Visual-motor integration in children with unilateral cerebral palsy: application of the computer-aided measure of visual-motor integration.

BACKGROUND: Children with unilateral cerebral palsy (UCP) are encouraged to participate in the regular school curriculum. However, even when using the less-affected hand for handwriting, children with UCP still experience handwriting difficulties. Visual-motor integration (VMI) is a predictor of handwriting quality. Investigating VMI in children with UCP is important but still lacking. Conventional paper-based VMI assessments is subjective and use all-or-nothing scoring procedures, which may compromise the fidelity of VMI assessments. Moreover, identifying important shapes that are predictive of VMI performance might benefit clinical decision-making because different geometric shapes represent different developmental stepping stones of VMI. Therefore, a new computer-aided measure of VMI (the CAM-VMI) was developed to investigate VMI performance in children with UCP and to identify shapes important for predicting their VMI performance. METHODS: Twenty-eight children with UCP and 28 typically-developing (TD) children were recruited. All participants were instructed to complete the CAM-VMI and Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery-VMI). The test items of the CAM-VMI consisted of nine simple geometric shapes related to writing readiness. Two scores of the CAM-VMI, namely, Error and Effort, were obtained by image registration technique. The performances on the Beery-VMI and the CAM-VMI of children with UCP and TD children were compared by independent t-test. A series of stepwise regression analyses were used to identify shapes important for predicting VMI performance in children with UCP. RESULTS: Significant group differences were found in both the CAM-VMI and the Beery-VMI results. Furthermore, Error was identified as a significant aspect for predicting VMI performance in children with UCP. Specifically, the square item was the only significant predictor of VMI performance in children with UCP. CONCLUSIONS: This study was a large-scale study that provided direct evidence of impaired VMI in school-aged children with UCP. Even when using the less-affected hand, children with UCP could not copy the geometric shapes as well as TD children did. The copied products of children with UCP demonstrated poor constructional accuracy and inappropriate alignment. Furthermore, the predictive model suggested that the constructional accuracy of a copied square is an important predictor of VMI performance in children with UCP.

Development and Psychometric Evaluation of the Computer-Aided Measure of Chinese Handwriting Legibility (CAM-CHL) for School-Age Children.

IMPORTANCE: Handwriting legibility is the main criterion for determining whether a child has handwriting difficulties. A comprehensive assessment of handwriting legibility with sound psychometrics is essential to timely identification of handwriting difficulties and outcome measurement after handwriting interventions. OBJECTIVE: To evaluate the psychometrics of the Computer-Aided Measure of Chinese Handwriting Legibility (CAM-CHL) and to investigate Chinese handwriting legibility in school-age children using the CAM-CHL. DESIGN: Cross-sectional, repeated observation, test-retest. SETTING: Elementary schools in Taiwan. PARTICIPANTS: We recruited 25 lower-grade children for the examination of test-retest reliability, 75 children from all grade levels, and 10 senior schoolteachers for the examination of the CAM-CHL's convergent validity and the investigation of handwriting legibility. OUTCOMES AND MEASURES: Children were asked to copy a set of Chinese characters as legibly as possible. We used the CAM-CHL to assess handwriting legibility in four domains: Size, Orientation, Position, and Deformation. The schoolteachers were asked to subjectively assess the handwriting legibility using a 3-point Likert-type scale. RESULTS: The CAM-CHL demonstrated good to excellent test-retest reliability and acceptable random measurement error in all legibility domains. The CAM-CHL had fair to moderate convergent validity with schoolteachers' perceptions. Additionally, upper-grade children had better handwriting legibility in the Size and Position domains than lower-grade children. CONCLUSIONS AND RELEVANCE: The CAM-CHL, a comprehensive and objective method of assessing Chinese handwriting legibility, has sound reliability and acceptable validity, suggesting its potential as an outcome measure for school-age children. What This Article Adds: The CAM-CHL can be used in comprehensive evaluations of Chinese handwriting legibility in school-age children. The CAM-CHL has acceptable psychometrics for use as an outcome measure.

