[Association between auditory processing and problem behaviors in preschool children: the mediating role of executive function]. / å¬å¤„ç†ä¸Žå­¦é¾„å‰å„¿ç«¥é—®é¢˜è¡Œä¸ºçš„å ³ç³»ï¼šæ‰§è¡ŒåŠŸèƒ½çš„ä¸­ä»‹ä½œç”¨.

OBJECTIVES: To investigate the association between auditory processing and problem behaviors in preschool children, as well as the mediating role of executive function. METHODS: A total of 2 342 preschool children were selected from 7 kindergartens in Nanjing, China from June to August 2021. They were evaluated using Preschool Auditory Processing Assessment Scale, Conners Parent Symptom Questionnaire, and Behavior Rating Inventory of Executive Functioning-Preschool version. Children with different demographic features were compared in the scores and the abnormality rates of auditory processing, problem behaviors, and executive function. The influencing factors of the total scores of auditory processing, problem behaviors, and executive function were evaluated using multiple linear regression analysis. Whether executive function was a mediating factor between auditory processing and executive function was examined. RESULTS: Sex and grade were the main influencing factors for the total score of auditory processing (P<0.05), and sex, grade, parental education level, and family economic status were the main influencing factors for the total scores of problem behaviors and executive function (P<0.05). The auditory processing score (rs=0.458, P<0.05) and problem behavior score (rs=0.185, P<0.05) were significantly positively correlated with the executive function score, and the auditory processing score was significantly positively correlated with the problem behavior score (rs=0.423, P<0.05). Executive function played a partial mediating role between auditory processing and problem behaviors, and the mediating effect accounted for 33.44% of the total effect. CONCLUSIONS: Auditory processing can directly affect the problem behaviors of preschool children and indirectly affect problem behaviors through executive function.

Roles of ApoE4 on the Pathogenesis in Alzheimer's Disease and the Potential Therapeutic Approaches.

The Apolipoprotein E ε4 (ApoE ε4) allele, encoding ApoE4, is the strongest genetic risk factor for late-onset Alzheimer's disease (LOAD). Emerging epidemiological evidence indicated that ApoE4 contributes to AD through influencing ß-amyloid (Aß) deposition and clearance. However, the molecular mechanisms of ApoE4 involved in AD pathogenesis remains unclear. Here, we introduced the structure and functions of ApoE isoforms, and then we reviewed the potential mechanisms of ApoE4 in the AD pathogenesis, including the effect of ApoE4 on Aß pathology, and tau phosphorylation, oxidative stress; synaptic function, cholesterol transport, and mitochondrial dysfunction; sleep disturbances and cerebrovascular integrity in the AD brains. Furthermore, we discussed the available strategies for AD treatments that target to ApoE4. In general, this review overviews the potential roles of ApoE4 in the AD development and suggests some therapeutic approaches for AD. ApoE4 is genetic risk of AD. ApoE4 is involved in the AD pathogenesis. Aß deposition, NFT, oxidative stress, abnormal cholesterol, mitochondrial dysfunction and neuroinflammation could be observed in the brains with ApoE4. Targeting the interaction of ApoE4 with the AD pathology is available strategy for AD treatments.

[Application of Preschool Auditory Processing Assessment Scale in children with attention deficit hyperactivity disorder]. / å­¦é¾„å‰å„¿ç«¥å¬å¤„ç†è¯„ä¼°é‡è¡¨åœ¨æ³¨æ„ç¼ºé™·å¤šåŠ¨éšœç¢å„¿ç«¥ä¸­çš„åº”ç”¨ç ”ç©¶.

OBJECTIVES: To investigate the characteristics of auditory processing (AP) in preschool children with attention deficit hyperactivity disorder (ADHD) using Preschool Auditory Processing Assessment Scale (hereafter referred to as "auditory processing scale"). METHODS: A total of 41 children with ADHD and 41 typically developing (TD) children were assessed using the auditory processing scale, SNAP-IV rating scale, and Conners' Kiddie Continuous Performance Test (K-CPT). The auditory processing scale score was compared between the TD and ADHD groups. The correlations of the score with SNAP-IV and K-CPT scores were assessed. RESULTS: Compared with the TD group, the ADHD group had significantly higher total score of the auditory processing scale and scores of all dimensions except visual attention (P<0.05). In the children with ADHD, the attention deficit dimension score of the SNAP-IV rating scale was positively correlated with the total score of the auditory processing scale (rs30=0.531, P<0.05; rs27=0.627, P<0.05) as well as the scores of its subdimensions, including auditory decoding (rs=0.628, P<0.05), auditory attention (rs=0.492, P<0.05), and communication (rs=0.399, P<0.05). The hyperactivity-impulsivity dimension score of the SNAP-IV rating scale was positively correlated with the hyperactivity-impulsivity dimension score of the auditory processing scale (rs=0.429, P<0.05). In the children with ADHD, the attention deficit dimension score of the K-CPT was positively correlated with the total score (rs30=0.574, P<0.05; rs27=0.485, P<0.05) and the hyperactivity-impulsivity dimension score (rs=0.602, P<0.05) of the auditory processing scale. CONCLUSIONS: Preschool children with ADHD have the risk of AP abnormalities, and the auditory processing scale should be used early for the screening and evaluation of AP abnormalities in children.

