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Multifocal electroretinogram (mfERG) is an important diagnostic tool in the clinical evaluation of central electro-retinal function of the macula. To enhance the diagnostic values and to improve its accuracy and internal consistency, it is crucial to examine carefully the endogenous and exogenous factors that affect mfERG recordings and clinical interpretations. This mini review focuses on three aspects of exogenous factors including (1) physiological variations pertaining to age and gender; (2) systemic changes owing to oxygen, blood pressure and glucose levels; (3) individual variables due to refractive status, pupil size, luminance and viewing condition.

BACKGROUND: Idiopathic mesenteric phlebosclerosis (IMP) is a rare disease, and its etiology and risk factors remain uncertain. AIM: To investigate the possible influence of Chinese herbal liquid containing geniposide on IMP. METHODS: The detailed formula of herbal liquid prescriptions of all patients was studied, and the herbal ingredients were compared to identify the toxic agent as a possible etiological factor. Abdominal computed tomography (CT) and colonoscopy images were reviewed to determine the extent and severity of mesenteric phlebosclerosis and the presence of findings regarding colitis. The disease CT score was determined by the distribution of mesenteric vein calcification and colon wall thickening on CT images. The drinking index of medicinal liquor was calculated from the daily quantity and drinking years of Chinese medicinal liquor. Subsequently, Spearman's correlation analysis was conducted to evaluate the correlation between the drinking index and the CT disease score. RESULTS: The mean age of the 8 enrolled patients was 75.7 years and male predominance was found (all 8 patients were men). The patients had histories of 5-40 years of oral Chinese herbal liquids containing geniposide and exhibited typical imaging characteristics (e.g., threadlike calcifications along the colonic and mesenteric vessels or associated with a thickened colonic wall in CT images). Calcifications were confined to the right-side mesenteric vein in 6 of the 8 patients (75%) and involved the left-side mesenteric vein of 2 cases (25%) and the calcifications extended to the mesorectum in 1 of them. The thickening of colon wall mainly occurred in the right colon and the transverse colon. The median disease CT score was 4.88 (n = 7) and the median drinking index was 5680 (n = 7). After Spearman's correlation analysis, the median CT score of the disease showed a significant positive correlation with the median drinking index (r = 0.842, P < 0.05). CONCLUSION: Long-term oral intake of Chinese herbal liquid containing geniposide may play a role in the pathogenesis of IMP.

At diagnosis, more than 70% of bladder cancers (BCs) are at the non-muscle-invasive bladder cancer (NMIBC) stages, which are usually treated with transurethral resection followed by intravesical instillation. For the remaining advanced cancers, systemic therapy is the standard of care, with addition of radical cystectomy in cases of locally advanced cancer. Because of the difference in treatment modalities, different models are needed to advance the care of NMIBC and advanced BC. This article gives a comprehensive review of both in vitro and in vivo BC models and compares the advantages and drawbacks of these preclinical systems in BC research.

Dynamic accommodation under natural viewings, such as driving, could be affected by the lighting condition. This study aimed to investigate the accommodation rock after the visual display unit (VDU) activity with and without ambient lighting. It was measured in cycle minute (cpm) with Hart Chart before and after each lighting condition's VDU activity. The VDU activity involved a one-hour visual task in 30 young adults. There was significant different [c2(3) = 23.42, p

This study aims to compare the accommodation microfluctuation before and after 5 mins of digital reading in the dark with night shift mode. Nineteen subjects were recruited using convenient sampling and a crossover design was used to compare the accommodation microfluctuations two viewing conditions. There was no significant difference in accommodation microfluctuations before and after 5-minute reading with night shift mode and without night shift mode. The insignificant findings in the accommodation microfluctuation comparison seemed to suggest that Night Shift Mode did not display as an advantage in controlling accommodation. Keywords: Digital eye strain, accommodation microfluctuations, digital reading, night shift mode. eISSN: 2398-4287© 2020. The Authors. Published for AMER ABRA cE-Bsby e-International Publishing House, Ltd., UK. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Peer–review under responsibility of AMER (Association of Malaysian Environment-Behaviour Researchers), ABRA (Association of Behavioural Researchers on Asians) and cE-Bs (Centre for Environment-Behaviour Studies), Faculty of Architecture, Planning & Surveying, Universiti Teknologi MARA, Malaysia. DOI: https://doi.org/10.21834/ebpj.v5iSI3.2568

The study aimed to perform field of human’s view analysis to predict the visual interference of drivers from street lights positioning. A concentric circle with 13 quadrants was superimposed onto a photograph taken at the reference point for the field of human's view analysis. Visual interference from light source located close to fovea would be most disturbing and gradually reduced to the peripheral. From the field of driver's view analysis superimposed with real-scenario photos, none of the street light sources was found to fall within the fovea ring. The visual interference from street lights was negligible from the driver's view. Keywords: Visual interference; streetlight; visual field; field of view. eISSN: 2398-4287© 2020. The Authors. Published for AMER ABRA cE-Bsby e-International Publishing House, Ltd., UK. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Peer–review under responsibility of AMER (Association of Malaysian Environment-Behaviour Researchers), ABRA (Association of Behavioural Researchers on Asians) and cE-Bs (Centre for Environment-Behaviour Studies), Faculty of Architecture, Planning & Surveying, Universiti Teknologi MARA, Malaysia. DOI: https://doi.org/10.21834/ebpj.v5iSI3.2580

Background lncRNAs and VEGF have been shown to have close connections with oral squamous cell carcinoma (OSCC). We explored the interaction between lncRNA NEAT1 and VEGF-A in OSCC. Methods RT-qPCR was implemented to measure levels of lncRNA NEAT1 and VEGF-A in OSCC cell lines and normal cell lines. Cell functions then were checked after regulating the expressions of lncRNA NEAT1 and VEGF-A separately. Cell viabilities were examined with CCK-8 and apoptosis rate was checked with flow cytometry. Meanwhile, EMT-related genes E-cadherin, N-cadherin, Vimentin, and Snail and Notch signaling genes Notch1, Notch2, and Jagged were evaluated by RT-qPCR. IMR-1 was applied for impeding Notch signaling pathway. Later, cell viabilities, apoptosis, and EMT were assessed. Results Expressions of lncRNA NEAT1 and VEGF-A were both increased significantly in OSCC cell lines especially in TSCC1 cell line. Suppression of lncNRA NEAT1 was associated with lower cell viabilities and EMT and higher apoptosis rate in the TSCC1 cell line. Meanwhile, knockdown of VEGF-A significantly repressed cell viabilities and EMT in the TSCC1 cell line. Magnifying functions of inhibited lncRNA NEAT1 Notch signaling pathway was obviously activated with overexpressions of lncRNA NEAT1 and VEGF-A. Adding IMR-1 significantly downregulated cell viabilities and EMT and sharply increased apoptosis in the context of lncRNA NEAT1 and VEGF-A overexpression. Conclusion LncRNA NEAT1 may upregulate proliferation and EMT and repress apoptosis through activating VEGF-A and Notch signaling pathway in vitro, suggesting an underlying regulatory factor in OSCC. Nevertheless, further research is necessary to gain a greater understanding of lncRNA NEAT1 and connections with VEGF-A in vivo and in clinical study.

