Objective To explore the application value of simultaneous multi-slice(SMS)technique in diffusion tensor imaging(DTI)for evaluating brain glioma.Methods Thirty-four brain glioma patients were prospectively enrolled,and brain conventional DTI and SMS-DTI were acquired.The subjective scores of image quality,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were compared between SMS-DTI and conventional DTI,so were the numbers of whole brain fiber bundles,tumor relative fractional anisotropy(rFA)and relative mean diffusivity(rMD)obtained based on SMS-DTI and conventional DTI.Results Among 34 patients,there were 23 cases of high-grade glioma and 11 cases of low-grade glioma.No significant difference of subjective scores of image quality,tumor edge clarity nor magnetic susceptibility artifacts was found between SMS-DTI and conventional DTI(all P＞0.05).SNR and CNR on SMS-DTI were both lower than those on conventional DTI(both P＜0.05).No significant difference of the numbers of whole brain fiber bundles,rFA nor rMD of gliomas with different pathological grades was detected based on SMS-DTI compared with those on conventional DTI(all P＞0.05).Conclusion SMS applicated in DTI for evaluating brain gliomas was able to shorten acquisition time under the condition of ensuring image quality and quantitative analysis accuracy.

Two methods including gas chromatography tandem mass spectrometry (GC-MS/MS) and high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) were established to detect common alkyl sulfonates and aryl sulfonates genotoxic impurities. Four alkyl sulfonates and methyl benzenesulfonate were determined by GC-MS/MS using butyl methanesulfonate as the internal standard, the chromatographic column was HP-5MS UI (30 mm × 0.25 mm, 0.25 µm), the carrier gas was helium, the flow rate was 1.0 mL·min^-1 in a constant flow mode, the sample inlet temperature was set to 250 ℃, the split ratio was 10∶1, and the initial temperature of the heating program was 80 ℃, maintained for 1 minute, and then increased to 240 ℃ at a heating rate of 30 ℃·min^-1 for 2 minutes. The mass spectrometry detector was an electron bombardment ion source (EI source), the data collection condition was multi reaction monitoring mode (MRM), and method validation using the raw material of clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of four alkyl sulfonates and methyl benzenesulfonate were good at 3-50 ng·mL^-1 and 9-150 ng·mL^-1, with a correlation coefficient of r > 0.999, The spiked recovery was 80%-120%. The detection limits were 1 and 3 ng·mL^-1; Ten aryl sulfonates determined by LC-MS/MS, the chromatographic column was CSH Fluoro phenyl (100 mm × 2.1 mm, 1.7 µm), the mobile phase was methanol (B)-5 mmol·L^-1 ammonium formate (D), with a flow rate of 0.2 mL·min^-1, and gradient elution was performed. The gradient program (T/% B) was set as 0/20, 25/90, 35/90, 42/20. The mass spectrometer detector was electro spray ionization with positive ionization mode (ESI⁺), the data collection was in dynamic multi reaction monitoring mode (dMRM), and the method was validated using the raw material of the clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of aryl sulfonates were good at 9-2 000 ng·mL^-1, 3-100 ng·mL^-1 and 0.9-30 ng·mL^-1, respectively. The correlation coefficient r > 0.999, the spiked recovery was 80%-120%. The detection limits were 30, 1 and 0.3 ng·mL^-1. Two detection methods did not detect potential sulfonate genotoxicity impurities in the above APIs. The established analytical methods are reliable and effective, which can provide reference for drug quality control and detection.

Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3％,and that of non-infected group was 23.1％,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2％(95％CI:-2.3％-22.8％).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P＞0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P＞0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.

The paper is to establish an UPLC-MS/MS method for the simultaneous determination of 19 components in Microctis Folium from different production areas. The 50% methanol was used as extraction solvent. The Agilent ZORBAX SB C18 (150 mm × 2.1 mm, 1.8 μm) column was used; mobile phase was acetonitrile - 0.1% acetic acid with gradient elution, flow rate was 0.3 mL·min^-1, colume temperature was 30 ℃, and the injection volume was 2 μL; electrospray ionizaton source was used and detected in negative ion mode. The results showed that the established UPLC-MS/MS method could well separate the 19 components, and the methodological investigation results of 19 components were good. By means of orthogonal partial least squares discriminant analysis (OPLS-DA), 28 batches of Microctis Folium samples from different production areas can be divided into three categories, Guangdong, Guangxi and Hainan are each classified into one category, and 10 signature compounds which affecting the quality differences of different production areas were screened out. The established method is accurate, reliable, sensitive and reproducible. It can provide a basis for the establishment of the quality standard of Microctis Folium, as well as for safety and quality research.