[Study on protective effect of water extract from Sabia parviflora on liver injury in mice induced by acetaminophen].

The aim of this study was to observe the protective effect of water extract from Sabia parviflora on mice with acute liver injury induced by acetaminophen, and investigate its possible mechanism. Fifty-eight Kunming mice were divided into 6 groups, 8 in the normal group, 10 in the model group, 10 in the biphenyl diester group, and 10 each in the low, medium and high dose groups. After adaptive feeding for one week, the mice in normal group were intragastrically administered with an equal volume of 0.5% sodium carboxymethylcellulose sodium(CMC-Na), and the mice in other groups were intragastrically administered with corresponding drugs at 20 mL·kg~(-1) once a day. Then acetaminophen(200 mg·kg~(-1)) was administered after the above drug administration except the normal group. The behavior and signs of the experimental animals were observed every day and the samples were taken for experiments on the next day of the final administration. The liver mass and mass index were calculated. The blood was collected from the abdominal aorta and centrifuged to obtain the serum for detecting aspartate aminotransferase(AST) activity and alanine aminotransferase(ALT) activity. The liver tissue homogenate was used to detect superoxide dismutase(SOD) activity, glutathione(glutathione, r-glutamyl cysteingl+glycine, GSH) activity and malondialdehyde(MDA) content. Liver tissue was analyzed for histological analysis. The results showed that S. parviflora could alleviate the lipid peroxidation damage in the liver caused by acetaminophen, reduce the ALT and AST activities in serum, increase the levels of SOD and GSH in liver tissue, decrease the content of MDA in liver tissue, and inhibit the apoptosis. S. parviflora could also improve the live histopathological profile, protect liver cells and restore liver function. Among them, the high dose had the most significant effect and showed dose-effect relationship. This study indicated that S. parviflora had a significant protective effect on acetaminophen-induced liver injury in mice, and its mechanism may be related to its anti-oxidation effect and inhi-bitory effect on apoptosis.

Toxicity of chemotherapy regimens in advanced and metastatic pancreatic cancer therapy: A network meta-analysis.

This network meta-analysis is adopted in order to compare the toxicity of different chemotherapy regimens in the treatment of advanced/metastatic pancreatic cancer (PC). Randomized controlled trials (RCTs) about different chemotherapy regimens for advanced/metastatic PC were included in this network meta-analysis using Cochrane Library and PubMed electronic databases. The network meta-analysis was performed to combine direct and indirect evidence in order to calculate the odd ratios (OR) and draw a surface under the cumulative ranking (SUCRA) curve. A total of 19 RCTs were enrolled in this network meta-analysis including 12 chemotherapy regimens (Gemcitabine, Gemcitabine + S-1 [tegafur], Gemcitabine + nab-paclitaxel, Gemcitabine + Capecitabine, Gemcitabine + Cisplatin, FOLFIRINOX [oxaliplatin + irinotecan + fluorouracil + leucovorin], Gemcitabine + oxaliplatin, Gemcitabine + irinotecan, Gemcitabine + Exatecan, Gemcitabine + pemetrexed, Gemcitabine + 5-FU, S-1). The incidence of anemia of Gemcitabine + Capecitabine regimen was higher compared with Gemcitabine regimen, Gemcitabine + pemetrexed regimen exhibited the highest incidence rates of anemia and neutropenia; while Gemcitabine + S-1, Gemcitabine + Cisplatin and FOLFIRINOX regimens exhibited the highest incidence rates of neutropenia. However, S-1 regimen exhibited lower incidence rates of leukopenia and thrombocytopenia. Moreover, the incidence rates of nausea/vomiting and rash of Gemcitabine + S-1 regimen were higher compared with Gemcitabine regimen, while Gemcitabine + Cisplatin regimen had the highest incidence rate of nausea/vomiting. This study demonstrated that the hematologic toxicity of S-1 regimen was the lowest, while Gemcitabine regimen exhibited the lowest incidence rate of non-hematologic toxicity, providing guidance for the treatment of advanced/metastatic PC.

[Estrogenic Activities of Alcohol Extract from Phellinus lonicerinus].

