ObjectiveTo explore the molecular mechanism implicated in the treatment of primary myelofibrosis （PMF） using Chinese medicinal herbs （CMH） by bioinformatics and molecular dynamics. MethodsData mining was performed to find the high-frequency CMH in treating PMF between the year of 1985 and 2024 by searching CNKI， Chinese Science and Technology Journal Database （CCD）， and China Academic Journal Database （CSPD）. TCMSP， SwissTargetPrediction and related reports were used to collect the main active ingredients of high-frequency CMH and their targets. The PMF datasets GSE44426 and GSE124281 were downloaded from GEO database， and R software was used for data normalization and differentially expressed genes （DEGs） screening. Key module hub genes were obtained by weighted gene co-expression network analysis （WGCNA） analysis. The common intersection genes of active ingredient targets， DEGs and key module hub genes of CMH were selected， and the target network was generated using Cytoscape 3.9.2 software. The core target network was generated by topological analysis， while key pathways were selected by GO and KEGG pathway enrichment analysis， and protein interaction relationships were obtained from the String database， so as to construct drug-ingredient-target network and protein interaction network （PPI） relationship diagrams. Discovery Studio 2020 software was used to perform molecular docking， and the GROMACS program was used to perform molecular dynamics simulation. ResultsA total of 21 prescriptions were collected involving 121 herbs. There were 9 herbs with a frequency ≥10 times， which were Danshen （Radix et Rhizoma Salviae Miltiorrhizae）， Huangqi （Radix Astragali）， Baizhu （Rhizoma Atractylodis Macrocephalae）， Danggui （Radix Angelicae Sinensis）， Dangshen （Radix Codonopsis）， Gancao （Radix et Rhizoma Glycyrrhizae）， Baishao （Radix Paeoniae Alba）， Fuling （Poria） and Shudihuang （Radix Rehmanniae Praeparata） from high- to low-frequency. A total of 98 active ingredients and 1125 potential targets were obtained from 9 high-frequency CMH. GSE44426 and GSE124281 data sets screened out 24 gene samples， including 14 of the healthy control group and 10 of the PMF group， and identified 319 DEGs between the two groups， including 122 up-regulated genes and 197 down-regulated genes. WGCNA screened out 24 co-expression module genes and found that the five modules closely related to the onset of PMF were MEpink， MEdarkred， MEblack， MEgrey， and MEturquoise， involving 7112 key module hub genes. The GO and KEGG enrichment analyses indicated that lipids and the atherosclerosis pathways were mainly involved in the mechanism of above high-frequency CMH in treating PMF， which included six hub protein targets： HSP90AA1， HSP90AB1， SRC， MAPK1， IL1B and IL10. From the drug-ingredient-target network， seven active ingredients of CMH targeting at these six hub targets were found， including verbascoside， verbascos isoflavone， kaempferol， luteolin， naringenin， quercetin and pachymic acid. The molecular docking and molecular dynamics analyses showed that the key CMH were Shudihuang， Huangqi， Baishao， Danshen， Gancao and Fuling， and among the seven active ingredients， calycosin had the highest binding affinity with HSP90AB1. ConclusionThe main CMH for the treatment of PMF may be Shudihuang， Huangqi， Baishao， Danshen， Gancao and Fuling， and the active ingredients include verbascoside， verbascos isoflavones， kaempferol， luteolin， naringenin， quercetin and pachymic acid. The relevant targets are HSP90AA1， HSP90AB1， SRC， MAPK1， IL-10， and IL-1β， and the most critical pathways are lipid and atherosclerosis pathways.

OBJECTIVES: To investigate the effect of oral microscope-assisted surface decontamination on implants in vitro. METHODS: Twelve implants that fell off because of severe peri-implantitis were collected, and decontamination was carried out on the surfaces of implants through curetting, ultrasound, titanium brushing, and sandblasting at 1×, 8×, or 12.8× magnifications. The number and sizes of residues on the implants' surfaces after decontamination were determined, and the decontamination effect was analyzed according to the thread spacing in the different parts of the thread. RESULTS: 1) The 8× and 12.8× groups scored lower for implant surface residues than the 1× group (P<0.000 1), and the 12.8× group scored lower than the 8× group (P<0.001); 2) no difference in residue score was found between the wide and narrow thread pitch (P>0.05), and the 8× and 12.8× groups had lower scores than the 1× group (P<0.001); 3) the lowest number of contaminants was observed at the tip of the thread, whereas the highest was observed below the thread, and the difference was significant (P<0.001). However, the thread pitch had no effect on the number of contaminants in different areas (P>0.05); 4) the residue scores of the 8× and 12.8× groups were lower than those of the 1× group at the thread tip and above, sag, and below the thread of the implants (P<0.05). CONCLUSIONS Residues on the surfaces of contaminated implants can be effectively removed by using an oral microscope. After decontamination, the residues of pollutants were mainly concentrated below the thread of the implants, and the thread pitch of the implants had no significant effect on the residues.
Humans ; Dental Implants ; Decontamination ; Surface Properties ; Peri-Implantitis ; Titanium

