Aim To investigate whether alisol A (AA) could improve the blood brain barrier (BBB) mediated cortex cerebral ischemia-repeifusion injury (CIRI) by inhibiting matrix metalloproteinase 9 (MMP-9). Methods The global cerebral ischemia- reperfusion (GCI/R) model in mice was established, and the AA was intragastric injected subsequently for seven days. The modified neurological severity scores (mNSS), open field test and Y-maze test were applied to detect neurological function. Magnetic resonance spectroscopy (MRS) was used to detect relevant neu- rosubstance metabolism in cortex of mice. Transmission electron microscope (TEM) was employed to observe the ultrastructure of BBB in cortex. Western blot and immunohistochemistry were used to detect the MMP-9 level in cortex. The binding possibility of A A and MMP-9 was determined by molecular docking. Results Compared with Sham group, mice in GCI/R group have an increased mNSS score but decreased at total distance and center distance to total distance ratio in open field test as well as alternation rate in Y-maze test (P<0.01). While mice in GCI/R + AA group have a decreased mNSS score but increased at total distance and center distance to total distance ratio in open field test as well as alternation rate in Y-maze test (P<0.01) compared with GCI/R group. MRS results found that in cortex of GCI/R group mice, the level of GABA and NAA significantly decreased while the Cho, mI and Tau level increased (P<0.01). Whereas in GCI/R + AA group mice, the GABA and NAA level increased and the Cho, ml and Tau decreased significantly (P<0.01). By TEM we observed that the basilemma of cerebral microvessels collapsed, the lumen narrowed, the endothelial cells were active and plasma membranes ruffled, gaps between cells were enlarged and tight junctions were damaged and the end feet of astrocytes were swollen in GCI/R group mice. While in GCI/R + AA group mice, the lumen was filled, plasma membranes of endothelial cells were smooth, tight junctions were complete and end feet of astrocytes were in normal condition. Western blot and immunohistochemistry both found that the MMP-9 level increased in GCI/R group mice (P < 0.01) and decreased in GCI/R + AA group mice (P < 0.05). Molecular docking proved the binding between aliso A and MMP9 through TYR-50 and ARG-106, and the binding energy was calculated as -6.24 kcal · mol

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86. Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer. Results In total,143 patients were enrolled(NH group,n = 49;NA group,n = 47;P group,n = 47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001. Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

ObjectiveTo explore the possible mechanism of Changweiqing （肠胃清） in the treatment of colorectal cancer. MethodsHCT 116 cancer cells were used to prepare intestinal cancer cells with silenced polypyrimidine region binding protein 3 （PTBP3） gene and stably transfected cells with overexpressed PTBP3 gene. Stably transfected cells with silenced PTBP3， stably transfected cells with overexpressed PTBP3 and untransfected cancer cells were injected into the armpit of 72 nude mice to construct three different subcutaneous transplanted tumor models of colorectal cancer cells， including the silenced model， the overexpressed model and the control model， with 24 mice per model. Mice of each transplanted tumor modelwere randomly divided into Changweiqing （CWQ） group， oxaliplatin （OXA） group and normal saline （NS） group， with 8 mice in each group. The CWQ groups were given intragastric administration of 35.9625 g/kg of Changweiqing oral liquid and were intraperitoneally injected with 0.2ml of normal saline； the NS groups were given 0.5ml of normal saline by gavage， and intraperitoneal injection of 0.2ml of normal saline； the OXA groups were intraperitoneally injected with 5 mg/kg （0.2 ml） of oxaliplatin and given 0.5ml of normal saline by gavage. Each group was given intragastric administration once a day and intraperitoneal injection three times a week. After 31 days， the weight of subcutaneous tumors in each group was measured， and the tumor inhibition rate of the groups in each model were measured. Immunohistochemistry and other methods were used to detect the expression level of cell proliferation cell nuclear antigen Ki67 and apoptosis index. Real-time PCR and Western Blot were used to detect mRNA and protein expressions of PTBP3， signal transducer and activator of transcription 3 （STAT3） splicing isoform α （STAT3α）， STAT3 splicing isoform β （STAT3β）， B-cell lymphoma/leukemia-2 （Bcl-2） splicing isoform α （Bcl-2α）， and Bcl-2 splicing isoform β （Bcl-2β） in subcutaneous tumor cells in each group. ResultsFor all three transplanted tumor models， the weight of the subcutaneous tumors and Ki67 expression level of subcutaneous tumor tissue in all CWQ groups and OXA groups were lower than those of the corresponding NS groups， while the apoptosis level were higher （P＜0.05 or P＜0.01）. The mRNA and protein expressions of PTBP3， STAT3α， and Bcl-2α in the subcutaneous tumor tissues of the silenced model CWQ group and the overexpressed model CWQ group were lower than those of the corresponding NS groups， while the mRNA and protein expression levels of STAT3β and Bcl-2β were higher （P＜0.05 or P＜0.01）. All there groups of silenced model had lower subcutaneous tumor weight， Ki67 expression level， and mRNA and protein expression levels of PTBP3， STAT3α， and Bcl-2α in subcutaneous tumor tissue， as well as higher apoptosis level and mRNA and protein expression levels of STAT3β and Bcl-2β than those in all groups of control model； all groups of overexpressed model had higher subcutaneous tumor weight， Ki67 expression level， and mRNA and protein expression levels of PTBP3， STAT3α， and Bcl-2α ， while lower apoptosis level and mRNA and protein expression levels of STAT3β and Bcl-2β than those in all control model groups （P＜0.05 or P＜0.01）. In the control model， compared with the NS group， The tumor inhibition rate of all OXA groups was higher than that of corresponding CWQ groups， respectively. Compared to that of each control model group， the tumor inhibition rate was positive value of each silenced model group， and negative value of each overexpressed model group. ConclusionPTBP3 can promote the proliferation and inhibit apoptosis of intestinal cancer cells， upregulate the expression of STAT3α and Bcl-2α， and downregulate the expression of STAT3β and Bcl-2β in intestinal cancer cells. The meachnism of action of Changweiqing in the treatment of colorectal cancer maybe related to the inhibition of PTBP3， and regulation of the expression of STAT3α， STAT3β， Bcl-2α， and Bcl-2β.