Objective: To investigate the estrogenic activities of alcohol extract from Phellinus lonicerinus( AEPL). Methods: Estrogen and anti-estrogen effects were evaluated by cell proliferation experiment in vitro. Through elevating young rat uterine weight, castrated female rats, and adult female rats uterus index serum estradiol( E2) and progesterone( P) were analyzed by enzyme immune methods, and uterine estrogen receptor α( ERα) and estrogen receptor ß( ERß) protein expressions were measeured by immunohistochemisty, and investigated the histopathological of uterus, ovary, and breast of adult female rats. Results: Compared with the control group, AEPL promoted estrogen-sensitive MCF-7 proliferation significantly( P < 0. 05 or P < 0. 01) in the doses of 5 ~ 50 µg / m L in vitro experiment; compared with the E2 control group, it also presented anti-estrogenic effect in E2-induced MCF-7 cells at the doses of 10 ~ 100 µg / m L( P < 0. 05 or P < 0. 01). In the animal experiments, AEPL remarkably increased serum E2 content and promoted growth of uterus in primary female mice at the dose of 300 mg / kg; and raised the serum E2 and P content, alleviated uterine atrophy caused by estrogen deficiency in castrated rats at the dose of 240 mg / kg. In adult female rats, AEPL markedly increased the serum P content at the dose of 120 mg / kg, and also markedly increased the serum E2 content at the dose of 120,240 mg / kg, and regulated the protein expressions of ERαand ERß. AEPL has no effects on histopathological changes of uterus, ovary and mammary gland in rats. Conclusion: AEPL shows estrogenic effects with fewer adverse reaction, which possesses the replacement of estrogen application prospects.

[Effects of Ethanol Extracts of Phellinus lonicerinus on Hepatic Stellate Cells of Fibrosis Liver in Rats].

OBJECTIVE: To study the effects of ethanol extracts of Phellinus lonicerinus on hepatic stellate cells of fibrosis liver in rats. METHODS: The model rats of hepatic fibrosis were established by intraperitoneally injection of CCl4 olive oil solution at the dose of 2 mL/kg. And then the model rats were administered orally ethanol extract of Phellinus lonicerinus with 1 g/(kg · d) and 0.5 g/( kg · d) for consecutive eight weeks. Serum transforming growth factor-ß1, (TGF-ß1), liver total antioxidant capacity (T-AOC), total superoxide dismutase( T-SOD) activity and the content of malondialdehyde ( MDA) were determined. The α-smooth muscle actin (α-SMA), matrix metalloproteinases-1 (MMP-1) and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) were determined by immunohistochemical. RESULTS: Compared to the model group, the ethanol extracts of Phellinus lonicerinus decreased the content of serum TGF-ß1 and MDA in liver tissue, as well as increased the activity of T-SOD and the level of T-AOC. Immunohistochemical showed that the ethanol extracts of Phellinus lonicerinus downregulated the expression of α-SMA in liver tissue and the expression of TIMP-1, as well as upregulated the expression of MMP-1. CONCLUSION: The ethanol extracts of Phellinus lonicerinus has good antioxidative activity with application prospects in prevention of hepatic fibrosis. The mechanism may be related to inhibiting the activation of hepatic stellate cells induced by oxidative stress,reducing the TGF-ß1, and cytokines activating the hepatic stellate cells,and upregulating the expression of MMP-1 promoting the collagen degradation.

Review: Research progress on seasonal succession of phyllosphere microorganisms.

Phyllosphere microorganisms have recently attracted the attention of scientists studying plant microbiomes. The origin, diversity, functions, and interactions of phyllosphere microorganisms have been extensively explored. Many experiments have demonstrated seasonal cycles of phyllosphere microbes. However, a comprehensive comparison of these separate investigations to characterize seasonal trends in phyllosphere microbes of woody and herbaceous plants has not been conducted. In this review, we explored the dynamic changes of phyllosphere microorganisms in woody and non-woody plants with the passage of the season, sought to find the driving factors, summarized these texts, and thought about future research trends regarding the application of phyllosphere microorganisms in agricultural production. Seasonal trends in phyllosphere microorganisms of herbaceous and woody plants have similarities and differences, but extensive experimental validation is needed. Climate, insects, hosts, microbial interactions, and anthropogenic activities are the diverse factors that influence seasonal variation in phyllosphere microorganisms.