Treating Subthreshold Depression in Primary Care: A Randomized Controlled Trial of Behavioral Activation With Mindfulness.

PURPOSE: We undertook a randomized controlled trial to assess the efficacy of group-based behavioral activation with mindfulness (BAM) for treating subthreshold depression in primary care in Hong Kong. METHODS: We recruited adult patients aged 18 years or older with subthreshold depression from public primary care clinics and randomly assigned them to a BAM intervention group or a usual care group. The BAM group was provided with eight 2-hour weekly BAM sessions by trained allied health care workers. Patients in the usual care group received usual medical care with no additional psychological interventions. The primary outcome was depressive symptoms measured by the Beck Depression Inventory-II at 12 months. Secondary outcomes included incidence of major depressive disorder at 12 months. We assessed quality of life, activity and circumstances change, functional impairment, and anxiety at baseline, end of intervention, 5 months, and 12 months. RESULTS: We randomly allocated 115 patients to the BAM intervention and 116 patients to usual care. At 12 months, compared with usual care peers, BAM patients had a slightly more favorable change in levels of depressive symptoms on the Beck Depression Inventory-II (between-group mean difference in score = -3.85; 95% CI, -6.36 to -1.34; Cohen d = -0.46, 95% CI, -0.76 to -0.16). Incidence of major depressive disorder was lower with BAM (10.8% vs 26.8%, P = .01), whereas groups did not differ significantly on other secondary outcomes at 12 months. CONCLUSIONS: Group BAM appears to be efficacious for decreasing depressive symptoms and reducing the incidence of major depression among patients with subthreshold depression in primary care, although generalizability of our findings may be limited.

Mindfulness-based stress reduction for family carers of people with dementia.

