regression analysis showed that the hypertension ( OR=4.055, 95% CI 1.178-3.962) and 24 hour urinary protein ( OR=1.036, 95% CI 1.020-1.053) were associated with the increased risk of FSGS ( P values were 0.026 and <0.001). ROC curve ananlysis showed that the optimal critical value of 24 hour urinary protein was 85.65 mg/(kg·24 h) in FSGS. After treatment, complete remission was 61.8%(63/102), partial remission was 14.7%(15/102), and no remission was 23.5%(24/102). By the end of follow-up the treatment effective rate in the small lesion group (94.1%(32/34)) was higher than that in the FSGS Group (51.3%(19/37)), and the difference between the two groups was statistically significant (χ 2=16.02, P<0.001). In the initial immunosuppressive treatment, the complete remission rate of hormone combined with calcineurin inhibitor group (77.1%(37/48)) was higher than that of hormone combined with cyclophosphamide Group (11.1%(3/27)). There was significant difference between the two groups ( Z=32.28, P<0.001). Conclusion:The most common pathological type in children with SRNS was FSGS, and the age of onset was generally small. The prognosis of patients with pathological type FSGS was the worst, and the prognosis of small lesions was better. Hypertension and 24-hour urinary protein quantification were the risk factors of FSGS. Calcineurin inhibitors were the first choice for the second-line immunosuppressants of SRNS in children.
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Objective:To analyze the gene mutation, clinical manifestations and prognosis of children with steroid resistant nephrotic syndrome (SRNS), and to provide reference for the treatment of hereditary SRNS in children.Methods:The clinical data of 29 patients with SRNS and whole exon sequencing (WES) diagnosed in Xi′an Children′s Hospital from January 1, 2018 to December 31, 2020 were retrospectively analyzed.Results:In 29 cases of SRNS with genetic testing, 10 cases (34.5%) were gene mutations, including 2 cases of congenital nephrotic syndrome. The onset age of the patients with gene mutation ranged from 0.1 to 10.7(4.06±3.73)years, and the median age of onset was 3.3 years. The clinical type was mainly nephritis (8/10), and the pathological type was mainly focal segmental glomerulosclerosis (FSGS) (5/7). The main mutant genes were NPHS1 (2 cases), NPHS2 (2 cases), WT1 (2 cases), SMARCAL1 (1 case), COQ8B (1 case), TRPC6 (1 case) and COL4A3 gene (1 case). The main types of genetic variation were missense mutations, and 6 (60%) cases were new mutations that had never been reported in the database containing human pathogenic mutations before. Compared with the non-gene mutation group, 24 hour urinary protein was higher [(177.92±164.59)mg/(kg·24 h) vs (84.99±40.79)mg/(kg·24 h)] in gene mutation group, with statistically significant difference ( P<0.05). In the gene mutation group, there were 2 cases of complete remission, including 1 case of complete remission treated with coenzyme Q10, 1 case of partial remission, and 8 cases of immunosuppression treatment, with an effective rate of 2/8, while in the non-gene mutation group, the effective rate of immunosuppression treatment was 17/19, with statistically significant difference in prognosis between the two groups ( P<0.05). Conclusions:The pathological type of children with hereditary SRNS is mainly FSGS, which are often ineffective to immunosuppressive therapy, poor prognosis and easy to progress to end-stage renal disease. Gene detection is of great significance for etiological diagnosis, treatment and prognosis evaluation in children with SRNS.
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Chemical investigation on the deep-sea-derived fungus Chaetomium globosum led to the isolation of nine compounds. By extensive analyses of the 1D and 2D NMR as well as HR-ESI-MS spectra, their structures were elucidated as xylariol A (1), 1,3-dihydro-4,5,6-trihydroxy-7-methylisobenzofuran (2), epicoccone B (3), epicoccolide B (4), chaetoglobosin G (5), chaetoglobosin Fex (6), cochliodone A (7), cochliodone B (8), and chaetoviridin A (9), assorting as four phenolics (1-4), two cytochalosans (5-6), and three azaplilones (7-9). Compounds 1-3 were firstly reported from C.â globosum. Under the concentrations of 20 µg/mL, 1, 2, and 3 exhibited potent inâ vitro anti-HIV activity with the inhibition rates of 70 %, 75 %, and 88 %, respectively.
