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Obstructive sleep apnea (OSA) is a common sleep disordered breathing disorder. As a major global public health problem, untreated OSA can lead to a variety of adverse health outcomes, including various cardiovascular and cerebrovascular diseases, metabolic disorders, and psychiatric disorders such as anxiety and depression. Traditional OSA therapies such as positive airway pressure (PAP), weight loss, oral appliance, upper airway surgery, and postural therapy focus on the anatomical factors of OSA. However, the pathogenesis of OSA is heterogeneous, and non-anatomical factors also play an important role in most patients. Although there is no drug with exact efficacy for the treatment of OSA, with the deepening understanding of the pathophysiological mechanism of OSA, more and more clinical studies are devoted to the study of drug treatment of OSA and its complications, and a series of results have been achieved. The following is a review of the relevant studies on drug treatment of OSA in recent years, hoping to provide literature support and theoretical basis for future research on drug treatment of OSA.
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Mesenchymal stem cells(MSCs)are self-regenerating,rapidly proliferating pluripotent stem cells that depend primarily on their derived pro-angiogenic,inflammatory regulatory,and tro-phic factors to exert beneficial effects that attenu-ate deleterious inflammatory responses,reduce vascular damage,and promote tissue repair and re-generation.Obstructive sleep apnea hypoventila-tion syndrome(OSAHS)is a chronic disorder marked by oropharyngeal collapse during sleep,re-sulting in transient reduced airflow,large fluctua-tions in intrathoracic pressure,and intermittent hy-poxia and hypercapnia.OSAHS subsequently cyto-kine-mediated inflammatory cascades,oxidative stress,and ischemia,recruit MSCs from inflamed and damaged tissues through MSCs-derived of anti-inflammatory and pro-angiogenic factor activity,re-duce hypoxia,suppress inflammation,promote re-generation,and prevent fibrosis in OSAHS-injured tissues.In this paper,we will describe the patho-genesis of inflammation,oxidative stress,fibrosis and ischemia from the perspective of OSAHS,high-lighting the current research progress on MSCs-de-pendent regulation of OSAHS-related pathology.
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Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible and typical chronic fibrotic lung disease. In recent years, significant progress has been made in the pathophysiology, clinical diagnosis and treatment of IPF. However, to date, there is still no cure for IPF. The second messenger cyclic adenosine monophosphate (cAMP) inhibits fibroblast proliferation or differentiation into myofibroblasts during the development of IPF. Phosphodiesterase 4 (PDE4) is a major camp-degrading enzyme in lung fibroblasts, which is up-regulated during the progression of fibrosis. PDE4 inhibitors have anti-fibrosis effects in vivo and in vitro in IPF models. In addition, PDE4 is widely involved in inflammatory processes, which are also active in the pathogenesis of IPF. Thus, PDE4 inhibition is a potential therapeutic approach for IPF. This article reviews the pathogenesis of IPF and the physiological function of PDE subtype 4 inhibitors in the treatment of IPF.
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Mammalian cell defense mechanisms are constantly evolving in response to increasing endogenous and exogenous oxidative stress factors. In recent years, as research has deepened, nuclear factor E2-related factor 2 (Nrf2) has been hailed as a "star" molecule in antioxidant damage defense. Billions of dollars have been spent internationally on developing targeted activators or inhibitors. Obstructive sleep apnea (OSA) is the most common form of sleep breathing disorder in clinical practice. Oxidative stress is one of its main pathological mechanisms and is closely related to target organ damage in the heart, brain, lungs, kidneys, and other systems. Recent research has revealed the mechanistic relationship of the Nrf2 pathway in OSA complications, and some natural Nrf2 activators have demonstrated emerging therapeutic effects in animal experiments. However, the activation mode and effect pathway of Nrf2 in different target organs of OSA have not been clarified. Therefore, this article reviews the research progress of the Nrf2 pathway in OSA and its complications, to deepen understanding of the mechanism of OSA complications and provide a potential treatment strategy.