Understanding the regulatory networks for germ cell fate specification is necessary to developing strategies for improving the efficiency of germ cell production in vitro. In this study, we developed a coupled screening strategy that took advantage of an arrayed bi-molecular fluorescence complementation (BiFC) platform for protein-protein interaction screens and epiblast-like cell (EpiLC)-induction assays using reporter mouse embryonic stem cells (mESCs). Investigation of candidate interaction partners of core human pluripotent factors OCT4, NANOG, KLF4 and SOX2 in EpiLC differentiation assays identified novel primordial germ cell (PGC)-inducing factors including BEN-domain (BEND/Bend) family members. Through RNA-seq, ChIP-seq, and ATAC-seq analyses, we showed that Bend5 worked together with Bend4 and helped mark chromatin boundaries to promote EpiLC induction in vitro. Our findings suggest that BEND/Bend proteins represent a new family of transcriptional modulators and chromatin boundary factors that participate in gene expression regulation during early germline development.
Animals ; Cell Differentiation/genetics* ; Chromatin/metabolism* ; Embryonic Stem Cells ; Germ Cells/metabolism* ; Germ Layers/metabolism* ; Mice

【Objective】 To investigate the risk factors of frailty syndrome in elderly patients with acute coronary syndrome （ACS） and their impact on prognosis. 【Methods】 The elderly patients with ACS aged 65 and over， who were hospitalized in the Department of Cardiology and Geriatric Cardiology of The First Affiliated Hospital of Xi’an Jiaotong University from September 2020 to February 2021， were selected in the cross-sectional survey. The patients were divided into frailty syndrome and non-frailty syndrome groups via the Chinese revised version of Tilburg Frailty Scale. We collected the patients’ activities of daily living， nutrition， depression， sleep quality， total cholesterol， triglycerides， low-density lipoprotein， and adverse events during hospitalization and within 30 days of discharge. We then performed LOG-BINOMIAL regression to analyze the risk factors of frailty syndrome. 【Results】 A total of 250 elderly ACS patients were enrolled， and 118 patients were diagnosed with frailty syndrome with 47.2% prevalence of frailty syndrome. There was a significant difference in the average score between the frailty syndrome group and the non-frailty syndrome group （11.06±2.53 vs. 5.77±1.54， P<0.01）. Multivariate regression analysis revealed that age （PR=2.01 CI： 1.81-2.22， P<0.001）， hypertension （PR=1.20 CI： 1.09-1.30， P<0.001）， chronic kidney disease （PR=1.16 CI：1.04-1.29， P=0.012）， and NT-proBNP （PR=1.20 CI： 1.07-1.35， P=0.004） were risk factors for frailty syndrome in elderly ACS patients. The incidence of arrhythmia and pulmonary infection during hospitalization and the rate of readmission within 30 days after discharge were significantly higher in the frailty syndrome group than those in the non-frailty syndrome group （P<0.05）. 【Conclusion】 There is a higher incidence of frailty syndrome in elderly patients with ACS. Older age， hypertension， chronic kidney disease and high NT-proBNP can increase the risk of frailty syndrome. In clinical practice， attention should be paid to the above factors， and reasonable intervention should be provided in time.

Objective:To develop an evidence-based nursing program for a patient with oral complications of dysphagia due to cerebral infarction.Methods:According to the principle of PICO, and the problem of patients' clinical manifestations, using the method of combining subject words and free words, the database of Uptodate, NICE, SIGN. RNAO, medical pulse guide network, BMJ, Cochranc library, PubMed, EMbase, CINAHL, China National Knowledge Infrastructure were searched and collected the clinical guidelines, systematic evaluation and randomized controlled trial of oral complications in patients with dysphagia of cerebral infarction.Results:Totally 1 clinical decision, 5 clinical guidelines, 4 expert consensus, 2 systematic evaluations, 1 Meta-analysis, 3 randomized controlled trial (RCT) were included. Based on the search results and the patient′s condition and wishes, nurses performed swallowing function tests every two days according to the Standard Swallowing function rating Scale (SSA), raised the head of the bed 40°~45° and holded it for 1 hour. Three times a day, the teeth were brushed with chlorhexidine oral care solution under negative pressure. Sputum scab was removed by mechanical scrubbing. The back of tongue was scrubbed by 6x tongue scraping technique every night. After the infection was controlled, the teeth were washed twice a day with 0.9% sodium chloride solution. Oral condition and swallowing function were evaluated daily. High flow humidification oxygen therapy and mask spray atomization inhalation were used. Swallowing training was performed on the third day after admission. Seven days after the evidence was applied to clinical practice, the oral mucosa was moist without peculiar smell and sputum scab, and the swallowing function was changed from grade IV to grade II.Conclusion:Nursing cerebral infarction patients with dysphagia, nurses should timely assess the patient's oral cavity and swallowing function, the application of chlorhexidine and 0.9% sodium chloride solution oral care solution mechanical scrubbing method and negative pressure washing brushing method can effectively remove sputum scab, use 6x tongue scraping technology to scrub the back of tongue, can reduce micro organisms, reduce halitosis; the application of nasal mask high flow humidification oxygen therapy and spray atomization inhalation humidification effect is obvious Therefore, early swallowing training can reduce the incidence of oral complications.

