[Preliminary practice in the postoperative cardiopulmonary exercise testing for children with congenital heart disease].

Objective: To investigate the postoperative cardiopulmonary fitness of children with congenital heart diseases (CHD). Methods: This is a retrospective study. A total of 136 children after cardiac correction undergoing cardiopulmonary exercise test (CPET) in Shanghai Children's Medical Center from March 1 to June 30, 2021 were selected. According to the surgical procedure, the children were divided into two groups: the biventricular correction group (BV group) (n=75) and single ventricular correction group (SV group) (n=61). The BV group was divided into two subgroups: simple congenital heart disease (S-CHD) group (n=35) and complex congenital heart disease (C-CHD) group (n=40). CPET parameters, including VO2 max, VO2/kg max, VO2/kg@AT, O2/HR max, HRR, PetCO2 max, CI, HRR at 1 min, VE/VCO2 slope, OUES/kg and EOV, were analyzed. CPET parameters of patients underwent different procedure were compared. In the subgroup analysis, CPET parameters of patients in S-CHD group and C-CHD group were compared. The parameters of the BV group were compared with the normal value. Linear correlation analysis was used to identify the correlation between the CPET parameters. Results: A total of 136 children with CHD after surgery were enrolled. The age was (9.4±3.1) (ranged 6.2-16.0) years, and there was 84 (61.8%) male. All the children completed CPET examination safely without experiencing serious circulation abnormalities. Compared with the SV group, the VO2/kg max ((32.6±6.9) ml·kg-1·min-1 vs. (23.5±5.9) ml·kg-1·min-1, P<0.001), O2/HR max ((7.24±2.93) ml/beat vs. (6.35±2.17)ml/beat, P=0.030), HRR at 1 min ((32.5±13.9) beat/min vs. (26.3±12.5) beat/min, P=0.036), OUES/kg (36.9±8.8 vs. 29.7±11.8, P=0.001) were significantly higher, VE/VCO2 slope (29.1±5.20 vs. 35.1±8.0, P<0.001) and incidence of EOV (32.0%(24/75) vs. 57.4%(31/61), P=0.027) were significantly lower in BV group. Compared with the simple CHD subgroup, VE/VCO2 slope and the incidence of EOV were higher, VO2/kg max, O2/HR max, HRR at 1 min and OUES/kg were lower in the complex CHD subgroup (all P<0.05). Cardiopulmonary function parameters of the BV group were lower than the normal value. Linear correlation analysis showed that VO2/kg@AT was strongly correlated with VO2/kg max (r=0.86, P<0.001), VO2/kg max was strongly correlated with OUES/kg (r=0.63, P<0.001), HRR was strongly correlated with CI (r=0.91, P<0.001), and VO2/kg max was strongly correlated with OUES/kg (r=0.63, P<0.001). VE/VCO2 slope was strongly correlated with PetCO2 max (r=1.00, P<0.001). Conclusions: The exercise cardiopulmonary function of children after single ventricular correction is weaker than that of biventricular correction, and the exercise tolerance of children after biventricular correction is lower than that of normal children. Among the children after biventricular correction, the exercise tolerance of children with complex CHD is lower than that of children with simple CHD. Postoperative CPET is of important realistic significance for CHD children.

Neuroprotective effect of CTRP3 overexpression against sevoflurane anesthesia-induced cognitive dysfunction in aged rats through activating AMPK/SIRT1 and PI3K/AKT signaling pathways.