OBJECTIVE To evaluate the ability of macular ganglion cell and inner plexiform layer (mGCIPL) and retinal nerve fiber layer (RNFL) thickness measurements by long-wavelength swept-source optical coherence tomography (SS-OCT) to assess retinal ganglion cell (RGC) damage in nonarteritic anterior ischemic optic neuropathy (NAION). METHODS A retrospective study of 20 patients with unilateral NAION was performed. SS-OCT scanning of the macular and peripapillary areas was performed to measure the total and six-sector thicknesses of macular RNFL (mRNFL) and mGCIPL, as well as peripapillary RNFL (pRNFL) thicknesses in global and 12 clock-hour sectors. Further comparison of these thicknesses between NAION involved eyes and uninvolved counterparts was performed in 12 of the 20 patients at 4 visits. The thickness map and en face images generated by volume data of the posterior pole over a 12 × 9-mm area were used for RNFL analysis. RESULTS Median time intervals between the visual symptom onset and first thinning occurrences of mGCIPL, mRNFL, and pRNFL were 17 days (95% Confidence Interval [CI] 14-18 days), 43 days (95% CI 32-48 days), and 70 days (95% CI 62-80 days), respectively. The thickness map indicated a significantly reduced pRNFL in the superior temporal sectors or temporal sectors after 9 weeks, and retinal damage corresponded to the superior hemisphere's mRNFL and mGCIPL. En face images showed that the RNFL thinning area gradually expanded along the retinal nerve fiber direction and progressed toward the optic nerve head. CONCLUSIONS The patterns of RGC damage in the macular and peripapillary areas of NAION eyes can be revealed by SS-OCT. Objective measurement of SS-OCT is valuable in characterizing NAION.

BACKGROUND: Perturbation of the CDK4/6 pathway is frequently observed in advanced bladder cancer. We investigated the potential of targeting this pathway alone or in combination with chemotherapy or immunotherapy as a therapeutic approach for the treatment of bladder cancer METHODS: The genetic alterations of the CDK4/6 pathway in bladder cancer was first analyzed with The Cancer Genome Atlas (TCGA) database and validated in our bladder cancer patient-derived tumor xenografts (PDXs). Bladder cancer cell lines and mice carrying PDXs with the CDK4/6 pathway perturbations were treated with a CDK4/6 inhibitor palbociclib to determine its anti-cancer activity and the underlying mechanisms. The combination index method was performed to assess palbociclib and gemcitabine drug-drug interactions. Syngeneic mouse bladder cancer model BBN963 was used to assess whether palbociclib could potentiate anti-PD-1 immunotherapy. RESULTS: Of the 413 bladder cancer specimens, 79.2% harbored pertubations along the CDK4/6 pathway. Palbociclib induced G0/G1 cell cycle arrest but with minimal apoptosis in vitro. In mice carrying PDXs, palbociclib treatment reduced tumor growth and prolonged survival from 14 days to 32 days compared to vehicle only controls (p=0.0001). Palbociclib treatment was associated with a decrease in Rb phosphorylation in both cell lines and PDXs. Palbociclib and gemcitabine exhibited antagonistic cytotoxicity in vitro (CI >3) and in vivo, but significantly enhanced the treatment efficacy of anti-PD1 immunotherapy and induced CD8+ T lymphocyte infiltration in syngeneic mouse models. CONCLUSIONS: The CDK4/6 pathway is feasible as a potential target for the treatment of bladder cancer, especially in combination with immunotherapy. A CDK4/6 inhibitor should not be combined with gemcitabine.

Background Parents play important role in providing information regarding their children’s health status to healthcare providers. However, parents’ ability in reporting signs and symptoms of eye problems among their children required more in-depth investigation. Our study aimed to compare the differences of parental report regarding eye problems among their children using two different question approaches. Methods A total of 416 parents with children aged between two months old and 17 years old were participated in this cross-sectional survey. The responses of parents’ observation on signs and symptoms of eye problems were compared between one open-ended question and ten close-ended questions. We also examined the demographic contributing factors that could influence parental responses. Results The total count of reported signs and symptoms through open-ended and close-ended question was 164 and 529 reports, respectively. Parents reported more diverse (70% higher) categories of signs and symptoms in open-ended compared to close-ended questions. Parent’s ability to report eye problems using open-ended question was associated with their gender (p

To compare the thoracic magnetic resonance imaging (TMRI) features between peripheral lung cancer (PLC) and progressive massive fibrosis (PMF) of coal silicosis (CS), and to excavate information of differential diagnostic value. 68 patients with PLC (68 lesions) were selected as lung cancer group (LCG), and 50 patients with PMF of CS (78 lesions) were selected as coal silicosis group (CSG). TMRI was performed in both groups, and T1-weighted imaging (T1WI), T2-weighted imaging (T2WI) and Spectral pre-saturated inversion recovery (SPIR) were used. The differences and characteristics of TMRI between the two groups were analyzed. 55 cases of pulmonary masses (PM) in LCG showed iso-signal intensity on T1WI (80.9%), and 63 cases showed high-signal intensity on T2WI and SPIR (92.6%); 65 cases of PMF in CSG showed iso-signal intensity on T1WI (83.5%), and high-signal intensity on T2WI and SPIR was found in 4 cases (5.1%), but 67 cases showed low-signal intensity (85.9%). PMF in CSG with high-signal intensity on T2WI and SPIR were significantly lower than PM in LCG(P < 0.1). Compared with TMRI of PLC showed high-signal intensity on T2WI and SPIR, PMF in CS showed low-signal intensity on T2WI and SPIR. This feature is of important significance in differential diagnosis.

AIM: To evaluate the quality of life of recruits after refractive surgery. METHODS: Population-based, cross-sectional study. Using the Quality of Life Impact of Refractive Correction (QIRC) questionnaire, the quality of life in 615 recruits underwent refractive surgery was evaluated. The overall score and each question score of QIRC were compared between subgroups of different strength of preoperative refractive error, postoperative interval, type of surgical procedure and postoperative recovery. RESULTS: The mean overall QIRC score of recruits underwent refractive surgery was 49.15±7.89. Significant difference was found for strength of preoperative refractive error (F=4.16, P0.05). Scores of recruits underwent mechanical microkeratome laser in situ keratomileusis (MK-LASIK), Sub-Bowman’s keratomileusis (SBK), femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK), femtosecond lenticule extraction (ReLEx flex) or small-incision lenticule extraction (ReLEx SMILE) procedure showed no significant difference too. Recruits had adverse complaints postoperatively (45.85±6.66) scored lower when compared with all underwent refractive surgery (t=5.28, P

