Objective:To investigate the toxic effect of chlorambucil combined with ibrutinib on mantle cell lymphoma(MCL)cell line Jeko-1 and its related mechanism.Methods:The MCL cell line Jeko-1 was incubated with different concentrations of chlorambucil or ibrutinib or the combination of the two drugs,respectively.CCK-8 assay was used to detect the proliferation of the cells,and Western blot was used to measure the protein expression levels of BCL-2,caspase-3,PI3K,AKT and P-AKT.Results:After Jeko-1 cells were treated with chlorambucil(3.125,6.25,12.5,25,50 μmol/L)and ibrutinib(3.125,6.25,12.5,25,50 μmol/L)alone for 24,48,72h respectively,the cell proliferation was inhibited in a time-and dose-dependent manner.Moreover,the two drugs were applied in combination at low doses(single drug inhibition rate＜50％),and the results showed that the combination of two drugs had a more significant inhibitory effect(all P＜0.05).Compared with the control group,the apoptosis rate of the single drug group of chlorambucil(3.125,6.25,12.5,25,50 μmol/L)and ibutinib(3.125,6.25,12.5,25,50 μmol/L)was increased in a dose-dependent manner.The combination of the two drugs at low concentrations(3.125,6.25,12.5 μmol/L)could significantly increase the apoptosis rate compared with the corresponding concentration of single drug groups(all P＜0.05).Compared with control group,the protein expression levels of caspase-3 in Jeko-l cells were upregulated,while the protein expression levels of BCL-2,PI3K,and p-AKT/AKT were downregulated after treatment with chlorambucil or ibrutinib alone.The combination of the two drugs could produce a synergistic effect on the expressions of the above-mentioned proteins,and the differences between the combination group and the single drug groups were statistically significant(all P＜0.05).Conclusion:Chlorambucil and ibrutinib can promote the apoptosis of MCL cell line Jeko-1,and combined application of the two drugs shows a synergistic effect,the mechanism may be associated with the AKT-related signaling pathways.

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.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Psoriasis is a chronic skin disease and an important health concern. Western medicine and therapies are the main treatment strategies for psoriasis vulgaris (PV); however, the overall prognosis of patients with PV is still poor. Therefore, PV prevention is especially crucial. Chinese medicine (CM) has a long history of treating psoriasis, and it has unique wisdom in different cognitive angles and treatment modes from modern medicine. In this review, we first summarized the herbs and ancient CM formulas that have therapeutic effects on PV. Second, the research status and obstacles to the current development of CM in modern medicine were reviewed. Finally, the future of CM in the context of precision medicine and integrated medicine was discussed. After a detailed reading of the abundant literature, we believe that CM, through thousands of years of continuous development and clinical practice, has achieved high effectiveness and safety for PV treatment, despite its surrounding controversy. Moreover, precise analyses and systematic research methods have provided new approaches for the modernization of CM in the future. The treatment of PV with CM is worth popularizing, and we hope it can benefit more patients.
Humans ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Psoriasis/therapy* ; Research Design ; Drug Therapy, Combination

This study aims to investigate the molecular mechanism of tanshinone Ⅱ_(A )(TaⅡ_A) combined with endothelial progenitor cells-derived exosomes(EPCs-exos) in protecting the aortic vascular endothelial cells(AVECs) from oxidative damage via the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt) pathway. The AVECs induced by 1-palmitoyl-2-(5'-oxovaleroyl)-sn-glycero-3-phosphocholine(POVPC) were randomly divided into model, TaⅡ_A, EPCs-exos, and TaⅡ_A+EPCs-exos groups, and the normal cells were taken as the control group. The cell counting kit-8(CCK-8) was used to examine the cell proliferation. The lactate dehydrogenase(LDH) cytotoxicity assay kit, Matrigel assay, DCFH-DA fluorescent probe, and laser confocal microscopy were employed to examine the LDH release, tube-forming ability, cellular reactive oxygen species(ROS) level, and endothelial cell skeleton morphology, respectively. The enzyme-linked immunosorbent assay was employed to measure the expression of interleukin(IL)-1β, IL-6, and tumor necrosis factor(TNF)-α. Real-time fluorescence quantitative PCR(qRT-PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of PI3K and Akt. Compared with the control group, the model group showed decreased cell proliferation and tube-forming ability, increased LDH release, elevated ROS level, obvious cytoskeletal disruption, increased expression of IL-1β, IL-6, and TNF-α, and down-regulated mRNA and protein levels of PI3K and Akt. Compared with the model group, TaⅡ_A or EPCs-exos alone increased the cell proliferation and tube-forming ability, reduced LDH release, lowered the ROS level, repaired the damaged skeleton, decreased the expression of IL-1β, IL-6, and TNF-α, and up-regulated the mRNA and protein levels of PI3K and Akt. TaⅡ_A+EPCs-exos outperformed TaⅡ_A or EPCs-exos alone in regulating the above indexes. The results demonstrated that TaⅡ_A and EPCs-exos exerted a protective effect on POVPC-induced AVECs by activating the PI3K/Akt pathway, and the combination of the two had stronger therapeutic effect.
Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Signal Transduction ; Reactive Oxygen Species/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/metabolism* ; Endothelium, Vascular ; Oxidative Stress ; Endothelial Progenitor Cells ; RNA, Messenger/metabolism* ; Abietanes

