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.

In this study, we investigated the anti-osteoporotic activity and mechanism of action of extract of Panax quiquefolium L. based on zebrafish model combined with metabolomics technology. A zebrafish model of prednisolone-induced osteoporosis was used to compare the anti-osteoporotic activity of Panax quiquefolium L., and the expression of osteoblast-associated genes and osteoclast-associated genes in zebrafish was detected by quantitative real-time PCR (qRT-PCR), using bone fluorescence area and fluorescence density as evaluation indexes. Metabolomics based on ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) was used to explore the change patterns of biomarkers and the metabolic pathways affected. The results showed that the 50% ethanol extracts of Panax quiquefolium L. from Jilin, Canada, Wenden and the United States can significantly improve the bone fluorescence area of zebrafish compared with model group. Furthermore, four sources 50% ethanol extracts of Panax quiquefolium L. except United States also can significantly improve the bone fluorescence density of zebrafish. In addition, PCR showed that extract of Panax quiquefolium L. can significantly up-regulated the expression of vitamin D receptor b (vdrb), collagen type I α2 (col1a2) and cysteine-rich acidic secreted protein (sparc) genes, and down-regulated the expression of matrix metalloproteinase 9 (mmp9), anti-tartrase acid phosphatase (trap) and cathepsin K (ctsk) genes. Metabolomic analysis identified 24 key differential metabolites. Furthermore, pathway analysis showed that Panax quiquefolium L. could regulate the levels of 10 key biomarkers by participating in purine metabolism, tricarboxylic acid cycle and pentose phosphate metabolism and improve the osteoporosis status of zebrafish. This study preliminically revealed the anti-osteoporosis mechanism of 50% ethanol extract from Panax quiquefolium L. through multi-component, multi-target and multi-pathway and also provides theoretical basis for clinical development and utilization of anti-osteoporosis products of Panax quiquefolium L. This experiment was approved by the Experimental Animal Welfare Ethics Committee of the Institute of Biology, Shandong Academy of Sciences (approval number: SWS20181002).

Humans ; Phosphorylation ; Serine ; Protein Serine-Threonine Kinases/metabolism* ; Spasms, Infantile

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective:To evaluate the safety of thymic surgery in patients aged 65 years and over.Methods:A total of 696 patients who underwent thymectomy/thymoma resection in the Department of Thoracic Surgery of Beijing Hospital from November 2011 to March 2022 were collected and divided into two groups according to the age of 65 years old.The preoperative course of disease, MG stage, dosage of pyridostigmine bromide, American College of Anesthesiologists(ASA)score, surgical method, intraoperative bleeding, postoperative drainage, postoperative complications, Clavien-dindo score(CDC), and myasthenic crisis were recorded and statistically analyzed.Results:A total of 696 patients were enrolled, including 364 males and 332 females, aged 15~86 years, with an average age of 49.1 years.There were 309 patients with thymoma, 565 patients with MG, and 178 patients with both.There were 124 cases in the elderly group(≥65 years old)and 572 cases in the non-elderly group(<65 years old). The incidence of thymoma was higher in the elderly group(54.8 % versus 42.1 %, χ2=6.664, P=0.010), while the incidence of MG was lower(67.7 % versus 84.1 %, χ2=17.827, P<0.001). The ASA score of the elderly group was higher than that of the non-elderly group( χ2=52.372, P=0.000), and the preoperative ventilation function FEV1 and FEV1/FVC were also significantly lower than those of the non-elderly group( z=8.187, 4.580, P=0.000 for all). The drainage volume in the first 3 days after operation and postoperative drainage tube time in the elderly group were significantly higher than those in the non-elderly group( P=0.018, P=0.003). The incidence of postoperative myasthenia crisis in the elderly group was higher than that in the non-elderly group( P=0.034). There was no significant difference in the incidence of postoperative complications between the two groups, but after Clavien-dindo classification, the score of the elderly group was higher than that of the non-elderly group( P=0.003). Although the ASA score and Clavien-dindo score of the elderly group were both higher than those of the non-elderly group, there was no correlation between the two. Conclusions:Although the preoperative ASA score and pulmonary function of elderly patients were poorer than those in the non-elderly group, while the incidence of postoperative myasthenia crisis was higher, and the incidence of postoperative complications was not higher, the Clavien-dindo classification, however, was higher in elderly patients than that of the non-elderly group.After careful preoperative evaluation and strengthening perioperative management, most elderly patients can receive thymus surgery safely with acceptable risks.