To observe the effects of electroacupuncture (EA) on the protein and gene expressions of Bax, Caspase-3 and Bcl-2 in cerebral cortex of type 2 diabetic rats with cognitive impairment (CI), and to explore the mechanism of EA in improving the learning and memory abilities. A total of 100 Sprague-Dawley (SD) rats were divided into a normal group (n=10) and a model group (n=90) by random number table method. Rats in the model group were intraperitoneally injected with a small dose of streptozotocin (STZ) to establish the type 2 diabetic models, after being fed with high-fat and high-sugar diet for 1 month. Twenty CI rats were selected from the 50 successful model rats by the Morris water maze (MWM) test and randomly divided into a model group and an EA group according to the blood glucose level and MWM data (n=10). Rats in the EA group received acupuncture at Zusanli (ST 36), Neiting (ST 44) and Yishu (Extra), of which Zusanli (ST 36) and Neiting (ST 44) were stimulated by EA apparatus, 20 min/time, once a day for 6 d a week and 4 consecutive weeks. The rats in the model and the normal groups were fixed without treatment. After 4-week treatment, the random blood glucose level of the rats was measured; the learning and memory abilities of rats were measured by MWM; terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was used to detect apoptotic cells; Western blot (WB) and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the protein and gene expressions of Bax, Caspase-3 and Bcl-2 in cerebral cortex. After modeling, the random blood glucose level and the escape latency tested by MWM were significantly increased, and the number of crossing the platform tested by the MWM was decreased in the EA and model groups, and were significantly different from those in the normal group (P 0.05). After 4-week treatment, the random glucose level and the escape latency tested by MWM were significantly increased (both P

Background: Transcranial alternating current stimulation (tACS) offers a new approach for adult patients with major depressive disorder (MDD). The study is to evaluate the efficacy and safety of tACS treating MDD. Methods: This is an 8-week, double-blind, randomized, placebo-controlled study. Ninety-two drug-naive patients with MDD aged 18 to 65 years will receive 20 daily 40-min, 77.5-Hz, 15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas on weekdays for 4 consecutive weeks (week 4), following a 4-week observation period (week 8). The primary outcome is the remission rate defined as the 17-item Hamilton depression rating scale (HDRS-17) score ≤7 at week 8. Secondary outcomes are the rates of response at weeks 4 and 8 and rate of remission at week 4 based on HDRS-17, the proportion of participants having improvement in the clinical global impression-improvement, the change in HDRS-17 score (range, 0–52, with higher scores indicating more depression) over the study, and variations of brain imaging and neurocognition from baseline to week 4. Safety will be assessed by vital signs at weeks 4 and 8, and adverse events will be collected during the entire study. Discussion: The tACS applied in this trial may have treatment effects on MDD with minimal side effects. Trial registration: Chinese Clinical Trial Registry, ChiCTR1800016479; http://www.chictr.org.cn/showproj.aspx?proj=22048. Key words: Major depressive disorder; Transcranial alternating current stimulation; Treatment; Trial

Purpose Incorporating mass pediatric vision screening programs as part of a national agenda can be challenging. This review assessed the implementation strategy of the existing pediatric vision screening program. Methods A search was performed on PubMed, EBSCO host MEDLINE Complete, and Scopus databases encompassing the past ten years for mass pediatric screening practice patterns that met the selection criteria regarding their objectives and implementation. Results were analyzed from 18 countries across five continents. Results Eight countries (44%) offered screening for distance visual acuity only, where the majority of the countries (88%) used either Snellen or Tumbling E chart. High-income countries initiated screening earlier and applied a more comprehensive approach, targeting conditions other than reduced vision only, compared with middle-income countries. Chart-based testing was most commonly performed, with only three countries incorporating an instrument-based approach. Lack of eyecare and healthcare practitioners frequently necessitated the involvement of non-eyecare personnel (94%) as a vision screener including parent, trained staff, and nurse. Conclusions Implementation of a vision screening program was diverse within countries preceded by limited resources issues. Lack of professional eyecare practitioners implied the need to engage a lay screener. The limitation of existing tests to detect a broader range of visual problems at affordable cost advocated the urgent need for the development of an inexpensive and comprehensive screening tool.

Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide. Atherosclerosis is the main pathological basis of cardiovascular diseases and it is closely associated with hyperlipidemia, endothelial injury, macrophage-derived foam cells formation, proliferation and migration of vascular smooth muscle cells (VSMCs), platelet aggregation, and altered gut microbiota. Various symptomatic treatments, that are currently used to inhibit atherosclerosis, need to be administered in long term and their adverse effects cannot be ignored. Berberine (BBR) has beneficial effects on atherosclerosis through regulating multiple aspects of its progression. This review highlights the recent advances in understanding the anti-atherosclerosis mechanism of BBR. BBR alleviated atherosclerosis by attenuation of dyslipidemia, correction of endothelial dysfunction, inhibition of macrophage inflammation and foam cell formation, activation of macrophage autophagy, regulation of the proliferation and migration of VSMCs, attenuation of platelet aggregation, and modulation of gut microbiota. This review would provide a modern scientific perspective to further understanding the molecular mechanism of BBR attenuating atherosclerosis and supply new ideas for atherosclerosis management.

Background: Several echocardiographic methods to estimate pulmonary vascular resistance (PVR) in patients with pulmonary hypertension (PH) have been proposed. So far, most studies have focused on relatively low PVR. We aimed to clarify the clinical usefulness of our new echocardiographic index of evaluating markedly elevated PVR in pre-capillary PH patients. Methods: We studied 129 consecutive patients with pre-capillary PH. We estimated the mean pulmonary artery pressure using echocardiography (mPAPEcho) and measured LV internal diameter at end diastole (LVIDd). The ratio of mPAPEcho / LVIDd was then correlated with invasive PVR. Using receiver operating characteristic curve analysis, a cutoff value for the index was generated to identify patients with PVR > 15 Wood units (WU). Results: mPAPEcho / LVIDd correlated well with PVR (r = 0.70, P < 0.0001). There was a better correlation between PVR and mPAPEcho / LVIDd in patients with PVR > 15 WU compared with TRV2 /TVIRVOT and sPAPEcho / LVIDd. A cut-off value of 1.14 had an 80.0% sensitivity and 74.7% specificity to determine PVR > 15 WU (AUC=0.840, pConclusions: The index of mPAPEcho / LVIDd could be a valuable noninvasive and simple method of estimating markedly elevated PVR in pre-capillary PH patients.

Allergy is a major public health concern, the main treatment for which is symptomatic relief with anti-inflammatory drugs. A key clinical challenge is to induce specific tolerance in order to control allergen-specific memory B and T cells, and specifically block effector cell responses. Our lab recently developed antigen-specific regulatory T-cell (Treg) therapies as a treatment for adverse responses. Recently, we created a chimeric antigen receptor (CAR) approach in which we engineered a target protein antigen, ovalbumin (OVA), linked with the transmembrane and signal transduction domains, CD28-CD3ζ to directly target B cells and sensitized mast cells in an allergy model. We named this receptor “BAR” for B-cell Antibody Receptor. Murine or human Tregs, transduced with a BAR containing OVA or control Tregs expressing an unrelated antigen, were successfully expanded in vitro and tested in the murine OVA-alum allergy model with measurable titers of anti-OVA IgE. Because BAR Tregs express the target antigen and could interact with specific IgE on sensitized mast cells, we first demonstrated that intravenously injected OVA-BAR Tregs did not directly lead to a drop in temperature or release of mediators in plasma indicative of anaphylaxis. Forty-eight hours later, mice were challenged intraperitoneally with 200 μg OVA to induce an anaphylactic reaction, and temperature immediately measured for 30 min. We found that OVA-BAR Tregs protected mice from hypothermia, whereas mice given control BARs (expressing an unrelated antigen) or PBS showed substantial temperature drops indicative of anaphylaxis when systemically challenged with OVA. Importantly, this effect was also demonstrated in a passive anaphylaxis model in which mice that received anti-OVA IgE antibody were protected from hypothermia when treated with OVA-BAR Tregs prior to systemic OVA challenge. These results provide proof of principle that engineered allergen-specific T-regulatory cells can provide clinical protection against severe allergic reactions in individuals already IgE-sensitized to an allergen.