With prominent medicinal value, Gelsemium elegans has been overexploited, resulting in the reduction of the wild resource. As a result, artificial cultivation turns out to be a solution. However, this medicinal species is intolerant to low temperature, and thus genes responding to the low temperature are important for the cultivation of this species. Based on the transcriptome database of G. elegans at 4 ℃, 29 differentially expressed GeERF genes were identified. Bioinformatics analysis of 21 GeERF gene sequences with intact open reading frames showed that 12 and 9 of the GeERF proteins respectively clustered in DREB subgroup and ERF subgroup. GeDREB1 A-1-GeERF6 B-1, with molecular weight of 23.78-50.96 kDa and length of 212-459 aa, were all predicted to be hydrophilic and in nucleus. Furthermore, the full-length cDNA sequence of GeERF2B-1 was cloned from the leaves of G. elegans. Subcellular localization suggested that GeERF2B-1 was located in the nucleus. According to the quantitative reverse-transcription PCR(qRT-PCR), GeERF2B-1 showed constitutive expression in roots, stems, and leaves of G. elegans, and the expression was the highest in roots. In terms of the response to 4 ℃ treatment, the expression of GeERF2B-1 was significantly higher than that in the control and peaked at 12 h, suggesting a positive response to low temperature. This study lays a scientific basis for the functional study of GeERF transcription factors and provides gene resources for the improvement of stress resistance of G. elegans.
DNA, Complementary ; Gene Expression Regulation, Plant ; Phylogeny ; Plant Proteins/metabolism* ; Temperature ; Transcription Factors/metabolism*

Four new prenylflavonoid glycosides, namely koreanoside H-K (1-4), together with eleven known ones (5-15) were isolated from the leaves of Epimedium koreanum Nakai. Their structures were elucidated by 1D NMR, 2D NMR, HR-ESI-MS, IR and UV. The identification of the sugar moieties was carried out by means of acid hydrolysis and HPLC analysis of their derivatives. It is worth noting that compound 3 and compound 4 were elucidated to contain fucose and quinovose moieties, which were two extremely rare sugar units from the genus Epimedium. The anti-pulmonary fibrosis activity of the new compounds was evaluated using A549 cell line. Compounds 1, 2 and 4 showed significant anti-pulmonary fibrosis activities.
Chromatography, High Pressure Liquid ; Epimedium/chemistry* ; Glycosides/pharmacology* ; Plant Extracts/pharmacology* ; Plant Leaves/chemistry*

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

By preparing 15 batches of substance benchmarks of Taohong Siwu Decoction, the methodology of the characteristic spectrums of substance benchmarks was established. The paste-forming rate range, the contents and the transfer rate range of the index components, hydroxy safflower yellow A, ferulic acid and paeoniflorin, the characteristic peaks and the similarity range of the characteristic spectrums of Taohong Siwu Decoction were determined to define key quality attributes of substance benchmarks of Taohong Siwu Decoction.In the 15 batches of substance benchmarks of Taohong Siwu Decoction, the similarity of characteristic spectrums was higher than 0.9. Furthermore, based on summarization of the characteristic peak information, there were 13 characteristic peaks in the whole decoction. Baishao had three characteristic peaks, Honghua had seven characteristic peaks, and Chuanxiong and Danggui had three characteristic peaks. The paste-forming rate of the 15 batches of substance benchmarks was controlled at 33.11%-40.62%. The content of hydroxy safflower yellow A was 0.129%-0.203%, with the average transfer rate of 16.596%±0.669%.The content of ferulic acid was 0.043%-0.055%, with the average transfer rate of 20.489%±1.772%.The content of paeoniflorin was 0.676%-0.943%, with the average transfer rate of 29.112%±3.273%.The quality value transfer of substance benchmarks of classical prescription Taohong Siwu Decoction was analyzed by the combination of characteristic spectrums, paste-forming rate and the content of index components. The established substance benchmark quality evaluation method was stable and feasible, and could provide a basis for quality control and subsequent development of relevant preparations of Taohong Siwu Decoction.
Benchmarking ; Drugs, Chinese Herbal ; Quality Control

【Objective】 To compare the volumes of brain regions and the white matter hyperintensities(WMH) in Alzheimer's disease(AD) and vascular dementia(VaD) patients, and discuss values of magnetic resonance imaging (MRI) in the differential diagnosis of AD and VaD. 【Methods】 The clinical data and MRI images of 35 patients with VaD and 74 patients with AD were retrospectively analyzed. Volumes of different brain regions and WMH were measured by using AccuBrain^TM system and visual rating scale was used to assess WMH. We then compared the volumes of brain regions and the WMH between AD and VaD. The principal component analysis(PCA) and logistic regression analysis were adopted for differential diagnosis. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic efficiency of the indexes. 【Results】 ①Compared with VaD patients, AD patients showed statistically smaller volumes of total intracranial volume, brain parenchyma, gray matter, white matter, hippocampus, amygdala, hypothalamus, frontal lobe(left, right), occipital lobe(left, right), temporal lobe(left, right), parietal lobe(left, right), hippocampus (left, right), amygdala(left, right), hypothalamus(left, right) (P<0.05). ②There was statistically significant difference in the visual scores for deep WMH(DWMH) between AD and VaD patients(P=0.015). The absolute and relative volumes of WMH in VaDpatients were statistically larger than those in AD patients(P<0.05). ③PCA revealed eight important parameters including brain parenchyma, hippocampus, amygdala, hypothalamus, frontal lobe(left), occipital lobe(left), temporal lobe(left) and parietal lobe(left) .The identification model consisting of amygdala, occipital lobe (left) and absolute volume of WMH was established based on logistic regression analysis. ④Among all the indexes, the identification model had the best diagnostic performance to differentiate AD from VaD and its sensitivity and specificity were 81.1% and 74.3%, respectively. 【Conclusions】 There are significant differences in both volumes of certain brain regions and severity of WMH between VaD and AD patients. The cranial MRI is of great value for the differential diagnosis of VaD and AD.