Subject(s)
Anti-HIV Agents/chemistry , Chaetomium/chemistry , Seawater/microbiology , Anti-HIV Agents/isolation & purification , Anti-HIV Agents/pharmacology , Cell Line , Chaetomium/metabolism , Genes, Reporter/drug effects , Humans , Magnetic Resonance Spectroscopy , Molecular Conformation , Phenols/chemistry , Phenols/isolation & purification , Phenols/pharmacology , Spectrometry, Mass, Electrospray IonizationABSTRACT
The yellow Monascus pigments (YMPs) named monascin and ankaflavin and the orange Monascus pigments (OMPs) named rubropunctatin and monascorubrin are two groups of bioactive components in a mixture state in the Monascus fermented products. In order to separate these two groups of bioactive pigments, a facile macroporous resin-based method was developed. The weak-polar resin CAD-40 was selected from the seven tested macroporous resins as it revealed better properties for the adsorption and desorption of the YMPs and OMPs. Then, CAD-40 resin was used for column-chromatographic separation. After eluted by 4 bed volumes of ethanol, the yellow group (monascin and ankaflavin) and the orange group (rubropunctatin and monascorubrin) were successfully separated and purified, with an increased content from 49.3% and 44.2% in the crude pigment extract to 85.2% and 83.0% in the final products, respectively. This method would be helpful for the large-scale separation and purification of Monascus pigment products with specific bioactivity.
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Andrastones are unusual 6,6,6,5-tetracyclic meroterpenoids that are rarely found in nature. Previously, three andrastones were obtained from the rice static fermentation extract of the deep-sea-derived fungus Penicillium allii-sativi MCCC 3A00580. Inspired by one strain many compounds (OSMAC) approach, the oat static fermentation on P. allii-sativi was conducted. As a result, 14 andrastones were isolated by UV-guided isolation. The chemical structures of the nine new compounds (1-9) was established by comprehensive analysis of the NMR, MS, ECD, and X-ray crystallography and the five known ones (10-14) were assigned by comparing their NMR, MS, and OR data with those reported in literature. Compound 1 bears a novel hemiketal moiety while 2 is the first example to possess a novel tetrahydrofuran moiety via C-7 and C-15. All isolates were tested for anti-allergic bioactivity. Compound 10, 3-deacetylcitreohybridonol, significantly decreased degranulation with the IC50 value of 14.8 µM, compared to that of 92.5 µM for the positive control, loratadine. Mechanism study indicated 10 could decrease the generation of histamine and TNF-α by reducing the accumulation of Ca2+ in RBL-2H3 cells. These findings indicate andrastones could be potential to discover new anti-allergic candidate drugs.
Subject(s)
Drug Discovery , Penicillium/chemistry , Sesquiterpenes/chemistry , Animals , Dose-Response Relationship, Drug , Fermentation , Histamine/metabolism , Molecular Structure , Penicillium/metabolism , Rats , Sesquiterpenes/isolation & purification , Sesquiterpenes/metabolism , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
Objective:To understand the swallowing function of the elderly in welfare homes of Wenzhou City,Zhejiang Province and to analyze the related factors of swallowing dysfunction. Methods:A total of 507 elderly people aged 60 years and over were surveyed by questionnaires in three welfare homes of Wenzhou City from January 2018 to January 2020.Hinds time-limited water drinking test was used to screen dysphagia. Multivariate unconditional logistic regression analysis was used to analyze the related factors of swallowing dysfunction. Results:The incidence of swallowing dysfunction was 26.04% (132 out of 507). Univariate analysis showed that there were significant differences in the incidence of swallowing dysfunction among the elderly in terms of age, spouse condition, self-care ability, health status, taking sleeping pills, cerebrovascular disease, nervous system disease and depression (P<0.05). Multivariate logistic regression analysis showed that the following factors were related to swallowing dysfunction among the elderly: age ≥80 years old, taking sleeping pills, cerebrovascular diseases, nervous system diseases and depression. Conclusion:The incidence of swallowing dysfunction in elderly people in welfare homes of Wenzhou City is high, especially those aged ≥80 years who need more attention. In addition, taking sleeping pills, cerebrovascular diseases, nervous system diseases and depression all increase the risk of swallowing dysfunction. Corresponding preventive and intervention measures should be formulated.