BACKGROUND: Caring for people with dementia is highly challenging, and family carers are recognised as being at increased risk of physical and mental ill-health. Most current interventions have limited success in reducing stress among carers of people with dementia. Mindfulness-based stress reduction (MBSR) draws on a range of practices and may be a promising approach to helping carers of people with dementia. OBJECTIVES: To assess the effectiveness of MBSR in reducing the stress of family carers of people with dementia. SEARCH METHODS: We searched ALOIS - the Cochrane Dementia and Cognitive Improvement Group's Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (all years to Issue 9 of 12, 2017), MEDLINE (Ovid SP 1950 to September 2017), Embase (Ovid SP 1974 to Sepetmber 2017), Web of Science (ISI Web of Science 1945 to September 2017), PsycINFO (Ovid SP 1806 to September 2017), CINAHL (all dates to September 2017), LILACS (all dates to September 2017), World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, and Dissertation Abstracts International (DAI) up to 6 September 2017, with no language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) of MBSR for family carers of people with dementia. DATA COLLECTION AND ANALYSIS: Two review authors independently screened references for inclusion criteria, extracted data, assessed the risk of bias of trials with the Cochrane 'Risk of bias' tool, and evaluated the quality of the evidence using the GRADE instrument. We contacted study authors for additional information, then conducted meta-analyses, or reported results narratively in the case of insufficient data. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included five RCTs involving 201 carers assessing the effectiveness of MBSR. Controls used in included studies varied in structure and content. Mindfulness-based stress reduction programmes were compared with either active controls (those matched for time and attention with MBSR, i.e. education, social support, or progressive muscle relaxation), or inactive controls (those not matched for time and attention with MBSR, i.e. self help education or respite care). One trial used both active and inactive comparisons with MBSR. All studies were at high risk of bias in terms of blinding of outcome assessment. Most studies provided no information about selective reporting, incomplete outcome data, or allocation concealment.1. Compared with active controls, MBSR may reduce depressive symptoms of carers at the end of the intervention (3 trials, 135 participants; standardised mean difference (SMD) -0.63, 95% confidence interval (CI) -0.98 to -0.28; P<0.001; low-quality evidence). We could not be certain of any effect on clinically significant depressive symptoms (very low-quality evidence).Mindfulness-based stress reduction compared with active control may decrease carer anxiety at the end of the intervention (1 trial, 78 participants; mean difference (MD) -7.50, 95% CI -13.11 to -1.89; P<0.001; low-quality evidence) and may slightly increase carer burden (3 trials, 135 participants; SMD 0.24, 95% CI -0.11 to 0.58; P=0.18; low-quality evidence), although both results were imprecise, and we could not exclude little or no effect. Due to the very low quality of the evidence, we could not be sure of any effect on carers' coping style, nor could we determine whether carers were more or less likely to drop out of treatment.2. Compared with inactive controls, MBSR showed no clear evidence of any effect on depressive symptoms (2 trials, 50 participants; MD -1.97, 95% CI -6.89 to 2.95; P=0.43; low-quality evidence). We could not be certain of any effect on clinically significant depressive symptoms (very low-quality evidence).In this comparison, MBSR may also reduce carer anxiety at the end of the intervention (1 trial, 33 participants; MD -7.27, 95% CI -14.92 to 0.38; P=0.06; low-quality evidence), although we were unable to exclude little or no effect. Due to the very low quality of the evidence, we could not be certain of any effects of MBSR on carer burden, the use of positive coping strategies, or dropout rates.We found no studies that looked at quality of life of carers or care-recipients, or institutionalisation.Only one included study reported on adverse events, noting a single adverse event related to yoga practices at home AUTHORS' CONCLUSIONS: After accounting for non-specific effects of the intervention (i.e. comparing it with an active control), low-quality evidence suggests that MBSR may reduce carers' depressive symptoms and anxiety, at least in the short term.There are significant limitations to the evidence base on MBSR in this population. Our GRADE assessment of the evidence was low to very low quality. We downgraded the quality of the evidence primarily because of high risk of detection or performance bias, and imprecision.In conclusion, MBSR has the potential to meet some important needs of the carer, but more high-quality studies in this field are needed to confirm its efficacy.

Comparing the Effects of Mindfulness-Based Cognitive Therapy and Sleep Psycho-Education with Exercise on Chronic Insomnia: A Randomised Controlled Trial.

BACKGROUND: Mindfulness-based cognitive therapy (MBCT) is a potential treatment for chronic insomnia. We evaluated the efficacy of MBCT for insomnia (MBCT-I) by comparing it with a sleep psycho-education with exercise control (PEEC) group. METHODS: Adults with chronic primary insomnia (n = 216) were randomly allocated to the MBCT-I or PEEC group. The MBCT-I included mindfulness and psycho-education with cognitive and behavioural components under cognitive behavioural therapy for insomnia. PEEC included psycho-education of sleep hygiene and stimulus control, and exercises. Any change in insomnia severity was measured by the Insomnia Severity Index (ISI). Secondary outcomes included sleep parameters measured by a sleep diary, health service utilisation, absence from work and mindfulness measured by the Five Facet Mindfulness Questionnaire. RESULTS: The ISI score significantly decreased in the MBCT-I group compared with the PEEC group at 2 months (i.e., post-intervention) (p = 0.023, effect size [95% CI] -0.360 [-0.675, -0.046]) but not at 5 or 8 months. Treatment response rates and remission rates based on the ISI cut-off scores were not significantly different between groups. Wake time after sleep onset (WASO) was less in the MBCT-I group at 2 and 5 months. At 8 months, both groups showed a reduced ISI score, sleep onset latency and WASO, and increased sleep efficiency and total sleep time; however, no group differences were seen. Other outcome measures did not significantly improve in either group. CONCLUSIONS: Long-term benefits were not seen in MBCT-I when compared with PEEC, although short-term benefits were seen.

A rice virescent-yellow leaf mutant reveals new insights into the role and assembly of plastid caseinolytic protease in higher plants.

