RCAN1 deficiency aggravates sepsis-induced cardiac remodeling and dysfunction by accelerating mitochondrial pathological fission.

OBJECTIVE: Cardiac dysfunction and remodeling are serious complications of sepsis and are the main causes of death in sepsis. RCAN1 is a feedback regulator of cardiac hypertrophy. Here, we aim to investigate the role of RCAN1 in septic cardiomyopathy. METHODS: Mice were randomly divided into control-WT, control-RCAN1-/-, LPS-induced WT and LPS-induced RCAN1-/- groups, some with Midiv-1 or KN93 treatment. The protein levels of RCAN1, p-ERK1/2, NFAT3, Drp1, p-Drp1, p-CaMKII in mouse hearts or cultured cardiomyocytes were determined by Western blotting. Myocardial function was assessed by echocardiography. Cardiac hypertrophy and fibrosis were detected by H&E and Masson's trichrome staining. Mitochondrial morphology was examined by transmission electron microscope. Serum level of LDH was detected by ELISA. RESULTS: Our data show that RCAN1 was downregulated in septic mouse heart and LPS-induced cardiomyocytes. RCAN1-/- mice showed a severe impairment of cardiac function, and increased myocardial hypertrophy and fibrosis. The protein levels of NFAT3 and p-ERK1/2 were significantly increased in the heart tissues of RCAN1-/- mice. Further, RCAN1 deficiency aggravated sepsis-induced cardiac mitochondrial injury as indicated by increased ROS production, pathological fission and the loss of mitochondrial membrane potential. Inhibition of fission with Mdivi-1 reversed LPS-induced cardiac hypertrophy, fibrosis and dysfunction in RCAN1-/- mice. Moreover, RCAN1 depletion promoted mitochondrial translocation of CaMKII, which enhanced fission and septic hypertrophy, while inhibition of CaMKII with KN93 reduced excessive fission, improved LPS-mediated cardiac remodeling and dysfunction in RCAN1-/- mice. CONCLUSIONS: Our finding demonstrated that RCAN1 deficiency aggravated mitochondrial injury and septic cardiomyopathy through activating CaMKII. RCAN1 serves as a novel therapeutic target for treatment of sepsis-related cardiac remodeling and dysfunction.

SodA Contributes to the Virulence of Avian Pathogenic Escherichia coli O2 Strain E058 in Experimentally Infected Chickens.

Strains of avian pathogenic Escherichia coli (APEC), the common pathogen of avian colibacillosis, encounter reactive oxygen species (ROS) during the infection process. Superoxide dismutases (SODs), acting as antioxidant factors, can protect against ROS-mediated host defenses. Our previous reports showed that the sodA gene (encoding a Mn-cofactor-containing SOD [MnSOD]) is highly expressed during the septicemic infection process of APEC. sodA has been proven to be a virulence factor of certain pathogens, but its role in the pathogenicity of APEC has not been fully identified. In this study, we deleted the sodA gene from the virulent APEC O2 strain E058 and examined the in vitro and in vivo phenotypes of the mutant. The sodA mutant was more sensitive to hydrogen peroxide in terms of both its growth and viability than was the wild type. The ability to form a biofilm was weakened in the sodA mutant. The sodA mutant was significantly more easily phagocytosed by chicken macrophages than was the wild-type strain. Chicken infection assays revealed significantly attenuated virulence of the sodA mutant compared with the wild type at 24 h postinfection. The virulence phenotype was restored by complementation of the sodA gene. Quantitative real-time reverse transcription-PCR revealed that the inactivation of sodA reduced the expression of oxidative stress response genes katE, perR, and osmC but did not affect the expression of sodB and sodC Taken together, our studies indicate that SodA is important for oxidative resistance and virulence of APEC E058.IMPORTANCE Avian colibacillosis, caused by strains of avian pathogenic Escherichia coli, is a major bacterial disease of severe economic significance to the poultry industry worldwide. The virulence mechanisms of APEC are not completely understood. This study investigated the influence of an antioxidant protein, SodA, on the phenotype and pathogenicity of APEC O2 strain E058. This is the first report demonstrating that SodA plays an important role in protecting a specific APEC strain against hydrogen peroxide-induced oxidative stress and contributes to the virulence of this pathotype strain. Identification of this virulence factor will enhance our knowledge of APEC pathogenic mechanisms, which is crucial for designing successful strategies against associated infections and transmission.

