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.

Objective: To investigate the effects and molecular mechanisms of mechano-growth factor (MGF) on the proliferation and differentiation of periodontal ligament stem cells (PDLSCs). Methods: PDLSCs were obtained using magnetic bead sorting. Flow cytometry was performed to identify biomarkers. The clonogenicity and multidifferentiation potential of PDLSCs were identified by colony-forming unit, osteogenic and adipogenic differentiation assays. A CCK8 assay was used to detect the cell activity under different concentrations of mechano-growth factors (MGF-Ct24E). Western blot was used to detect the protein expression of proliferating cell nuclear antigen(PCNA), Scleraxis, collagen type I alpha 1 (COL1A1）, Osterix, Yes-associated protein (YAP) and phosphorylation Yes-associated protein (P-YAP）in PDLSCs. YAP protein expression was observed by immunofluorescence. Knockdown of YAP expression by a siRNA, detected the expression of PCNA, Scleraxis and COL1A1under MGF-Ct24E in PDLSCs. Results : PDLSCs showed high expression of stem cell markers (CD29, CD90 and CD105) and low expression of hematopoietic markers (CD34 and CD45). PDLSCs also have a strong ability to clone. Red calcium junctions were observed by Alizarin red staining, and red lipid droplets were observed by Oil red O staining. After treatment with 50 ng/mL and 100 ng/mL MGF-Ct24E for 24 h, the cell activity of periodontal ligament stem cells was significantly enhanced (P<0.05). The protein expression of PCNA, Scleraxis and COL1A1 was significantly upregulated, and the protein expression of Osterix was significantly downregulated (P<0.05). After treatment with 50 ng/mL mechano-growth factor for 24 h, the phosphorylation of YAP protein was significantly enhanced (P<0.05), and YAP protein was observed to accumulate in the nucleus by immunofluorescence. Following inhibition of YAP expression, PCNA and Scleraxis had significantly downregulated expression caused by MGF-Ct24E (P<0.05). Conclusion MGF promotes proliferation and fibrogenesis via upregulation of YAP activities.

As a biocatalyst, enzyme has the advantages of high catalytic efficiency, strong reaction selectivity, specific target products, mild reaction conditions, and environmental friendliness, and serves as an important tool for the synthesis of complex organic molecules. With the continuous development of gene sequencing technology, molecular biology, genetic manipulation, and other technologies, the diversity of enzymes increases steadily and the reactions that can be catalyzed are also gradually diversified. In the process of enzyme-catalyzed synthesis, the majority of common enzymatic reactions can be achieved by single enzyme catalysis, while many complex reactions often require the participation of two or more enzymes. Therefore, the combination of multiple enzymes together to construct the multi-enzyme cascade reactions has become a research hotspot in the field of biochemistry. Nowadays, the biosynthetic pathways of more natural products with complex structures have been clarified, and secondary metabolic enzymes with novel catalytic activities have been identified, discovered, and combined in enzymatic synthesis of natural/unnatural molecules with diverse structures. This study summarized a series of examples of multi-enzyme-catalyzed cascades and highlighted the application of cascade catalysis methods in the synthesis of carbohydrates, nucleosides, flavonoids, terpenes, alkaloids, and chiral molecules. Furthermore, the existing problems and solutions of multi-enzyme-catalyzed cascade method were discussed, and the future development direction was prospected.
Biological Products/chemistry* ; Catalysis ; Alkaloids ; Biocatalysis

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 investigate the spatial distribution characteristics and correlation between the prevalence of dental fluorosis and the chemical elemental composition of drinking water sources in coal-fired fluorosis areas. Methods: Based on the survey data on the prevalence of dental fluorosis at CDC in Guizhou Province in 2022, 274 original surface drinking water sources were collected in typical coal-fired fluorosis areas, and fluoride (F), calcium (Ca), magnesium (Mg), aluminum (Al), titanium (Ti), chromium (Cr), manganese (Mn), iron (Fe), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), molybdenum (Mo), cadmium (Cd), barium (Ba), lead (Pb) 17 elements; apply Moran's I index, Getis-Ord Gi* hotspot analysis of the global spatial autocorrelation of chemical elements in drinking water and the degree of aggregation of each element on the local area, and correlation analysis with the prevalence of dental fluorosis in the region. Results: Except for Cu, Zn, and Cd, global spatial autocorrelation Moran's I was negative, and all other elements were positive. F, Ca, Al, Ti, As, Mo, Cd, and Cu elements showed high values of aggregation in the southeastern low-altitude area; Mg, Ba, Pb, Cr, Mn, and Fe elements were mainly aggregated in the central altitude terrain transition area, Zn and Se elements in water sources are significantly positively correlated with the prevalence of dental fluorosis (P<0.05). In contrast, F, Mg, Al, Ti, As, Mo, Cd, Ba, and Pb elements negatively correlate (P<0.05). Elements in the central region were high-high aggregation, as a hot spot aggregation area with high disease incidence, while F, Al, Mn, Mo, Cd, and Ba elements in the western region were low-low aggregation, as a cold spot aggregation area with a low incidence of fluorosis. Conclusions: The risk of population fluoride exposure in surface drinking water sources is shallow. However, the chemical element content of drinking water sources in coal-fired polluted endemic fluorosis areas has prominent spatial geographical distribution characteristics. There is a significant spatial aggregation effect with the prevalence of dental fluorosis, which may play a synergistic or antagonistic effect on the occurrence and prevalence of dental fluorosis.
Humans ; Drinking Water ; Prevalence ; Coal ; Fluorides/adverse effects* ; Cadmium ; Fluorosis, Dental/epidemiology* ; Lead ; Selenium ; Arsenic

