Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Humans ; Rural Population ; Hyperglycemia/genetics* ; Receptors, Calcitriol/genetics*

OBJECTIVE: To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC). METHODS: This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC). RESULTS: This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified. CONCLUSION Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.
Adolescent ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carcinoma, Hepatocellular/drug therapy* ; Cisplatin/therapeutic use* ; Humans ; Liver Neoplasms/drug therapy* ; Lung Neoplasms/pathology* ; Nasopharyngeal Neoplasms/drug therapy*

Objective To study the inhibitory effect of T lymphocytes secreting EphrinAl-Caspase-3 in vivo and on the growth of cancer cells in nude mice with breast cancer. Methods Nude mice (n = 35) were inoculated with breast cancer cells to construct a nude mouse model of breast cancer. When the tumor volume reached 0. 1 cm3, 30 nude mice with average size tumor tissue were randomly divided into PBS group, uninfected adenovirus group, T lymphocyte infected with Ad-EphrinAl-Caspase-3 group, and intratumoral transplantation. Tumor size was measured every day 2 to 3. Three groups of tumor-bearing nude mice were selected. After the above-mentioned cell transplantation, the subcutaneous tumor tissue homogenate was obtained every day 2 to 3, and the content of EphrinAl-Caspase-3 was detected by ELISA. At the end of the experiment, the animals in each group were sacrificed by cervical dissection and sliced. The presence of T lymphocytes expressing green fluorescent protein was observed under a fluorescence microscope, and Caspase-3 and Ki-67 were detected by immunofluorescence. Results After one week of inoculation of breast cancer cells into nude mice, the presence of subcutaneous tumors could be touched by hand, which proved that the tumor-bearing animals of breast cancer cells were successfully modeled. On the 8th day after inoculation, the tumor volume of the nude mice in each group became larger, and the difference between the treatment group and the PBS group/T lymphocyte group was extremely significant ( P<0.05). Although the tumor volume of the T lymphocyte transplantation group was slower than that of the PBS control group, there was no statistically significant difference between the two. The expression of EphrinAl-Caspase-3 was detected in the EphrinAl-Caspase-3 treatment group on the 2nd day, reached the peak on the 8th day, and then the secretion decreased gradually. No expression of EphrinAl-Caspase-3 was detected in the PBS control group and the T lymphocyte group. The presence of dispersed green fluorescent protein-labeled EphrinAl-Caspase-3-T lymphocytes was observed in the tumor tissues of the treatment group, while the presence of green fluorescent protein was not detected in the PBS group and the T lymphocyte groups. In the infected cells of the treatment group, the proportion of Caspase-3 positive cells was up- regulated, and the proportion of Ki-67 positive cells was down-regulated. No expression of EphrinAl-Caspase-3 was detected in the PBS group and the T lymphocyte group. Conclusion EphrinAl-Caspase-3 can significantly inhibit the growth of breast cancer cells, thereby exerting an anti-tumor effect.

Ziziphi Spinosae Semen is one of the Chinese herbal medicine being susceptible to aflatoxins contamination. To investigate the sources of aflatoxins contamination and toxigenic fungi species on Ziziphi Spinosae Semen,32 samples were collected from multiple steps during the post-harvest processing in this study. Aflatoxins in these samples were determined by immunoaffinity column and HPLC coupled with post-column photochemical derivatization. The dilution-plate method was applied to the fungi isolation. The isolated fungi strains were identified by morphological characterization and molecular approaches. The results showed that aflatoxins were detected in 28 samples from every step during the processing of Ziziphi Spinosae Semen. Three samples were detected with aflatoxin B_1 and 2 samples with both aflatoxin B_1 and total aflatoxin exceeding the limit of Chinese Pharmacopoeia. Especially the samples from the washing step,with the highest detected amounts of AFB_1 and AFs were reached 94. 79,121. 43 μg·kg~(-1),respectively. All 32 samples were contaminated by fungi. The fungal counts on the newly harvested samples were 2. 20 × 10~2 CFU·g~(-1). Moreover,it increased as tphreocessing progresses,and achieved 1. 16×10~6 CFU·g~(-1) after washing. A total of 321 isolates were identified to 17 genera. Aspergillus flavus was the main source of aflatoxins during the processing and storage of Ziziphi Spinosae Semen. One isolate of A. flavus was confirmed producing AFB_1 and AFB_2. The fungal count was significantly increased by composting,and Aspergillus was the predominant genus after shell breaking. The contamination level of aflatoxins was increased by composting and washing.
Aflatoxins ; analysis ; Aspergillus ; Chromatography, High Pressure Liquid ; Fungi ; isolation & purification ; Seeds ; chemistry ; microbiology ; Ziziphus ; chemistry