New continuous fluorometric assay for bacterial transglycosylase using Förster resonance energy transfer.

The emergence of antibiotic resistance has prompted scientists to search for new antibiotics. Transglycosylase (TGase) is an attractive target for new antibiotic discovery due to its location on the outer membrane of bacteria and its essential role in peptidoglycan synthesis. Though there have been a few molecules identified as TGase inhibitors in the past thirty years, none of them have been developed into antibiotics for humans. The slow pace of development is perhaps due to the lack of continuous, quantitative, and high-throughput assay available for the enzyme. Herein, we report a new continuous fluorescent assay based on Förster resonance energy transfer, using lipid II analogues with a dimethylamino-azobenzenesulfonyl quencher in the lipid chain and a coumarin fluorophore in the peptide chain. During the process of transglycosylation, the quencher-appended polyprenol is released and the fluorescence of coumarin can be detected. Using this system, the substrate specificity and affinity of lipid II analogues bearing various numbers and configurations of isoprene units were investigated. Moreover, the inhibition constants of moenomycin and two previously identified small molecules were also determined. In addition, a high-throughput screening using the new assay was conducted to identify potent TGase inhibitors from a 120,000 compound library. This new continuous fluorescent assay not only provides an efficient and convenient way to study TGase activities, but also enables the high-throughput screening of potential TGase inhibitors for antibiotic discovery.

Chidamide, Decitabine, Cytarabine, Aclarubicin, and Granulocyte Colony-stimulating Factor Therapy for Patients with Relapsed/Refractory Acute Myeloid Leukemia: A Retrospective Study from a Single-Center.

OBJECTIVE: Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia. However, their efficacy in patients with relapsed/refractory acute myeloid leukemia (R/R AML) remains unclear. METHODS: Clinical data of R/R AML patients who received a CDCAG regimen (chidamide, decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor) from July 1, 2018 to October 31, 2021 at our center were retrospectively assessed, and the safety and efficacy of the CDCAG regimen were evaluated. Patients were followed up until November 30, 2021, with a median follow-up of 21.6 months (95% CI: 10.0-33.2 months). RESULTS: A total of 67 patients were enrolled. Two patients died within 3 weeks after the initiation, and therefore only 65 patients underwent the assement for clinical response and survival. It was found that 56.9% patients achieved complete remission with a median overall survival (OS) of 9.6 months. The median OS of responders was 25.9 months, while that of non-responders was 5.0 months (P<0.0001). Patients with gene mutations had a superior overall response rate (ORR) (80.4% vs. 45.5%, P=0.043) compared to those without gene mutations. The presence of DNA methyltransferase 3 A (DNMT3A), ten-eleven translocation-2 (TET2), and isocitrate dehydrogenase 1/2 (IDH1/2) mutations did not affect the response rate (88.2% vs. 68.9%, P=0.220) and reflected a better OS (not attained vs. 9.0 months, P=0.05). The most common non-hematologic adverse events were pulmonary infection (73.1%), followed by febrile neutropenia (23.9%) and sepsis (19.4%). CONCLUSIONS: The CDCAG regimen was effective and well-tolerated in R/R AML patients, increasing the potential for allogeneic hematopoietic stem cell transplantation. Moreover, patients with DNMT3A, TET2, and IDH1/2 mutations might benefit from this regimen.

[Efficacy and Survival of Venetoclax Based Regimen in the Treatment of Acute Myeloid Leukemia].

