Ligustrazine, one of the major effective components of the Chinese traditional medicinal herb Ligusticum Chuanxiong Hort, has been reported plenty of biological activities, such as protect cardiovascular and cerebrovascular, neuroprotection and anti-tumor, et al. Because of its remarkable effects, studies on structural modification of ligustrazine have attracted much attention. Ligustrazine synthetic derivatives reported in recent decades are mainly derived from four primary intermediates (TMP-COOH, TMP-OH, TMP-NH2, HO-TMP-OH). To explore the neuroprotection activitiy of ligustrazine intermediates, six ligustrazine intermediates (2, 5, 8, 11, 12, 13) were synthesized and their protective effects against CoCl2-induced neurotoxicity in differentiated PC12 cells were studied. The target compounds were prepared via different chemical methods, including oxidation, substitution, esterification and amidation without changing the structure nucleus of ligustrazine. Compared with TMP (EC50 = 56.03 micromol x L(-1)), four compounds (2, 5, 12 and 13) exhibited higher activity (EC50 < 50 micromol x L(-1)) respectively, of which, compound 2 displayed the highest protective effect against the damaged PC12 cells (EC50 = 32.86 micromol x L(-1)), but target compounds 8 and 11 appeared lower activity (EC50 > 70 micromol x L(-1)). By structure-activity relationships analysis, the introduction of carboxyl, amino to the side chain of ligustrazine and appropriately increase the proportion of ligustrazine may contribute to enhance its neuroprotective activity, which provides a reference for the design, synthesis and activity screening of relevant series of ligustrazine derivatives in the future.
Animals ; Cell Differentiation ; drug effects ; Chemistry Techniques, Synthetic ; Cobalt ; toxicity ; Drugs, Chinese Herbal ; chemistry ; Neuroprotective Agents ; chemical synthesis ; chemistry ; pharmacology ; Neurotoxins ; toxicity ; PC12 Cells ; Pyrazines ; chemical synthesis ; chemistry ; pharmacology ; Rats

Objective The study aims to investigate the prevalence of gestational diabetes mellitus (GDM) among pregnant women in Tongzhou district of Beijing and its related risk factors. Methods Information of 34 637 singleton pregnancies delivered in a maternal and child health care hospital in Tongzhou district of Beijing were collected from January 1, 2013 to December 31, 2017. GDM prevalence of pregnant women were calculated. Multivariable logistic regression analysis was used to analyze the association between GDM and its related factors. Results The prevalence of GDM in 34 637 singleton pregnant women in Tongzhou district of Beijing was 23.2% (8 034/34 637). Multivariate analysis showed that advanced maternal age(aOR=1.87, 95% CI: 1.71-2.05), high level of education(aOR=1.19-1.23), delivering during 2016-2017(aOR=1.46, 95% CI: 1.38-1.55), macrosomia(aOR=1.27, 95% CI: 1.02-1.59), history of cesarean section(aOR=1.18, 95% CI: 1.08-1.30), history of spontaneous abortion(aOR=1.23, 95% CI:1.10-1.37), history of induced abortion(aOR=1.08, 95% CI:1.01-1.14), family history of diabetes(aOR=1.51, 95% CI:1.26-1.83), multipara(aOR=1.24, 95% CI:1.15-1.34), pre-pregnancy overweight(aOR=2.02, 95% CI:1.89-2.15), pre-pregnancy obesity(aOR=3.11, 95% CI:2.81-3.43)and conceived by assisted reproductive technology(aOR=1.47, 95% CI:1.03-2.10)were the independent risk factors for GDM. Conclusions Prevalence of GDM is high in pregnant women in Tongzhou district of Beijing. Health education before and during pregnancy should be carried out to monitor and prevent the occurrence of GDM in time to ensure maternal and child health.