Objective:To explore the application of metagenomic next-generation sequencing (mNGS) in critically ill children with hematological disorders and evaluate its diagnostic value.Methods:A retrospective analysis was conducted on the clinical data of children with hematological diseases, tumors, and hematopoietic stem cell transplantation who underwent traditional culture and mNGS testing in the pediatric intensive care unit of the Xiangya Hospital, Central South University from September 2019 to June 2022. The detection rate and diagnostic value of traditional culture and mNGS for pathogens were analyzed and compared.Results:Among the 50 patients, there were 29 males and 21 females, with a median age of 9.00(4.75-13.00) years. A total of 60 samples were sent for mNGS testing, including 40 blood samples, 10 bronchoalveolar lavage fluid samples, 7 cerebrospinal fluid samples, and 1 bone marrow, 1 skin, and 1 pleural fluid sample each. 49 positive samples were detected by mNGS, including 20 cases of viruses, 14 cases of bacteria, 8 cases of mixed samples, and 7 cases of fungi. The detection rate of mNGS in this study was significantly higher than that in traditional pathogen culture (81.7% vs 16.7%), and the difference was statistically significant ( P<0.01). Based on clinical diagnostic cases, the sensitivity of mNGS was significantly higher than that of traditional culture (85.2% vs 29.6%), with a statistically significant difference ( P<0.01), while its specificity was not statistically significant ( P>0.05) compared to traditional culture (50.0% vs 83.3%). Conclusions:mNGS has a higher detection rate and sensitivity than traditional pathogen culture, and can early identify viral, fungal, and mixed infections, providing strong assistance for precise treatment of critically ill children with hematological conditions.

Objective To investigate the regulatory effect of swimming exercise(SE)on lipid metabolism in nonalcoholic fatty liver disease(NAFLD)mice.Methods A total of 27 C57BL/6J mice were divided into the control group(normal diet),high fat diet(HFD)group and HFD+SE group,with 9 mice in each group.Twelve weeks later,liver tissues were collected for untargeted lipidomics detection by LC-MS.Dimensional statistical analysis of lipidomics profiles was carried out by constructing OPLS-DA model,and combined with the t-test,the lipids with OPLS-DA VIP>1,P<0.05 were screened out from all samples as significantly different lipids.Results There were 81 different lipids between HFD group and the control group;and there were 27 different lipids between HFD+SE group and HFD group.The different lipids mainly belong to glycerides,glycerophospholipids and sphingomyelins.Conclusion Lipid metabolism profile of NAFLD mice has been changed,and swimming exercise can improve lipid metabolism of NAFLD mice.