The plastidic caseinolytic protease (Clp) of higher plants is an evolutionarily conserved protein degradation apparatus composed of a proteolytic core complex (the P and R rings) and a set of accessory proteins (ClpT, ClpC, and ClpS). The role and molecular composition of Clps in higher plants has just begun to be unraveled, mostly from studies with the model dicotyledonous plant Arabidopsis (Arabidopsis thaliana). In this work, we isolated a virescent yellow leaf (vyl) mutant in rice (Oryza sativa), which produces chlorotic leaves throughout the entire growth period. The young chlorotic leaves turn green in later developmental stages, accompanied by alterations in chlorophyll accumulation, chloroplast ultrastructure, and the expression of chloroplast development- and photosynthesis-related genes. Positional cloning revealed that the VYL gene encodes a protein homologous to the Arabidopsis ClpP6 subunit and that it is targeted to the chloroplast. VYL expression is constitutive in most tissues examined but most abundant in leaf sections containing chloroplasts in early stages of development. The mutation in vyl causes premature termination of the predicted gene product and loss of the conserved catalytic triad (serine-histidine-aspartate) and the polypeptide-binding site of VYL. Using a tandem affinity purification approach and mass spectrometry analysis, we identified OsClpP4 as a VYL-associated protein in vivo. In addition, yeast two-hybrid assays demonstrated that VYL directly interacts with OsClpP3 and OsClpP4. Furthermore, we found that OsClpP3 directly interacts with OsClpT, that OsClpP4 directly interacts with OsClpP5 and OsClpT, and that both OsClpP4 and OsClpT can homodimerize. Together, our data provide new insights into the function, assembly, and regulation of Clps in higher plants.

Baicalin protects PC-12 cells from oxidative stress induced by hydrogen peroxide via anti-apoptotic effects.

PRIMARY OBJECTIVE: To examine the neuroprotection of baicalin, a flavonoid compound derived from the dried root of Scutellaria baicalensis Georgi, on neurons. RESEARCH DESIGN: A rat PC12 cell line was used to study the neuroprotection and possible mechanisms of baicalin on H2O2-induced neuron damage. METHODS: Three anti- and one pro-apoptosis genes in PC12 cells were examined. Cell apoptosis was induced by H2O2 and apoptotic rate was obtained by flow cytometry. MTT for cell viability, immunofluorescence microscopy for promoter activity and western blot for gene expression were also employed. RESULTS: Data of MTT reduction assay and flow cytometry revealed that viability loss and apoptotic rate were reduced by pre-treatment of PC12 cells with baicalin for 24 hours. Baicalin was also found to increase SOD, GSH-Px activities and to decrease MDA level. Results from Western blot and immunofluorescence microscopy showed baicalin increased the expressions of survivin, Bcl-2 and p-STAT3 and decreased caspase-3 expression which were attenuated by AG-490. CONCLUSIONS: The results point to the possibility of the neuroprotective effects of baicalin on neuronal apoptosis induced by oxidative stress and indicate that activation of the JAK/STAT signalling pathway might involve the anti-apoptotic effect of baicalin.

Comparative efficacy and safety between endoscopic submucosal dissection, surgery and definitive chemoradiotherapy in patients with cT1N0M0 esophageal cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) and surgical resection are the standard of care for cT1N0M0 esophageal cancer (EC), whereas definitive chemoradiotherapy (d-CRT) is a treatment option. Nevertheless, the comparative efficiency and safety of ESD, surgery and d-CRT for cT1N0M0 EC remain unclear. AIM: To compare the efficiency and safety of ESD, surgery and d-CRT for cT1N0M0 EC. METHODS: We retrospectively analyzed the hospitalized data of a total of 472 consecutive patients with cT1N0M0 EC treated at Sun Yat-sen University Cancer center between 2017-2019 and followed up until October 30th, 2022. We analyzed demographic, medical recorded, histopathologic characteristics, imaging and endoscopic, and follow-up data. The Kaplan-Meier method and Cox proportional hazards modeling were used to analyze the difference of survival outcome by treatments. Inverse probability of treatment weighting (IPTW) was used to minimize potential confounding factors. RESULTS: We retrospectively analyzed patients who underwent ESD (n = 99) or surgery (n = 220) or d-CRT (n = 16) at the Sun Yat-sen University Cancer Center from 2017 to 2019. The median follow-up time for the ESD group, the surgery group, and the d-CRT group was 42.0 mo (95%CI: 35.0-60.2), 45.0 mo (95%CI: 34.0-61.75) and 32.5 mo (95%CI: 28.3-40.0), respectively. After adjusting for background factors using IPTW, the highest 3-year overall survival (OS) rate and 3-year recurrence-free survival (RFS) rate were observed in the ESD group (3-year OS: 99.7% and 94.7% and 79.1%; and 3-year RFS: 98.3%, 87.4% and 79.1%, in the ESD, surgical, and d-CRT groups, respectively). There was no difference of severe complications occurring between the three groups (P ≥ 0.05). Multivariate analysis showed that treatment method, histology and depth of infiltration were independently associated with OS and RFS. CONCLUSION: For cT1N0M0 EC, ESD had better long-term survival and lower hospitalization costs than those who underwent d-CRT and surgery, with a similar rate of severe complications occurring.

