ABSTRACT
@#Objective To predict the probability of lymph node metastasis after thoracoscopic surgery in patients with lung adenocarcinoma based on nomogram. Methods We analyzed the clinical data of the patients with lung adenocarcinoma treated in the department of thoracic surgery of our hospital from June 2018 to May 2021. The patients were randomly divided into a training group and a validation group. The variables that may affect the lymph node metastasis of lung adenocarcinoma were screened out by univariate logistic regression, and then the clinical prediction model was constructed by multivariate logistic regression. The nomogram was used to show the model visually, the receiver operating characteristic (ROC) curve, calibration curve and clinical decision curve to evaluate the calibration degree and practicability of the model. Results Finally 249 patients were collected, including 117 males aged 53.15±13.95 years and 132 females aged 47.36±13.10 years. There were 180 patients in the training group, and 69 patients in the validation group. There was a significant correlation between the 6 clinicopathological characteristics and lymph node metastasis of lung adenocarcinoma in the univariate logistic regression. The area under the ROC curve in the training group was 0.863, suggesting the ability to distinguish lymph node metastasis, which was confirmed in the validation group (area under the ROC curve was 0.847). The nomogram and clinical decision curve also performed well in the follow-up analysis, which proved its potential clinical value. Conclusion This study provides a nomogram combined with clinicopathological characteristics, which can be used to predict the risk of lymph node metastasis in patients with lung adenocarcinoma with a diameter≤3 cm.
ABSTRACT
@#Esophageal cancer is the seventh most common cancer worldwide. On August 29, 2023, National Comprehensive Cancer Network (NCCN) released the NCCN esophageal and esophagogastric junction cancers clinical practice guidelines in oncology (version 3. 2023). This article aims to highlight the key updates in treatment and follow-up recommendations between the version 3 and the version 2 in 2023, providing the latest guidance for the management of esophageal cancer in our country.
ABSTRACT
Xenotransplantation is an efficient pathway to solve the problem of transplant organ source deficiency in clinical settings. With the increasing progress of gene editing technique and immune suppression regimen, important development has been achieved on researches regarding pig to non-human primate kidney xenotransplantation, which provides a good condition for the introduction of the technique in the clinical application. In view of the substantial difference between human and non-human primate, and to meet the needs of current ethic requirements, it is necessary to perform subclinical studies for pig to human kidney xenotransplantation. In recent years, such subclinical studies with regard to the genetically modified pig to brain death recipient kidney xenotransplantation had been performed, indicating that kidney xenotransplantation gradually began to transit to the clinical development stage. However, donor/recipient selection and immune suppression regimen has not reached a consensus yet, and has to be clarified in subclinical studies. In this article, the current status and confronted problems of donor/recipient selection, immune suppression regimen and post transplantation management in the subclinical studies of kidney xenotransplantation were reviewed, aiming to promote the clinical transformation of kidney xenotransplantation to the clinical application.
ABSTRACT
ObjectiveTo explore the mechanism of Bushen Huoxue enema in treating the rat model of kidney deficiency and blood stasis-thin endometrium （KDBS-TE） by transcriptome sequencing. MethodThe rat model of KDBS-TE was established by administration of tripterygium polyglycosides tablets combined with subcutaneous injection of adrenaline. The pathological changes of rat endometrium in each group were then observed. Three uterine tissue specimens from each of the blank group， model group， and Bushen Huoxue enema group were randomly selected for transcriptome sequencing. The differentially expressed circRNAs， lncRNAs， and miRNAs were screened， and the disease-related specific competitive endogenous RNA （ceRNA） regulatory network was constructed. Furthermore， the gene ontology （GO） functional annotation and the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment were performed for the mRNAs in the network. ResultCompared with the blank group， the model group showed endometrial dysplasia， decreased endometrial thickness and endometrial/total uterine wall thickness ratio （P<0.01）， and differential expression of 18 circRNAs， 410 lncRNAs， and 7 miRNAs. Compared with the model group， the enema and estradiol valerate groups showed improved endometrial morphology and increased endometrial thickness and ratio of endometrial to total uterine wall thickness （P<0.05）. In addition， 21 circRNAs， 518 lncRNAs， and 17 miRNAs were differentially expressed in the enema group. The disease-related specific circRNA-miRNA-mRNA regulatory network composed of 629 nodes and 664 edges contained 2 circRNAs， 34 miRNAs， and 593 mRNAs. The lncRNA-miRNA-mRNA regulatory network composed of 180 nodes and 212 edges contained 5 lncRNAs， 10 miRNAs， and 164 mRNAs. The mNRAs were mainly enriched in Hippo signaling pathway， autophagy-animal， axon guidance， etc. ConclusionBushen Huoxue enema can treat KDBS-TE in rats by regulating specific circRNAs， lncRNAs， and miRNAs in the uterus and the ceRNA network.