OBJECTIVE: To explore the efficacy and survival of venetoclax based (VEN-based) regimen in the treatment of acute myeloid leukemia（AML）. METHODS: A retrospective study was conducted in patients who received VEN-based regimen and completed at least 1 course of efficacy evaluation at the The First Affiliated Hospital of Nanchang University from July 2019 to July 2022. The incidence of complete remission （CR）/CR with incomplete hematologic recovery （CRi） rate, objective remission rate（ORR） and survival of patients with different risk strati- fication and gene subtypes were analyzed. RESULTS: A total of 79 patients were enrolled, including 43 patients with newly diagnosed unfit AML （unfit AML） and 36 relapsed/refractory AML (R/R AML). The median age of the patients was 62(14-83) years old. 36 out of 79 patients achieved CR/CRi and the ORR of the whole cohort was 64.6%. The CR/CRi rate of unfit AML patients was significantly higher than that of R/R AML patients (60.5% vs 27.8%, P=0.004). In unfit AML cohort, the patients with NPM1 and IDH1/2 mutations were benefited, 8 out of 9 patients ahcieved CR/CRi, 7/8 and 5/8 patients achieved minimal residual disease (MRD) negativity, respectively. Six out of 9 patients with TET2 mutation achieved CR/CRi, 3/6 patients achieved MRD negativity. In R/R AML cohort, 2 out of 3 patients with RUNX1 mutation achieved CR/CRi, without MRD negative, while the CR/CRi rate of patients with other gene mutations was lower than 40%. The median follow-up time was 10.1(95%CI: 8.6-11.6) months. In whole cohort, the median overall survival (mOS) time was 9.1 months and the relapse free survival (RFS) time was not reached. The mOS and RFS of unfit AML patients were significantly longer than those of R/R AML patients (14.1 vs 6.8 months, P=0.013; not reached vs 3.3 months, P=0.000). In unfit AML cohort, the mOS of patients with NPM1 or IDH1/2 mutations was not reached, while that of patients without NPM1 or IDH1/2 mutations was 8.0 months (P=0.009; P=0.022). Furthermore, the mOS of patients with TP53 mutaion was significantly shorter than that of patients without TP53 mutation (5.2 vs 14.1 months， P=0.049). In R/R AML cohort, there was no significant difference in mOS between patients with mutation in each gene subtype and those without gene mutation (P>0.05). All patients had hematology adverse reactions, 91.1% patients had AE grade≥3. The most common non-hematology adverse reactions was infection, with an incidence of 91.1%. VEN-based regimen was tolerable for AML patients. CONCLUSION: VEN-based regimen can achieve a high response rate, especially in unfit AML with acceptable safety, and some patients can achieve MRD negative. It is also effective in NPM1-, IDH1/2-positive patients with long survival time.

The optimal timing of laparoscopic cholecystectomy in patients with mild gallstone pancreatitis: A meta-analysis.

BACKGROUND: The optimal timing of laparoscopic cholecystectomy (LC) in patients with mild acute gallstone pancreatitis (MAGP) is controversial. The aim of this study was to systematically evaluate and compare the safety and efficacy of early laparoscopic cholecystectomy (ELC) and delayed laparoscopic cholecystectomy (DLC) in patients with MAGP. METHODS: A strict search was conducted of the electronic databases, including PubMed, MEDLINE Embase, the ISI Web of Science, and Cochrane Library for all relevant English literature and RevMan5.3 software for statistical analysis was used. RESULTS: A total of 19 studies comprising 2639 patients were included. There was no significant difference in intraoperative complications [risk ratio (RR) = 1.46; 95% confidence interval (CI) = 0.88-2.41; P = .14)], postoperative complications (RR = 0.81; 95% CI = 0.58-1.14; P = .23), rate of conversion to open cholecystectomy (RR = 1.00; 95% CI = 0.75-1.33; P = .99), operative time (MD = 1.60; 95% CI = -1.36-4.56; P = .29), and rate of readmission (RR = 0.63; 95% CI = 0.19-2.10; P = .45) between the ELC and DLC groups. However, the ELC group was significantly correlated with lower length of hospital stay (MD = -2.01; 95% CI = -3.15 to -0.87; P = .0006), fewer gallstone-related events rates (RR = 0.17; 95% CI = 0.07-0.44; P = .0003), and lower endoscopic retrograde cholangiopancreatography (ERCP) usage (RR = 0.83; 95% CI = 0.71-0.97; P = .02) compared with the DLC group. CONCLUSION: Early laparoscopic cholecystectomy is safe and effective for patients with MAGP, but the indications and contraindications must be strictly controlled.