Study Objective The purpose of this study was to determine if there are any genetic changes with whole-exome sequencing associated with distal vaginal atresia. Design This was a retrospective genetics study of 5 patients who presented with distal vaginal atresia who were recruited between 2017 and 2018. Whole-exome sequencing was performed in each subject with distal vaginal atresia. Sanger sequencing was used to confirm the potential causative genetic mutation. Setting Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China. Participants and Main Outcome Measures The main outcome measure was the rare mutations potentially associated with distal vaginal atresia in 5 patients. Results A truncating mutation c.266delC (p.P89Rfs*5) in the T-box transcription factor 6 (TBX6) gene, which is highly expressed in the human vagina, was identified in 1 patient using whole-exome sequencing. The deletion of the 16p11.2 region containing the TBX6 locus has also been reported previously to have the clinical feature of Mullerian agenesis. This mutation was paternally inherited by the patient. This truncating mutation was absent from all of the databases we checked, suggesting that the variant is rare and pathogenic. Conclusion We showed, to our knowledge, for the first time, that the mutation in TBX6 might be associated with human distal vaginal atresia.

Near work, accommodative inaccuracy and ambient lighting conditions have all been implicated in the development of myopia. However, differences in accommodative responses with age and refractive error under different visual conditions remain unclear. This study explores differences in accommodative ability and refractive error with exposure to differing ambient illumination and visual demands in Malay schoolchildren and adults.Sixty young adults (21-25 years) and 60 schoolchildren (8-12 years) were recruited. Accommodative lag and accommodative fluctuations at far (6 m) and near (25 cm) were measured using the Grand Seiko WAM-5500 open-field autorefractor. The effects of mesopic room illumination on accommodation were also investigated.Repeated-measures ANOVA indicated that accommodative lag at far and near differed significantly between schoolchildren and young adults [F(1.219, 35.354) = 11.857, p 0.05]. Post hoc tests using the Bonferroni correction showed that at near, there was a greater lag in schoolchildren (0.486 ± 0.181 D) than young adults (0.259 ± 0.209 D, p 0.05). Repeated-measures ANOVA also revealed that accommodative lag at near demands differed statistically between the non-myopic and myopic groups in young adults and schoolchildren [F(3.107, 31.431) = 12.187, p 0.05]. Post hoc tests with Bonferroni correction showed that accommodative lag at near was significantly greater in myopic schoolchildren (0.655 ± 0.198 D) than in non-myopic schoolchildren (0.202 ± 0.141 D, p 0.05) and myopic young adults (0.316 ± 0.172 D, p 0.05), but no significant difference was found between myopic young adults (0.316 ± 0.172 D) and non-myopic young adults (0.242 ± 0.126 D, p 0.05). Accommodative lag and fluctuations were greater under mesopic room conditions for all ages [all p 0.05].Greater accommodative lag was found in myopes than in emmetropes, in schoolchildren than in adults, and under mesopic conditions than under photopic conditions. Accommodative fluctuations were greatest in myopes and in mesopic conditions. These results suggest that differences exist in the amount of blur experienced by myopes and non-myopes at different ages and under different lighting conditions.

Aim To investigate the effect of age on reading acuity and reading speed in attaining text information in healthy eyes. Methods Reading acuity, critical print size, reading speed and maximum reading speed were measured in groups of 40 children (8 to 12 years old), 40 teenagers (13 to 19 years old), 40 young adults (20 to 39 years old), and 40 adults (40 years old and above) using the Buari-Chen Malay Reading Chart [contextual sentences (CS) set and random words (RW) set] in a cross-sectional study design. Results Reading acuity was significantly improved by 0.04 logMAR for both CS set and RW set from children to teenagers, then gradually worsened from young adults to adults (CS set: 0.06 logMAR; RW set: 0.08 logMAR). Critical print size for children showed a significant improvement in teenagers (CS set: 0.14 logMAR; RW set: 0.07 logMAR), then deteriorated from young adults to adults by 0.09 logMAR only for CS set. Reading speed significantly increased from children to teenagers, [CS set: 46.20 words per minute (wpm); RW set: 42.06 wpm], then stabilized from teenagers to young adults, and significantly reduced from young adults to adults (CS set: 28.58 wpm; RW set: 24.44 wpm). Increment and decrement in maximum reading speed measurement were revealed from children to teenagers (CS set: 39.38 wpm; RW set: 43.38 wpm) and from young adults to adults (CS set: 22.26 wpm; RW set: 26.31 wpm) respectively. Conclusion The reference of age-related findings in term of acuity and speed of reading should be incorporated in clinical practice to enhance reading assessment among healthy eyes population.

This work develops a heuristic method for the design of batch water-using networks of multiple contaminants with regeneration unit based on the concepts of concentration potential. A water-using network involving regeneration unit can be formed by adding the regenerated stream(s) into the network involving reuse only. In the design procedure of the network operated in a single batch mode, time is taken as the primary factor and concentration potentials as the secondary one. For the networks operated in a repeated mode, the design procedure is similar to that for continuous processes, besides designing the storage tanks with the rules proposed. Continuous regeneration unit is selected in this work. With the proposed method, the network structure corresponding to the minimum freshwater consumption can be obtained. It is shown that the method proposed in this article is simple, effective and has clear engineering meaning.

Purpose A meta-analysis on sleep duration and patterns in patients with diabetes in China. Design and methods Two investigators independently carried out a systematic literature search in both international and Chinese databases. Findings A total of 47 studies with 98 911 patients were included. The pooled mean sleep duration was 7.15 hours/day in patients with diabetes and 7.49 hours/day in healthy controls. The estimated percentage of short sleep duration of less than 6 hours/day was 23.0% in patients with diabetes and 12.3% in healthy controls, while the proportion of short sleep duration of less than 7 hours/day was 38.0% in patients with diabetes and 14.1% in healthy controls. Practice implications Short sleep duration was common in Chinese patients with diabetes.

Aim: To evaluate feasibility, safety, and clinical efficiency of optometrists in conducting diabetic retinopathy screening and ocular health screening. Methods: This was a prospective observational trial study of newly developed optometric service pathways established at a community health clinic for diabetic retinopathy screening and a hospital ophthalmology clinic for ocular health screening. The study was carried out to assess the feasibility and safety of eye examinations conducted by optometrists. Patients were examined by optometrists using a standard eye examination at both clinics and re-examined by ophthalmologists as the reference standard. Optometrists recorded diagnoses of ocular conditions and classified referral urgency for each patient and these were compared with the diagnoses made by ophthalmologists, who were masked to the optometrists’ findings. Results: There was a high concordance of 87.0% (95% CI 80.4%-93.6%) for the diagnoses between the optometrists and ophthalmologists. Of 26 patients considered by the optometrists to need ophthalmology referral, 23 were agreed as such by the ophthalmologists, giving good agreement, κ = 0.76 (95% CI 0.53 -0.94) between the optometrists and ophthalmologists on referral classification. Agreement by the ophthalmologists for referral urgency classifications (very urgent/urgent or non-urgent) was very good (κ = 0.85, 95%CI 0.62-1.00). Conclusions: Ocular health examination by optometrists using optometric-eyecare pathways is feasible and safe. Optometrists showed strong agreement with ophthalmologists when diagnosing patients who had a range of ocular conditions. Optometrists were also able to triage referrals and their urgency accurately, suggesting that they could play an extensive role as primary eye care providers, thus reducing unnecessary referrals to ophthalmology clinics.