ABSTRACT
Objective@#The objective of this study was to analyze the different brain oxygen metabolism statuses in preeclampsia using magnetic resonance imaging and investigate the factors that affect cerebral oxygen metabolism in preeclampsia. @*Materials and Methods@#Forty-nine women with preeclampsia (mean age 32.4 years; range, 18–44 years), 22 pregnant healthy controls (PHCs) (mean age 30.7 years; range, 23–40 years), and 40 non-pregnant healthy controls (NPHCs) (mean age 32.5 years; range, 20–42 years) were included in this study. Brain oxygen extraction fraction (OEF) values were computed using quantitative susceptibility mapping (QSM) plus quantitative blood oxygen level-dependent magnitude-based OEF mapping (QSM + quantitative blood oxygen level-dependent imaging or QQ) obtained with a 1.5-T scanner. Voxel-based morphometry (VBM) was used to investigate the differences in OEF values in the brain regions among the groups. @*Results@#Among the three groups, the average OEF values were significantly different in multiple brain areas, including the parahippocampus, multiple gyri of the frontal lobe, calcarine, cuneus, and precuneus (all P-values were less than 0.05, after correcting for multiple comparisons). The average OEF values of the preeclampsia group were higher than those of the PHC and NPHC groups. The bilateral superior frontal gyrus/bilateral medial superior frontal gyrus had the largest size of the aforementioned brain regions, and the OEF values in this area were 24.2 ± 4.6, 21.3 ± 2.4, and 20.6 ± 2.8 in the preeclampsia, PHC, and NPHC groups, respectively. In addition, the OEF values showed no significant differences between NPHC and PHC. Correlation analysis revealed that the OEF values of some brain regions (mainly involving the frontal, occipital, and temporal gyrus) were positively correlated with age, gestational week, body mass index, and mean blood pressure in the preeclampsia group (r = 0.361–0.812). @*Conclusion@#Using whole-brain VBM analysis, we found that patients with preeclampsia had higher OEF values than controls.
ABSTRACT
Objective: To investigate the diagnosis and treatment of Chiari malformation patients with hoarseness and other otorhinolaryngological symptoms. Methods: The clinical data of 18 patients of Chiari malformation with hoarseness were retrospectively collected, which was composed of 5 men and 13 women, aged 3-71 with median age of 52. All the patients were admitted to the Affiliated Hospital of Qingdao University from January 1989 to January 2020. All patients underwent brain MRI and laryngoscopy. The patient's symptoms and first diagnosis department, diagnosis time, total course of disease, hoarseness course, diagnosis and treatment, and postoperative recovery time were summarized. Follow-up time was 3-16 years, with median follow-up time of 6.5 years. Descriptive methods were used for analysis. Results: The first visit departments of 18 patients included neurology (9 cases), otorhinolaryngology head and neck surgery (5 cases), pediatrics (2 cases), orthopedics (1 case) and respiratory department (1 case). Except for the 7 cases in neurology department, the other 11 patients were not diagnosed in time. The disease duration of 18 patients with Chiari malformation ranged from 2 months to 5 years, and hoarseness was present from 20 days to 5 years. After diagnosis, 9 patients underwent posterior fossa decompression surgery, and 1 of them underwent syrinx drainage at the same time. The symptoms of 8 cases improved significantly after operation, with the improvement time from 1 to 30 days. In addition, 9 patients chose conservative treatment, among whom 8 had no improvement in symptoms and 6 progressed. Conclusions: Posterior fossa decompression is an effective treatment for Chiari malformation, and the prognosis is good. Timely diagnosis and treatment can improve the prognosis of patients.
Subject(s)
Male , Humans , Female , Child , Hoarseness/etiology , Retrospective Studies , Conservative Treatment , Drainage , LaryngoscopyABSTRACT
Objective:To investigate the value of spectral CT based iodine concentration (IC) parameters for preoperative prediction of lymphovascular invasion (LVI) in gastric cancer.Methods:Between January 2021 and November 2021, 266 patients diagnosed as gastric adenocarcinomas by endoscopy and undergoing gastrectomy at the Affiliated Cancer Hospital of Zhengzhou University were recruited prospectively. They were divided into LVI and non-LVI groups according to pathological reports. Triple phase contrasted enhanced CT scans, including arterial phase (AP), venous phase (VP) and delayed phase (DP) were performed on a spectral CT platform within one week before surgery. The IC of gastric cancer lesions at three enhanced phases were measured based on iodine maps, and the normalized IC (nIC) was calculated. The thickness of the tumor was measured. Clinicopathological features were collected, including ulceration, pathological tumor staging (pT), pathological node staging (pN), histodifferentiation, Lauren subtype, perineural invasion (PNI), positive node numbers and positive node ratio. Student′s t tes t or Mann-Whitney U test were used to compare the differences of continuous variables between the two groups, while Chi-square test or Fisher′s exact test was used for categorical data. Multivariable logistic regression analysis was used to screen independent risk factors of LVI, and to build a combined parameter based on risk factors. The receiver operating characteristic curve analysis was performed to determine the predictive efficacy of IC parameters and the combined parameter for LVI. DeLong′s test was used to compare the differences among different area under the curve (AUC). Results:There were statistical differences in tumor thickness, ulceration, pT, pN, histodifferentiation, positive node numbers, positive node ratio, Lauren subtype and PNI between LVI and non-LVI groups ( P<0.05). The values of IC VP, IC DP, nIC VP, nIC DP in LVI group were statistically higher than those in non-LVI group ( t=3.77, 4.23, 4.25, 6.12, all P<0.001), with the AUC (95%CI) of 0.674 (0.610-0.738), 0.677 (0.614-0.741), 0.731 (0.671-0.792), 0.700 (0.636-0.764) for predicting LVI, respectively. Multivariable logistic regression analysis revealed that tumor thickness (OR=1.148, 95%CI 1.085-1.237, P<0.001) and nIC VP (OR=209.904, 95%CI 14.874-644.362, P<0.001) were independent predictors for LVI, the combined parameter incorporating these two factors yielded an AUC (95%CI) of 0.790 (0.736-0.937), which was statistically higher than any single parameter of IC VP, IC DP, nIC VP and nIC DP ( Z=3.07, 3.29, 2.10, 2.60, P=0.002, 0.001, 0.036, 0.009). Conclusion:The IC and nIC values of gastric cancer lesions derived from the VP and DP on spectral CT can effectively predict LVI status in gastric adenocarcinomas, and the combination of nIC VP and tumor thickness can further improve the predictive efficacy.