OBJECTIVE: To investigate the effects of C1q/tumor necrosis factor-related protein-3 (CTRP3) on postoperative cognitive dysfunction (POCD) and elucidate the potential regulatory mechanism in sevoflurane anesthesia-induced aged rats. MATERIALS AND METHODS: A sevoflurane anesthesia-induced POCD aged rat model was established and hematoxylin and eosin (H&E) staining was used to detect pathological changes of hippocampal neurons. Morris water maze task test was performed to determine the learning and memory ability of rats. Immunofluorescence, quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot were used to detect CTRP3 expression. Enzyme-linked immunosorbent assay (ELISA) or qRT-PCR assays were used to evaluate the changes of markers of brain damage and inflammatory cytokines. Terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) assay was used to assess the apoptosis of nerve cells in hippocampus. Western blot assay were used to measure the expression levels of apoptosis-related protein, and AMP-activated protein kinase (AMPK)/SIRT1 and PI3K/AKT pathway. RESULTS: Sevoflurane exposure led to brain injury, cognitive dysfunction in aged rats and decreased the expression of CTRP3. Overexpression of CTRP3 could suppress nerve cell apoptosis, inhibit neuronal inflammation, reduce brain tissue damage and improve cognitive dysfunction of aged rats after sevoflurane anesthesia. Further studies showed that CTRP3 may play a role in POCD by regulating AMPK/SIRT1 and PI3K/AKT signaling pathways. CONCLUSIONS: CTRP3 may effectively protect against sevoflurane-induced cognitive dysfunction and served as a potential predictive indicator and therapy target for POCD.

Adjuvant chemotherapy for patients with gastric neuroendocrine carcinomas or mixed adenoneuroendocrine carcinomas.

BACKGROUND: The aim of this study was to evaluate whether adjuvant chemotherapy is associated with improved survival in patients with resectable gastric neuroendocrine carcinomas (G-NECs) or mixed adenoneuroendocrine carcinomas (G-MANECs). METHODS: The study included patients with G-NECs or G-MANECs who underwent surgery in one of 21 centres in China between 2004 and 2016. Propensity score matching analysis was used to reduce selection bias, and overall survival (OS) in different treatment groups was estimated by the Kaplan-Meier method. RESULTS: In total, 804 patients with resectable G-NECs or G-MANECs were included, of whom 490 (60·9 per cent) received adjuvant chemotherapy. After propensity score matching, OS in the chemotherapy group was similar to that in the no-chemotherapy group. Among patients with G-NECs, survival in the fluorouracil (5-FU)-based chemotherapy group and the non-5-FU-based chemotherapy group was similar to that in the no-chemotherapy group. Similarly, etoposide plus cisplatin or irinotecan plus cisplatin was not associated with better OS in patients with G-NECs. Among patients with G-MANECs, OS in the non-5-FU-based chemotherapy group was worse than that in the no-chemotherapy group. Patients with G-MANECs did not have better OS when platinum-based chemotherapy was used. CONCLUSION: There was no survival benefit in patients who received adjuvant chemotherapy for G-NECs or G-MANECs.

ANTECEDENTES: El objetivo de este estudio fue evaluar si la quimioterapia adyuvante mejoraba la supervivencia en pacientes con carcinomas gástricos resecables neuroendocrinos (gastric neuroendocrine carcinomas, G-NECs) y carcinomas adenoneuroendocrinos mixtos (mixed adenoneuroendocrine carcinomas, G-MANECs). MÉTODOS: Se incluyeron pacientes con G-NECs y G-MANECs tratados quirúrgicamente en 21 centros en China entre 2004 y 2016. Se utilizó un análisis de emparejamiento por puntaje de propensión para reducir el sesgo de selección y el método de Kaplan-Meier para estimar la supervivencia global (overall survival, OS) de los pacientes en los diferentes grupos de tratamiento. RESULTADOS: En total, se incluyeron en el estudio 804 pacientes con G-NECs y G-MANECs resecables y 490 pacientes (60,9%) recibieron quimioterapia adyuvante. Después del emparejamiento por puntaje de propensión, la OS del grupo con quimioterapia fue similar a la del grupo sin quimioterapia. En los pacientes con G-NECs, la supervivencia en los grupos con quimioterapia basada en 5-FU (fluorouracilo) y de quimioterapia sin 5-FU fue similar a la del grupo sin quimioterapia. Asimismo, la combinación de etopósido y cisplatino o de irinotecán y cisplatino no se asoció con una mejor OS en pacientes con G-NECs. En pacientes con G-MANECs, la OS del grupo con quimioterapia sin 5-FU fue peor que la del grupo sin quimioterapia. Los pacientes con G-MANECs no presentaron una mejor OS cuando se administró quimioterapia basada en platinos. CONCLUSIÓN: La administración de quimioterapia adyuvante en pacientes con G-NECs y G-MANECs no mejoró la supervivencia.