The dysfunction of the medial prefrontal cortex is associated with affective disorders and non-motor features in Parkinson’s disease. However, the exact role of the mediodorsal thalamic nucleus in the function of the prefrontal cortex remains unclear. To study the possible effects of the mediodorsal thalamic nucleus on the neurological function of the medial prefrontal cortex, a model of Parkinson’s disease was established by injecting 8 µg 6-hydroxydopamine into the substantia nigra compacta of rats. After 1 or 3 weeks, 0.3 µg ibotenic acid was injected into the mediodorsal thalamic nucleus of the midbrain. At 3 or 5 weeks after the initial injury, neuronal discharge in medial prefrontal cortex of rat brain was determined electrophysiologically. The numbers of dopamine-positive neurons and tyrosine hydroxylase immunoreactivity in substantia nigra compacta and ventral tegmental area were detected by immunohistochemical staining. Results demonstrated that after injury, the immunoreactivity of dopamine neurons and tyrosine hydroxylase decreased in the substantia nigra compacta and ventral tegmental areas of rats. Compared with normal medial prefrontal cortical neurons, at 3 and 5 weeks after substantia nigra compacta injury, the discharge frequency of pyramidal neurons increased and the discharge pattern of these neurons tended to be a burst-discharge, with an increased discharge interval. The discharge frequency of interneurons decreased and the discharge pattern also tended to be a burst-discharge, but the discharge interval was only higher at 3 weeks. At 3 weeks after the combined lesions, the discharge frequency, discharge pattern and discharge interval were restored to a normal level in pyramidal neurons and interneurons in medial prefrontal cortex. These findings have confirmed that mediodorsal thalamic nucleus is involved in regulating neuronal activities of the medial prefrontal cortex. The changes in the function of the mediodorsal thalamic nucleus may be associated with the abnormal discharge activity of the medial prefrontal cortex neurons after substantia nigra compacta injury. All experimental procedures were approved by the Institutional Animal Care and Use Committee of Xi’an Jiaotong University, China (approval No. XJTULAC2017-067) on August 26, 2017.

Endothelial damage and blood brain barrier disruption contribute to ischemic stroke and brain injury. Gliptins are a novel class of treatment agents for diabetes, and recent studies have linked the use of gliptins to neuroprotection. Alogliptin is a type of orally available gliptin that was approved for clinical use by the FDA in 2013. In this study, we investigated the neurovascular protective effects of alogliptin both in vivo and in vitro. In a murine middle cerebral artery occlusion (MCAO) stroke model, administration of alogliptin ameliorated cerebral infarction and disruption of brain vascular permeability, and restored expression of the endothelial tight junction proteins occludin and zona occludens 1 (ZO-1). In brain vascular endothelial cells exposed to oxygen and glucose deprivation/reperfusion (OGD/R), alogliptin prevented OGD/R-induced high permeability of the endothelial monolayer. Alogliptin treatment recovered the reduction in occludin and ZO-1 induced by OGD/R. Moreover, alogliptin treatment prevented OGD/R-induced induction of metalloproteinase (MMP)-2 and MMP-9, and restored expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. Collectively, our data indicate that alogliptin can improve neurovascular integrity and exerts neuroprotective effects.

Objective The goal of this study is to explore effective treatments for peripheral facial paralysis and to evaluate the clinical efficacies of warm needling therapy and acupuncture in peripheral facial paralysis. Methods PubMed (1979–2017), the Chinese National Knowledge Infrastructure database (CNKI, 1979–2017), Wanfang databases (1990–2017), and the Chongqing VIP full-text periodical database (VIP, 1989–2017) were searched by computer. Randomized controlled trials of warm needling therapy and acupuncture in the treatment of peripheral facial paralysis were collected. The clinical trials that met the inclusion criteria were selected for quality assessment using the Cochrane 5.0 Handbook for systematic evaluation. RevMan5.3 was used for statistical analysis. Results A total of 23 articles with 1756 patients met the inclusion criteria. (1) The meta-analysis of 11 articles showed that the total effective rate of warm needling therapy for peripheral facial paralysis was higher than that of acupuncture [RR = 1.18, 95% CI (1.11,1.25) , P Conclusion The results of this meta-analysis showed that warm needling therapy is superior to acupuncture in treating peripheral facial paralysis, providing a therapeutic option for the treatment of peripheral facial paralysis. However, due to the small sample size and the low quality of the included studies, the above conclusion still needs to be validated with high-quality, large-scale, randomized, blinded controlled trials.

BackgroundAccording to the 8th edition AJCC staging manual, a least of 16 lymph nodes retrieval (LNRs) is the minimal requirement for lymph nodes (LNs) dissection of gastric cancer surgery. Previous studies have shown that increasing the number of LNRs (≥30) prolongs survival for selected patients. However, the necessity of retrieving 30 or more LN for stage II gastric cancer patients is still under debate.AimThis study aims to explore the impact of retrieving 30 or more lymph nodes on the survival of stage II cancer patients.MethodsA total of 1,177 patients diagnosed with stage II gastric cancer were enrolled in this study. The clinicopathological parameters and the impact of different LNRs (ResultsThe mean number of LNRs was 34 ± 15. A total of 44% (518/1,177) of patients had an LNRs 60 years/male/underwent total gastrectomy/stage IIB. For N+ patients, higher NR was significantly correlated with poor survival.ConclusionThe survival benefit of retrieving 30 LNs varies in different subgroups. An LNRs of 30 is mandatory for selected stage II gastric cancer patients.

Objective: To investigate the link between glaucomatous visual field defects and reading performance by assessing reading speed and eye movements in reading. Methods: Eight glaucoma patients and 8 normal-sighted participants were recruited using convenience sampling in this cross-sectional study. The visual field was evaluated using the Humphrey Matrix 24-2. Reading speed was assessed in words per minute using Buari-Chen Malay Reading Chart and the SAH reading passages compendium. Eye movements in reading were recorded using 3D video-oculography. Results: Glaucoma and control groups displayed significant differences in reading speed (t=3.12; p0.05). Conclusion: The association of defect areas and types with reading speed but not with eye movements might suggest a different coping strategy between eye movement adjustment and reading adaptation in response to visual field defects. Significant association with fixation but not with saccades might indicate that the disengaged and engaged mechanisms of visual attention are affected differently by visual field defects.