[Analysis of utilization situation of harm reduction services among drug users and its impact factors].

OBJECTIVE: To study the utilization situation of harm reduction services among drug users and to analyze the reasons of the drug users' absence in the services as well as their evaluation of the services quality based on the gender perspective, and then to provide advice on the improvement of harm reduction services in the future. METHODS: Cross-sectional surveys were carried out in four cities of Yunnan Province. The information was collected from the drug users in the drug rehabilitation centers and communities through outreach workers. The utilization of methadone maintenance treatment (MMT) and needle exchange service, the reason of the drug users' absence in the services and the evaluation towards the convenience, acceptability, as well as services quality were all surveyed. RESULTS: The valid samples were 579 with sex ratio 50.8% (male) and 49.2% (female). Most of the respondents (56.3%) had an educational level of junior high school and 44.0% were single. There were 61.8% (358/579) of respondents who used to utilize MMT service with female participation rate being 57.5%, which was lower than the male one (P<0.05). And there were 58.2% (223/383) of the respondents who used to exchange needles from the outreach workers or needle exchange points with female participation rate being 52.9%, which was lower than the male one (P<0.05). The leading cause of the drug users' absence in the services was their lack of understanding about the services. Among the people who used to utilize the services, the evaluations of women were better than those of men. CONCLUSION: Drug users have a low awareness of harm reduction services and female drug users are lack of the utilization towards services. More publicity and concern on harm reduction services in the future as well as exploration of the services which better fit the traits of women and privacy protection are suggested.

Signaling molecule glutamic acid initiates the expression of genes related to methylglyoxal scavenging and osmoregulation systems in maize seedlings.

Glutamic acid (Glu) is not only a protein amino acid, but also a signaling molecule, which takes part in various physiological processes in plants. Our previous study found that root-irrigation with Glu could improve the heat tolerance of maize seedlings by plant Glu receptor-like channels-mediated calcium signaling (Protoplasma, 2019; 256:1165-1169), but its molecular mechanism remains unclear. In this study, based on the our previous work, the maize seedlings were treated with 1 mM Glu prior to be exposed to heat stress (HS), and then the expression of genes related to related to methylglyoxal (MG)-scavenging and osmoregulation systems was quantified. The results showed that Glu treatment up-regulated the gene expression of Zea mays aldo-keto reductase (ZmAKR) under both non-HS and HS conditions. Also, the gene expression of Zea mays alkenal/alkenone reductase (ZmAAR), glyoxalase II (ZmGly II), pyrroline-5-carboxylate synthase (ZmP5CS), betaine dehydrogenase (ZmBADH), and trehalase (ZmTRE) was up-regualted by exogenous Glu treatment under HS conditions. These data imply that signaling molecule Glu initiated the expression of genes related to MG-scavenging and osmoregulation systems in maize seedlings, further supporting the fact that Glu-enhanced heat tolerance in plants.

Sleep-Wake Disorders in Alzheimer's Disease: A Review.

Alzheimer's disease (AD) is a multifactorial disease, and it has become a serious health problem in the world. Senile plaques (SPs) and neurofibrillary tangles (NFTs) are two main pathological characters of AD. SP mainly consists of aggregated ß-amyloid (Aß), and NFT is formed by hyperphosphorylated tau protein. Sleep-wake disorders are prevalent in AD patients; however, the links and mechanisms of sleep-wake disorders on the AD pathogenesis remain to be investigated. Here, we referred to the sleep-wake disorders and reviewed some evidence to demonstrate the relationship between sleep-wake disorders and the pathogenesis of AD. On one hand, the sleep-wake disorders may lead to the increase of Aß production and the decrease of Aß clearance, the spreading of tau pathology, as well as oxidative stress and inflammation. On the other hand, the ApoE4 allele, a risk gene for AD, was reported to participate in sleep-wake disorders. Furthermore, some neurotransmitters, such as acetylcholine, glutamate, serotonin, melatonin, and orexins, and their receptors were suggested to be involved in AD development and sleep-wake disorders. We discussed and suggested some possible therapeutic strategies for AD treatment based on the view of sleep regulation. In general, this review explored different views to find novel targets of diagnosis and therapy for AD.