Long noncoding RNA NEAT1 functions as an oncogene in human laryngocarcinoma by targeting miR-29a-3p.

OBJECTIVE: Long noncoding RNAs (lncRNAs) have been reported to participate in the progression and development of many human diseases. In this study, we are committed to uncover the potential function of lncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) in the development of laryngocarcinoma. PATIENTS AND METHODS: LncRNA NEAT1 expression in laryngocarcinoma cells and 54 paired laryngocarcinoma samples was detected by Real-time quantitative polymerase chain reaction (RT-qPCR). Furthermore, the regulatory effects of NEAT1 on the proliferation and metastasis of laryngocarcinoma cells were evaluated. Biological role of NEAT1/miR-29a-3p axis was finally explored in regulating the progression of laryngocarcinoma. RESULTS: NEAT1 was upregulated in laryngocarcinoma tissues and cell lines. NEAT1 knockdown suppressed growth and invasive abilities in laryngocarcinoma cells, while overexpression of NEAT1 enhanced such abilities. Further experiments showed that miR-29a-3p was directly targeted by NEAT1, and participated in NEAT-mediated progression of laryngocarcinoma. CONCLUSIONS: NEAT1 is a novel oncogene in laryngocarcinoma and could enhance growth and invasion of laryngocarcinoma cells by targeting miR-29a-3p.

LncRNA SNHG1 promotes cell proliferation in laryngeal cancer via Notch1 signaling pathway.

OBJECTIVE: We aimed at elucidating the potential function of long noncoding ribonucleic acids (lncRNAs) small nucleolar RNA host gene 1 (SNHG1) in the progression of laryngeal cancer (LC) and its underlying mechanism. PATIENTS AND METHODS: Relative level of SNHG1 in LC tissues and controls was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Its expression in LC patients with different tumor stages and statues of lymph node metastasis was examined as well. Correlation between SNHG1 expression and prognosis of LC patients was evaluated by the Kaplan-Meier method. SNHG1 siRNA (si-SNHG1) was constructed for downregulation of SNHG1 expression. Potential effects of downregulated SNHG1 on viability and proliferation of LC cells were detected by cell counting kit-8 (CCK-8) and colony formation assay, respectively. After knockdown of SNHG1, relative levels of Notch1 and hairy, and enhancer of split homolog-1 (Hes1) were determined by qRT-PCR and Western blot. Regulatory effects of SNHG1/Notch1 axis on biological behaviors of LC were finally evaluated. RESULTS: SNHG1 was upregulated in LC tissues than that of controls. Besides, its level was higher in LC with T3-T4 relative to those of T1-T2. Higher abundance of SNHG1 was identified in LC patients with lymph node metastasis compared with those non-metastatic patients. Survival analysis indicated that LC patients with high-level SNHG1 had worse overall survival. Knockdown of SNHG1 in Tu212 and Hep2 cells downregulated relative levels of Notch1 and Hes1. Moreover, SNHG1 knockdown resulted in decreased viability and proliferative ability of LC cells. Notch1 overexpression could reverse the regulatory effects of SNHG1 on viability and proliferation of LC cells. CONCLUSIONS: LncRNA SNHG1 is highly expressed in LC tissues. It promotes the proliferation of LC cells by inhibiting Notch1 pathway, thereby promoting the progression of LC.

Detection of bone marrow oedema in knee joints using a dual-energy CT virtual non-calcium technique.