Background An accurate diagnosis for high-suspicion nodules based on the 2015 American Thyroid Association (ATA) guidelines would reduce unnecessary invasive examinations. Elastography is a useful tool for discriminating benign and malignant thyroid nodules. The aim of this study is to investigate the diagnostic efficiency of elastography for high-suspicion thyroid nodules based on the 2015 ATA guidelines in the Chinese population. Methods Thyroid nodules with high-suspicion characteristics based on the 2015 ATA guidelines were subjected to conventional ultrasound (US) and ultrasound strain elastography (USE) examinations at 12 hospitals from 4 geographic regions across China. Cytology/histology of thyroid nodules was used as a reference method. Receiver operating characteristic (ROC) curves were plotted to evaluate the diagnostic performance of the elasticity score (ES) and strain ratio (SR). Logistic regression analysis was used to determine the predictors of malignancy. Results Overall, a total of 1445 thyroid nodules (834 malignant, 611 benign) from 12 centers were included in the final analysis. The areas under the curve of the ES and SR were 0.828 and 0.732, respectively. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of the ES were 92.4, 60.7, 79.0, 76.3 and 85.5%, respectively, and those of the SR were 81.1, 50.1, 68.9, 65.9 and 67.9%, respectively. The combination of the Thyroid Imaging Reporting and Data System (TI-RADS) and ES led to a significant increase in the sensitivity and NPV (97.1 and 91.9%, respectively) compared with the TI-RADS alone. Logistic regression analysis showed that microcalcifications (OR = 5.290), taller than wide (OR = 12.710), irregular margins (OR = 10.117), extrathyroidal extension (ETE; OR = 6.412), the ES (OR = 3.741) and the SR (OR = 1.083) were independent predictors of malignant thyroid nodules. The sensitivity, specificity, accuracy, PPV and NPV of the ES were all superior in nodules ≥1 cm than in those Conclusions Elastography combined with the ES is a valuable tool for the assessment of high-suspicion thyroid nodules based on the 2015 ATA guidelines, especially in nodules ≥1 cm.

Environmental influence is one of the attributing factors for health status. Chronic interaction with electronic display technology and lack of outdoor activities might lead to health issues. Given the concerns about the digital impact on lifestyle and health challenges, we aimed to investigate the daily activity inclination and health complaints among the Malaysian youth. A self-administered questionnaire covering lifestyle and health challenges was completed by 220 youths aged between 16 and 25. There were a total of 22 questions. Seven questions inspected the patterns of indoor and outdoor activities. Fifteen questions focused on the visual and musculoskeletal symptoms linked to both mental and physical health. The total time spent indoors (15.0 ± 5.4 hours/day) was significantly higher than that spent outdoors (2.5 ± 2.6 hours/day) (t = 39.01, p < 0.05 ). Total time engrossed in sedentary activities (13.0 ± 4.5 hours/day) was significantly higher than that in nonsedentary activities (4.5 ± 3.8 hours/day) comprised of indoor sports and any outdoor engagements (t = 27.10, p < 0.05 ). The total time spent on electronic related activities (9.5 ± 3.7 hours/day) was were higher than time spent on printed materials (3.4 ± 1.6 hours/day) (t = 26.01, p < 0.05 ). The association of sedentary activities was positive in relation to tired eyes (χ2 = 17.58, p < 0.05 ), sensitivity to bright light (χ2 = 12.10, p < 0.05 ), and neck pain (χ2 = 17.27, p < 0.05 ) but negative in relation to lower back pain (χ2 = 8.81, p < 0.05 ). Our youth spent more time in building and engaged in sedentary activities, predominantly electronic usage. The health-related symptoms, both visual and musculoskeletal symptoms, displayed a positive association with a sedentary lifestyle and a negative association with in-building time.

It is of great significance to introduce regeneration/treatment units into a water system. Regeneration units and treatment units are the same in function and application, but different in destination of the outlet streams. The outlet streams of the regeneration units will be reused/recycled in the water system. The outlet streams of the treatment units will be discharged to environment. This paper provides a review of the development in designing and targeting of continuous water systems involving regeneration/treatment units. The features of Pinch Analysis methods and mathematical programming methods are discussed for the integration of regeneration system, treatment system and total water system separately. For a water system involving regeneration unit, it is addressed that the system can be formed by adding one or more additional source(s), regenerated stream(s), into a water system involving reuse only. The contribution of Liu's group based on the above insight is outlined. Finally, this review offers a guide for future efforts in the integration of water systems involving regeneration/treatment.

Our study examined the choroidal thickness profile of children with myopic anisometropic amblyopia and compared the thickness with the fellow eyes. The choroidal thickness was measured with the enhanced depth imaging with spectral-domain optical coherence tomography. Manual segmentations of the choroid were performed on a 25-raster horizontal scan. The choroidal thickness measurements of the 9 subfields defined by the Early Treatment Diabetic Retinopathy Study (ETDRS) were evaluated. The mean spherical equivalent of the amblyopic eyes was -10.80 ± 0.41 D and the fellow eyes was -4.40 ± 2.05 D. The mean best corrected visual acuity of the amblyopic eyes and the fellow eyes were 0.94 ± 0.27 and 0.14 ± 0.05 logMAR respectively. The amblyopic eyes have longer axial length (26.46 ± 0.44 mm) compared to the fellow eyes (23.59 ± 1.18 mm). The average subfoveal choroidal thickness was 124.30 ± 40.71 µm in the amblyopic eyes and 246.80 ± 58.63 µm in the fellow eyes. The horizontal and vertical distribution pattern of choroidal thickness in amblyopic eyes was different from the fellow eyes. In amblyopic eye the choroidal thickness reduced from the temporal region to the nasal region. The fellow eyes had thickest choroid at the subfoveal area, followed by the temporal region and nasal region. In conclusion, the choroid was thinner in the amblyopic eyes than that of the fellow eyes at all regions.

This article presents a design method for the following wastewater treatment networks: a treatment process can remove multiple contaminants and/or a contaminant can be removed by multiple treatment processes. The method is developed by improving the numerical indicator of total mixing influence potential (TMIP), which was proposed by Li et al. (2015, AIChE J, 61: 3223–3231) based on the minimum treatment flowrate calculated with pinch-based method. The design procedure presented in this work includes two steps. First, calculate the values of TMIP with pinch method together with a linear programming approach for the processes which can remove multiple contaminants. Based on the TMIP values, the performing order of treatment processes can be identified and the initial network can be built. Secondly, for the situation when a contaminant needs to be removed by multiple processes, a heuristic rule and mass balance have been used to adjust the initial network for obtaining the final result. The proposed method has the advantages of noncomplicated calculation and engineering significance. It can provide the results close to those published in the literature.

The need to produce cleaner fuels under the constraints of stricter environmental regulations, heavier and sour crude oils, and petroleum market needs has resulted in increased hydrogen demand in oil refineries. These demands are usually served by hydrogen networks, which collect hydrogen-containing streams from refinery processes and, after potential processing, redistribute the hydrogen content to recipient processes within the same site. Often, pure hydrogen is also necessary in order to satisfy the final demand. The introduction of one or more purification units into a hydrogen network is an economical way to reduce fresh hydrogen consumption. In the design and optimization of a hydrogen system, it is often important to find the target values (optimal lower bounds) for the fresh hydrogen consumption and the flowrate of the purified stream. However, the procedure for obtaining these targets becomes very complex when purification units are added, compared to that for a hydrogen network involving reuse only. This article presents a simple method for predicting the target values based on the balances of mass and flowrate and the features of the purification units. The proposed method not only can simplify the targeting procedure but can also provide valuable insights for the analysis and optimization of single-impurity hydrogen networks with purification units.