Curcumin Inhibits Cell Damage and Apoptosis Caused by Thapsigargin-Induced Endoplasmic Reticulum Stress Involving the Recovery of Mitochondrial Function Mediated by Mitofusin-2.

Endoplasmic reticulum stress (ERS) and mitochondrial dysfunction have been suggested to relate with the pathology of Alzheimer's disease (AD). However, their cross-talk is needed to investigate further. Mitofusin-2 (Mfn2) is a member of mitochondria-associated membrane (MAM), which connects endoplasmic reticulum (ER) and mitochondria. This study investigated the protective effect of curcumin on thapsigargin (TG)-induced ERS and cell apoptosis and the role of Mfn2 on mitochondrial dysfunction. The cell viability of SH-SY5Y cells was decreased and cell damage and apoptosis were increased in a concentration-dependent manner when cells were treated with TG. TG upregulated the protein levels of GRP78, pSer981-PERK, and pSer51-eIF2α. Curcumin attenuated TG-induced damage on cell viability and apoptosis and downregulated the protein levels of GRP78, pSer981-PERK, and pSer51-eIF2α. TG caused the increases in intracellular reactive oxygen species (ROS) and in the protein levels of pSer40-Nrf2 and hemoglobin oxygenase 1 (HO-1). Curcumin decreased the TG-induced intracellular ROS but did not alter the protein levels of pSer40-Nrf2 and HO-1. TG resulted in the upregulation on Mfn2 expression and mitochondrial spare respiratory capacity but the downregulation on mitochondrial basal respiration and ATP production. Curcumin attenuated the TG-induced Mfn2 expression and mitochondrial stress. When Mfn2 was silenced by shRNA interference, curcumin failed to recovery the TG-damaged mitochondrial function. In general, the TG-induced ERS trigged mitochondrial dysfunction and cell apoptosis. Curcumin attenuates TG-induced ERS and the cell damage and apoptosis. Mfn2 is required for curcumin's protection against the TG-induced damage on mitochondrial functions.

Adjuvant Chemotherapy in Node-Negative Advanced Gastric Cancer Patients.

Currently, there is still controversy on postoperative adjuvant chemotherapy for node-negative advanced gastric cancer. Herein, we sought to evaluate the role of postoperative adjuvant chemotherapy in these patients. We retrospectively analyzed the clinical and pathological characteristics of 363 node-negative advanced gastric cancer patients in our hospital from 1996 to 2007 who underwent gastrectomy and D2 lymphadenectomy. We compared the survival rate of the surgery-only group with that of the adjuvant chemotherapy treatment group. The 5-year survival rates of patients in the surgery-only group and the chemotherapy treatment group were 70.7% and 73.8%, respectively. There was no significant difference in the survival rate between patients receiving postoperative chemotherapy and patients not receiving chemotherapy (P=0.328). However, postoperative chemotherapy treatment significantly increased the survival rate of pT4aN0M0 patients (P=0.020), although it did not exert a direct effect on the survival rate in pT2N0M0 and pT3N0M0 patients (P=0.990 and P=0.895). We also summarized and analyzed the side effects and safety of postoperative adjuvant chemotherapy. The rate of chemotherapy-related adverse events was 79.9%. Although 61 (36.1%) patients had to adjust their chemotherapy dose, no patient died from side effects. In conclusion, postoperative chemotherapy treatment is safe but did not show a direct impact on the survival rate of the node-negative advanced gastric cancer patients. However, pT4aN0M0 patients can benefit from postoperative adjuvant chemotherapy after undergoing D2 radical resections.

Involvement of osmoregulation, glyoxalase, and non-glyoxalase systems in signaling molecule glutamic acid-boosted thermotolerance in maize seedlings.

Glutamic acid (Glu) is not only an important protein building block, but also a signaling molecule in plants. However, the Glu-boosted thermotolerance and its underlying mechanisms in plants still remain unclear. In this study, the maize seedlings were irrigated with Glu solution prior to exposure to heat stress (HS), the seedlings' thermotolerance as well as osmoregulation, glyoxalase, and non-glyoxalase systems were evaluated. The results manifested that the seedling survival and tissue vitality after HS were boosted by Glu, while membrane damage was reduced in comparison with the control seedlings without Glu treatment, indicating Glu boosted the thermotolerance of maize seedlings. Additionally, root-irrigation with Glu increased its endogenous level, reinforced osmoregulation system (i.e., an increase in the levels of proline, glycine betaine, trehalose, and total soluble sugar, as well as the activities of pyrroline-5-carboxylate synthase, betaine dehydrogenase, and trehalose-5-phosphate phosphatase) in maize seedlings under non-HS and HS conditions compared with the control. Also, Glu treatment heightened endogenous methylglyoxal level and the activities of glyoxalase system (glyoxalase I, glyoxalase II, and glyoxalase III) and non-glyoxalase system (methylglyoxal reductase, lactate dehydrogenase, aldo-ketoreductase, and alkenal/alkenone reductase) in maize seedlings under non-HS and HS conditions as compared to the control. These data hint that osmoregulation, glyoxalase, and non-glyoxalase systems are involved in signaling molecule Glu-boosted thermotolerance of maize seedlings.