Transfer learning assisted deep neural network for OSNR estimation.

We propose a transfer learning assisted deep neural network (DNN) method for optical-signal-to-noise ratio (OSNR) monitoring and realize fast remodel to response to various system parameters changing, e.g. optical launch power, residual chromatic dispersion (CD) and bit rate. By transferring the hyper-parameters of DNN at the initial stage, we can fast response to the channel variation with fewer training set size and calculations to save consumptions. For feature extraction processing, we use amplitude histograms of received 56-Gb/s QPSK signals as the input for DNN at the initial stage, which shows the root mean squared error (RMSE) of OSNR estimation is less than 0.1 dB with the OSNRs ranging from 5 to 35 dB. Then, we change several system parameters and find superior capabilities of fast remodeling and data resource saving with the proposed method. The required training epochs have about four times reduction, and the required training set size is only one-fifth compared to retraining the network without any accuracy penalty. The DNN assisted by transfer learning can save resources and will be beneficial for real-time application on OSNR estimation.

Fast remodeling for nonlinear distortion mitigation based on transfer learning.

We have proposed and demonstrated a transfer learning (TL)-assisted deep learning network (DNN) for nonlinear distortion compensation in optical side-band PAM-4 modulation and direct-detection transmission. Since there exists partial correlation of nonlinear distortions, we can transfer the parameters of the trained DNN to the target model to speed up remodeling and reduce complexity. We conduct experiments to demonstrate the effectiveness of the proposed scheme in Nyquist PAM-4 transmissions. The required iterations or train size with TL can be less than half of that with retraining without any performance degradation in single-channel transmission. We also extend the proposed scheme into multi-channel transmissions. Since all channels co-propagate on the same fiber, the correlation of nonlinear distortions enables TL to share the parameters among different channels and realize fast remodeling with a better starting rather than a stochastic beginning. The experimental results show that the iterations of TL are one-fourth that of retraining without performance penalty in five-channel transmission.

[Analysis of FANCA gene mutation in a child with refractory leukocytopenia and thrombocytopenia].

OBJECTIVE: To explore the genetic basis of a child affected with refractory leukocytopenia and thrombocytopenia. METHODS: Clinical manifestation and auxiliary examination of the child were discussed. Whole exome next generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA) were used to detected potential mutations of the FANCA gene. RESULTS: Repeated blood tests indicated that the child had abnormal WBC count at (2.7-3.98)×10^9;/L, platelet at (33-81) ×10^9;/L and hemoglobin at (100-120) g/L. NGS showed that she and her mother both carried a heterozygous c.3181A>G mutation (non-pathogenic) and a c.3788_3790del mutation of the FANCA gene. MLPA showed that she and her father both had heterozygous deletion of exons 11 to 14 of the FANCA gene. CONCLUSION: The compound heterozygous mutations of c.3788_3790del and deletion of exons 11 to 14 of the FANCA gene probably underlie the refractory leukocytopenia and thrombocytopenia in the child.

Pretreatment quality of life as a predictor of survival for patients with nasopharyngeal carcinoma treated with IMRT.

BACKGROUND: To evaluate the prognostic significance of pretreatment quality of life for patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy. METHODS: We performed a prospective, longitudinal study on 554 newly diagnosed patients with NPC from April 2011 to January 2015. A total of 501 consecutive NPC patients were included. Patients were asked to complete the EORTC QLQ-C30 (version 3.0) and QLQ-H&N35 questionnaires before treatment. RESULTS: Global health status among QLQ-C30 correlates with EBV DNA(P = 0.019). In addition, pretreatment appetite loss was significantly correlated with EBV DNA(P = 0.02). Pretreatment teeth, opening mouth, feeding tube was significantly correlated with EBV DNA, with P value of 0.003, < 0.0001, and 0.031, respectively. In multivariate analysis, pretreatment cognitive functioning of QLQ-C30 was significantly associated with LRFS, with HR of 0.971(95%CI 0.951-0.990), P = 0.004. Among scales of QLQ-H&N35 for multivariate analysis, pretreatment teeth (P = 0.026) and felt ill (P = 0.012) was significantly associated with PFS, with HR of 0.984 (95%CI 0.971-.998) and 1.004 (95%CI 1.001-1.007), respectively. Felt ill of QLQ-H&N35 was significantly associated with DMFS, with HR of 1.004(95%CI 1.000-1.007), P = 0.043. There is no QoL scale significantly associated with OS after multivariate analysis. CONCLUSIONS: In conclusion, our analysis confirms that pretreatment teeth and felt ill was significantly associated with PFS in NPC patients treated with IMRT. In addition, the posttreatment EBV DNA was significantly associated with OS.