Programmed cell death ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) cascade is an effective therapeutic target for immune checkpoint blockade (ICB) therapy. Targeting PD-L1/PD-1 axis by small-molecule drug is an attractive approach to enhance antitumor immunity. Using flow cytometry-based assay, we identify tubeimoside-1 (TBM-1) as a promising antitumor immune modulator that negatively regulates PD-L1 level. TBM-1 disrupts PD-1/PD-L1 interaction and enhances the cytotoxicity of T cells toward cancer cells through decreasing the abundance of PD-L1. Furthermore, TBM-1 exerts its antitumor effect in mice bearing Lewis lung carcinoma (LLC) and B16 melanoma tumor xenograft

Objective:To investigate the clinical features and associated chronic pain in corticobasal syndrome (CBS).Methods:Clinical data of 8 patients diagnosed as probable CBS or possible CBS admitted to Beijing Hospital during January 2010 to June 2020 were retrospectively analyzed. The clinical information included sex, age, course of disease, chief complaint, neurological examination, blood biochemistry, tumor marker, infection and other laboratory tests; the neuropsychological evaluation included Mini-Mental State Examination (MMSE) scale and Hamilton Depression Scale (HAMD); the imaging studies included cranial magnetic resonance imaging (MRI) and/or 18F-Fluorodeoxyglucose positron emission tomography ( 18F-FDG PET). Results:The main clinical manifestations were asymmetrical movement disorders, including rigidity, tremor, myoclonus and abnormalities in posture and gait. Patients showed poor response to levodopa treatment. Among 8 patients, 7 had apraxia, 5 patients had alien hand, and 5 patients had various degrees of cognitive dysfunction. The cranial MRI demonstrated mild cerebral atrophy which was slightly more severe in the contralateral side of the initially affected limb in 7 of the 8 patients. The 18F-FDG PET scan revealed asymmetric decreased metabolism in the frontal, parietal, temporal, and occipital lobe, as well as in basal ganglia, which was more severe in the contralateral side of the initially affected limb in 5 of the 8 patients. Six of the 8 patients were associated with pain, including dystonic pain in 3 patients, neuropathic pain in 1 patient, musculoskeletal pain in 1 patient, and unexplained pain in 1 patient. Pain was the onset symptom in 1 patient and pain was relieved by taking levodopa in another patient. Conclusions:CBS is characterized by asymmetric dyskinesia and cognitive impairment, and often associated with apraxia, cortical sensory deficits, and alien limb. The MRI and PET are helpful for CBS diagnosis. Pain may be one of the common non-motor symptoms in CBS.

Objective:To investigate the pathogenic spectrum of hand, foot and mouth disease(HFMD)from 2017 to 2019 in Guangzhou, and analyze molecular epidemiological characteristics of coxsackievirus A6 (CV-A6).Methods:Enterovirus A71 (EV-A71), CV-A16, CV-A6 and enterovirus were tested by reverse transcription-quantitative polymerase chain reaction(RT-qPCR). The CV-A6 representative samples were isolated and the VP1 region of isolates were amplified and analized by Mega5.0 and SeqMen.Results:A total of 7 578 enterovirus-positive specimens were detected from 2017 to 2019, 320 specimens were positive for EV-A71, 1481 specimens were positive for CV-A16, 3171specimens were positive for CV-A6, and 2606 specimens were positive for other enterovirus. Children under the age of 5 years were the most vulnerable population, and the male/female incidence ratio was 1.56∶ 1.The incidence occurred in all seasons, one peak between May and July, the other between September and November. The virus was isolated from 80 CV-A6 positive specimens and the full length of VP1 gene region was sequenced and nucleotide sequence similarity analysis was performed. The nucleotide homology in the VP1 region was 93%-100%, and the amino acid homology was 98%-100%. The nucleotide homology with the CV-A6 prototype strain (Gdula) VP1 region was 79%-81%, and the amino acid homology was 95%-97%. The nucleotide homology with the representative strain of D3 subtype was 92%-98%, and the amino acid homology was 98%-100%. Phylogenetic tree shows that all CV-A6 belonged to the sub-genotype D3 and distributed in multiple branches.Conclusions:CV-A6 is emerging as one of the major pathogen causing HFMD in Guangzhou, and all insolates belonged to D3 subtype. Closely monitoring the molecular characteristics of CV-A6 and changes in the pathogen spectrum can provide scientific basis for HFMD prevention and control.