Objective: To analyze the clinical and molecular diagnostic status of Fanconi anemia (FA) in China. Methods: The General situation, clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) and the Chinese Children Blood and Marrow Transplantation Registry Group (CCBMTRG) from August 2009 to January 2022 were analyzed retrospectively. Children with FANCA gene variants were divided into mild and severe groups based on the type of variant, and Wilcoxon-test was used to compare the phenotypic differences between groups. Results: Of the 176 registered FA patients, 69 (39.2%) cases were excluded due to lack of definitive genetic diagnosis results, and the remaining 107 children from 15 hospitals were included in the study, including 70 males and 37 females. The age at transplantation treatment were 6 (4, 9) years. The enrolled children were involved in 10 pathogenic genes, including 89 cases of FANCA gene, 7 cases of FANCG gene, 3 cases of FANCB gene, 2 cases of FANCE gene and 1 case each of FANCC, FANCD1, FANCD2, FANCF, FANCJ, and FANCN gene. Compound heterozygous or homozygous of loss-of-function variants account for 69.2% (72/104). Loss-of-function variants account for 79.2% (141/178) in FANCA gene variants, and 20.8% (37/178) were large exon deletions. Fifty-five children (51.4%) had chromosome breakage test records, with a positive rate of 81.8% (45/55). There were 172 congenital malformations in 80 children.Café-au-Lait spots (16.3%, 28/172), thumb deformities (16.3%,28/172), polydactyly (13.9%, 24/172), and short stature (12.2%, 21/172) were the most common congenital malformations in Chinese children with FA. No significant difference was found in the number of congenital malformations between children with severe (50 cases) and mild FANCA variants (26 cases) (Z=-1.33, P=0.185). Conclusions: FANCA gene is the main pathogenic gene in children with FA, where the detection of its exon deletion should be strengthened clinically. There were no phenotypic differences among children with different types of FANCA variants. Chromosome break test is helpful to determine the pathogenicity of variants, but its accuracy needs to be improved.
Male ; Female ; Humans ; Child ; Fanconi Anemia/genetics* ; Chromosome Breakage ; Retrospective Studies ; Exons ; China/epidemiology*

Objective: To assess the feasibility of using donors with novel coronavirus disease 2019 (COVID-19) for allogeneic hematopoietic stem cell transplantation (allo-HSCT) when there are no other available donors and allo-HSCT cannot be delayed or discontinued. Methods: Seventy-one patients with malignant hematological diseases undergoing allo-HSCT between December 8, 2022, and January 10, 2023, were included. Of these, 16 received grafts from donors with mild COVID-19 (D-COVID(+) group) and 55 received grafts from donors without COVID-19 (D-COVID(-) group). The graft compositions were compared between the two groups. Engraftment, acute graft-versus-host disease (aGVHD), overall survival (OS), and relapse were also evaluated. Results: There were no serious side effects or adverse events in the D-COVID(+) group. The mononuclear cell dose and CD34(+) cell dose were comparable between the two groups, and no additional apheresis was required. There were no significant differences in the lymphocyte, monocyte, and T-cell subset doses between the two groups. The median natural killer cell dose in the D-COVID(+) group was significantly higher than that in the D-COVID(-) group (0.69×10(8)/kg vs. 0.53×10(8)/kg, P=0.031). The median follow-up time was 72 (33-104) days. All patients achieved primary engraftment. The 60-day platelet engraftment rates in the D-COVID(+) and D-COVID(-) groups were 100% and (96.4±0.2) %, respectively (P=0.568). There were no significant differences in neutrophil (P=0.309) and platelet (P=0.544) engraftment times. The cumulative incidence of grade 2-4 aGVHD was (37.5±1.6) % vs. (16.4±0.3) % (P=0.062), and of grade 3-4 aGVHD was 25.0% ±1.3% vs. 9.1% ±0.2% (P=0.095) in the D-COVID(+) and D-COVID(-) groups, respectively. The probabilities of 60-day OS were 100% and 98.1% ±1.8% (P=0.522) in the D-COVID(+) and D-COVID(-) groups, respectively. There was no relapse of primary disease during the study period. Conclusion: When allo-HSCT cannot be delayed or discontinued and no other donor is available, a donor with mild COVID-19 should be considered if tolerable. Larger sample sizes and longer follow-up periods are required to validate these results.
Humans ; COVID-19 ; SARS-CoV-2 ; Hematopoietic Stem Cell Transplantation ; Tissue Donors ; Graft vs Host Disease