Objective To establish a height prediction model of Chinese Han male based on the reported 547 height-associated single nucleotide polymorphisms (SNPs) loci in Europeans, and assess its accuracy for height estimation. Methods The DNA typing was analyzed in 59 Han male samples of Shandong province by Affymetrix SNP Array 6.0 chip and HiSeq 4000 sequencing platform. Prediction model was established using 547 height-associated SNPs loci as predictors and weight allele sums (WAS) as com-puting method. The accuracy of height prediction model was analysed using receiver operating characteris-tic (ROC) curve and area under curve (AUC). Results There was no height-associated SNPs locus was found by genome-wide association studies. In present study, height prediction model was established by WAS and obtained an AUC of 0.67 (95％CI:0.53-0.90). Conclusion It has reference value for predicting the height of Han male in Shandong province by WAS model based on 547 SNPs loci, while it is still necessary to further promote the accuracy of the prediction model by screening more height-associated SNPs loci with population heterogeneity.

BACKGROUND: How to efficiently and uniformly disperse carbon nanotubes (CNTs) into a tissue-engineered scaffold is crucial to construct an ideal CNTs-Polymer composite scaffold and it is also a hotspot of research in the tissue engineering. OBJECTIVE: To review the advances in the methodology progress of constructing a scaffold for cardiac tissue engineering, which contains uniformly and stably dispersed CNTs. METHODS: The Web of Science Core Collection and PubMed were searched by the first author for related papers about CNTs dispersion in the cardiac tissue engineering published from October 2004 to January 2017. The key words were "carbon nanotubes, dispersion, cardiac tissue engineering" in English. Original research papers were searched, which were screened through titles, abstracts and contents, and then reviewed. RESULTS AND CONCLUSION: CNTs are easy to aggregate because of high surface area, high aspect ratio and rough surface. Thus, it is one of the key points to construct an ideal CNTs-Polymer composite scaffold that whether CNTs could be uniformly and stably dispersed in polymer scaffolds. In the cardiac tissue engineering, covalent or non-covalent surface modification of CNTs significantly enhances the uniformity and stability of CNTs in the polymer scaffolds, which is conducive to construct the uniformly and stably CNTs-dispersed scaffold for cardiac tissue engineering, leading to notable improvement in mechanical and electrical properties of engineered cardiac tissues.

OBJECTIVETo investigate the change in the expression of tight junction protein ZO-1 in intestinal epithelial cells (Caco-2 cells) and the protective effect of eicosapentaenoic acid (EPA) after adherent-invasive Escherichia coli (E.coli) LF82 infection.

METHODSThe Caco-2 cell line was used to establish an in vitro model of tight junction of intestinal epithelial cells. Caco-2 cells were divided into EPA treatment groups (0, 25, 50, 100, and 200 μmol/L EPA) and EPA (0, 25, 50, 100, and 200 μmol/L EPA)+E.coli LF82 treatment (0, 6, and 12 hours) groups. A microscope was used to observe the morphological characteristics of the cells. MTT assay was used to determine the cell growth curve. The activity of alkaline phosphatase (ALP) at both sides of the cell membrane was compared to evaluate the Caco-2 cell model. MTT assay and flow cytometry were used to investigate the effects of different concentrations of EPA on the survival rate and apoptosis rate of Caco-2 cells. RT-qPCR was used to measure the mRNA expression of ZO-1 in Caco-2 cells after EPA and/or E.coli LF82 treatment. ELISA was used to measure the change in the level of tumor necrosis factor-α (TNF-α) in culture supernatant.