AIM: To investigate whether Toll-like receptor 4 ( TLR4 ) and Nod-like receptor protein 3 (NLRP3) inflammasome were involved in contrast medium (CM)-induced inflammation and injury in renal tubular epithe-lial cells.METHODS: Iopromide was used to injure NRK-52E cells in the study.The cell viability was measured by CCK-8 assay.The protein levels of TLR4, NLRP3, apoptosis-associated speckle-like protein (ASC), caspase-1 and cleaved caspase-3 were determined by Western blot .The releases of interleukin ( IL )-1βand IL-18 were detected by ELISA .The apoptotic rate was evaluated by Hoechst staining , and mitochondrial membrane potential ( MMP) was analyzed by JC-1 staining.siRNA was transfected into the NRK-52E cells to silence NLRP3 expression.RESULTS:CM decreased the viability of NRK-52E cells (P<0.05).CM also elevated the protein levels of cleaved caspase-3, TLR4, NLRP3, IL-1βand IL-18 (P<0.05).Silencing NLRP3 attenuated CM-induced releases of inflammatory cytokines .Moreover, treat-ment with TLR4 inhibitor TAK-242 or knockdown of NLRP3 by siRNA transfection both attenuated cell apoptosis and loss of MMP caused by CM .CONCLUSION:TLR4/NLRP3 inflammasome takes part in the pathogenesis of CM-induced acute kidney injury , and mediates CM-induced injury and inflammation in renal tubular epithelial cells .

Neural stem cells (NSCs) posse the specialty of tumor tropism and be able to migrate specifically to tumor cells. NSCs are also cross the blood brain barrier. NSCs keep in touch with tumor cells preferentially under the tumor microenvironment, and surround the target cells. Based on these characteristics, NSCs can be used as a carrier for therapeutic virus, enzymes/prodrugs, genes or suicide genes, etc. which are selectively delivered to the glioma cells. NSCs may be modified by a variety of different genes to establish a reliable, safe and effective therapy for glioma.

OBJECTIVES: To study the difference in cognitive impairment between the children with benign childhood epilepsy with centrotemporal spikes (BECT) and attention deficit hyperactivity disorder (ADHD) and those with BECT or ADHD alone. METHODS: A prospective study was performed on 80 children with BECT and ADHD, 91 children with BECT, and 70 children with ADHD , who were diagnosed with the diseases for the first time. Seventy children of the same age who underwent physical examination were enrolled as the healthy control group. Event-related potential P300, Wechsler Intelligence Scale for Children, and integrated visual and auditory continuous performance test were used to measure and compare each index between groups. RESULTS: Compared with the healthy control group, the BECT+ADHD group, the BECT group, and the ADHD group had a significantly prolonged P300 latency, a significant reduction in the amplitude of P300, and significant reductions in the scores of verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), processing speed index (PSI), full scale intelligence quotient (FSIQ), auditory response control quotient (ARCQ), visual response control quotient, full response control quotient (FRCQ), auditory attention quotient (AAQ), visual attention quotient, and full attention quotient ( CONCLUSIONS Compared with the children with BECT or ADHD alone, the children with both BECT and ADHD have basically the same fields of cognitive impairment but a higher degree of cognitive impairment in some fields.
Attention Deficit Disorder with Hyperactivity ; Child ; Cognitive Dysfunction/etiology* ; Epilepsy ; Humans ; Prospective Studies ; Wechsler Scales

ObjectiveTo investigate the diagnosis and treatment of familial hypokalemic periodic paralysis with acidosis. MethodsThe proband's medical history， clinical manifestations， laboratory examinations and imaging characteristics were retrospectively analyzed， and prevalence situation of family members was investigated in detail. Next generation sequencing technology was used to detect the pathogenic gene loci related to periodic paralysis， and the relevant literatures were summarized. ResultsThe proband was definitely diagnosed as familial hypokalemic periodic paralysis. There was a heterozygous mutation in the SCN4A gene of the proband， which was c.2006G>A， resulting in amino acid changes R669H.The proband's grandfather， father and uncle shared the same variation. ConclusionsFamilial hypokalemic periodic paralysis with paroxysmal acidosis is rare， which is easily misdiagnosed as renal tubular acidosis. c 2006G>A mutation in SCN4A gene is the molecular basis of the disease in this family. The clinical phenotypes of different gene mutations are different， and gene screening is helpful for diagnosis and treatment.