AIM: To evaluate bone marrow oedema in knee joints quantitatively and qualitatively using a dual-energy computed tomography (CT) virtual non-calcium (VNCa) technique. MATERIALS AND METHODS: Thirty-five patients with knee joint injuries underwent both dual-energy CT and magnetic resonance imaging (MRI) between March 2018 and November 2018. The presence of bone marrow oedema was assessed by two independent radiologists with the use of colour-coded dual-energy CT VNCa images and measured attenuation on them. The biggest area of bone marrow oedema on axial images was measured by another radiologist using the dual-energy CT and MRI images, respectively. Attenuation values were subjected to receiver operating characteristic (ROC) curve analysis and oedema area sizes were subjected to paired t-test analysis. RESULTS: In qualitative analysis, colour-coded VNCa images had an overall sensitivity of 88.4%, specificity of 98%, positive predictive value of 92.7%, negative predictive value of 96.8%, and accuracy of 95.9%. Attenuation values obtained from colour-coded VNCa images were significantly different in knee joint regions with and without oedema (p<0.001). ROC curve analysis revealed an area under the curve (AUC) of 0.910. A cut-off value of -67 HU provided a sensitivity of 81.4%, specificity of 99.3%, accuracy of 90.4%, positive predictive value of 99.1%, and negative predictive value of 84.2% for the differentiation of oedematous knee joint regions. Significant differences in the size of oedema area were not found between them. CONCLUSION: Dual-energy CT VNCa can be used to evaluate bone marrow oedema effectively.

FBLN3 inhibited the invasion and metastasis of colorectal cancer through the AKT/mTOR pathway.

Fibulin-3(FBLN3) levels are different in different types of cancers. We found that fibulin-3 was downregulated in colorectal (CRC) cells, particularly in the SW480 cell line. By comparison, transfecting SW480 cells with a lentivirus overexpressing fibulin-3 RNA could inhibit proliferation, induce G1/S arrest, and promote cell apoptosis. Fibulin-3 overexpression further suppressed the invasion and metastasis of CRC. These effects were regulated through the AKT/mTOR signaling pathway.

Expression of lamin A/C protein in degenerated human intervertebral disc.

OBJECTIVE: This study aimed to evaluate the expression characteristics of lamin A/C proteins in intervertebral disc degeneration (IVD) specimens from patients with different degeneration grades. Lamin A/C proteins have been shown to result in age-related changes in the osteoarticular system. However, the expression characteristics of these nuclear proteins in degenerated human IVD tissues have not been explored previously. PATIENTS AND METHODS: Degenerated human IVD tissues were obtained during spinal surgery. Articular cartilage samples after total knee replacement surgery were used as controls. Sections of these tissues were stained with hematoxylin and eosin, Masson, safranin O, and immunostained using lamin A/C antibody. Western blot was performed to evaluate lamin A/C expression in IVD tissues. Lamin A/C expression was analyzed based on different degeneration grades. RESULTS: In patients with IVD degeneration, mild or moderate degenerative discs contained high amounts of lamin A/C proteins. Lamin A/C expression was primarily localized in the nuclear envelope of IVD cells, and associated with apoptosis in cell nuclei, as determined by immunostaining and TUNEL assay. CONCLUSIONS: This paper is the first to report that lamin A/C proteins are present in IVD tissues and its expression may be related to disc degeneration.

[The role of Th1/Th2 cells imbalance in the pathogenesis of secretory otitis media].

Objective:The aim of this study is to explore the role of Th1/Th2 cells imbalance in the pathogenesis of secretory otitis media. Method:Ninety secretory otitis media patients were enrolled in observation group. According to medical history, they were divided into acute and chronic group. In addition, 90 healthy volunteers during the same period were selected as the control group. The levels of Th1-type cytokines IFN-γ, Th2-type cytokines interleukin-4 (IL-4) and IFN-γ/IL-4 in peripheral blood were compared between observation group and control group. Compare with acute and chronic secretory otitis media patients IFN-γ, IL-4, IFN-γ/IL-4 levels as well as the compare with middle ear effusion and peripheral blood sIFN-γ, IL-4, IFN-γ/IL-4 levels in observation group. Result:The level of IFN-γ, IL-4 and IFN-γ/IL-4 in the peripheral blood in the observation group were higher than those of the control group (P<0.05). The levels of IFN-γ, IL-4 and IFN-γ/IL-4 in the peripheral blood of patients in the chronic group were higher than those in the acute group. There was no significant difference in IL4, IFN-γ/IL-4 levels between the observation group and the middle ear effusion (P>0.05), IFN-γ levels in peripheral blood were lower than those of the middle ear effusion IFN-γ (P<0.05). Conclusion:Abnormal IFN-γ, IL-4 levels of the peripheral blood and the middle ear effusion have some relationship with secretory otitis media, and Th1/Th2 imbalance may be a risk factor for secretory otitis media.