Objective: To find out the source and the epidemic pattern of norovirus outbreak in July, 2016 to June, 2017 in Guangzhou. Methods: The stool samples and clinical information of diarrhea cases were collected by the sentinel hospitals and CDCs; a real-time RT-PCR method was used to detect the norovirus nucleic acids from the samples, the positive ones were amplified and sequenced; the partial sequences of norovirus were aligned by an online BLAST alignment, and a phylogenetic tree was constructed by a neighbor-joining method . Results: A total of 854 cases with infectious diarrhea were reported by Guangzhou diarrhea surveillance network from July, 2016 to June, 2017; the gender ratio (male versus female) was 1∶0.67; 78.33% of the cases were preschool children under the age of 7 years. Totally 220 samples were detected norovirus G II+ (25.76%, including 5 double-positive samples with G I+ ). GII.Pe-GII.4.Sydney_2012 was the prevalent genotype in the second half of 2016 (94.64%), which was replaced by GII.P16-GII.2 in the first half of 2017 (67.65%). Since September 2016, the reported number of norovirus-caused diarrhea epidemic was increased gradually; the peak of epidemic curve emerged in February to March of 2017, and the number started to decrease since April. In May to June there were only 2-3 epidemics reported monthly. All the endemics from September to November 2016 were caused by genotype GII.Pe-GII.4.Sydney_2012; the endemics from December 2016 to April 2017 were mainly caused by genotype GII.P16-GII.2. Some samples from kitchen workers and babysitters were detected GII+ , which was consistent with the result of the cases′ samples. Conclusions It was the first time that the novel GII.P16-GII.2 recombinant strain outbroke occurred in Guangzhou City and homology analysis also suggested that GII.P16-GII.2 was the main source of those epidemics in 2016 -2017 winter and spring season. Furthermore, The kitchen workers and babysitters may have played an important role in the spread of norovirus.

Objective To evaluate the effect of atorvastatin preconditioning on cognitive function in isoflurane-anaesthetized mice.Methods Forty-eight healthy male C57BL/6 mice,aged 3 months,weighing 27-41 g,were divided into 3 groups (n =16 each) using a random number table:control group (group C),isoflurane anesthesia group (group Ⅰ) and atorvastatin preconditioning plus isoflurane anesthesia group (group AI).Atorvastatin 10 mg/kg was given through a gastric tube into the stomach at the same time every day for 7 consecutive days in group AI.In Ⅰ and AI groups,1.5％ isoflurane was inhaled for 6 h with fresh gas flow of 2 L/min at 1 day after the end of administration.Open field test and Morris water maze test were performed at 1 day after the end of anesthesia.The mice were sacrificed at 1 day after the end of Morris water maze test,and hippocampi were isolated for determination of caspase-3,Bax and Bcl-2 expression (by Western blot) and contents of interleukin-1beta (IL-1β),tumor necrosis factor-alpha (TNF-α) and soluble Aβ1-42 in hippocampal tissues (by enzyme-linked immunosorbent assay).Results There was no significant difference in the parameters of open field test among the three groups (P＞0.05).Compared with group C,the escape latency was significantly prolonged at each time point,the time of staying at the original platform quadrant was shortened,the frequency of crossing the original platform was decreased,the contents of IL-1β,TNF-α and soluble Aβ1-42 were increased,the expression of caspase-3 and Bax was up-regulated,and Bcl-2 expression was down-regulated in Ⅰ and AI groups (P＜0.05).Compared with group Ⅰ,the escape latency was significantly shortened at each time point,the time of staying at the original platform quadrant was prolonged,the frequency of crossing the original platform was increased,the contents of IL-1β,TNF-α and soluble Aβ1-42 were decreased,the expression of caspase-3 and Bax was downregulated,and Bcl-2 expression was up-regulated in group AI (P＜0.05).Conclusion Atorvastatin preconditioning can improve cognitive function in isoflurane-anaesthetized mice,and the mechanism may be association with attenuating hippocampal inflammatory responses,inhibiting over-expression of Aβ1-42 and inhibiting neuronal apoptosis.