Resveratrol (RES), a natural polyphenolic phytochemical, has been suggested as a putative anti-aging molecule for the prevention and treatment of Alzheimer's disease (AD) by the activation of sirtuin 1 (Sirt1/Sir2). In this study, we tested the effects of RES and Sirt1/Sir2 on sleep and courtship memory in a Drosophila model by overexpression of amyloid precursor protein (APP), whose duplications and mutations cause familial AD. We found a mild but significant transcriptional increase of Drosophila Sir2 (dSir2) by RES supplementation for up to 17 days in APP flies, but not for 7 days. RES and dSir2 almost completely reversed the sleep and memory deficits in APP flies. We further demonstrated that dSir2 acts as a sleep promotor in Drosophila neurons. Interestingly, RES increased sleep in the absence of dSir2 in dSir2-null mutants, and RES further enhanced sleep when dSir2 was either overexpressed or knocked down in APP flies. Finally, we showed that Aβ aggregates in APP flies were reduced by RES and dSir2, probably via inhibiting Drosophila β-secretase (dBACE). Our data suggest that RES rescues the APP-induced behavioral deficits and Aβ burden largely, but not exclusively, via dSir2.
Animals ; Alzheimer Disease/metabolism* ; Amyloid beta-Peptides ; Amyloid beta-Protein Precursor/metabolism* ; Drosophila/physiology* ; Drosophila Proteins/metabolism* ; Resveratrol/pharmacology* ; Sirtuin 1 ; Sleep

In this study, the toxicological/pharmacological research method of "quantity-weight-evidence" network was first proposed and practiced to supplement the existing methodology of network toxicology. We transformed the traditional qualitative network into a quantitative network in this study by attributing weights to toxic component content and target frequency, which improved the reliability of data and provided a research idea for the systematic safety evaluation and toxicological research of Chinese medicinal herbs. Firstly, 50% ethanol extract of Dysosma versipellis(DV) was administrated to rats via gavage and the potential hepatotoxic components were identified by serum pharmacochemistry. Then, the component targets were obtained from SwissTargetPrediction, PharmMapper and other online databases, and the target weights were given according to the relative content of components and target fishing frequency. Meanwhile, the targets of hepatotoxicity were predicted from online databases such as Comparative Toxicology Database(CTD) and GeneCards. Subsequently, protein-protein interaction analysis and KEGG pathway enrichment were performed with the STRING database. Finally, the quantitative network of "toxic components-weighted targets-pathways" was constructed. Eleven potential toxic compounds were predicted, including podophyllotoxin, podophyllotoxone, deoxypodophyllotoxin, and 6-methoxypodophyllotoxin. A total of 106 hepatotoxic targets and 65 weighted targets(e.g., Cdk2, Egfr, and Cyp2 c9) were identified. The results of Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment showed that these targets could act on PI3 K-AKT, MAPK, and Ras signaling pathways to play a role in inflammatory response and oxidative stress. However, traditional network toxicology showed that 51 targets such as AKT1, Alb, and Stat3 may lead to hepatotoxicity by mediating inflammation and cell proliferation. In conclusion, we proposed "quantity-weight-evidence" network toxicology in this study and used it to study the mechanism of DV-induced hepatotoxicity in rats. This study confirms the feasibility of this new methodology in toxicological evaluation and further improves the systematic evaluation of the safety of Chinese medicinal herbs.
Animals ; Chemical and Drug Induced Liver Injury/etiology* ; Drugs, Chinese Herbal/toxicity* ; Ethanol ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Rats ; Reproducibility of Results

Child ; Consensus ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Respiratory System