Key role of reactive oxygen species-scavenging system in nitric oxide and hydrogen sulfide crosstalk-evoked thermotolerance in maize seedlings.

Nitric oxide (NO) and hydrogen sulfide (H2S) are novel signaling molecules, which participate in plant growth, development, and response to stress. In this study root-irrigation with 0.15 mM sodium nitroprusside (SNP, NO donor) up-regulated gene expression of L-CYSTEINE DESULFHYDRASE1 (LCD1), activities of L-cysteine desulfhydrase (LCD) and D-cysteine desulfhydrase (DCD), as well as an endogenous H2S level, compared to control seedlings. The SNP-up-regulated effects were enhanced by 0.5 mM sodium hydrosulfide (NaHS, H2S donor), but weakened by NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) and H2S scavenger hypotaurine (HT) alone. NaHS had no significant effect on gene expression and activity of nitrate reductase (NR, a NO candidate producing enzyme). These data indicate that NO could trigger the LCD/H2S signaling pathway in maize seedlings. To further investigate the effect of NO and H2S crosstalk on thermotolerance in maize seedlings, thermotolerance parameters and reactive oxygen species (ROS)-scavenging system were estimated. The results show that SNP increased survival rate and tissue viability, decreased malondialdehyde (MDA) accumulation, and electrolyte leakage in maize seedlings under heat stress (HS), implying NO could improve thermotolerance in maize seedlings. The NO-improved thermotolerance was impaired by H2S inhibitor DL-propargylglycine (PAG) and scavenger HT alone. Similarly, SNP up-regulated the gene expression of DEHYDROASCORBATE REDUCTASE (DHAR) and GLUTATHIONE REDUCTASE1 (GR1); activities of ascorbate peroxidase, glutathione reductase, and catalase; as well as levels of ascorbic acid, glutathione, flavonoids, carotenoids, and total phenols. SNP also reduced hydrogen peroxide and superoxide radical accumulation in maize seedlings under HS compared to the control. The effects of SNP on ROS and their scavenger system were weakened by PAG and HT alone. These data hint that NO could evoke thermotolerance in maize seedlings by triggering the LCD/H2S signaling pathway, and the ROS-scavenging system played a key role in the NO and H2S crosstalk-evoked thermotolerance.

Study of preoperative diagnostic modalities in Chinese patients with superficial esophageal squamous cell carcinoma.

BACKGROUND: Endoscopic ultrasonography (EUS) and magnifying endoscopy (ME) reliably determine indications for endoscopic resection in patients with superficial esophageal squamous cell carcinoma (SESCC). ME is widely accepted for predicting the invasion depth of superficial esophageal cancer with satisfying accuracy. However, the addition of EUS is controversial. AIM: To evaluate the diagnostic efficiency of ME vs EUS for invasion depth prediction and investigate the influencing factors in patients with SESCC to determine the best diagnostic model in China. METHODS: We retrospectively analyzed patients with suspected SESCC who completed both ME and EUS and then underwent endoscopic or surgical resection at Sun Yat-Sen University Cancer Center between January 2018 and December 2021. We evaluated and compared the diagnostic efficiency of EUS and ME according to histological results, and investigated the influencing factors. RESULTS: We included 152 lesions from 144 patients in this study. The diagnostic accuracies of ME and EUS in differentiating invasion depth were not significantly different (73.0% and 66.4%, P = 0.24); both demonstrated moderate consistency with the pathological results (ME: kappa = 0.58, 95% confidence interval [CI]: 0.48-0.68, P < 0.01; EUS: kappa = 0.46, 95%CI: 0.34-0.57, P < 0.01). ME was significantly more accurate in the diagnosis of high-grade intraepithelial (HGIN) or carcinoma in situ (odds ratio [OR] = 3.62, 95%CI: 1.43-9.16, P = 0.007) subgroups. Using a miniature probe rather than conventional EUS can improve the accuracy of lesion depth determination (82.3% vs 49.3%, P < 0.01). Less than a quarter of circumferential occupation and application of a miniature probe were independent risk factors for the accuracy of tumor invasion depth as assessed by EUS (< 1/4 circumferential occupation: OR = 3.07, 95%CI: 1.04-9.10; application of a miniature probe: OR = 5.28, 95%CI: 2.41-11.59, P < 0.01). Of the 41 lesions (41/152, 27.0%) that were misdiagnosed by ME, 24 were corrected by EUS (24/41, 58.5%). CONCLUSION: Preoperative diagnosis of SESCC should be conducted endoscopically using white light and magnification. In China, EUS can be added after obtaining patient consent. Use of a high-frequency miniature probe or miniature probe combined with conventional EUS is preferable.