This study aimed to investigate the mechanism of Jiu Wei Bu Xue Oral Liquid on insomnia rats combining the methods of network pharmacology, molecular docking and experimental verification. UPLC-Q-TOF-MS/MS method and TCMIP, TCMSP databases were used to collect the ingredients and targets of Jiu Wei Bu Xue Oral Liquid. Protein-protein interactions and network analysis were performed to screen the key network targets and putative active ingredients of Jiu Wei Bu Xue Oral Liquid in treatment of insomnia, and then following by biological function and KEGG pathway analysis. Then binding ability for key network targets and putative active ingredients were predicted with molecular docking. The prediction targets were validated in para-chlorophenylalanine (PCPA) induced insomnia rats with administration of Jiu Wei Bu Xue Oral Liquid (2, 4, 8 mL·kg^-1) for 7 days. Pentobarbital sodium induced sleeping test were performed to evaluate the synergistic sleep-aiding effect of Jiu Wei Bu Xue Oral Liquid. Then glutamic acid (Glu), γ-aminobutyrate (GABA) content and glutamate decarboxylase 1 (GAD67) activity in hypothalamus or hippocampus were evaluated, and the expressions of GAD67, γ-aminobutyric acid receptor subunit α1 (GABRA1) and γ-aminobutyric acid receptor subunit β2 (GABRB2) in hippocampus were detected by qRT-PCR and Western blot methods. Animal experiments were approved by the Institutional Committee on Animal Care of Guangxi Institute of Chinese Medicine & Pharmaceutical Science (the number of permission: 2022060802). Results showed that 16 key network targets and 16 putative active ingredients were obtained by analyzing the herbs-ingredients-targets network of Jiu Wei Bu Xue Oral Liquid in treatment of insomnia. Network pharmacology and molecular docking all indicated these active ingredients, for example atractylenolide Ⅲ, showed better binding ability with GABRA1 and GABRB2. Animal study indicated that, compared to PCPA-induced insomnia model, Jiu Wei Bu Xue Oral Liquid remarkably shortened the sleeping latency and increased the sleeping duration, increased GAD67 activity and the production of GABA in hippocampus of insomnia rats, as well as the expressions of GAD67, GABRA1 and GABRB2, while decreased Glu content in hypothalamus, leading to decreasing of Glu/GABA ratio and recovery of Glu-GABA balance. These results indicated that Jiu Wei Bu Xue Oral Liquid improved insomnia symptoms and helped maintain the Glu-GABA balance within hypothalamus and hippocampus, and reduced the excitatory neurotoxicity within brain. The mechanism may due to the elevation of GAD67 expression and enzyme activity, and the enhancement of type-A GABA receptor (GABA_AR)-mediated neurons inhibition.

ObjectiveTo observe the effect of Flemiphilippinin D on collagen-induced arthritis （CIA） in rats and explore its mechanism. MethodForty rats were randomly divided into normal group， CIA group， methotrexate （MTX） group （1.35 mg·kg^-1）， low-dose Flemiphilippinin D group （1.5 mg·kg^-1）， and high-dose Flemiphilippinin D group （3.0 mg·kg^-1）， with eight rats in each group. Except for the normal group， the CIA model was induced by type Ⅱ collagen. Each group was given corresponding liquid medicine or normal saline， once a week in the MTX group， and once a day in the Flemiphilippinin D groups for a total of 28 days. The arthritis score and joint swelling degree of rats were experimentally recorded. Pathological changes in the ankle joint of rats were observed by hematoxylin-eosin （HE） staining. Serum levels of inflammatory cytokines interleukin （IL）-1β， IL-6， IL-8， and tumor necrosis factor （TNF）-α were detected by enzyme-linked immunoabsorbent assay （ELISA）， and the mRNA expression of Toll-like receptor 2 （TLR2）， myeloid differentiation factor 88 （MyD88）， and nuclear transcription factor-κB （NF-κB） p65 were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the protein expressions of TLR2， MyD88， and NF-κB p65 were detected by Western blot. ResultCompared with the normal group， the ankle joint of the CIA group was significantly swollen， and the clinical score of arthritis and the degree of joint swelling were significantly increased （P<0.01）. The ankle joint tissue structure was significantly damaged， and the levels of inflammatory factors IL-1β， IL-6， IL-8， and TNF-α in serum were significantly increased （P<0.01）. The mRNA levels and protein levels of TLR2， MyD88， and NF-κB p65 were significantly increased（P<0.01）. Compared with the CIA group， arthritis clinical score and joint swelling of rats in each administration group were significantly reduced （P<0.05， P<0.01）， and the pathological changes in the ankle joint were significantly improved. The contents of serum IL-1β， IL-6， IL-8， and TNF-α were significantly decreased （P<0.05， P<0.01）. The mRNA levels and protein levels of TLR2， MyD88， and NF-κB p65 in the ankle joint were significantly decreased （P<0.05， P<0.01）. ConclusionTo a certain extent， Flemiphilippinin D can reduce the expression of inflammatory factors in rheumatoid arthritis rats and play a good therapeutic effect. It works perhaps by inhibiting the activation of the TLR2/MyD88/NF-κB signaling pathway and thus shows an anti-inflammatory effect.