ABSTRACT
Hip fractures are among the most common fractures in the elderly, presenting to be a leading cause of disability and mortality. Surgical treatment is currently the main treatment method for hip fractures. The incidence of perioperative malnutrition is increased after hip fractures in the elderly due to the comorbidities, decreased basal metabolic rate, accelerated protein breakdown, weakened anabolism and surgical stress. However, malnutrition not only increases the incidence of postoperative complications, but also leads to increased mortality, indicating an important role of perioperative nursing management of nutrition for the elderly patients with hip fractures. At present, there still lacks scientific guidance and application standards on perioperative nursing management of nutrition for the elderly patients with hip fractures. Therefore, the Orthopedic Nursing Committee of Chinese Nursing Association and the Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Expert consensus on perioperative nursing management of nutrition for elderly patients with hip fractures ( version 2023) according to evidence-based medical evidences and their clinical experiences. Fourteen recommendations were made from aspects of nutrition screening, nutrition assessment, nutrition diagnosis, nutrition intervention and nutrition monitoring to provide guidance for perioperative nursing management of nutrition in elderly patients with hip fractures.
ABSTRACT
Hip fracture is considered as the most severe osteoporotic fracture characterized by high disability and mortality in the elderly. Improved surgical techniques and multidisciplinary team play an active role in alleviating prognosis, which places higher demands on perioperative nursing. Dysfunction, complications, and secondary impact of anaesthesia and surgery add more difficulties to clinical nursing. Besides, there still lack clinical practices in perioperative nursing for elderly patients with hip fracture in China. In this context, led by the Orthopedic Nursing Committee of Chinese Nursing Association, the Expert consensus on clinical practice in perioperative nursing for elderly patients with hip fracture ( version 2023) is developed based on the evidence-based medicine. This consensus provides 11 recommendations on elderly patients with hip fracture from aspects of perioperative health education, condition monitoring and inspection, complication risk assessment and prevention, and rehabilitation, in order to provide guiding advices for clinical practice, improve the quality of nursing and ameliorate the prognosis of elderly patients with hip fracture.
ABSTRACT
Objective:To investigate the clinical efficacy of conbercept combined with whole retina laser photocoagulation in the treatment of ischemic central retinal vein occlusion (iCRVO) with macular edema (ME) and its effect on visual prognosis and retinal blood flow.Methods:A prospective study was conducted on 80 patients (80 eyes) with iCRVO and ME admitted to the Chongqing Aier Eye Hospital from January 2019 to November 2020. They were randomly divided into two groups using a random number table method, with 40 patients in each group. Among them, the observation group was treated with conbercept combined with whole retina laser photocoagulation, while the control group was treated with whole retina laser photocoagulation alone. We compared the clinical efficacy and safety between two groups. Before and after treatment, the best corrected visual acuity (BCVA), central macular thickness (CMT), and retinal blood flow parameters [retinal superficial capillary plexus (SCP) blood flow density, and macular foveal avascular zone (FAZ) area] were examined in both groups of patients. The Low Vision Quality of Life Scale (CLVQOL) was used to evaluate the quality of life of patients before and after treatment.Results:The total effective rate of the observation group was 95.00%(38/40), which was higher than 77.50%(31/40) of the control group ( P<0.05). The BCVA at 1 week, 1 month, and 3 months after treatment in both groups was significantly higher than that before treatment in this group, while the CMT was significantly lower than that before treatment in this group (all P<0.05). The BCVA of the observation group at 1 week, 1 month, and 3 months after treatment was significantly higher than that of the control group at the same time point (all P<0.05), while the CMT of the observation group at 3 months after treatment was significantly lower than that of the control group at the same time point (all P<0.05). There were no significant changes in SCP blood flow density and macular FAZ area before and after treatment in both groups (all P>0.05). The CLVQOL scale scores and total scores at 1 week, 1 month, and 3 months after treatment in the observation group were significantly higher than before treatment (all P<0.05). After 1 week, 1 month, and 3 months of treatment, the scores and total scores of the CLVQOL scale for distant vision, movement and light perception, and regulatory ability in the control group were significantly higher than those before treatment (all P<0.05); At 1 and 3 months after treatment, the scores of reading, fine work, and daily living ability on the CLVQOL scale were significantly higher than those before treatment (all P<0.05). The CLVQOL scale scores and total scores of distant vision, movement and light perception, reading and fine work in the observation group at 1 and 3 months after treatment were significantly higher than those in the control group at the same time point (all P<0.05); The regulatory ability dimension score of the CLVQOL scale at 3 months after treatment was significantly higher than that of the control group at the same time point (all P<0.05). There was no serious adverse event in both groups during the treatment. Conclusions:Conbercept combined with whole retina laser photocoagulation for iCRVO with ME can safely and effectively improve patients′ vision, promote ME regression, and improve their quality of life. Although the impact on retinal blood flow is not significant, it is beneficial for delaying the progression of the disease.