RESULTSAfter EPA treatment (25 and 50 μmol/L), the proliferation of Caco-2 cells was induced in a dose-dependent manner. The survival rates of the cells were significantly higher than those in the control group (P<0.05). The EPA treatment (100 and 200 μmol/L) groups had a significant inhibitory effect on the proliferation of Caco-2 cells in a dose-dependent manner. The survival rates of the cells were significantly lower than those in the control group (P<0.05). The EPA treatment (100 and 200 μmol/L) groups had a significant increase in cell apoptosis rate compared with the control group (P<0.05). The 6- and 12-hour E.coli LF82 treatment groups had decreasing mRNA expression of ZO-1 in Caco-2 cells over the time of treatment and had significantly lower mRNA expression of ZO-1 than the untreated group (P<0.05). The Caco-2 cells treated with E.coli LF82 and 25 or 50 μmol/L EPA for 6 or 12 hours showed an increase in the mRNA expression of ZO-1 with the increasing concentration of EPA, as well as significantly higher mRNA expression of ZO-1 than the Caco-2 cells treated with E.coli LF82 alone (P<0.05). The Caco-2 cells treated with E.coli LF82 alone for 6 or 12 hours had increasing secretion of TNF-α over the time of treatment and had significantly higher secretion than the untreated Caco-2 cells (P<0.05). The Caco-2 cells treated with E.coli LF82 and 25 or 50 μmol/L EPA for 6 or 12 hours showed a reduction in the secretion of TNF-α with the increasing concentration of EPA and had significantly lower secretion than the Caco-2 cells treated with E.coli LF82 alone (P<0.05).

CONCLUSIONSEPA can effectively prevent the destruction of tight junction of intestinal epithelial cells induced by E.coli LF82 infection and inhibit the secretion of inflammatory factors. Therefore, it has a certain protective effect on intestinal mucosal barrier.

Apoptosis ; drug effects ; Caco-2 Cells ; Eicosapentaenoic Acid ; pharmacology ; Escherichia coli ; pathogenicity ; Humans ; Intestinal Mucosa ; metabolism ; microbiology ; RNA, Messenger ; analysis ; Tight Junctions ; drug effects ; Tumor Necrosis Factor-alpha ; secretion ; Zonula Occludens-1 Protein ; genetics

In order to evaluate the efficiency of ITS2 and psbA-trnH sequences used as DNA barcodes to distinguish Plantaginis Semen from its adulterants, we collected 71 samples of Plantaginis Semen and its adulterants. The ITS2 and psbA-trnH sequences were aligned through Clustal W, and the genetic distances were calculated by kimura 2-parameter (K2P) model and the Neighbor-Joining (NJ) phylogenetic trees were constructed using MEGA 5.1. The results indicated that the ITS2 sequence lengths of Plantago asiatica and P. depressa were 199 bp and 200 bp, respectively; the maximum intra-specific K2P distance were lower than the minimum inter-specific K2P distance; the NJ tree based on ITS2 sequence indicated that Plantaginis Semen and its adulterants could be distinguished clearly. The sequence lengths of psbA-trnH of both P. asiatica and P. depressa were 340 bp; the maximum intra-specific K2P distances were lower than the minimum inter-specific K2P distance; the NJ tree based on psbA-trnH sequence showed that Plantaginis Semen can be distinguished clearly from its adulterants except for P. major. Therefore, ITS2 sequences can be used as an ideal DNA barcode to distinguish Plantaginis Semen from its adulterants.
Base Sequence ; DNA Barcoding, Taxonomic ; methods ; DNA, Plant ; genetics ; DNA, Ribosomal Spacer ; genetics ; Drug Contamination ; prevention & control ; Drugs, Chinese Herbal ; chemistry ; classification ; Molecular Sequence Data ; Phylogeny ; Plant Proteins ; genetics ; Plantago ; classification ; genetics ; Quality Control ; Seeds ; classification ; genetics

The phosphatidylinositol 3-kinase (PI3K) and its downstream target protein kinase B (Akt/PKB) can be activated by a variety of extracellular and intracellular signals. They are important signaling molecules and key survival factors involved in cell proliferation, differentiation, apoptosis and other cellular processes. Recently, many reports demonstrate that type I PI3K/Akt signaling pathway plays an important role in maintenance of self-renewal and pluripotency of embryonic stem (ES) cells. Further studies with regard to the self-renewal and pluripotency of ES cells and underlying molecular mechanisms are crucial to its application in cell replacement therapy, regenerative medicine and tissue engineering. The present review focuses on the recent progress on the mediation of PI3K/Akt signaling pathway on the maintenance of self-renewal and pluripotency of ES cells.
Cell Differentiation ; Cell Proliferation ; Embryonic Stem Cells ; cytology ; Humans ; Phosphatidylinositol 3-Kinases ; physiology ; Pluripotent Stem Cells ; cytology ; Proto-Oncogene Proteins c-akt ; physiology ; Signal Transduction