Objective: To investigate whether the cyclic adenosine monophosphate (cAMP) / exchange proteins directly activated by cAMP (Epac) / ras-related protein 1 ( Rap1 ) signalling pathway is involved in the intervening mechanisms of interleukin-1 β (IL-1 β) ，tumor necrosis factor-α (TNF-α) ，brain-derived neurotrophic factor (BDNF) and Jujuboside A(JuA) secretion by NG2 cells． Methods: NG2 cells were cultured in vitro and the experiment was divided into control group ，pertussis toxin ( PTX) group ，ESI-09 group，JuA group and positive drug group．The effect of different concentrations of JuA on the survival rate of NG2 cells was detected by CCK-8 method，and the expression of IL-1 β , TNF-α , BDNF，cAMP，Epac，Rap1 mRNA and protein in each group was detected by RT-PCR and Western blot. Results: Compared with the control group，the PTX group decreased the expression of IL-1 β and TNF-α mRNA and protein (P＜0. 01) and increased the expression of cAMP and BDNF mRNA and protein (P＜0. 01) ; the ESI-09 group increased the expression of IL-1 β and TNF-α mRNA and protein (P < 0. 05) and decreased the expression of BDNF，Epac and Rap1 mRNA and protein expression (P＜0. 01) ; the JuA group and positive drug group increased IL-1 β , TNF-α , BDNF，cAMP，Epac，Rap1 mRNA and protein expression (P＜0. 01) ． Conclusion The cAMP / Epac / Rap1 signaling pathway is involved in the secretion of IL-1 β , TNF- α , and BDNF by NG2 cells．JuA may act on cAMP / Epac / Rap1 signaling pathway to affect the secretion of BDNF by NG2 cells.

ObjectiveTo investigate the effect of Draconis Sanguis petroleum ether fraction （DSPEF） on the proliferation， apoptosis， migration， and autophagy of human gastric cancer HGC-27 and MGC-803 cells， and preliminarily elucidate its molecular mechanism. MethodCell counting kit-8 （CCK-8） assay was used to detect the effect of DSPEF at different concentrations （0， 20， 40， 60， 80 mg·L^-1） on the proliferation of HGC-27 and MGC-803 cells after 24， 48， 72 h. Hoechst staining and flow cytometry were used to explore the effects of DSPEF at different concentrations on the apoptosis and apoptosis rate of HGC-27 and MGC-803 cells after 48 h treatment， respectively. The wound healing assay and acridine orange staining were used to investigate the effects of DSPEF on the migration and autophagy of HGC-27 and MGC-803 cells， respectively. Western blot was used to detect the expression levels of signaling pathway-related proteins in HGC-27 and MGC-803 cells treated with DSPEF for 48 h. ResultCompared with the control group， DSPEF（30 mg·L^-1） inhibited the proliferation and migration of HGC-27 and MGC-803 cells in a concentration- and time-dependent manner （P<0.05）， and induced the apoptosis （P<0.01） and autophagy of HGC-27 and MGC-803 cells. DSPEF （60 mg·L^-1） down-regulated the protein levels of phosphorylated mammalian target of rapamycin （p-mTOR） （P<0.05， P<0.01） and down-regulated phospho-signal transducer and activator of transcription 3 （p-STAT3） in HGC-27 and MGC-803 cells （P<0.01）， suggesting that DSPEF presumedly inhibited the proliferation and migration of human gastric cancer HGC-27 and MGC-803 cells and induced their apoptosis and autophagy by inhibiting the mTOR/STAT3 signaling pathway. ConclusionThe down-regulation of the mTOR/STAT3 signaling pathway may be involved in the anti-gastric cancer effect of DSPEF. This study is expected to provide a reference for the investigation of the anti-tumor effect of Draconis Sanguis.