ObjectiveTo explore the molecular mechanism of Yishen Tongluo prescription in inhibiting the apoptosis of glomerular podocytes in rats with membranous nephropathy （MN） based on the miR-514a-5p/tumor necrosis factor superfamily member 15 （TNFSF15） signaling pathway. MethodEighty SD rats were pre-immunized and injected with cationized bovine serum albumin （C-BSA） into the tail vein for inducing MN， and the successfully modeled MN rats were randomly divided into the model group， high-， middle-， and low-dose （26.44， 13.22， 6.61 g·kg^-1） Yishen Tongluo prescription groups， and benazepril （10 mg·kg^-1） group， with 10 rats in each group， and another 20 healthy rats were classified into the normal group. Rats in each group were gavaged with the corresponding drugs， once a day， for four successive weeks. After the administration， the 24-hour urine total protein （UTP） level， serum total cholesterol （TC）， triglyceride （TG）， albumin （ALB）， creatinine （SCr）， and urea nitrogen （BUN） levels were measured. The miR-514a-5p and TNFSF15 mRNA expression levels in the rat kidney tissue were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the expression levels of podocyte marker proteins Nephrin， Podocin， Podocalyxin， Synaptopodin， TNFSF15， and podocyte apoptosis-related proteins B lymphocytoma-2 （Bcl-2）-related X protein （Bax）， Bcl-2-associated death promoter （BAD） protein， and B-cell lymphoma-extra large （Bcl-XL） by immunohistochemistry （IHC）. Western blot was used to detect the expression levels of TNFSF15， Bax， BAD， Bcl-2， and BCL-XL in the rat kidney tissue. The apoptosis rate of rat kidney tissue was measured using the in situ end labeling method （Tunnel）. ResultCompared with the normal group， the level of miR-514a-5p in the kidney tissue was significantly reduced （P<0.05）， and the TNFSF15 mRNA expression was significantly increased （P<0.05）. The expression levels of podocyte marker proteins Nephrin， Podocin， Podocalyxin， and Synaptopodin were down-regulated （P<0.05）. The protein expression levels of TNFSF15， Bax， and BAD were increased （P<0.05）， whereas the Bcl-2 and Bcl-XL protein expression levels were decreased （P<0.05）. The number of apoptotic cells diminished significantly （P<0.05）. Compared with the model group， the level of miR-514a-5p in the kidney tissue was significantly increased （P<0.05）， while the level of TNFSF15 mRNA was significantly decreased （P<0.05）. The expression levels of podocyte marker proteins Nephrin， Podocin， podocalyxin， and Synaptopodin were up-regulated （P<0.05）， whereas the TNFSF15， Bax， and BAD protein expression levels were down-regulated （P<0.05）. Bcl-2 and Bcl-XL protein expression levels rose （P<0.05）. The number of apoptotic cells significantly decreased （P<0.05）. ConclusionYishen Tongluo prescription reduces the apoptosis of rat kidney podocytes and alleviates the kidney injury of MN rats through the miR-514a-5p/TNFSF15 signaling pathway.

Cryopreservation of rare testicular-retrieved spermatozoa for intracytoplasmic sperm injection (ICSI) in patients with severe oligozoospermia and azoospermia remains a major challenge in clinical practice. This study evaluated the Cryopiece system as a potential technique to cryopreserve rare human spermatozoa for ICSI. Small numbers of ejaculated (24 patients) and testicular (13 patients) spermatozoa were cryopreserved using the Cryopiece system. The total number of recovered spermatozoa and motility were assessed after thawing. Thirty-seven couples underwent ICSI using spermatozoa cryopreserved by the Cryopiece system, and ICSI outcomes (rates of fertilization, embryo cleavage, and clinical pregnancy) were evaluated. The average sperm post-thaw retrieval rate was 79.1%, and motility was 29.7%. Ejaculated spermatozoa had a higher post-thaw motility (32.5%) than testicular spermatozoa (21.8%; P = 0.005). ICSI achieved a fertilization rate of 61.9%, embryo cleavage rate of 84.6%, and clinical pregnancy rate of 43.3%. The ICSI outcomes in the ejaculated and testicular frozen-thawed spermatozoa were similar. Assisted oocyte activation (AOA) after ICSI with motile (72.1%) or immotile (71.9%) spermatozoa resulted in a significantly higher fertilization rate than that when using motile spermatozoa without AOA (52.0%; P = 0.005). However, AOA did not enhance the clinical pregnancy rate (55.6% or 40.0% vs 35.3%; P = 0.703). The Cryopiece system is simple and useful for the cryopreservation of small numbers of ejaculated or testicular spermatozoa for ICSI in patients with severe oligozoospermia or nonobstructive azoospermia.
Azoospermia ; Cryopreservation ; Female ; Humans ; Male ; Oligospermia ; Pregnancy ; Pregnancy Rate ; Retrospective Studies ; Semen ; Sperm Injections, Intracytoplasmic ; Sperm Motility ; Spermatozoa ; Testis