Objective:To investigate the value of plasma Epstein-Barr virus (EBV) DNA detection in the screening of nasopharyngeal carcinoma (NPC) and its clinical application in non-high-risk areas.Methods:Plasma EBV DNA results in 1 153 newly diagnosed nasopharyngeal carcinoma patients who were treated in Sichuan Cancer Hospital from 2015 to 2020 and 244 healthy control cases with matched sex and age were retrospectively analyzed. EBV DNA were detected by quantitative real-time PCR. Positive rate of EBV DNA was determined by the cutoff value of 400 (≥400 copies/ml as positive) and optimization threshold method (presence of S amplification curve as positive). Further analyses were conducted to compare EBV DNA load in different clinical stage, TNM stage and regions distribution characteristics. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of the cutoff value of 400 and optimization threshold method for NPC.Results:Compared with healthy controls, EBV DNA increased significantly in newly diagnosed NPC patients ( P<0.001). Both evaluation methods revealed that the EBV DNA positive percentage increased with TNM and clinical stage ( P<0.001). With 400 copies/ml as cutoff value, the diagnostic sensitivity and specificity were 40.85% and 100%, respectively. The area under the curve was 0.704 (95% CI 0.676-0.733, P<0.001). Evaluated by the optimization threshold method, the sensitivity and specificity could improve to 82.0% and 99.2%, respectively, and the area under the curve reached 0.910 (95% CI 0.894-0.924, P<0.001). Conclusions:In the low prevalence area of nasopharyngeal carcinoma, the sensitivity for diagnosis of nasopharyngeal carcinoma is only 40.9% by the 400 copies/ml cutoff value method. The optimization threshold method is a better choice to improve the diagnostic sensitivity without lowering the diagnostic specificity.

UPLC-Q-TOF-MS combined with network pharmacology and experimental verification was used to explore the mechanism of acupoint sticking therapy(AST) in the intervention of bronchial asthma(BA). The chemical components of Sinapis Semen, Cory-dalis Rhizoma, Kansui Radix, Asari Radix et Rhizoma, and Zingiberis Rhizoma Recens were retrieved from TCMSP as self-built database. The active components in AST drugs were analyzed by UPLC-Q-TOF-MS, and the targets were screened out in TCMSP and Swiss-TargetPrediction. Targets of BA were collected from GeneCards, and the intersection of active components and targets was obtained by Venny 2.1.0. The potential targets were imported into STRING and DAVID for PPI, GO, and KEGG analyses. The asthma model induced by house dust mite(HDM) was established in mice. The mechanism of AST on asthmatic mice was explored by pulmonary function, Western blot, and flow cytometry. The results indicated that 54 active components were obtained by UPLC-Q-TOF-MS and 162 potential targets were obtained from the intersection. The first 53 targets were selected as key targets. PPI, GO, and KEGG analyses showed that AST presumedly acted on SRC, PIK3 CA, and other targets through active components such as sinoacutine, sinapic acid, dihydrocapsaicin, and 6-gingerol and regulated PI3 K-AKT, ErbB, chemokine, sphingolipid, and other signaling pathways to intervene in the pathological mechanism of BA. AST can improve lung function, down-regulate the expression of PI3 K and p-AKT proteins in lung tissues, enhance the expression of PETN protein, and reduce the level of type Ⅱ innate immune cells(ILC2 s) in lung tissues of asthmatic mice. In conclusion, AST may inhibit ILC2 s by down-regulating the PI3 K-AKT pathway to relieve asthmatic airway inflammation and reduce airway hyperresponsiveness.
Acupuncture Points ; Animals ; Asthma/drug therapy* ; Drugs, Chinese Herbal ; Immunity, Innate ; Lymphocytes ; Mice ; Network Pharmacology