DNA microarray-mediated transcriptional profiling of avian pathogenic Escherichia coli O2 strain E058 during its infection of chicken.

Avian pathogenic Escherichia coli (APEC) cause typical extraintestinal infections in poultry, including acute fatal septicemia, subacute pericarditis, and airsacculitis. These bacteria most often infect chickens, turkeys, ducks, and other avian species, and therefore pose a significant economic burden on the poultry industry worldwide. Few studies have analyzed the genome-wide transcriptional profile of APEC during infection in vivo. In this study, we examined the genome-wide transcriptional response of APEC O2 strain E058 in an in vivo chicken infection model to better understand the factors necessary for APEC colonization, growth, and survival in vivo. An Affymetrix multigenome DNA microarray, which contains most of the genomic open reading frames of E. coli K-12 strain MG1655, uropathogenic E. coli strain CFT073, and E. coli O157:H7 strain EDL 933, was used to profile the gene expression in APEC E058. We identified the in vivo transcriptional response of APEC E058 bacteria collected directly from the blood of infected chickens. Significant differences in expression levels were detected between the in vivo expression profile and the in vitro expression profile in LB medium. The genes highly expressed during infection were involved in metabolism, iron acquisition or transport, virulence, response to stress, and biological regulation. The reliability of the microarray data was confirmed by performing quantitative real-time PCR on 12 representative genes. Moreover, several significantly upregulated genes, including yjiY, sodA, phoB and spy, were selected to study their role in APEC pathogenesis. The data will help to better understand the mechanisms of APEC pathogenesis.

[Dual deletion of the kpsE and kpsD genes reduced the bacterial virulence of extraintestinal pathogenic Escherichia coli].

Objective: To study the role of capsule polysaccharide in pathogenesis of extraintesinal pathogenic Escherichia coli (ExPEC). Methods: By using λ Red recombination system, we generated the capsular polysaccharide transport associated genes kpsE and kpsD double knockout mutants E058ΔkpsED and U17ΔkpsED. We then compared and analyzed the characteristics of the mutant strains and wild-type strains. Results: The growth curves in Luria Bertani showed that the deletion of kpsED did not affect growth kinetics of the mutants. The abilities of resistance to serum and killing by chicken macrophages were significantly impaired. LD50 results showed that the double mutants completely abolished the virulence, whereas the complementation strains restored the virulence to resemble that of wild-type strains, and the colonization and coinfection model demonstrated that the deletion of kpsED led to attenuation of virulence, because the double mutant showed significantly decreased colonization compared with the wild-type strains in all organs tested in chickens. Conclusion: These results indicated that the virulence factors encoded by capsule genes were important for the pathogenesis of ExPEC.

rmhTNF-α combined with cisplatin inhibits proliferation of A549 cell line in vitro.

OBJECTIVE: To explore the inhibitory effect of recombinant mutant human tumor necrosis factor-Α (rmhTNF-Α) in combination with cisplatin on human lung adenocarcinoma cell line A549. METHODS: Human lung adenocarcinoma cell line A549 was treated with varying concentrations of rmhTNF-Α (0.38, 0.75, 1.50, 6.00 and 12.00 IU/ml) or cisplatin (3.91, 7.81, 15.63, 31.25 and 62.50 Μg/ml) for 24 hours. Viable cell number was analyzed by using crystal violet staining. The inhibitory rates of A549 cells growth by the two drugs were calculated. For analyzing whether there was a synergistic effect of rmhTNF-Α with cisplatin, A549 cells were treated with 0.75 IU/ml rmhTNF-Α and increased concentrations of cisplatin. RESULTS: rmhTNF-Α or cisplatin inhibited the growth of A549 cell lines in a dose-dependent manner. The inhibitory effect of rmhTNF-Α combined with cisplatin was significantly greater than cisplatin alone at the same concentration (all P<0.01). CONCLUSION: rmhTNF-Α combined with cisplatin might have synergistic inhibitory effect on human lung adenocarcinoma cell line A549.