ABSTRACT
OBJECTIVE Histamine is a conserved neuromodulator in mammalian brains and critically involved in many physiological functions.Understanding the precise structure of histaminergic network is the cor-nerstone in elucidating its function.METHODS Herein,using novel HDC-CreERT2 mice and genetic labeling strategies,we reconstructed a whole brain 3D structure of histaminergic neurons and their outputs at 0.32×0.32×2 μm3 pixel resolution with a cutting-edge fluorescence micro-optical sectioning tomography system(fMOST).And we dissect an appetite control circuit originating from the TMN to medial septal nucleus(MS)using fiber photometry,optogenetics,and chemogenetics interfer-ence.RESULTS We quantified the fluorescence density of all brain areas and found that histaminergic fiber density varied significantly among brain regions.The density of histaminergic fiber was positively correlated with the amount of histamine release induced by optogenetic stim-ulation or physiological aversive stimulation.Moreover,we reconstructed fine morphological structure of 60 hista-minergic neurons via sparse labeling,and uncovered the largely heterogeneous projection pattern of individual his-taminergic neuron.Lastly,we found that MS-projecting histaminergic circuit is functionally inhibited during food consumption,and bidirectionally modulates feeding behavior via downstream H2,but not H1,receptors on MS glutamatergic neurons.CONCLUSION Collectively,this study reveals an unprecedented whole-brain quanti-tative analysis of histaminergic projections at the meso-scopic level,providing a foundation for future functional histaminergic study.And we also demonstrate that this MS-projecting histaminergic circuit is critically involved in feeding,and H2Rs in MS glutamatergic neurons is a promising target for treating body weight problems.
ABSTRACT
OBJECTIVE Epilepsy is considered a cir-cuit-level dysfunction associated with imbalanced excita-tion-inhibition,it is therapeutically necessary to identify key brain regions and related circuits in epilepsy.The subic-ulum is an essential participant in epileptic seizures,but the circuit mechanism underlying its role remains largely elusive.METHODS Here we deconstruct the diversity of subicular circuits in mouse models of epilepsy.Fiber pho-tometry was used to detect intrinsic activities of subicular PV,SST-positive interneurons and CaMK Ⅱ α-positive pyramidal neurons.Optogenetics and chemogenetics were used to selectively active or inactive subicular neu-rons or their projecting terminals.We also used in vivo and in vitro electrophysiology to record membrane charac-teristics of single neuron in distinct sub-regions of the subiculum.Finally,single pulse test was used to detect synaptic transmission strength between the subiculum and its downstream target.RESULTS First,we found that two majority of subicular interneurons,which inner-vate local pyramidal neurons to constrain their excitability,PV and SST-positive neurons showcase distinct calcium dynamics during hippocampal seizures.This could be attributed to distinct neural inputs from para-hippocampal regions of these two neuronal types.During epileptogen-esis,PV and SST neurons undergo different circuit reor-ganization patterns,that is,remarkable increase of exter-nal input to subicular PV neurons are seen after seizures,while SST cells receive decimated neural input.As their downstream targets,excitatory subicular pyramidal neu-rons are also intrinsically activated during hippocampal seizures.Moreover,we found that the subiculum hetero-geneously controls the generalization of hippocampal sei-zures by projecting to different downstream regions.No-tably,anterior thalamus projecting subicular neurons bidi-rectionally mediate seizures,while entorhinal cortex-pro-jecting subicular neurons act oppositely in seizure modu-lation.These two subpopulations are structurally and functionally dissociable.An intrinsically enhanced hyper-polarization-activated current and robust bursting intensity in anterior thalamus-projecting neurons facilitate synaptic transmission,thus contributing to the generalization of hippocampal seizures.CONCLUSION These results demonstrate that subicular neurons and circuits have diverse roles in epilepsy,suggesting the necessity to pre-cisely target specific subicular circuits for effective treat-ment of epilepsy.