Phosphorylation and Glycosylation of Amyloid-ß Protein Precursor: The Relationship to Trafficking and Cleavage in Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder in the central nervous system, and this disease is characterized by extracellular senile plaques and intracellular neurofibrillary tangles. Amyloid-ß (Aß) peptide is the main constituent of senile plaques, and this peptide is derived from the amyloid-ß protein precursor (AßPP) through the successive cleaving by ß-site AßPP-cleavage enzyme 1 (BACE1) and γ-secretase. AßPP undergoes the progress of post-translational modifications, such as phosphorylation and glycosylation, which might affect the trafficking and the cleavage of AßPP. In the recent years, about 10 phosphorylation sites of AßPP were identified, and they play complex roles in glycosylation modification and cleavage of AßPP. In this article, we introduced the transport and the cleavage pathways of AßPP, then summarized the phosphorylation and glycosylation sites of AßPP, and further discussed the links and relationship between phosphorylation and glycosylation on the pathways of AßPP trafficking and cleavage in order to provide theoretical basis for AD research.

Lipoxin A4 regulates microglial M1/M2 polarization after cerebral ischemia-reperfusion injury via the Notch signaling pathway.

Microglia are rapidly activated after acute ischemic stroke, and the polarization of microglial is associated with the prognosis of acute ischemic stroke. Lipoxin A4 (LXA4), an anti-inflammatory agent, has a protective effect against ischemic stroke. However, the role of LXA4 on the polarization of microglial after acute ischemic stroke remains undetermined. We hypothesized that LXA4 may exert the neuroprotective effect though regulating the polarization of microglial. In this study, clinical features of acute ischemic stroke were simulated using a rat model of model of middle cerebral artery occlusion (MCAO) in vivo and the BV2 microglia oxygen-glucose deprivation/reoxygenation model (OGD/R) in vitro. The protective effects of LXA4 on cerebral ischemia-reperfusion injury were determined using TTC staining, HE staining, and TUNEL staining. The expression of targeted genes was assayed using quantitative real-time PCR (qRT-PCR), immunofluorescence, and western blot to investigated the regulation of LXA4 on microglia polarization after acute ischemic stroke. We found that LXA4 exerted protective effects on focal cerebral ischemia-reperfusion injury and reduced the expression of the pro-inflammatory cytokines IL-1ß and TNF-α. Furthermore, LXA4 inhibited the expression of Notch-1, Hes1, iNOS and CD32 all of which are associated with the differentiation into M1 microglia. By contrast, LXA4 upregulated the expression of Hes5, Arg-1 and CD206 all of which are associated with M2 phenotype in microglia. In addition, blocking the Notch signaling pathway with the inhibitor DAPT significantly mitigated the effect of LXA4 on microglia differentiation. These data suggest that LXA4 may regulate the polarization of microglia after cerebral ischemia-reperfusion injury through the Notch signaling pathway.

New cyclopentenoneacrylic acid derivatives from a marine-derived fungus Trichoderma atroviride H548.

Three new cyclopentenoneacrylic acid derivatives, trichodermacid A (1), trichodermester A (2), and trichodermester B (3), together with thirteen known compounds, were isolated from an ethyl acetate extract of Trichoderma atroviride H548, a fungus derived from mangrove sediment. The structures of the new compounds were elucidated by spectroscopic methods including HR ESI-MS, 1H NMR, 13C NMR, and 2D-NMR techniques. The antifungal activity of the isolated compounds was evaluated against tea pathogenic fungus Pestalotiopsis theae. Trichodermester A (2) showed potent anti P. theae activity with MIC of 125 µg/disc, while the other compounds were inactive.