[Expert consensus on the diagnosis and treatment of cryptococcal meningitis].

Cryptococcal meningitis is a common and refractory central nervous system infection, with high rates of mortality and disability. The experts of the Society of Infectious Diseases of Chinese Medical Association have reached this consensus after a thorough discussion. Based on the current situation of cryptococcal meningitis in China, the management of cryptococcal meningitis includes 6 aspects: introduction, microorganism identification, clinical manifestations and diagnosis, principles of antifungal therapy, treatment of refractory and recurrent meningitis, treatment of intracranial hypertension. There is not a separate consensus on human immunodeficiency virus (HIV) infection in patients with cryptococcal meningitis. This article focuses on different antifungal regimens and reducing intracranial pressure by reference to Infectious Disease Society of America (IDSA) guidelines. The importance of early diagnosis, combined long-term antifungal therapy, control of intracranial hypertension are emphasized.

One-stage extreme lateral interbody fusion and percutaneous pedicle screw fixation in lumbar spine tuberculosis.

OBJECTIVES: We explored the efficacy of minimal invasive surgery including one-stage debridement and intervertebral fusion through extreme lateral channel (XLIF) combined with lateral or percutaneous posterior pedicle screw fixation for the treatment of lumbar spine tuberculosis. METHODS: Twenty two patients with lumbar tuberculosis who underwent surgery with XLIF technique and internal fixation were included in the study. Their data about operative time, intraoperative blood loss, bone fusion, kyphosis correction, and clinical recovery were retrospectively collected and analyzed. RESULTS: The mean intraoperative blood loss was 249.8±27.8 ml and the operative time 347.5±20.7 min. At the final follow-up, 11 to 15 months postoperatively, ESR and CRP were normal and pain (VAS) and Oswestry disability index (ODI) were significantly reduced (23.0±-3.1 vs 0.6±-0.7 and 57.2±-1.6 vs 6.4±-1.2 respectively) compared to preoperative values. Progression of the kyphotic deformity was effectively prevented (mean Cobb angle 23.9° +/-1.9° vs 24.5° +/-1.4°, P>0.05). There was one failure of the fixation associated to poor therapy adherence. All the patients showed neurological recovery. CONCLUSION: Debridement and interbody fusion by extreme lateral channel combined with lateral or percutaneous posterior pedicle screw fixation effectively retained the spine stability and provided clinical and neurologic recovery in selected patients with lumbar spine tuberculosis.

Mitochondrial DNA haplogroups and somatic mutations are associated with lung cancer in patients from Southwest China.

Mitochondrial DNA mutations play crucial roles in the pathogenesis and progression of human malignancies. Therefore, to determine whether maternal background or mitochondrial DNA somatic mutations were essential cofactors in the lung cancer of Chinese patients as well, the complete mitochondrial DNA displacement loop of the primary cancerous, matched para-cancerous normal and distant normal tissues for 79 Chinese patients with lung cancer were analyzed in this study. Our results indicated that the higher detected frequency of haplogroups prevalent in southern East Asia (53.16%; 42/79) versus those of northern East Asia in the studied population supported the southern East Asian characteristics of the Chinese lung cancer group. Further statistical analysis revealed that the haplogroups F* and G* contributed to the susceptibility to lung cancer in Chinese patients. In addition, by comparing sequences from different tissues of the same patients, a total of eight somatic mutations from six patients were detected. Combined with the fourteen somatic mutations identified in our previous study, the somatic mutation spectrum of the 79 Chinese patients with lung cancer was 25.32% (20/79). Our results suggest that mitochondrial DNA haplogroups and somatic mutations are associated with lung cancer in patients from Yunnan, Southwest China, and that somatic mitochondrial DNA mutations in the displacement loop can serve as potential biomarkers for clinical utility.