This paper reviews concentration potential concepts and their applications in the design of water-using networks (WUNs) with multiple contaminants. The concentration potential concepts were proposed to determine the concentration order of water streams of multiple contaminants based on the overall allocating possibility of source streams to demand streams on the analogy of single contaminant WUNs. The precedence order of water-using processes, which is crucial for the network design, can be effectively identified by the values of Concentration Potential of Demands (CPDs). The concentration potential concepts, which were originally presented for the water networks of fixed contaminant load model, up to now have been successfully used to design a verity of water-using networks. Computing software has also been developed by combining the concentration potential concepts and linear programming approach. The methods proposed based on the concentration potential concepts have the advantages of simple calculation and clear engineering meaning. The results obtained based on the concentration potential concepts are comparable to that obtained by the literature methods. It is shown that the concentration potential concepts are powerful tools for the design of WUNs with multiple contaminants.

Precision cancer medicine seeks to target the underlying genetic alterations of cancer; however, it has been challenging to use genetic profiles of individual patients in identifying the most appropriate anti-cancer drugs. This spurred the development of patient avatars; for example, patient-derived xenografts (PDXs) established in mice and used for drug exposure studies. However, PDXs are associated with high cost, long development time and low efficiency of engraftment. Herein we explored the use of microfluidic devices or microchambers as simple and low-cost means of maintaining bladder cancer cells over extended periods of times in order to study patterns of drug responsiveness and resistance. When placed into 75 µm tall microfluidic chambers, cancer cells grew as ellipsoids reaching millimeter-scale dimeters over the course of 30 days in culture. We cultured three PDX and three clinical patient specimens with 100% success rate. The turn-around time for a typical efficacy study using microchambers was less than 10 days. Importantly, PDX-derived ellipsoids in microchambers retained patterns of drug responsiveness and resistance observed in PDX mice and also exhibited in vivo-like heterogeneity of tumor responses. Overall, this study establishes microfluidic cultures of difficult-to-maintain primary cancer cells as a useful tool for precision cancer medicine.

Objective To explore the effect of acupuncture on the endoplasmic reticulum stress IRE 1-CHOP signal pathway and the expression levels of related apoptosis genes in pancreatic tissue of rats with STZ-induced diabetes mellitus. Methods Eighty SD rats were selected, among which, 10 were fed with normal diet and taken as blank control group (“blank group” for short), the other 70 rats were fed with high fat and high glucose food and injected with small dosage of STZ intraperitoneally, and 30 models were established successfully. The models were randomly divided into acupuncture treatment group (“acupuncture group” for short), model control group (“model group” for short) and western medicine group (metformin) with 10 rats in each group. After treatment for 4 weeks, RBG, and the expression levels of CHOP, IRE 1, Bax, Bcl-2 protein and mRNA in pancreatic tissue of rats were determined. Result Compared with the conditions before treatment, RBG reduced obviously in the acupuncture group and western medicine group (P 0.05); the expression levels of CHOP, IRE 1 and Bax proteins in pancreatic tissue of rats in the model group were significantly higher than those in the blank group (P 0.05); the expression level of Bcl-2 mRNA in the model group was significantly lower than that in the blank group (P 0.05). Conclusion There was endoplasmic reticulum stress in the pancreatic tissue of rats with STZ-induced diabetes mellitus, and IRE 1-CHOP signal pathway was the main pathway for inhibiting the endoplasmic reticulum stress in the pancreatic tissue. Acupuncture can improve the endoplasmic reticulum stress in pancreatic tissue, inhibit apoptosis genes, and protect the pancreatic tissue through IRE 1-CHOP signal pathway.

This paper presents a new concept, distance potential, which is the sum of the distances from the source points to the demand point being considered (for supply chains), or the sum of the distances from the demand (customer) being considered to other demands and the depot (for vehicle routing problems). We also investigate the applications of the new concept to the design of regional biomass supply chains and solving vehicle routing problems. In designing a supply chain, the values of the distance potentials are used to determine the precedence order: the demand point with the largest distance potential value will be satisfied first. While satisfying a demand point, the source point with the shortest distance to the demand will be used first. In solving a vehicle routing problem, the new concept is used to identify the customer which should be included in the first routing to be considered. Then, the network can be designed starting from the customer identified, and based on a few heuristic rules proposed in this paper. The results obtained in this work are comparable to or even better than that obtained in the literature. It is shown that the method proposed is simple and of high computational efficiency.

Replacement therapy with factor VIII (FVIII) is used in patients with hemophilia A for treatment of bleeding episodes or for prophylaxis. A common and serious problem with this therapy is the patient's immune response to FVIII, because of a lack of tolerance, leading to the formation of inhibitory antibodies. Development of tolerogenic therapies, other than standard immune tolerance induction (ITI), is an unmet goal. We previously generated engineered antigen-specific regulatory T cells (Tregs), created by transduction of a recombinant T-cell receptor (TCR) isolated from a hemophilia A subject's T-cell clone. The resulting engineered T cells suppressed both T- and B-cell effector responses to FVIII. In this study, we have engineered an FVIII-specific chimeric antigen receptor (ANS8 CAR) using a FVIII-specific scFv derived from a synthetic phage display library. Transduced ANS8 CAR T cells specific for the A2 domain proliferated in response to FVIII and ANS8 CAR Tregs were able to suppress the proliferation of FVIII-specific T-effector cells with specificity for a different FVIII domain in vitro. These data suggest that engineered cells are able to promote bystander suppression. Importantly, ANS8 CAR-transduced Tregs also were able to suppress the recall antibody response of murine splenocytes from FVIII knockout mice to FVIII in vitro and in vivo. In conclusion, CAR-transduced Tregs are a promising approach for future tolerogenic treatment of hemophilia A patients with inhibitors.

This study is based on speech recognition and interaction, augmented reality, the movement of the head gesture interaction interactive technology, human-computer interaction system is designed to meet the power equipment installation, operation and maintenance operations, to enhance formation of reality for the show, with gestures and head movements as the main way of interaction, with voice commands and touch as a unified interactive model of secondary interaction the way.

Introduction The aim of our study was to determine the effect of metformin administration on juvenile type 1 diabetes mellitus and atherosclerosis in apolipoprotein E null (ApoE−/−) mice and to explore the mechanism involved. Methods Eighteen male ApoE−/− mice were injected with streptozotocin to induce diabetes (diabetic group) and 18 mice who received no streptozotocin injection were assigned to the control (non-diabetic) group. Six mice in each group were then orally administered metformin, simvastatin, or vehicle, respectively, following which the mice were euthanized and tissue samples collected. Results Fasting plasma glucose, low-density lipoprotein-cholesterol, and triglyceride concentrations were significantly higher in the three diabetic groups than in the three non-diabetic groups. Plasma N∈-(carboxymethyl)lysine and N∈-(carboxyethyl)lysine concentrations were higher in the diabetic mice than in the non-diabetic mice, but metformin treatment reduced these concentrations more effectively than simvastatin. All three diabetic groups demonstrated obvious arterial plaques, but these were largest in the vehicle-treated diabetic group. The expression of extracellular nitric oxide synthase was highest in the simvastatin-treated non-diabetic group, and in diabetic mice it was higher in the simvastatin-treated group than in the other two groups. No significant expression of AMP-activated protein kinase (AMPK) was measured in the three diabetic groups, but a low level of AMPK expression was detected in the non-diabetic groups. Conclusions Metformin can limit the development of atherosclerosis secondary to diabetes in young diabetic mice. A possible mechanism is the removal of methylglyoxal, thereby reducing the formation of advanced glycation endproducts, rather than by lowering the blood glucose level. Funding This work was supported by the National Natural Science Foundation of China (81901106) and Jinan clinical medical science and technology innovation plan (201907002).