Identifying novel clinical phenotypes of acute respiratory distress syndrome using trajectories of daily fluid balance: a secondary analysis of randomized controlled trials.

BACKGROUND: Previously identified phenotypes of acute respiratory distress syndrome (ARDS) could not reveal the dynamic change of phenotypes over time. We aimed to identify novel clinical phenotypes in ARDS using trajectories of fluid balance, to test whether phenotypes respond differently to different treatment, and to develop a simplified model for phenotype identification. METHODS: FACTT (conservative vs liberal fluid management) trial was classified as a development cohort, joint latent class mixed models (JLCMMs) were employed to identify trajectories of fluid balance. Heterogeneity of treatment effect (HTE) for fluid management strategy across phenotypes was investigated. We also constructed a parsimonious probabilistic model using baseline data to predict the fluid trajectories in the development cohort. The trajectory groups and the probabilistic model were externally validated in EDEN (initial trophic vs full enteral feeding) trial. RESULTS: Using JLCMM, we identified two trajectory groups in the development cohort: Class 1 (n = 758, 76.4% of the cohort) had an early positive fluid balance, but achieved negative fluid balance rapidly, and Class 2 (n = 234, 24.6% of the cohort) was characterized by persistent positive fluid balance. Compared to Class 1 patients, patients in Class 2 had significantly higher 60-day mortality (53.5% vs. 17.8%, p < 0.001), and fewer ventilator-free days (0 vs. 20, p < 0.001). A significant HTE between phenotypes and fluid management strategies was observed in the FACTT. An 8-variables model was derived for phenotype assignment. CONCLUSIONS: We identified and validated two novel clinical trajectories for ARDS patients, with both prognostic and predictive enrichment. The trajectories of ARDS can be identified with simple classifier models.

Dreaming during gastrointestinal endoscopy under propofol, ciprofol, or remimazolam anesthesia: study protocol for a parallel-design double-blind, single-center trial.

BACKGROUND: Dreaming sometimes occurs during sedation. It has been reported that factors such as different anesthetics, depth of anesthesia, age, sex, and preoperative psychological state may affect dreams. Ciprofol and remimazolam are novel choices for painless endoscopy. Herein, we aimed to investigate dreaming during gastrointestinal endoscopy under propofol, ciprofol, and remimazolam anesthesia respectively. METHODS: This is a prospective, parallel-design double-blind, single-center clinical trial. Three hundred and sixty subjects undergoing elective painless gastroscopy, colonoscopy, or gastroenteroscopy will be enrolled. Eligible subjects will undergo propofol-, ciprofol-, or remimazolam-induced anesthesia to finish the examination. Interviews about the modified Brice questionnaire will be conducted in the recovery room. Incidence of dreaming is set as the primary outcome. Secondary outcomes include type of dreams, improvement of sleep quality, evaluation of patients, incidence of insufficient anesthesia, and intraoperative awareness. Safety outcomes are the incidences of hypotension and hypoxia during examination and adverse events during recovery. DISCUSSION: This study may observe different incidences of dreaming and diverse types of dreams, which might lead to different evaluations to the anesthesia procedure. Based on the coming results, anesthesiologists can make a better medication plan for patients who are going to undergo painless diagnosis and treatment. TRIAL REGISTRATION: This trial was registered at the Chinese Clinical Trial Registry on May 18, 2023 (registration number ChiCTR2300071565).

Attachment of Acidithiobacillus ferrooxidans onto different solid substrates and fitting through Langmuir and Freundlich equations.

Attachments of Acidithiobacillus ferrooxidans ATCC 23270 onto elemental sulfur, quartz and complex chalcopyrite were investigated by analysis of its extracellular polymeric substances as well as applying Langmuir and Freundlich equations. The two equations fitted the adsorption equilibrium data with significant correlation coefficient over 0.9. This indicated that bacterial attachment is complicated and involves Langmuir and Freundlich characterizations. Sulfur-grown cells showed the highest affinity for the three solid substrates. The investigated complex chalcopyrite possessed a higher maximum adsorption capacity for A. ferrooxidans than elemental sulfur or quartz. The Freundlich fitting parameters suggested that quartz had a weaker adsorption capacity and smaller adsorption areas than elemental sulfur or the complex chalcopyrite. It is not the content of total carbohydrates or proteins in EPS but their ratios that determine the affinity differences between cells and substrates.