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Objective To investigate the current prevalence of human soil-borne nematode infections in Yunnan province, so as to provide the scientific evidence for formulating the soil-borne nematodiasis control strategy in the province. Methods In 2015, a total of 20 survey sites were sampled in 10 counties (cities) of Yunnan Province using the stratified cluster random sampling method. Stool samples were collected from all local permanent residents at ages of one year and older in each survey site, and the soil-borne nematode eggs were identified using the modified Kato-Katz technique and the egg number was counted. In addition, the hookworm species was identified using the filter-paperculture method, and Enterobius vermicularis eggs were detected using the cellophane tape method in children at ages of 3 to 6 years. Results A total of 5 067 residents received stool examinations, and 950 residents were detected with soil-borne nematode infections, with an overall prevalence rate of 18.75%. The prevalence of Ascaris lumbricoides, Trichuris trichura and hookworm was 7.52%, 8.47% and 9.02%, respectively. Among 446 children detected using the cellophane tape method, 5 children were detected with E. vermicularis infections. Among the 160 residents with hookworm infections, there were 139 residents with Necator americanus infections (86.88%), 16 with A. duodenale infections (10.00%) and 5 with mixed infections (3.12%). Mild A. lumbricoides (67.98%, 259/381), T. trichura (88.58%, 380/429) and hookworm infections (94.53%, 432/457) were predominant. Among the four ecological zones, the highest prevalence of human soilborne nematode infections was found in the East Tibet-South Sichuan Ecological Zone (31.79%), and among the 10 survey counties (cities), the greatest prevalence was seen in Gongshan Derung and Nu Autonomous County (50.13%), while the lowest prevalence was found in Ninglang Yi Autonomous County (0.40%). The prevalence of human soil-borne nematode infections was 5.67% (43/759), 26.67% (610/2 287) and 14.70% (297/2 021) in high-, moderate- and low-economic-level regions, respectively. There were no significant differences in the prevalence of human soil-borne nematode infections in terms of ecological regions, survey counties (cities) or economic development levels (χ2 = 342.20, 814.60 and 201.34, all P < 0.05). There was no significantdifference in the prevalence of human soil-borne nematode infections between male (18.21%, 441/2 422) and female residents (19.24%, 509/2 645) (χ2 = 0.89, P > 0.05), and soil-borne nematode infections were detected in residents at all age groups, with the greatest prevalence found in residents at ages of 1 to 9 years (25.88%). In addition, the highest prevalence of soil-borne nematode infections was seen in residents with the Dulong Ethnic Minority (82.09%), in preschool children (25.06%) and in illiterate residents (24.80%), and there was no age-, ethnicity-, occupation- or education level-specific prevalence of soil-borne nematode infections detected (χ2 = 46.50, 1 016.96, 36.33 and 52.43, all P < 0.05). Conclusions The prevalence of human soil-borne nematode infections remains high in Yunnan Province. The management of soil-borne nematodiasis requires to be reinforced among low-age children, farmers, old people and residents with low educations levels or ethnic groups.