Objective: To investigate the efficacy and safety of infliximab (IFX) therapy for children with Kawasaki disease. Methods: Sixty-eight children with Kawasaki disease who received IFX therapy in Children's Hospital of Fudan University from January 2014 to April 2021 were enrolled. The indications for IFX administration, changes in laboratory parameters before and after IFX administration, response rate, drug adverse events and complications and outcomes of coronary artery aneurysms (CAA) were retrospectively analyzed. Comparisons between groups were performed with unpaired Student t test or Mann-Whitney U test or chi-square test. Results: Among 68 children with Kawasaki disease, 52 (76%) were males and 16 (24%) were females. The age of onset was 2.1 (0.5, 3.8) years. IFX was administered to: (1) 35 children (51%) with persistent fever who did not respond to intravenous immunoglobulin (IVIG) or steroids, 28 of the 35 children (80%) developed CAA before IFX therapy; (2) 32 children (47%) with continuous progression of CAA; (3) 1 child with persistent arthritis. In all cases, IFX was administered as an additional treatment (the time from the onset of illness to IFX therapy was 21 (15, 30) days) which consisted of second line therapy in 20 (29%), third line therapy in 20 (29%), and fourth (or more) line therapy in 28 (41%). C-reactive protein (8 (4, 15) vs. 16 (8, 43) mg/L, Z=-3.38, P=0.001), serum amyloid protein A (17 (10, 42) vs. 88 (11, 327) mg/L, Z=-2.36, P=0.018) and the percentage of neutrophils (0.39±0.20 vs. 0.49±0.21, t=2.63, P=0.010) decreased significantly after IFX administration. Fourteen children (21%) did not respond to IFX and received additional therapies mainly including steroids and cyclophosphamide. There was no significant difference in gender, age at IFX administration, time from the onset of illness to IFX administration, the maximum coronary Z value before IFX administration, and the incidence of systemic aneurysms between IFX-sensitive group and IFX-resistant group (all P>0.05). Infections occurred in 11 cases (16%) after IFX administration, including respiratory tract, digestive tract, urinary tract, skin and oral infections. One case had Calmette-Guérin bacillus-related adverse reactions 2 months after IFX administration. All of these adverse events were cured successfully. One child died of CAA rupture, 6 children were lost to follow up, the remaining 61 children were followed up for 6 (4, 15) months. No CAA occurred in 7 children before and after IFX treatment, while CAA occurred in 54 children before IFX treatment. CAA regressed in 23 (43%) children at the last follow-up, and the diameter of coronary artery recovered to normal in 10 children. Conclusion: IFX is an effective and safe therapeutic choice for children with Kawasaki disease who are refractory to IVIG or steroids therapy or with continuous progression of CAA.
Child ; Coronary Aneurysm/etiology* ; Female ; Humans ; Immunoglobulins, Intravenous/therapeutic use* ; Infant ; Infliximab/adverse effects* ; Male ; Mucocutaneous Lymph Node Syndrome/drug therapy* ; Retrospective Studies