[Effects of Quercetin-3-O-ß-D-Glucuronide on Platelet Apoptosis and Activation in Mice with Immune-Mediated Bone Marrow Failure via PI3K/AKT Pathway].

OBJECTIVE: To investigate the effect of quercetin-3-O-ß-D-glucuronide(QG) on platelet apoptosis and activation in mice with immune-mediated bone marrow failure via PI3K/AKT pathway. METHODS: An immune-mediated bone marrow failure mice model was established and forty C57BL/6 mice were randomly assigned into 4 groups: normal group, model group,cyclosporine (CsA) group and QG group, with 10 mice in each group.The mice in CsA group were intragastrically administered with 0.027 g/kg CsA daily and the mice in QG group were intragastrically administered with 0.2 g/kg QG daily, while the mice in the normal group and model group were intragastrically administered with normal saline, respectively. After three days of modeling, the mice were euthanized, and the blood was collected through the tail vein. Part of the blood was used for blood routine examination, and the other part was used to prepare washed platelets. Some of the prepared washed platelets were used to detect the expressions of BAX, BAD, caspase-9, phosphatidylserine (PS), platelet activated complex-1 (PAC-1) and P-selectin by flow cytometry; some of washed platelets was used to determine the protein contents of PI3K, p-PI3k, AKT and p-AKT by Western blot; the other part of the washed platelets was used to measure the expressions of PI3K mRNA and AKT mRNA by real-time quantitative PCR (RT-qPCR). RESULTS: In the model group, the absolute platelet count of the mice was significantly decreased, and the levels of BAX, BAD, caspase-9, PS, PAC-1, and P-selectin in the washed platelets were significantly increased, compared to the normal group (P<0.05). At the same time, the expression levels of PI3K, p-PI3K, AKT, p-AKT proteins and PI3K mRNA, AKT mRNA in model group were significantly reduced, compared to the normal group (P<0.05). In the CsA group and QG group, the expression levels of BAX, BAD, caspase-9, PS, PAC-1, and P-selectin in the washed platelets were significantly reduced (P<0.05), while the levels of PI3K, p-PI3K, AKT, p-AKT and PI3K mRNA, AKT mRNA were significantly increased, compared to the model group (P<0.05). CONCLUSION: QG can reduce platelet apoptosis in mice with immune-mediated bone marrow failure, and activation of some platelets is involved, which may be related to the regulation of PI3K/AKT pathway.

Multi-trajectories of health-related quality of life and their associated factors in patients with nasopharyngeal carcinoma: A longitudinal study.

BACKGROUND: The trajectories of health-related quality of life (HRQoL) of nasopharyngeal carcinoma (NPC) during and after the treatment along with their associated factors are seldom investigated in longitudinal studies. This study aims to investigate the longitudinal trajectories of HRQoL over time and their associated factors in patients with newly diagnosed NPC. METHODS: Between July 2018 and September 2019, a total of 500 patients were finally involved in this study. HRQoL was measured at four time points, from before treatment to the follow-up period after treatment. Group-based multi-trajectory modeling was applied to identify trajectories of five HRQoL functioning domains during the longitudinal period. Multinomial logistic regression models were applied to investigate potential independent factors associated with the multi-trajectory groups. RESULTS: We identified four distinct multi-trajectory groups, including the "initially lowest functioning" group (19.8%), the "initially lower functioning" group (20.8%), the "initially higher functioning" group (46.0%), and the "consistently highest functioning" group (13.4%). Patients who were older than 45 years or had T4 stage disease were more likely to be in the "initially lowest functioning" group, while those with EBV DNA ≥ 1500 copies/mL before the treatment were more likely to be in the "initially lowest functioning" or the "initially lower functioning" groups. CONCLUSIONS: We report the presence of heterogeneity in HRQoL trajectories among patients with NPC, and found that older age, advanced T stage, and higher EBV DNA level before treatment were significantly associated with poor HRQoL trajectories. Further studies are needed to examine the generalizability of these identified HRQoL trajectories and their associations with psychosocial and survival outcomes.