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Objective:To construct a nomogram for predicting the occurrence of renal allograft rejection based on the combination of multimodal ultrasound features and clinical data.Methods:The ultrasound findings and clinical characteristics of 102 patients with transplanted kidneys who underwent renal biopsy in the General Hospital of Eastern Theater Command from January 2021 to March 2022 were analyzed retrospectively. Patients were divided into rejection group and nephropathy group according to Banff transplant kidney pathological diagnostic criteria (2017 edition). Multivariate Logistic regression was used to screen independent predictors related to the status of rejection, and nomograms were drawn based on the independent predictors. The internal validation of the nomogram was carried out by Bootstrap method, and the ROC curve and calibration curve were utilized to evaluate the diagnostic efficacy of the nomogram.Results:Blood urea nitrogen concentration, renal aortic resistance index, absolute time to peak and cortical echo were independent predictors of rejection( OR=1.073, 1.078, 0.843, 0.205; all P<0.05). Incorporating blood urea nitrogen concentration, renal aortic resistance index, absolute peak time and cortical echo, the nomogram was constructed. The AUC of the predictive model was 0.814(95% CI=0.722-0.905) and the cutoff value was 0.67(corresponding to a total score of about 157 points). Both internal verification (AUC=0.788) and calibration curve demonstrated the clinical usefulness of the nomogram. Conclusions:The nomogram for predicting the occurrence of rejection in renal allograft patients based on multimodal ultrasound features and clinical data can guide the individualized treatment of patients with renal dysfunction.
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INTRODUCTION: Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC), and provides a target for a dendritic cell (DC) vaccine. CD137 ligand (CD137L) expressed on antigen presenting cells, costimulates CD137-expressing T cells, and reverse CD137L signaling differentiates monocytes to CD137L-DC, a type of DC, which is more potent than classical DC in stimulating T cells. METHODS: In this phase I study, patients with locally recurrent or metastatic NPC were administered CD137L-DC pulsed with EBV antigens (CD137L-DC-EBV-VAX). RESULTS: Of the 12 patients treated, 9 received full 7 vaccine doses with a mean administered cell count of 23.9 × 106 per dose. Treatment was well tolerated with only 4 cases of grade 1 related adverse events. A partial response was obtained in 1 patient, and 4 patients are still benefitting from a progression free survival (PFS) of currently 2-3 years. The mean pre-treatment neutrophil: lymphocyte ratio was 3.4 and a value of less than 3 was associated with prolonged median PFS. Progressors were characterized by a high frequency of naïve T cells but a low frequency of CD8+ effector T cells while patients with a clinical benefit (CB) had a high frequency of memory T cells. Patients with CB had lower plasma EBV DNA levels, and a reduction after vaccination. CONCLUSION: CD137L-DC-EBV-VAX was well tolerated. The use of CD137L-DC-EBV-VAX is demonstrated to be safe. Consistent results were obtained from all 12 patients, indicating that CD137L-DC-EBV-VAX induces an anti-EBV and anti-NPC immune response, and warranting further studies in patients post effective chemotherapy. PRECIS: The first clinical testing of CD137L-DC, a new type of monocyte-derived DC, finds that CD137L-DC are safe, and that they can induce an immune response against Epstein-Barr virus-associated nasopharyngeal carcinoma that leads to tumor regression or prevents tumor progression.
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Infecciones por Virus de Epstein-Barr , Neoplasias Nasofaríngeas , Ligando 4-1BB/genética , Células Dendríticas , Herpesvirus Humano 4 , Humanos , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapiaRESUMEN
Objective:To investigate the clinical value of conventional ultrasound combined with automated breast volume scanner (ABVS) in predicting axillary lymph node metastasis (ALNM) of patients with invasive ductal carcinoma.Methods:A retrospective analysis was performed in 96 patients in the General Hospital of Eastern Theater Command from January 2014 to December 2020. All patients were examined by conventional ultrasound and ABVS before treatment. The patients were divided into the ALNM group and non-axillary lymph node metastasis (N-ALNM) group according to the postoperative pathological results. The differences of ultrasound parameters between the two groups were compared, and Logistic regression was used to analyze the independent predictive factors of ALNM. The ROC curve was plotted to evaluate the diagnostic efficacy for ALNM.Results:Compared with the N-ALNM group, the ALNM group had the characteristics of larger long diameters, unclear boundary, uneven internal echo, Adler blood flow grade Ⅱ-Ⅲ and retraction phenomenon (all P<0.05). Logistic regression analysis showed that the long diameter, uneven internal echo, and retraction phenomenon were independent predictors of ALNM ( OR=1.051, 4.055, 3.493, all P<0.05). The area under curve of ALNM was 0.752(0.653-0.834), the sensitivity and specificity were 54.7% and 83.7%, respectively. Conclusions:The long diameter, uneven internal echo, and retraction phenomenon measured by conventional ultrasound and ABVS are independent predictors of ALNM. The combination of the three can provide imaging references for the evaluation of ALNM of breast cancer.