Deciphering the spectrum of somatic mutations in the entire mitochondrial DNA genome.

The mitochondrion is a crucial intracellular organelle responsible for regulating cellular energy metabolism, producing free radicals, initiating and executing the apoptotic pathways. Previous studies have shown that somatic mutations in mitochondrial DNA are associated with various tumors, which may be involved during carcinogenesis and tumor progression. To examine the mutation pattern in cancer, 625 reported somatic mutations in the mitochondrial DNA genome were analyzed. We found that, except for deletions and insertions, most somatic mutations were point mutations, accounting for 89.44% of somatic mutations. Transition was the predominant form of somatic mutation in the entire mitochondrial DNA genome, accounting for 87.12% of point mutations, most of which were homoplastic. Frequency statistics analysis of point mutations indicated that, except for 3 tRNA genes, the mutations were distributed on all resting genes and in the D-loop region, with the latter showing the highest frequency of somatic mutation (19.34%), followed by the tRNA leucine 2 gene and non-coding regions between base pairs 5892 and 5903, while 13 coding-region genes and 2 rRNA genes showed a relatively lower frequency of somatic point mutations. Nonsynonymous mutations and terminal amino acid changes were the primary point somatic mutations detected from 13 coding-region genes, which may cause mitochondrial dysfunction in cancer cells. We found that the somatic mutations may affect the mitochondrial DNA genome; the non-coding region should be examined to identify somatic mutations as potential diagnostic biomarkers for early detection of cancer.

Identification of warm day and cool night conditions induced flowering-related genes in a Phalaenopsis orchid hybrid by suppression subtractive hybridization.

The influence of warm day and cool night conditions on induction of spikes in Phalaenopsis orchids has been studied with respect to photosynthetic efficiency, metabolic cycles and physiology. However, molecular events involved in spike emergence induced by warm day and cool night conditions are not clearly understood. We examined gene expression induced by warm day and cool night conditions in the Phalaenopsis hybrid Fortune Saltzman through suppression subtractive hybridization, which allowed identification of flowering-related genes in warm day and cool night conditions in spikes and leaves at vegetative phase grown under warm daily temperatures. In total, 450 presumably regulated expressed sequence tags (ESTs) were identified and classified into functional categories, including metabolism, development, transcription factor, signal transduction, transportation, cell defense, and stress. Furthermore, database comparisons revealed a notable number of Phalaenopsis hybrid Fortune Saltzman ESTs that matched genes with unknown function. The expression profiles of 24 genes (from different functional categories) have been confirmed by quantitative real-time PCR in induced spikes and juvenile apical leaves. The results of the real-time PCR showed that, compared to the vegetative apical leaves, the transcripts of genes encoding flowering locus T, AP1, AP2, KNOX1, knotted1-like homeobox protein, R2R3-like MYB, adenosine kinase 2, S-adenosylmethionine synthetase, dihydroflavonol 4-reductase, and naringenin 3-dioxygenase accumulated significantly higher levels, and genes encoding FCA, retrotransposon protein Ty3 and C3HC4-type RING finger protein accumulated remarkably lower levels in spikes of early developmental stages. These results suggested that the genes of two expression changing trends may play positive and negative roles in the early floral transition of Phalaenopsis orchids. In conclusion, spikes induced by warm day and cool night conditions were complex in Phalaenopsis orchids; nevertheless, several molecular flowering pathway-related genes were found. The acquired data form the basis for a molecular understanding of spike induction by warm day and cool night conditions in Phalaenopsis orchids.

Promoting positive health behaviours--'tooth worm' phenomenon and its implications.