ABSTRACT
OBJECTIVE Cognitive deficit is a com-mon comorbidity in temporal lobe epilepsy(TLE)and that is not well controlled by current therapeutics.Currently,how epileptic seizure affects cognitive performance remains largely unclear.The subiculum is the major out-put of the hippocampus,which projects to entorhinal cor-tex and other more distinct brain regions.Physiologically,the subiculum codes spatial working memory and naviga-tion information including place,speed,and trajectory.Importantly,prior studies have noted the importance of the subiculum in the beginning,spreading,and generaliz-ing process of hippocampal seizure.How seizure-activated neurons in subiculum participate in cognitive impairment remains largely elusive.METHODS In this study,we sought to label the subicular seizure-activated c-fos+ neu-rons with a special promoter with enhanced synaptic activity-responsive element E-SARE in the subiculum,combined with chemogenetics and designer receptors exclusively activated by designer drugs(DREADDs),Ca2+ fiber photometry approaches,and behavioral tasks,to reveal the role of these neurons in cognitive impairment in epilepsy.RESULTS We found that chemogenetic inhibi-tion of subicular seizure-tagged c-fos+ neurons(mainly CaMK Ⅱ α+ glutamatergic neurons)alleviates seizure generalization and improves cognitive performance in the hippocampal CA3 kindling TLE model.While inhibition of seizure-labeled c-fos+ GABAergic interneuron shows no effect on seizure and cognition.As a comparison,che-mogenetic inhibition of the whole subicular CaMK Ⅱ α+ neuron impairs cognitive function in na?ve mice in basal condition.Notably,inhibition of subicular seizure-tagged c-fos+ neurons enhances the recruitment of cognition-responsive c-fos+ neurons via increasing neural excitability during cognition tasks.CONCLUSION Our results dem-onstrate that subicular seizure-activated c-fos+ neurons contribute to cognitive impairment in TLE,suggesting sei-zure-tagged c-fos+ neurons as the potential therapeutic target to alleviate cognitive impairment in TLE.
ABSTRACT
OBJECTIVE Epileptic networks are char-acterized as two states,seizures or more prolonged inter-ictal periods.However,cellular mechanisms underlying the contribution of interictal periods to ictal events remain unclear.METHODS Here,we present the procedure for labeling seizure-activated and interictal-activated neuro-nal ensembles in mouse hippocampal kindling model using an enhanced-synaptic-activity-responsive element.This technique is combined with genetically encoded effectors to characterize and manipulate neuronal ensembles recruited by focal seizures(FS-Ens)and interictal periods(IP-Ens)in piriform cortex,a region that plays a key role in seizure generation.RESULTS Ca2+ activities and histo-logical evidence reveal a disjointed correlation between the two ensembles during FS dynamics.Optogenetic acti-vation of FS-Ens promotes further seizure development,while IP-Ens protects against it.Interestingly,both ensem-bles are functionally involved in generalized seizures(GS)due to circuit rearrangement.IP-Ens bidirectionally modulates FS but not GS by controlling coherence with hippocampus.CONCLUSION This study indicates that the interictal state may represent a seizure-preventing environment,and the interictal-activated ensemble may serve as a potential therapeutic target for epilepsy.
ABSTRACT
Sepsis-associated acute kidney injury (SA-AKI), as a common renal dysfunction in sepsis, has become one of the major diseases threatening human health with increasing morbidity and mortality. Based on the theory of "gut-kidney axis", the intestine and kidney have a two-way synergistic relationship in sepsis. Intestinal flora imbalance, endogenous metabolite imbalance, and impaired endothelial barrier integrity are involved in renal injury, and the increase of renal inflammatory mediators interferes with the composition of intestinal microorganisms. Therefore, understanding the intestinal-renal crosstalk mechanism of SA-AKI will help to provide a potential basis for new treatment strategies for SA-AKI.
ABSTRACT
Objective:To explore the protective effect of sivelestat (SV) against sepsis-induced acute kidney injury (AKI) and its molecular mechanism.Methods:According to the random number table method, 64 male Wistar rats were divided into sham operation group (Sham group), sepsis due to cecal ligation and puncture group (CLP group), low dose of SV treatment group (SL group, 50 mg/kg SV was injected into the tail vein at 12 hours and 24 hours after CLP), and high dose of SV treatment group (SH group, 100 mg/kg SV was injected into the tail vein at 12 hours and 24 hours after CLP), with 16 rats in each group. 48 hours after CLP, the 48-hour survival of rats were recorded, all rats were sacrificed and samples were harvested. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of kidney injury molecule-1 (KIM-1), interleukins (IL-1β, IL-6), tumor necrosis factor-α (TNF-α) and neutrophil elastase (NE). Hematoxylin-eosin (HE) staining was used to observe histopathological changes and assess renal tubule injury score. Masson staining was used to detect the collagen volume fraction (CVF) of kidney tissue. Western blotting was used to detect the protein expressions of phosphatidylinositol 3-kinase (PI3K), phosphorylation PI3K (p-PI3K), protein kinase B (AKT), phosphorylation AKT (p-AKT), nuclear factor-κB p65 (NF-κB p65) and NE. The protein expressions of p-PI3K, p-AKT, NF-κB p65 were detected by immunohistochemistry.Results:Compared with Sham group, the 48-hour survival rate of CLP group was significantly reduced. Histopathological results showed that large tubular epithelial cells and brush margins were shed, tubular casts were formed, some tubular atrophy, glomerular hyperemia, renal interstitial inflammatory cell infiltration and increased renal tubular injury score. Renal interstitial fibrosis was obvious and CVF increased. The levels of KIM-1, IL-1β, IL-6, TNF-α and NE in serum were significantly elevated in the CLP group. The proteins expression of inflammatory pathway-related p-PI3K/PI3K, p-AKT/AKT, NF-κB p65 and NE were significantly increased in kidney tissue. It suggested that septic rats had renal injury and the PI3K/AKT inflammatory pathway was activated. Compared with CLP group, there was no significant difference in 48-hour survival in SL group and SH group (68.75%, 75.00% vs. 56.25%, both P > 0.05), but kidney injury was significantly relieved. Specifically: renal tubular injury score and CVF significantly decreased [tubular injury score: 2 (1, 2), 1 (1, 1) vs. 2 (2, 3); CVF: (22.36±0.86)%, (18.74±1.05)% vs. (58.38±0.79)%, all P < 0.05]; the serum levels of KIM-1, IL-1β, IL-6, TNF-α and NE also decreased significantly [KIM-1 (ng/L): 145.03±8.88, 117.58±7.02 vs. 158.22±12.00; IL-1β (ng/L): 108.32±9.00, 92.98±8.06 vs. 133.78±8.48; IL-6 (ng/L): 124.33±10.11, 115.42±8.17 vs. 165.19±5.70; TNF-α (ng/L): 321.56±19.29, 289.68±21.57 vs. 424.88±22.76, NE (mol/L): 93.84±9.14, 75.01±10.56 vs. 113.45±6.39, all P < 0.05]; the proteins expression of inflammatory pathway-related p-PI3K/PI3K, p-AKT/AKT, NF-κB p65 and NE were significantly decreased (p-PI3K/PI3K: 0.93±0.06, 0.67±0.04 vs. 1.27±0.08; p-AKT/AKT: 0.78±0.09, 0.47±0.05 vs. 0.96±0.12; NF-κB p65/GAPDH: 1.43±0.13, 0.85±0.08 vs. 1.88±0.17; NE/GAPDH: 1.45±0.06, 0.91±0.04 vs. 1.71±0.08, all P < 0.05), the positive expressions of p-PI3K, p-AKT and NF-κB p65 in kidney tissue were decreased [p-PI3K positive expression area: (13.36±1.84)%, (8.03±1.12)% vs. (21.56±1.20)%; p-AKT positive expression area: (21.57±0.91)%, (15.21±2.76)% vs. (30.81±2.12)%; NF-κB p65 positive expression area: (25.17±1.38)%, (17.07±2.11)% vs. (37.85±2.50)%, all P < 0.05]. Serum inflammatory factor level, and PI3K/AKT pathway related protein, NF-κB p65, NE protein expression level and p-PI3K, p-AKT, NF-κB p65 positive area and other indicators in renal tissue in SH group were further lower than those in SL group (all P < 0.05). Conclusions:SV can ameliorate sepsis-induced AKI. The mechanism may be related to the inhibition of PI3K/AKT pathway, and high dose of SV has better efficacy.
ABSTRACT
Objective:To investigate whether silence information regulator 1 (SIRT1) could regulate nuclear factor E2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signaling pathway and its role in acute lung injury (ALI) in sepsis rats.Methods:Twenty-four male Sprague-Dawley (SD) rats were randomly divided into sham operation group (Sham group), cecal ligation and puncture (CLP) induced sepsis group (CLP group), sepsis+SIRT1 specific agonist group (CLP+SRT1720 group,10 mg/kg SRT1720 was intraperitoneally injected 2 hours before CLP), sepsis+SIRT1 specific inhibitor group (CLP+EX527 group, 10 mg/kg EX527 was intraperitoneally injected 2 hours before CLP), with 6 rats in each group. The rats were killed 24 hours after modeling and their lung tissues were taken for pathological score (Smith score), superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), tumor necrosis factor-α (TNF-α), interleukins (IL-6, IL-1β), and SIRT1, Nrf2 and HO-1 mRNA and protein expression were detected.Results:The lung tissue of the CLP group mice was severely damaged, the alveolar interval was widened and a large number of inflammatory cells infiltrated, and there was visible pulmonary capillary hyperemia. The Smith score, the levels of TNF-α, IL-6, IL-1β, MDA and 8-OHdG were significantly increased, the levels of SOD, GSH, SIRT1, Nrf2 and HO-1 were significantly decreased in CLP group. After using SIRT1 specific agonist, the lung injury in CLP+SRT1720 group was significantly alleviated compared with that in CLP group, Smith score and lung tissue TNF-α, IL-6, and IL-1β levels were significantly decreased [Smith score: 2.83±0.75 vs. 5.67±0.52, TNF-α (ng/L): 36.78±5.36 vs. 66.99±5.44, IL-6 (ng/L): 23.97±3.76 vs. 45.70±4.16, IL-1β (ng/L): 16.76±1.39 vs. 39.64±2.59, all P < 0.05], SOD activity and GSH content increased [SOD (kU/g): 115.88±3.31 vs. 101.65±1.09, GSH (μmol/g): 8.42±0.81 vs. 5.74±0.46, both P < 0.05], MDA and 8-OHdG contents decreased [MDA (μmol/g): 5.24±0.33 vs. 9.86±0.66, 8-OHdG (ng/L): 405.76±8.54 vs. 647.12±10.64, both P < 0.05], the mRNA and protein expressions of SIRT1, Nrf2 and HO-1 were increased [SIRT1 mRNA (2 -ΔΔCT): 1.49±0.15 vs. 0.64±0.03, Nrf2 mRNA (2 -ΔΔCT): 1.19±0.08 vs. 0.84±0.02, HO-1 mRNA (2 -ΔΔCT): 1.80±0.41 vs. 0.64±0.11, SIRT1 protein (SIRT1/β-actin): 1.03±0.06 vs. 0.52±0.05, Nrf2 protein (Nrf2/β-actin): 1.14±0.10 vs. 0.63±0.05, HO-1 protein (HO-1/β-actin): 1.01±0.11 vs. 0.73±0.03, all P < 0.05]. The lung injury in CLP+EX527 group was more severe than that in CLP group, Smith score and lung tissue TNF-α, IL-6, IL-1β levels were significantly increased [Smith score: 8.00±0.89 vs. 5.67±0.52, TNF-α (ng/L): 87.15±4.23 vs. 66.99±5.44, IL-6 (ng/L): 66.79±2.93 vs. 45.70±4.16, IL-1β (ng/L): 58.99±2.12 vs. 39.64±2.59, all P < 0.05], SOD activity and GSH content decreased [SOD (kU/g): 72.84±3.85 vs. 101.65±1.09, GSH (μmol/g): 3.30±0.67 vs. 5.74±0.46, both P < 0.05], the contents of MDA and 8-OHdG were increased [MDA (μmol/g): 14.14±0.70 vs. 9.86±0.66, 8-OHdG (ng/L): 927.66±11.47 vs. 647.12±10.64, both P < 0.05], the mRNA and protein expressions of SIRT1, Nrf2 and HO-1 were decreased [SIRT1 mRNA (2 -ΔΔCT): 0.40±0.07 vs. 0.64±0.03, Nrf2 mRNA (2 -ΔΔCT): 0.48±0.07 vs. 0.84±0.02, HO-1 mRNA (2 -ΔΔCT): 0.27±0.14 vs. 0.64±0.11, SIRT1 protein (SIRT1/β-actin): 0.20±0.05 vs. 0.52±0.05, Nrf2 protein (Nrf2/β-actin): 0.45±0.01 vs. 0.63±0.05, HO-1 protein (HO-1/β-actin): 0.36±0.08 vs. 0.73±0.03, all P < 0.05]. Conclusions:In the rat model of ALI induced by sepsis, SIRT1 can regulate the activation of Nrf2/HO-1 signaling pathway, upregulate the expression of downstream antioxidant enzymes, reduce oxidative stress injury, and then alleviate the ALI induced by sepsis in rats.
ABSTRACT
Objective:To investigate the prognostic value of the ratio of veno-arterial carbon dioxide partial pressure difference to arterio-venous oxygen content difference (Pv-aCO 2/Ca-vO 2) in children with primary peritonitis-related septic shock. Methods:A retrospective study was conducted. Sixty-three children with primary peritonitis-related septic shock admitted to department of intensive care unit of the Children's Hospital Affiliated to Xi'an Jiaotong University from December 2016 to December 2021 were enrolled. The 28-day all-cause mortality was the primary endpoint event. The children were divided into survival group and death group according to the prognosis. The baseline data, blood gas analysis, blood routine, coagulation, inflammatory status, critical score and other related clinical data of the two groups were statistics. The factors affecting the prognosis were analyzed by binary Logistic regression, and the predictability of risk factors were tested by the receiver operator characteristic curve (ROC curve). The risk factors were stratified according to the cut-off, Kaplan-Meier survival curve analysis compared the prognostic differences between the groups.Results:A total of 63 children were enrolled, including 30 males and 33 females, the average age (5.6±4.0) years old, 16 cases died in 28 days, with mortality was 25.4%. There were no significant differences in gender, age, body weight and pathogen distribution between the two groups. The proportion of mechanical ventilation, surgical intervention, vasoactive drug application, and procalcitonin, C-reactive protein, activated partial thromboplastin time, serum lactate (Lac), Pv-aCO 2/Ca-vO 2, pediatric sequential organ failure assessment, pediatric risk of mortality Ⅲ in the death group were higher than those in the survival group. Platelet count, fibrinogen, mean arterial pressure were lower than those in the survival group, and the differences were statistically significant. Binary Logistic regression analysis showed that Lac and Pv-aCO 2/Ca-vO 2 were independent risk factors affecting the prognosis of children [odds ratio ( OR) and 95% confidence interval (95% CI) were 2.01 (1.15-3.21), 2.37 (1.41-3.22), respectively, both P < 0.01]. ROC curve analysis showed that the area under curve (AUC) of Lac, Pv-aCO 2/Ca-vO 2 and their combination were 0.745, 0.876 and 0.923, the sensitivity were 75%, 85% and 88%, and the specificity were 71%, 87% and 91%, respectively. Risk factors were stratified according to cut-off, and Kaplan-Meier survival curve analysis showed that the 28-day cumulative probability of survival of Lac ≥ 4 mmol/L group was lower than that in Lac < 4 mmol/L group [64.29% (18/28) vs. 82.86% (29/35), P < 0.05]. Pv-aCO 2/Ca-vO 2 ≥ 1.6 group 28-day cumulative probability of survival was less than Pv-aCO 2/Ca-vO 2 < 1.6 group [62.07% (18/29) vs. 85.29% (29/34), P < 0.01]. After a hierarchical combination of the two sets of indicator variables, the 28-day cumulative probability of survival of Pv-aCO 2/Ca-vO 2 ≥ 1.6 and Lac ≥ 4 mmol/L group significantly lower than that of the other three groups (Log-rank test, χ2 = 7.910, P = 0.017). Conclusion:Pv-aCO 2/Ca-vO 2 combined with Lac has a good predictive value for the prognosis of children with peritonitis-related septic shock.