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BackgroundSince late December 2019, the outbreak of the novel coronavirus disease, COVID-19, that began in Wuhan, has become endemic in China and more than 100 countries and regions in the world. So far, there is rare data on the prevalence of COVID-19 in patients with chronic myelogenous leukemia (CML). We aimed to describe the clinical course, outcomes of CML patients with COVID-19 and prevalence of COVID-19 in CML patients. MethodsIn this multicentre, cross-sectional survey, the clinical data of CML patients with COVID-19 in each center were collected. Simultaneously, an online survey was conducted for information about the CML patients under the management at each center by asking the CML patients to complete a questionnaire,from February 15, 2020 to February 21, 2020. The questionnaire includes demographic data, place of residence, smoking status, CML diagnosis and treatment, comorbidities, combined medications, epidemiological history, symptoms(fever, cough, shortness of breath, etc) during the epidemic. Additional clinical data was collected on respondents suspected or confirmed to have COVID-19. We described and analyzed the prevalence of COVID-19 in CML patients, and focus on the clinical characteristics and outcomes of COVID-19 patients. Data were compared between the CML patients with optimal response and those with non-optimal response. The primary outcome was prevalence of COVID-19 in CML patients, as of Feb 21, 2020. Secondary outcomes included the history of epidemiology of CML patients, the clinical characteristics and outcomes of CML patients with COVID-19. FindingsOf 392 respondents, 223(56.9%) were males, and 240(61.2%) were 50 years or younger. Only 10 patients took drugs irregularly due to the influence of the epidemic because of traffic control, pharmacies unable to operate normally, etc. In the history of epidemiology, there were 4 patients with definite contact with COVID-19, of which 3 were remote contact and 1 was close contact. 12 respondents had fever, cough or shortness of breath during the epidemic, 1 case (common type) was confirmed with COVID-19 and cured after treatment. 1 patient was clinically diagnosed and succumbed. 1 of 299 (0.3%) patients with an optimal response was diagnosed with COVID-19. Of the 50 patients who failed to respond to CML treatment or had a poor response, 1 patient (2%) had a clinical diagnosis of COVID-19. InterpretationWhile the 392 CML respondents required regular referrals to hospitals, they did not have much contact with COVID-19 patients during the outbreak. Patients who failed to achieved an optimal response to CML therapy appear more likely to have a symptomatic infection with SARS-CoV-2. Older patients with comorbidities are at increased risk of death. FundingThis work was supported by grants from the National Natural Science Foundation of China(NSFC)(81873440&81700142).
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Urinary tract infections (UTI) are one of the most common bacterial infections in children up to 30% of who suffer from recurrent infections during the first 6 to 12 months after initial UTI.UTI can be the first sign in almost 30% of children with urinary tract abnormalities, so UTI may be an outpost event of underlying renal disorders.UTI in infants is often associated with congenital abnormalities of the kidney and urinary tract, such as vesicoureteral reflux.Children with recurrent infection are prone to renal damaging and scarring, which further leads to end-stage renal disease.Therefore, early identification, timely treatment and reasonable management are extremely important to improving the prognosis.In this article, domestic and foreign relevant literature in recent years were reviewed to provide reference for diagnosis and treatment of UTI in children.
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Objective:To investigate the clinical features of children with kidney diseases who developed posterior reversible encephalopathy syndrome (PRES), explore the risk factors of PRES in these children, improve the understanding of the diseases, and help early diagnosis and effective treatment of the diseases.Methods:The clinical manifestations, laboratory inspection results, magnetic resonance imaging(MRI) material as well as the prognosis of 10 children with kidney diseases complicated by PRES who were admitted to the Department of Nephrology, Xi′an Children′s Hospital from November 2016 to August 2018 were analyzed retrospectively.Results:A total of 10 children were recruited, including 1 boy and 9 girls, with the onset age ranging from 4 years and 3 months to 13 years [(8.53±3.09) years]. The diagnosed kidney diseases in these patients were primary nephritic syndrome (6 cases), lupus nephritis (1 case), Hepatitis B-related nephritis (1 case), polyarteritis (1 case) and hemorrhagic fever with renal syndrome (1 case). Eight children received corticosteroids and 4 of them received other immunosuppressants simultaneously.Nine children suffered from the infections.All of them had acute onset, and the main symptoms were hypertension (10/10 cases, 100.0%), headache and dizziness (5/10 cases, 50.0%), nausea and vomiting (5/10 cases, 50.0%), visual disturbance (3/10 cases, 30.0%) and convulsions by the ways of seizures definitely (9/10 cases, 90.0%). There was nothing positive in the examinations of the nervous system and fundus.Computer tomography examinations of 9 cases showed nonspecific low-density foci.The cranial MRI scan showed abnormal signals on the cerebral cortex of frontal lobe, parietal lobe and occipital lobe in all these 10 cases.The hyperintensities were observed on the fluid-attenuated inversion recovery sequences of all the 10 cases.Slight hyperintensities on diffusion-weighted images of 4 cases indicated that PRES progressed from reversible angiogenic edema to irreversible cytotoxic edema, meaning a poor prognosis.After blood purification treatment and reducing intracranial pressure, these 4 cases recovered.After timely treatment upon PRES diagnosis, patients had no recurrence and showed a good outcome.Conclusions:Children with kidney diseases and PRES also suffer from hypertension, and the treatment with immunosuppressive agents may precede the occurrence of PRES.Cranial MRI is important for the diagnosis of PRES.