Several studies have demonstrated through resting-state functional magnetic resonance imaging (fMRI) that functional connectivity changes are important in the recovery from Bell's palsy (BP); however, these studies have only focused on the cortico-cortical connectivity. It is unclear how corticostriatal connectivity relates to the recovery process of patients with BP. In the present study, we evaluated the relationship between longitudinal changes of caudate-based functional connectivity and longitudinal changes of facial performance in patients with intractable BP. Twenty-one patients with intractable BP underwent resting-state fMRI as well as facial behavioral assessments prior to treatment (PT) and at the middle stage of treatment (MT); and 21 age- and sex-matched healthy controls (HC) were recruited and received the same protocol. The caudate was divided into dorsal and ventral sub-regions and separate functional connectivity was calculated. Compared with HC, patients with intractable BP at the PT stage showed decreased functional connectivity of both the dorsal and ventral caudate mainly distributed in the somatosensory network, including the bilateral precentral gyrus (MI), left postcentral gyrus, media frontal gyrus, and superior temporal gyrus (STG). Alternatively, patients in the MT stage showed decreased functional connectivity primarily distributed in the executive network and somatosensory network, including the bilateral cingulate cortex (CC), left anterior cingulate cortex (LACC), inferior prefrontal gyrus (IFG), MI, STG, and paracentral lobe. The longitudinal changes in functional connectivity of both the dorsal and ventral caudate were mainly observed in the executive network, including the right ACC, left CC, and IFG. Functional connectivity changes in the right ACC and left IFG were significantly correlated with changes in facial behavioral performance. These findings indicated that corticostriatal connectivity changes are associated with recovery from BP.

With the development of science and technology, Internet technology has gradually integrated into all walks of life, and has injected fresh blood into all trades and professions, thus promoting the development of all trades and professions under the current "Internet +" background. At the same time, the use of the Internet, for the accounting industry, is also an earth-shaking change, which not only brings opportunities, but also a series of problems. Therefore, in the face of the current "Internet +" background, mankind should firmly grasp the opportunities, strive to make scientific and effective use of Internet tools, and constantly innovate and develop, so as to promote the development of accounting industry in the direction of informatization. At present, Internet technology is also shining in different fields. In addition, "Internet +" is constantly promoting the development of all aspects of human production and life. At the same time, "Internet + accounting" emphasizes the combination of Internet technology and traditional accounting industry. This research mainly analyzes from the perspective of "Internet +", and explores the direction of accounting development in the era of "Internet +", hoping to provide some reference for other research scholars.

BACKGROUND: This study aims to investigate the effects of education with health belief model (HBM) on anxiety and fatigue among patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: Patients with AECOPD admitted into Taizhou People’s Hospital, Jiangsu, China between December 2012 and October 2013 were randomly selected for the present study according to random number table. A total of 99 cases with anxiety were included. These patients were divided into two groups: experimental group educated by HBM (n=47), and control group educated by conventional method (n=52). The scores for anxiety and fatigue were evaluated using the self-rating anxiety scale (SAS) and multidimensional fatigue inventory (MFI-20). RESULTS: After educational intervention by HBM, patients achieved a significant decrease in anxiety and fatigue scores, when compared to patients in the control group, who were educated by the conventional method at the time of admission, discharge, and 6 weeks after discharge (P

Background: Not all adults with chronic insomnia respond to the recommended therapeutic options of cognitive behavioral therapy and approved hypnotic drugs. Transcranial alternating current stimulation (tACS) may offer a novel potential treatment modality for insomnia. Objectives: This study aimed to examine the efficacy and safety of tACS for treating adult patients with chronic insomnia. Methods: Sixty-two participants with chronic primary insomnia received 20 daily 40-min, 77.5-Hz, 15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas in the laboratory on weekdays for 4 consecutive weeks, followed by a 4-week follow-up period. The primary outcome was response rate measured by the Pittsburgh Sleep Quality Index (PSQI) at week 8. Secondary outcomes were remission rate, insomnia severity, sleep onset latency (SOL), total sleep time (TST), sleep efficiency, sleep quality, daily disturbances, and adverse events at the end of the 4-week intervention and at the 4-week follow-up. Results: Of 62 randomized patients, 60 completed the trial. During the 4-week intervention, 1 subject per group withdrew due to loss of interest and time restriction, respectively. Based on PSQI, at 4-week follow-up, the active group had a higher response rate compared to the sham group (53.4% [16/30] vs. 16.7% [5/30], p = 0.009), but remission rates were not different between groups. At the end of the 4-week intervention, the active group had higher response and remission rates than the sham group (p < 0.001 and p = 0.026, respectively). During the trial, compared with the sham group, the active group showed a statistically significant decrease in PSQI total score, a shortened SOL, an increased TST, improved sleep efficiency, and improved sleep quality (p < 0.05 or p < 0.001). Post hoc analysis revealed that, in comparison with the sham group, the active group had improved symptoms, except for daily disturbances, at the end of the 4-week intervention, and significant improvements in all symptoms at the 4-week follow-up. No adverse events or serious adverse responses occurred during the study. Conclusion: The findings show that the tACS applied in the present study has potential as an effective and safe intervention for chronic insomnia within 8 weeks.

Patients with acute myeloid leukemia have a very poor prognosis related to a high rate of relapse and drug-related toxicity. The ability of leukemia stem cells (LSCs) to survive chemotherapy is primarily responsible for relapse, and eliminating LSCs is ultimately essential for cure. We developed novel disulfide-crosslinked CLL1-targeting micelles (DC-CTM), which can deliver high concentrations of daunorubicin (DNR) into both bulk leukemia cells and LSCs. Compared to free DNR, DC-CTM-DNR had a longer half-life, increased DNR area under the curve concentration by 11-fold, and exhibited a superior toxicity profile. In patient-derived AML xenograft models, DC-CTM-DNR treatment led to significant decreases in AML engraftment and impairment of secondary transplantation compared to control groups. Collectively, we demonstrate superior anti-LSC/AML efficacy, and preferable pharmacokinetic and toxicity profiles of DC-CTM-DNR compared to free DNR. DC-CTM-DNR has the potential to significantly improve treatment outcomes and reduce therapy-related morbidity and mortality for patients with AML. Leukemia stem cells (LSC) could repopulate the leukemia after chemotherapy resulting recurrence. CLL1 only expressed on LSC but not hematopoietic stem cells, and thus we developed CLL1 targeting micelles to deliver high dose of chemotherapeutic cells to eradicate LSC and bulk leukemia. This strategy cure leukemia from the root.