ABSTRACT
Objective:To analyze the incidence of complications of central venous catheterization and risk factors in the Pediatric Intensive Care Unit of Xi'an Children 's Hospital.Methods:The clinical data of 310 children who underwent central venous catheterization in the Pediatric Intensive Care Unit of Xi 'an Children's Hospital from June 2020 to February 2021 were retrospectively analyzed. The incidence of complications of central venous catheterization and risk factors were analyzed.Results:A total of 334 central venous catheters were used in 310 chidren. Among the 310 children who underwent central venous catheterization, 102 children (30.54%) had complications related to central venous catheterization. The complications related to central venous catheterization included catheter infection (13.17%), catheter malposition (8.38%), exudation at the puncture site (4.79%), catheter occlusion (2.99%), accidental removal (0.60%), and central venous thrombosis (0.60%). Central venous catheters were removed in 82 children (24.55%) because of complications. There was a significant difference in the incidence of central venous thrombosis among three surgical approaches: femoral vein, internal jugular vein, and subclavian vein ( χ2 = 7.06, P = 0.029). Longer time for catheterization resulted in a higher incidence of complications, including catheter-related infection ( χ2 = 7.17, P = 0.028), puncture point exudation and obstruction ( χ2 = 8.59, P = 0.014), central venous thrombosis ( χ2 = 6.78, P = 0.034). Regression analysis showed that suture shedding and bleeding at the insertion sites were the main risk factors for catheter-related complications (suture shedding OR = 4.85, P = 0.001; bleeding at the insertion sites OR = 1.83, P = 0.008). Conclusion:The most common complications of central venous catheterization in the Pediatric Intensive Care Unit of Xi'an Children's Hospital include catheter-related infection, catheter malposition, and puncture site exudation. Risk factors for complications during catheter retention include suture shedding and bleeding at the insertion sites.
ABSTRACT
Objective:To follow up the iodine nutrition and intellectual development of school children aged 8-10 years old in Nangqian County of Qinghai Province after 9 years of the implementation of iodine deficiency disorders intervention measures with iodine supplement as the main measure.Methods:In order to improve the iodine nutritional status of the population in Nangqian County, free iodized salt distribution, health education and other intervention measures for iodine deficiency disorders were implemented for 9 consecutive years since 2013. In May 2012 (before iodine supplementation) and September 2021 (after iodine supplementation), the same 5 townships (towns) were selected, and children aged 8-10 years old (half male and half female, age balanced) born locally in the central primary school of each township (town) were selected as the survey subjects. Household edible salt samples and random urine samples were collected for salt iodine and urinary iodine detection; the second revised version of the Chinese Combined Raven's Test (rural version) was used to assess the intelligence quotient (IQ) of children. The Flynn effect (FE) gain was used to adjust IQ, the corrected IQ = (IQ starting point value - current year's IQ value) - FE gain (calculated by 0.74/year). The differences of salt iodine and urinary iodine related indexes, IQ value and corrected IQ were compared before and after iodine supplementation.Results:After iodine supplementation, the coverage rate of iodized salt reached 100.00% (300/300), and the consumption rate of qualified iodized salt reached95.00% (285/300), the median urinary iodine increased to 157.20 μg/L, and all indexes met the elimination standard of iodine deficiency disorders. The IQ value of children aged 8-10 years old after iodine supplementation was 99.00 ± 14.90, significantly higher than that before iodine supplementation (82.00 ± 13.20, F = 156.82, P < 0.001). The FE gain in 9 years was 6.66, and the actual IQ gain of children aged 8-10 years old after iodine supplementation was 10.34. There were statistically significant differences in IQ value before and after iodine supplementation in male and female children ( F = 78.84, 78.88, P < 0.001). After iodine supplementation, there was a statistically significant difference in IQ value between children in the 8-year-old group and the 10-year-old group ( P = 0.010). There were statistically significant differences in IQ value before and after iodine supplementation in 8, 9 and 10 years old groups ( F = 55.23, 65.79, 36.85, P < 0.001). Conclusion:Intervention measures for iodine deficiency disorders, mainly iodine supplement, can significantly improve the iodine nutrition status of children aged 8-10 years old, and significantly promote the intellectual development of children.