UNLABELLED: 'Tooth worm' is a traditional belief about the pathogen of dental caries (tooth decay). Nevertheless, in our previous study, parental 'tooth worm' belief was linked to a reduced caries risk of their children. OBJECTIVES: This study aimed to further characterize the impact of parental 'tooth worm' belief on their children's caries experience and its psychobehavioural mechanisms. BASIC RESEARCH DESIGN: analytic observational study. SETTING: Thirteen randomly selected kindergartens in Singapore. PARTICIPANTS: 1,782 preschoolers aged 3-6 years. METHODS: Each child received an oral examination and microbiological tests. Parents completed a self-administered questionnaire on their socio-demographic background, oral health knowledge/attitude and child's oral health habits. RESULTS: Multivariate analysis confirmed a reduced chance of 'high caries rate' (number of affected teeth > 2) among children whose parents held the 'tooth worm' belief (Odds Ratio = 0.41; 95% Confidence Interval = 0.19-0.89). With such perception among parents, children brushed their teeth more frequently (p = 0.042). Since no difference in oral hygiene was observed, the health benefit of the "tooth worm" perception may be acquired through the delivery of fluoride (an agent with proven anti-caries effect) during frequent toothbrushing episodes. CONCLUSIONS: This study revealed a 'tooth worm' phenomenon, indicating that parental 'tooth worm' belief is associated with early establishment of regular toothbrushing habit and reduction of dental caries in children. This phenomenon and its psychobehavioural mechanisms, enriching our understanding of oral health behaviours, have implications for effective health education.

Capecitabine for the treatment for advanced gastric cancer: efficacy, safety and ethnicity.

WHAT IS KNOWN AND OBJECTIVE: Capecitabine- and 5-fluorouracil (5-FU)-based regimens are widely used for the treatment for advanced gastric cancer (AGC). We aimed to compare the efficacy of the two regimens for both Caucasian and Asian subjects, through a meta-analysis of the available trial evidence. METHODS: We searched PubMed, ASO, ECCO, ESMO, Wanfang database (Chinese), CNKI (Chinese), Weipu database (Chinese) and J-STAGE (Japanese) using combinations of keywords, including 'capecitabine', '5-fluorouracil', 'chemotherapy', 'stomach neoplasms' and 'gastric cancer'. We identified relevant trial evidence and pooled the results on both efficacy and adverse events. RESULTS AND DISCUSSION: Capecitabine-based chemotherapy for AGC prolonged the overall survival (OS; 10·7 months vs. 9·5 months, P = 0·03) and enhanced the response rate (RR; OR = 1·32; 95% CI, 1·11-1·57; P = 0·002) over 5-FU-based chemotherapy. Similar trends were observed in both Caucasian and Asian patients. Capecitabine-based regimens were associated with reduced incidence rates of grade 3 or grade 4 leukopenia (OR = 0·42; P = 0·005), stomatitis (OR = 0·43; P = 0·004) and nausea and vomiting (OR = 0·60; P = 0·002) compared with 5-FU-based treatment. Incidence of haematological toxicity such as anaemia (OR = 0·88; P = 0·53), thrombocytopenia (OR = 0·58; P = 0·06), neutropenia (OR = 1·03; P = 0·78) and treatment-related mortality was similar between capecitabine- and 5-FU-based treatments. Higher frequency of grade 3 or grade 4 hand-foot syndrome (HFS; OR 2·45; P = 0·0007) was observed in capecitabine-based combination therapies. Asian patients with AGC receiving capecitabine-based combination therapies showed less frequent occurrence of grade 3 or grade 4 gastrointestinal toxicity including nausea and vomiting (OR = 0·24; P = 0·0002) and stomatitis (OR = 0·33; P = 0·02) than those receiving 5-FU-based regimens. These differences in GI toxicity between treatment regimens were not significant in Caucasian subjects. No significant difference was found for the occurrence of anaemia (Caucasian subgroup: OR = 0·97, P = 0·88; Asian subgroup: OR = 0·63, P = 0·29), neutropenia (Caucasian subgroup: OR = 1·16, P = 0·27; Asian subgroup: OR = 0·75, P = 0·21) or thrombocytopenia (Caucasian subgroup: OR = 0·62, P = 0·18; Asian subgroup: OR = 0·51, P = 0·17) between the two ethnic subgroups. WHAT IS NEW AND CONCLUSION: Capecitabine-based chemotherapy strategies show prolonged OS and enhanced ORR compared with traditional 5-FU-based treatments and therefore should be considered as one of the first choices for treatment for AGC. Asian patients also showed less grade 3 or grade 4 gastrointestinal toxicity with the capecitabine-based regimens.