Malignant tumor is a serious threat to human life and health. The prevalence and mortality of malignancies in China are increasing year by year. Conquering cancer has become a difficult problem for human beings. Chemical drug therapy combined with molecular targeted therapy is a general and preferred anti-tumor clinical scheme， but the side effects and the drug resistance of cancer cells often hinder the efficacy. Therefore， it is of great significance to study the mechanism of drug resistance and the methods to reverse drug resistance. Chinese medicine has the characteristics of complex components， multiple targets， low toxicity， etc. A large number of experimental studies have demonstrated that the effective components or extracts of Chinese medicine can inhibit the proliferation， migration， and invasion of cancer cells， and induce apoptosis， autophagy， differentiation， and senescence. In clinical practice， Chinese medicine has been applied to the protection against ttumor， adjuvant treatment， and later consolidation. The research on Chinese medicine is expected to promote drug resistance reversal and cancer therapy. Studies have shown that the combination of Chinese medicine and chemotherapy can reverse drug resistance and increase efficacy， which has become the mainstream trend of cancer treatment. This study reviewed the mechanisms of the drug resistance of cancer cells induced by self-protective autophagy， gene mutation， high expression of enzymes， abnormal signaling pathways， and abnormal expression of RNA and protein， and summarized how compounds isolated from Chinese medicine， single drug and its extract， and classic anti-cancer prescription reversed the drug resistance to lay a solid foundation for the further investigation of the anti-tumor effect of Chinese medicine.

Objective: To explore the predictive value of the impedance measured during leadless pacemaker Micra implantation on the trend of changes of pacing threshold post implantation. Methods: This is a retrospective cross-sectional study. Patients who received implantation of leadless pacemaker Micra at the Second Xiangya Hospital of Central South University from December 2019 to August 2020 were enrolled. The clinical data and the intraoperative electrical parameters during leadless pacemaker implantation were collected. The impedance and pacing threshold data were analyzed at three time points: immediate release, 5-10 min after release, and after traction test. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to analyze the value of the impedance at immediate release on predicting the trend of changes of pacing threshold post implantation. Results: A total of 21 patients (mean age: (72.2±12.5) years, 12 males) were included. The impedance of 21 patients was (798.1±35.3) Ω immediately after implantation, (800.9±35.6) Ω after 5-10 minutes of release, and (883.6±31.7) Ω after traction test. Impedance was similar between the three time points (P>0.05). The threshold was (0.97±0.11) V/0.24 ms immediately after implantation, (0.95±0.12) V/0.24 ms at 5-10 min after the release, and (0.59±0.06) V/0.24 ms after the traction test. The threshold was significantly lower after the traction test than that immediately after release (P=0.003) and than that at 5-10 minutes after release (P=0.008), suggesting a decreased tendency of the threshold over time. According to the analysis of the ROC curve, the immediate impedance after the release ≥680 Ω could predict the ideal pacing threshold after the traction test (AUC=0.989, 95%CI 0.702-0.964, P<0.001), the prediction sensitivity was 87%, and the specificity was 100%. The pacing threshold would be not ideal with the immediate impedance ≤ 520 Ω (95%CI 0.893-1.000, P<0.001), the sensitivity was 100%, and the specificity was 80%. Conclusions: The impedance immediately after the release has predictive value for the changing trend of threshold post leadless pacemaker Micra implantation. Impedance ≥680 Ω immediately after release is often related with ideal pacing threshold after the traction test. In contrast, the impedance ≤ 520 Ω pacing is often related with unsatisfactory threshold after the traction test, therefore, it is recommended to find a new pacing site to achieve the impedance ≥680 Ω immediately after release during leadless pacemaker Micra implantation.
Aged ; Aged, 80 and over ; Cardiac Pacing, Artificial ; Cross-Sectional Studies ; Electric Impedance ; Humans ; Male ; Middle Aged ; Pacemaker, Artificial ; Retrospective Studies ; Treatment Outcome

In light of related methods in Chinese Pharmacopoeia(2020 edition), this study established the quality standard for Lobeliae Chinensis Herba. The TLC identification method was established with silica gel GF_(254) thin layer plate, diosmin standard, linarin standard, and the reference material of Lobeliae Chinensis Herba. The loss on drying, total ash, acid-insoluble ash, and ethanol-soluble extracts of 18 batches of Lobeliae Chinensis Herba samples were determined according to the general principles in Chinese Pharmacopoeia. Then, HPLC was adopted in the establishment of characteristic chromatogram and content determination. The results showed that the established method can achieve good separation for diosmin, linarin, and lobetyolin. Based on the results of detection for 18 batches of Lobeliae Chinensis Herba samples, the draft quality standard was established, which was expected to provide reference for the revision of this medicinal herb in Chinese Pharmacopoeia.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/standards* ; Lobelia/chemistry* ; Plants, Medicinal/chemistry*