Objective To explore the clinical characteristics of pediatric patients with cerebral palsy(CP)who also have comorbid epilepsy.Methods A retrospective analysis was conducted on the clinical data of 155 pediatric patients with CP and comorbid epilepsy admitted to the Third Affiliated Hospital of Zhengzhou University from January 2019 to December 2022.Patients were divided into 4 groups based on CP subtype:spastic diplegia group(n=29),spastic hemiplegia group(n=33),spastic quadriplegia group(n=73),and non-spastic group(n=20).Differences in sex,season of birth,birth weight,gestational age,and the relationship between gestational age and weight were compared among the groups.Additionally,the relationships between perinatal risk factors,MRI classification system(MRICS),gross motor function classification system(GMFCS),and the age of the first onset of epilepsy with respect to CP subtype were analyzed.Results Among the 155 patients,101 were male and 54 were female.A lower proportion of patients with spastic hemiplegia was observed with a gestational age of 28-31+6 weeks compared with those with spastic diplegia and spastic quadriplegia(P=0.009).The proportion of patients with a history of asphyxia in spastic hemiplegia group was significantly lower than that in the other 3 groups,and the proportion of patients with hypoxic-ischemic encephalopathy(HIE)in spastic hemiplegia group was significantly lower than in that both spastic quadriplegia group and non-spastic group(P<0.05).The proportion of patients in spastic quadriplegia group who had their first seizure at an age of<1 year was significantly higher than that in spastic diplegic group(P=0.041).The spastic diplegia group exhibited a higher percentage of white matter damage compared with the other 3 groups,and had a lower percentage of gray matter damage compared with both spastic hemiplegic group and non-spastic group(P=0.001).The proportion of patients with GMFCS levels Ⅳ-Ⅴ in spastic quadriplegia group was higher than those in the other 3 groups(P<0.001),and the proportion of patients with levels Ⅰ-Ⅲ in spastic hemiplegia group was significantly higher than those in spastic quadriplegia group and non-spastic group(P<0.001).Conclusion Significant differences were observed among pediatric patients with different subtypes of CP and comorbid epilepsy in factors such as gestational age,history of asphyxia,HIE history,age of first seizure,MRICS classification and GMFCS levels.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Fourteen flavonoids were isolated and purified from Epimedium sagittatum by various chromatography techniques such as macroporous adsorbent resin, silica gel, ODS, Sephadex LH-20, HW-40C and semi-preparative HPLC. Their structures were identified by analysis of physicochemical properties and spectral data, and determined as 3′-hydroxy-baohuoside-Ⅱ (1), huazhongilexone-7-O-β-D-glucopyranoside (2), kaempferol-3-O-α-L-rhamnoside (3), baohuoside-Ⅱ (4), icariside-Ⅱ (5), kaempferol 3,7-di-O-α-L-rhamnopyranoside (6), (+)-aromadendrin (7), kaempferol 3-O-(2-O-β-D-apiofuranosyl)-α-L-rhamnopyranoside (8), sagittatoside A (9), 2″-O-rhamnosyl icariside-II (10), apigenin-7-O-β-D-glucoside (11), quercetin 3-O-β-D-apiofuranoyl-(1→2)-α-L-rhamnopyranoside (12), kaempferol (13), icariin (14). Among them, compound 1 is a new compound, while compounds 2, 6-8, 11, and 12 were isolated from E.sagittatum for the first time.

The chemical constituents from the stems and leaves of Cratoxylum cochinchinense were isolated and purified using silica gel, ODS gel, and Sephadex LH-20 gel column chromatography, as well as preparative HPLC. The chemical structures of all isolated compounds were identified on the basis of their physicochemical properties, spectroscopic analyses, and the comparison of their physicochemical and spectroscopic data with the reported data in literature. As a result, 21 compounds were isolated from the 90% ethanol extract of the stems and leaves of C. cochinchinense, which were identified as cratocochine(1), 1-hydroxy-3,7-dimethoxyxanthone(2), 1-hydroxy-5,6,7-trimethoxyxanthone(3), ferrxanthone(4), 3,6-dihydroxy-1,5-dimethoxyxanthone(5), 3,6-dihydroxy-1,7-dimethoxyxanthone(6), 1,2,5-trihydroxy-6,8-dimethoxyxanthone(7), securixanthone G(8), gentisein(9), 3,7-dihydroxy-1-methoxyxanthone(10), pancixanthone B(11), garcimangosxanthone A(12), pruniflorone L(13), 9-hydroxy alabaxanthone(14), cochinchinone A(15), luteolin(16), 3,5'-dimethoxy-4',7-epoxy-8,3'-neolignane-5,9,9'-triol(17), N-benzyl-9-oxo-10E,12E-octadecadienamide(18), 15-hydroxy-7,13E-labdadiene(19), stigmasta-4,22-dien-3-one(20), and stigmast-5-en-3β-ol(21). Among these isolates, compound 1 was a new xanthone, compounds 2-5, 7, 8, 12, and 16-21 were isolated from the Cratoxylum plant for the first time, and compounds 11 and 13 were obtained from C. cochinchinense for the first time. Furthermore, all isolated compounds 1-21 were appraised for their anti-rheumatoid arthritis activities by MTS method through measuring their anti-proliferative effect on synoviocytes in vitro. As a result, xanthones 1-15 displayed notable anti-rheumatoid arthritis activities, which showed inhibitory effects on the proliferation of MH7A synoviocytes with the IC_(50) values ranging from(8.98±0.12) to(228.68±0.32) μmol·L~(-1).
Synoviocytes ; Clusiaceae/chemistry* ; Xanthones/analysis* ; Plant Leaves/chemistry* ; Cell Proliferation ; Arthritis