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Decellularized (DC) organs/tissues offer a promising scaffold for regenerative bioengineering. However, it is not clear whether the diabetic mellitus (DM) pancreas can be used in decellularized and recellularized bioengineering. For assessment of these questions, murine pancreatic scaffolds of normal, type 1DM (T1DM) and type 2 DM (T2DM) pancreas were generated using a perfusion decellularization technique and assessed by histology, scanning electron microscopy, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA). The capacity of DC pancreatic scaffolds to support attachment and proliferation of human umbilical vein endothelial cells (HUVECs) and MIN-6 ß cells was also assessed. Our results showed that DC pancreatic scaffolds were successfully produced from T1DM and T2DM pancreas and maintained their extracellular matrix (ECM) composition, 3D ultrastructure, and various cytokines. All of the pancreatic scaffolds were sufficiently cytocompatible and were able to support proliferation and adhesion of HUVECs and MIN-6 ß cells. The preliminary results support the biological utility of diabetes mellitus pancreatic scaffolds and pave the way for further investigations to assess the potential ability of using diabetes mellitus pancreas as scaffolds for recellularization and eventual medical applications.
Subject(s)
Extracellular Matrix/chemistry , Insulin-Secreting Cells/cytology , Pancreas/chemistry , Pancreas/cytology , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Animals , Cell Line , Cell Proliferation , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Type 1/pathology , Diabetes Mellitus, Type 2/pathology , Human Umbilical Vein Endothelial Cells , Humans , Male , Pancreas/pathology , Pancreas/ultrastructure , Rats , Rats, Sprague-DawleyABSTRACT
OBJECTIVE@#The effects of the staurosporine on contraction of self-assembled constructs and extracellular matrix syntheses of goat temporomandibular joint discs were investigated.@*METHODS@#Goat temporomandibular joint disc cells were isolated and cultured to P3, and 5.5×10⁶ cells were combined with different concentrations of staurosporine (0, 0.1, 1, 10, 100 nmol·L⁻¹) in agarose wells and cultured for one week. The samples were frozen and sectioned. Safranin-O, Picro-sirius red and immunohistochemical staining were performed to observe the distributions of the extracellular matrix and the expression of alpha-smooth muscle actin (α-SMA). Enzyme linked immunosorbent assay (ELISA) and Blyscan kits were utilized to quan--titatively detect the contents of type Ⅰ collagen (ColⅠ) and glycosaminoglycans (GAGs).@*RESULTS@#Each group of goat temporo-mandibular joint disc cells in the agarose wells were gathered to self-assemble into a disc-shaped base for 4 hours and then to gradually contract into a round shape. The Picro-sirius red staining was strong and indicated collagen distribution. The Safranin-O staining observed GAGs throughout the entire construct. The expression of ColⅠ was strongly posi-tive in the staurosporine groups; however, the expression of α-SMA was weak. ColⅠ and GAGs contents in the stau-rosporine groups were greater than that of the control group, especially in the 10 nmol·L⁻¹ group (P<0.01).@*CONCLUSIONS@#Staurosporine has a certain effect on the shrinkage of self-assembled constructs; however, such effect is not prominent. Staurosporine contributes to the construction synthesis of extracellular matrix.