Clinical observations on the dose-effect relationship of gegen qin lian decoction on 54 out-patients with type 2 diabetes.

OBJECTIVE: To observe the therapeutic effect of different dosages of Gegen Qin Lian Decoction on type 2 diabetic patients. METHODS: Fifty-four type 2 diabetic patients from low dosage group (20 cases), medium dosage group (19 cases) and high dosage group (15 cases) were treated with different dosage of Gegen Qin Lian Decoction for 12 weeks. Fasting blood-glucose (FBG), postprandial blood sugar (PBG) and Hemoglobin A1c (HbA1c) were determined before and after treatment. RESULTS: With the increase of dosage, the overall effective rate of glycaemic control increased, and FBG, PBG HbA1c decreased. The overall effective rate of blood glucose control of high dosage, medium dosage and low dosage group were 80%, 47%, 30% respectively, and there were significant differences between high dosage group and low dosage group. The decrease of FBG, PBG and HbA1c of high dosage showed significant differences from low dosage too. These data was analyzed by trend chi2 test and covariance analysis. CONCLUSION: The result indicated that different dosage of Gegen Qin Lian Decoction has dose-effect relationship in reducing HbA1c and FBG.

The Effect of Prolonged Duration of Intensity Modulated Radiotherapy for Nasopharyngeal Carcinoma.

PURPOSE: Radiotherapy is the most important primary treatment for patients with nasopharyngeal carcinoma. Generally, the treatment duration of radiotherapy takes six or six and half weeks with 30 to 33 fractions. The current study was conducted to evaluate the association between prognosis and the duration of radiotherapy in nasopharyngeal carcinoma patients. METHODS: Patients with primary nasopharyngeal carcinoma who were treated with intensity-modulated radiotherapy and concurrent cisplatin-based chemotherapy, with or without induction chemotherapy between January, 2008 and December, 2013 at a single institution were retrospectively reviewed. RESULTS: In total, 1292 patients were included. At a median follow-up of 71.0 months (range 2.0-126.0 months), locoregional recurrence, distant failure and death were observed in 8.8%, 12.2% and 15.6% of all patients, respectively. Estimated 5-year locoregional relapse-free survival, distant metastasis-free survival, progression-free survival and overall survival in patients with radiation ≤ 7 weeks versus patients with radiation >7 weeks were: 93.2% versus 87.0% (P < 0.001), 89.4% versus 84.4% (P = 0.016), 79.8% versus 70.6% (P < 0.001) and 87.2% versus 78.4% (P < 0.001), respectively. CONCLUSIONS: Prolonged duration of radiotherapy with a significantly higher risk of distant metastasis and death in nasopharyngeal carcinoma patients. Understanding this point, healthcare providers should make efforts to avoid prolonged duration of radiotherapy to minimize the risk of treatment failure.

The impact of induction chemotherapy on long-term quality of life in patients with locoregionally advanced nasopharyngeal carcinoma: Outcomes from a randomised phase 3 trial.

BACKGROUND: Our previous trial confirmed that induction chemotherapy (IC) improved long-term survival outcomes in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). In this study, we investigated the impact of IC on long-term quality of life (QoL) in this cohort. METHODS: Our trial was a randomised, open-label phase 3 trial comparing IC followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients with stage III-IVB (except T3N0-1) NPC. All participants completed two self-administered questionnaires, the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) and the EORTC QLQ Head and Neck Cancer-Specific Module (H&N35). As per protocol, the questionnaires had to be completed before knowledge of treatment allocation by the patient (baseline). Patients were then approached to enroll at the time of the present study period. RESULTS: Ultimately, QoL data from 228 patients were included in the analysis. Most scales were both statistically and clinically decreased in both groups between baseline and the latest follow-up. The IC followed by CCRT group had significantly better outcome in role functioning, cognitive functioning, social functioning, fatigue, pain, and constipation in QLQ-C30 scales at the last follow-up. Similarly, in H&N35 scales, a significantly better result was observed in pain, sexuality, sticky saliva, pain killers use, nutritional supplements, and weight loss, but a poorer result in senses problems, for those treated by IC followed by CCRT. CONCLUSION: IC followed by CCRT seemed to have better long-term QoL outcomes compared with CCRT alone in patients with locoregionally advanced NPC.