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Objective:To investigate the value of ultrasound in predicting pathological complete response(PCR) of breast cancer patients after neoadjuvant chemotherapy(NAC).Methods:A retrospective analysis was performed in 125 patients(127 breast cancer masses) who underwent NAC in General Hospital of Eastern Theater Command from January 2014 to December 2020. All patients underwent ultrasound examination before and after NAC. The patients were divided into PCR group and non-pathological complete response(NPCR) group according to the postoperative pathological results. The differences of ultrasound parameters between the PCR group and NPCR group before NAC were compared, and Logistic regression was used to analyze the independent predictive factors of PCR. The ROC curve was plotted to evaluate the diagnostic efficacy in predicting PCR.Results:Before NAC, the longest diameter of breast cancer in the PCR group was smaller than that in the NPCR group ( P<0.05). There were significant differences in tumor shape, boundary, angulation/crab foot sign, and lateral acoustic shadowing between the two groups (all P<0.05). Logistic regression analysis showed that the longest tumor diameter, clear boundary, and lateral acoustic shadowing were independent predictors of PCR( OR=0.935, 0.321, 5.710, all P<0.05). The area under curve(AUC) of PCR was 0.810 (95% CI=0.731-0.874), the sensitivity and specificity were 61.8% and 88.2% respectively. Conclusions:The longest tumor diameter, boundary, and lateral acoustic shadow assessed by ultrasound are independent predictors of PCR. The combination of the three parameters can provide imaging references for the clinical treatment of breast cancer.
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Objective To evaluate the efficacy of dexmedetomidine in preventing postoperative de-lirium in the patients with schizophrenia. Methods Ninety patients with schizophrenia of both sexes, with American Society of Anesthesiologists physical status Ⅰ or Ⅱ, aged 20-60 yr, weighing 45-90 kg, with a history of long-term use of antipsychotics, scheduled for elective emergency operation under general anes-thesia, were divided into 3 groups ( n=30 each) using a random number table method: high-dose dexme-detomidine group ( group HD ) , low-dose dexmedetomidine group ( group LD ) and control group ( group C) . In HD and LD groups, dexmedetomidine was intravenously injected in doses of 1. 0 and 0. 5 μg∕kg, respectively, over 10 min prior to induction of anesthesia, followed by continuous infusion at 0. 4 and 0. 2μg · kg-1 · h-1 , respectively, until the end of operation. Anesthesia was maintained with propofol, remifentanil and sevoflurane, and bispectral index value was maintained at 40-55. Patient-controlled intra-venous analgesia was performed within 48 h after operation, and visual analogue scale score was main-tained≤3. The end-tidal concentration of sevoflurane ( ETsev) was recorded at 30 min after endotracheal intubation. The sleep quality was evaluated and scored at 6 h and 1, 2 and 3 days after operation. The oc-currence of delirium during emergency from anesthesia and within 3 days after operation was recorded. The occurrence of postoperative adverse reactions such as bradycardia, hypotension and hypoxemia was also re-corded. Results Compared with group C, the ETsev, sleep quality scores at each time point after opera-tion and incidence of delirium during emergency from anesthesia and within 3 days after operation ( 3%) were significantly decreased in group HD, and the ETsev, sleep quality scores at 6 h after operation and in-cidence of delirium during emergency from anesthesia were significantly decreased ( P<0. 05) , and no sig-nificant change was found in the incidence of delirium within 3 days after operation in group LD ( P>0. 05) . The ETsev and incidence of delirium within 3 days after operation were significantly lower in group HD than in group LD ( P<0. 05) . There was no significant difference in the incidence of bradycardia, hypotension or hyoxemia among C, HD and LD groups (P>0. 05). Conclusion Dexmedetomidine given as a loading dose of 1. 0μg∕kg followed by a maintenance dose of 0. 4μg·kg-1 ·h-1 can prevent postoperative delirium effectively in the patients with schizophrenia.