Minocycline may be useful to prevent/treat postoperative cognitive decline in elderly patients.

Postoperative cognitive dysfunction (POCD) is reported to occur frequently after all types especially cardiac surgery in elderly patients. It can be short-term or long-term and some cases even develop into Alzheimer's disease (AD). Although multi-risk factors associated with POCD have been identified, the etiology and pathophysiological mechanisms of this surgical complication remain elusive. Therefore, developing strategies for preventing or treating POCD is still challenging. However, increasing evidence suggests that central and systemic inflammation triggered by surgery likely plays a fundamental role in POCD developing and progression. Minocycline, a tetracycline derivative with anti-inflammatory properties, has been shown to be effective in treating neuroinflammatory related conditions or neurodegenerative diseases such as AD, Parkinson's disease, Huntington's disease. Considering that inflammation may be a potential factor of POCD and minocycline is effective in improving cognitive dysfunction induced by inflammation, we hypothesize that minocycline may be useful to treat/prevent the POCD development after surgery in elderly patients.

Transcutaneous vagus nerve stimulation may attenuate postoperative cognitive dysfunction in elderly patients.

Postoperative cognitive dysfunction (POCD) is a decline in cognitive function for weeks or months after surgery. It may affect the patients' length of hospital stay, quality of life, the rehabilitation process, and work performance. Prolonged POCD occurs frequently after cardiac surgery, and the risk of POCD increases with age. The pathophysiology of POCD has not been well understood. However, emerging evidences indicate that various inflammatory mediators are involved in the pathophysiology of POCD and inflammatory response may a potential pathogenic factor. The vagus nerve stimulation has been shown to decrease production and release of pro-inflammatory cytokines through the cholinergic anti-inflammatory pathway (CAP) in both animal model and human. Considering that the inflammation plays a definite role in the pathogenesis of POCD and the vagus nerve can mediate inflammation via CAP, we hypothesize that the transcutaneous vagus nerve stimulation may attenuate POCD by decreasing inflammatory response in elderly patients.

Kaempferol stimulates large conductance Ca2+ -activated K+ (BKCa) channels in human umbilical vein endothelial cells via a cAMP/PKA-dependent pathway.

BACKGROUND AND PURPOSE: Kaempferol has been shown to possess a vasodilator effect but its mechanism of action remains unclear. In this study, experiments were carried out to study the effect of kaempferol on K+ channels in endothelial cells. EXPERIMENTAL APPROACH: K+ channel activities in human umbilical vein endothelial cells (HUVECs) were studied by conventional whole cell and cell-attached patch-clamp electrophysiology. KEY RESULTS: Kaempferol stimulated an outward-rectifying current in HUVECs in a dose-dependent manner with an EC50 value of 2.5+/-0.02 microM. This kaempferol-induced current was abolished by large conductance Ca2+ -activated K+ (BKCa) channel blockers, such as iberiotoxin (IbTX) and charybdotoxin (ChTX), whereas the small conductance Ca2+ -activated K+ (SKCa) channel blocker, apamin, and the voltage-dependent K+ (KV) channel blocker, 4-aminopyridine, had no effect. Cell-attached patches demonstrated that kaempferol increased the open probability of BkCa channels in HUVECs. Clamping intracellular Ca2+ did not prevent kaempferol-induced increases in outward current. In addition, the kaempferol-induced current was diminished by the adenylyl cyclase inhibitor SQ22536, the cAMP antagonist Rp-8-Br-cAMP and the PKA inhibitor KT5720, but was not affected by the guanylyl cyclase inhibitor ODQ, the cGMP antagonist Rp-8-Br-cGMP and the PKG inhibitor KT5823. The activation of BKCa channels by kaempferol caused membrane hyperpolarization of HUVECs. CONCLUSION AND IMPLICATIONS: These results demonstrate that kaempferol activates the opening of BKCa channels in HUVECs via a cAMP/PKA-dependent pathway, resulting in membrane hyperpolarization. This mechanism may partly account for the vasodilator effects of kaempferol.