H3K9 histone methyltransferase, KMT1E/SETDB1, cooperates with the SMAD2/3 pathway to suppress lung cancer metastasis.

Aberrant histone methylation is a frequent event during tumor development and progression. KMT1E (also known as SETDB1) is a histone H3K9 methyltransferase that contributes to epigenetic silencing of both oncogenes and tumor suppressor genes in cancer cells. In this report, we demonstrate that KMT1E acts as a metastasis suppressor that is strongly downregulated in highly metastatic lung cancer cells. Restoring KMT1E expression in this setting suppressed filopodia formation, migration, and invasive behavior. Conversely, loss of KMT1E in lung cancer cells with limited metastatic potential promoted migration in vitro and restored metastatic prowess in vivo. Mechanistic investigations indicated that KMT1E cooperates with the TGFß-regulated complex SMAD2/3 to repress metastasis through ANXA2. Together, our findings defined an essential role for the KMT1E/SMAD2/3 repressor complex in TGFß-mediated lung cancer metastasis.

[Clinical value of 64-slice spiral 3-phase CT enhanced scanning for preoperative TNM staging assessment of gastric carcinoma].

OBJECTIVE: To explore the clinical value of 64-slice spiral 3-phase CT enhanced scanning for preoperative TNM staging assessment of gastric carcinoma. METHODS: A retrospective study was performed to review the 64-slice spiral 3-phase CT enhanced scanning of 120 patients with gastric cancer diagnosed by biopsy prior to operation and postoperative pathological reports. All the findings were reviewed by two senior radiologic diagnosticians separately and compared with pathological findings. RESULTS: The accuracy of 64-slice spiral CT enhanced scan was 79.2%(95/120) for T staging, 66.7%(10/15) for T1, 66.7%(14/21) for T2, 84.0%(42/50) for T3, and 85.3%(29/34) for T4. For gastric wall with single layer and multiple layers, the accuracy of CT enhanced scanning was 59.4%(19/32) and 81.8%(72/88) for T staging, and the difference was statistically significant(P<0.05). The accuracy of 64-slice spiral CT enhanced scan was 73.9%(85/115) for N staging, 75.5%(37/49) for N0, 70.3%(26/37) for N1, 75.9%(22/29) for N2. The accuracy of 64-slice spiral CT enhanced scanning was 89.2% for M staging. CONCLUSION: 64-slice spiral CT 3-phase enhanced scanning can monitor the invasion, lymphatic metastasis, and distant metastasis of gastric cancer dynamically, which may become an important examination item for the preoperative evaluation of gastric cancer.

Crocetin induces cytotoxicity in colon cancer cells via p53-independent mechanisms.

OBJECTIVE: Crocin has been proposed as a promising candidate for cancer chemoprevention. The purpose of this investigation was to investigate the chemopreventive action and the possible mechanisms of crocin against human colon cancer cells in vitro. METHODS: Cell proliferation was examined using MTT assay and the cell cycle distribution fractions were analyzed using flow cytometric analysis after propidium iodide staining. Apoptosis was detected using the TUNEL Apoptosis Detection Kit with laser scanning confocal microscope. DNA damage was assessed using the alkaline single-cell gel electrophoresis assay, while expression levels of p53, cdk2, cyclin A and P21 were examined by Western blot analysis. RESULTS: Treatment of SW480 cells with crocetin (0.2, 0.4, 0.8 mmol/L) for 48 h significantly inhibited their proliferation in a concentration-dependent manner. Crocetin (0.8 mmol/L) significantly induced cell cycle arrest through p53-independent mechanisms accompanied by P21 induction. Crocetin (0.8 mmol/L) caused cytotoxicity in the SW480 cells by enhancing apoptosis and decreasing DNA repair capacity in a time-dependent manner. CONCLUSIONS: This report provides evidence that crocetin is a potential anticancer agent, which may be used as a chemotherapeutic drug.