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Objective To evaluate the effect of curcumin on lidocaine-induced nerve injury and the role of protein kinase B ( Akt) and extracellular signal-regulated kinase 1∕2 ( ERK1∕2) signaling pathway in rats. Methods Eighty SPF male Sprague-Dawley rats, aged 8-10 weeks, weighing 220-250 g, were di-vided into 8 groups ( n=10 each) using a random number table method: control group ( group C) , sham operation group (group S), lidocaine group ( group L), dimethyl sulfoxide ( DMSO) group, low-dose curcumin group ( group CL ) , high-dose curcumin group ( group CH ) , curcumin plus ERK inhibitor PD98059 group (group P) and curcumin plus Akt inhibitor MK-2206 group (group M). The model of nerve injury was established by injecting 2% lidocaine 10μl via the catheter in anesthetized rats in the other six groups except for C and S groups. Drugs were injected through a microcatheter for 14 consecutive days starting from 3rd day after IT catheterization as follows: DMSO 10μl, curcumin 100μg∕10μl and curcu-min 500 μg∕10 μl were injected once a day in D, CL and CH groups, respectively; curcumin 500 μg∕10μl was injected once a day, and D9805910μg and MK-220612μg ( in 5μl DMSO) were intraperitoneal-ly injected once a week in P and M groups, respectively. The mechanical paw withdrawal threshold ( MWT) and thermal paw withdrawal threshold ( TWL) on the operated side were measured on 1 day before IT catheterization, before administration on 3rd day after IT catheterization, and on 14th day after adminis-tration. The spinal cord was removed on 1st day after the end of administration for determination of the ex-pression of ERK1∕2, phosphorylated ERK1∕2 (p-ERK1∕2), Akt, phosphorylated Akt (p-Akt), c-fos, Bcl-2 and Bax ( by Western blot) and expression of ERK1∕2 and Akt mRNA ( by real-time polymerase chain reaction) . Results Compared with group C, the MWT was significantly decreased, the TWL was short-ened, the expression of ERK1∕2 protein and mRNA, p-ERK1∕2, c-fos, Akt protein and mRNA, p-Akt and Bcl-2 was down-regulated, and the expression of Bax was up-regulated in group L (P<0. 05). Com-pared with group L, the MWT was significantly increased, and the TWL was prolonged in CL, CH, P and M groups, the expression of p-ERK1∕2, c-fos, p-Akt and Bcl-2 was up-regulated, and the expression of Bax was down-regulated in CL and CH groups, the expression of p-Akt and Bcl-2 was up-regulated, and the expression of Bax was down-regulated in group P , and the the expression of p-ERK1∕2 and c-fos was up-regulated in group M ( P<0. 05) . Compared with group CH, the MWT was significantly decreased, and the TWL was shortened in P and M groups, the expression of p-ERK1∕2 and c-fos was down-regulated in group P, and the expression of p-Akt and Bcl-2 was down-regulated, and the expression of Bax was up-reg-ulated in group M ( P<0. 05) . Conclusion Curcumin can reduce lidocaine-induced nerve injury, and the mechanism may be partly related to enhancing the activity of Akt and ERK1∕2 signaling pathway in rats.
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Objective To investigate the clinical outcomes of immunocompromised (IC) children with pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU).Methods Fifty-six PADRS children were enrolled and the data of clinical characteristics,immunological status,complications,treatments and outcomes were collected and analyzed by using univariate and multivariate regression models.Results There were 20 children in the immunocompromised group and 36 in the control group.Immunocompromised children were older and weighted greater than the control ones (P=0.003 and P<0.01,respectively).Peripheral blood leukocyte,neutrophil and platelet counts were significantly lower in IC group compared with control group (P=0.060,P=0.006 and P=0.023,respectively).In addition,high-frequency oscillatory ventilation (HFOV) was used less frequently in the IC group (P=0.015).The PICU mortality of the IC group was significantly higher than that of control group (P=0.003).The proportion of IC patients and the incidence of ventilator-associated lung injury differed significantly between survivors and non-survivors (P=0.003 and P=0.046,respectively).After adjusting for other confounding factors by using multivariate logistic regression analysis,IC was associated with a higher mortality (OR=6.986,95% CI:1.812-26.930,P=0.005).Survival analysis also indicated that IC children with ARDS had lower 28-day survival rate than the non-IC children (P=0.022).Conclusions IC children with PARDS have a higher PICU mortality than children with normal immune function.Immunocompromise is an important predictor of poor outcomes in children with PARDS.
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This article analyzes the risk factors of cystospasm and the related nursing countermeasure during cystospasm. The risk factors of cystospasm were analyzed by checking literature published in recent years. These studies suggest that only by fully understanding the risk factors of cystospasm can we take corresponding nursing measures on the patients. At the same time the occurrence of cystospasm can be reduced. It also can relieve the patients' pain and anxiety and help the patients recover earlier.
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Multi-drug resistance(MDR) is the most frequent reason for tumor chemotherapeutic failure.ATP binding cassette(ABC) drug transporters play an important role in tumor MDR.ABCC1 is one of the members of ABC transporter super-family,which lead to drug risistance via discarding drug out of cell or changing the drug distribution in a cell.In this article,we reviewed the advance in MDR mediated by ABCC1 and its reverse.
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AIM:To investigate the effects of Fu Fang Xiao Chai Hu Tang(FFXCHT)on level of Interleukin-2 and value of CD4+/CD8+ in mice bearing Ehrlish ascites carcinoma(EAC).METHODS:The effects of FFXCHT on the EAC were observed and index of thymus and spleen were observed.The method of [3H]-TdR incorporation was used to measure the IL-2 level,and the value of CD4+/CD8+ was assayed by ELITE calibur flow cytometry.RESULTS:Compared with the model group,FFXCHT inhibited the growth of EAC(P