Objective: To investigate the inhibitory effect on Burkholderia pseudomallei (B. pseudomallei) strain HNBP001 of a bacillomycin D-like cyclic lipopeptide compound named bacillomycin DC isolated from Bacillus amyloliquefaciens HAB-2. Methods: The antibacterial effect of bacillomycin DC on B. pseudomallei was determined using the disk diffusion method. The minimum inhibitory concentrations were evaluated by microdilution assay. In addition, transmission electron microscopy was performed and quantitative real-time polymerase chain reaction assay was carried out to determine the expression of MexB, OprD2, and qnrS genes. Results: Bacillomycin DC produced an inhibition zone against B. pseudomallei with minimum inhibitory concentration values of 12.5 μg/mL 24 h after treatment and 50 μg/mL at 48 and 72 h. Transmission electron microscopy showed that bacillomycin DC resulted in roughening cell surface and cell membrane damage. Quantitative real-time polymerase chain reaction analysis showed low expression of MexB, OprD2 and qnrS genes. Conclusions: Bacillomycin DC inhibits the growth of B. pseudomallei and can be a new candidate for antimicrobial agents of B. pseudomallei. Rajaofera Mamy 1 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Kang Xun 2 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Jin Peng-Fei 3 Key Laboratory of Green Prevention and Control of Tropical Plant Diseases and Pests (Hainan University), Ministry of Education, Haikou 570228, Hainan Chen Xin 4 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Li Chen-Chu 5 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Yin Li 6 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Liu Lin 7 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Sun Qing-Hui 8 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Zhang Nan 9 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Chen Chui-Zhe 10 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan He Na 11 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Xia Qian-Feng 12 Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan Miao Wei-Guo 13 Key Laboratory of Green Prevention and Control of Tropical Plant Diseases and Pests (Hainan University), Ministry of Education, Haikou 570228, Hainan Kung CT, Lee CH, Li CJ, Lu HI, Ko SF, Liu JW. 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ObjectiveTo systematically and objectively characterize the pharmacological effects of Fufang Biejia Ruangan pills （FBRP） in the intervention of alcoholic liver disease （ALD） using acute and chronic ALD mouse models and to elucidate its molecular mechanisms. MethodFifty SPF-grade male BALB/c mice were randomly divided into the normal group， model group， and FBRP low-， medium-， and high-dose groups （9.6， 19.2， 38.4 mg·kg^-1）. Except for the normal group， the remaining groups were given 56° white wine by gavage to establish the acute ALD model， with samples collected after 4 weeks. Thirty SPF-grade male C57BL/6N mice were randomly divided into the normal group， model group， and FBRP medium-dose group （19.2 mg·kg^-1）. The chronic ALD mouse model was established using the Lieber-DeCarli method over a 10-week period. Inflammatory markers in liver tissues were assessed using hematoxylin-eosin （HE）， Sirius Red， oil red O staining， and enzyme-linked immunosorbent assay （ELISA）. Intoxication behaviors of each group were objectively evaluated through sobering-up time， net-catching， and pole-climbing tests. Further bioinformatics analyses based on clinical transcriptomic data were conducted to identify key targets and molecular mechanisms of FBRP in alleviating ALD through liver-brain dialogue， with experimental validation by ELISA， Western blot， and immunohistochemical staining. ResultCompared with the normal group, the levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT） in liver tissues of mice in the acute and chronic ALD model groups were significantly increased （P<0.05）. Compared with the model group， the levels of AST and ALT in liver tissue of mice in FBRP groups were significantly decreased （P<0.05）. Compared with the normal group， the time of grasping the net and climbing the pole in the acute ALD model group was significantly decreased within 4 weeks （P<0.01）. Compared with the model group， the grasping and climbing time of FBRP high dose groups increased significantly within 4 weeks （P<0.05）. Compared with the normal group， the expression of high mobility group protein B1 （HMGB1） protein in liver tissue and prefrontal lobe tissue of mice in the chronic ALD model group was significantly increased （P<0.01）. Compared with the model group， the expression of HMGB1 protein in FBRP medium dose group was significantly decreased （P<0.05，P<0.01）. Compared with the normal group， the expression of brain-derived neurotrophic factor （BDNF） protein and the release of γ-aminobutyric acid （GABA） in the prefrontal cortex of the model group were significantly decreased （P<0.01）. Compared with the model group, the expression of BDNF protein and the release of GABA in the FBRP medium dose group were significantly increased （P<0.05）. ConclusionThis study revealed that FBRP improved key pathological changes in ALD by modulating liver-brain dialogue mediated by the HMGB1-BDNF axis. These findings provide experimental evidence for the clinical use of FBRP in treating ALD and offer new insights for the development of ALD therapeutic agents.

OBJECTIVEThe aim of this study was to determine the repeatability and reproducibility of optical coherence tomography angiography (OCTA) based on optical microangiography (OMAG) measurements of macular vessels in normal eyes.

METHODSIn this prospective cohort study, 40 eyes of 40 healthy volunteers underwent repeated OCTA (Cirrus HD-OCT 5000 angiography system, Carl Zeiss Meditec, Inc.) scans on two separate visit days. On each visit day, the eyes were scanned three times. The following parameters were used to quantitatively describe the OCTA images of the superficial vascular network: vessel area density (VAD), vessel skeleton density (VSD), vessel diameter index (VDI), vessel perimeter index (VPI), vessel complexity index (VCI), flux, and foveal avascular zone (FAZ). Coefficient of variation (CV) and intraclass correlation coefficient (ICC) were calculated for evaluating intravisit and intervisit repeatability, as well as interobserver reproducibility.

RESULTSThe measurements showed high repeatability [CVs ⪕ 4.2% (intravisit) and ⪕ 4.6% (intervisit)] and interobserver reproducibility (ICCs ⪖ 0.923) for all parameters.

CONCLUSIONThis study demonstrated good repeatability and reproducibility of OCTA based on OMAG for the measurement of superficial vessel parameters in normal eyes.

Adult ; Cohort Studies ; Evaluation Studies as Topic ; Female ; Fluorescein Angiography ; standards ; Healthy Volunteers ; Humans ; Image Processing, Computer-Assisted ; Male ; Microvessels ; diagnostic imaging ; Middle Aged ; Prospective Studies ; Reproducibility of Results ; Retina ; diagnostic imaging ; Retinal Vessels ; diagnostic imaging ; Tomography, Optical Coherence ; standards ; Young Adult