Minimally invasive surgery alone compared with intensity-modulated radiotherapy for primary stage I nasopharyngeal carcinoma.

BACKGROUND: The National Comprehensive Cancer Network guidelines recommend intensity-modulated radiotherapy (IMRT) as the primary curative treatment for newly diagnosed nasopharyngeal carcinoma (NPC), but the radiation-related complications and relatively high medical costs remain a consequential burden for the patients. Endoscopic nasopharyngectomy (ENPG) was successfully applied in recurrent NPC with radiation free and relatively low medical costs. In this study, we examined whether ENPG could be an effective treatment for localized stage I NPC. METHODS: Ten newly diagnosed localized stage I NPC patients voluntarily received ENPG alone from June 2007 to September 2017 in Sun Yat-sen University Cancer Center. Simultaneously, the data of 329 stage I NPC patients treated with IMRT were collected and used as a reference cohort. The survival outcomes, quality of life (QOL), and medical costs between two groups were compared. RESULTS: After a median follow-up of 59.0 months (95% CI 53.4-64.6), no death, locoregional recurrence, or distant metastasis was observed in the 10 patients treated with ENPG. The 5-year overall survival, local relapse-free survival, regional relapse-free survival, and distant metastasis-free survival among the ENPG-treated patients was similar to that among the IMRT-treated patients (100% vs. 99.1%, 100% vs. 97.7%, 100% vs. 99.0%, 100% vs. 97.4%, respectively, P > 0.05). In addition, compared with IMRT, ENPG was associated with decreased total medical costs ($ 4090.42 ± 1502.65 vs. $ 12620.88 ± 4242.65, P < 0.001) and improved QOL scores including dry mouth (3.3 ± 10.5 vs. 34.4 ± 25.8, P < 0.001) and sticky saliva (3.3 ± 10.5 vs. 32.6 ± 23.3, P < 0.001). CONCLUSIONS: ENPG alone was associated with promising long-term survival outcomes, low medical costs, and satisfactory QOL and might therefore be an alternative strategy for treating newly diagnosed localized stage I NPC patients who refused radiotherapy. However, the application of ENPG should be prudent, and prospective clinical trials were needed to further verify the results.

[Mechanism of Mitochondria-mediated Pathway in the Platelet Apoptosis Resulted from Immune Bone Marrow Failure].

OBJECTIVE: To explore the mechamisms of mitochondria-mediated pathway in apoptosis of platelets resulted from in immune induced bone marrow failure. METHODS: Thirty C57BL/6 mice were randomly divided into 3 groups (10 mice in each group): normal group, model group, cyclosporine A(CsA) group. Mouse model of immune bone marrow failure were established. After mouse model was successfully established, the mice in normal group and model group were given saline orally, the mice in CsA group was treated with CsA orally. Blood routine examination of mice in each group was performed by automatic blood cell analyzer; the mitochondrial membrane potential(ΔΨm), cytochrome C(Cyt C), phosphatidylserine (PS), Ca2+ were measured by flow cytometry; expression of BAX, BAK, caspase-3, caspase-8, caspase-9 was detected by using Western blot method, the changes of bone marrow platelet ultrastructure were observed under transmission electron microscope. RESULTS: Compared with normal group, the platelet count of model group decreased significantly, while the level of ΔΨm, caspase-3, caspase-8, caspase-9 significantly decreased, the level of Cyt C, PS, Ca2+, BAX, BAK increased significantly (P<0.05). Compared with the model group, the platelet count of CsA group increased obviously, while the level of ΔΨm, caspase-3, caspase-8, caspase-9 of CsA group increased significantly, the level of Cyt C, PS, Ca2+, BAX, BAK of CsA group decreased significantly (P<0.05). Electron microscopy showed that compared with the model group, platelet damage in CsA group were alleviated. CONCLUSION: mitochondrial pathway plays an important role in the reduction of platelet resulted from immune bone marrow failure.

Study progress of berberine for treating cardiovascular disease.

Berberine (BBR) is a natural alkaloid isolated from the Coptis chinensis. While this plant has been used in Chinese medicine for more than 2500 years, interest in its effects in treating cardiovascular disease has been growing in the last decade. Recent researches showed that BBR had the effect of anti-heart failure, anti-hypertension, anti-hyperlipidemia, anti-insulin resistance, anti-arrhythmias, and anti-platelet aggregation.