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Objective To explore the clinical characteristics and treatment scheme of periprosthetic joint infection(PJI)caused by Cutibacterium avidum(C.avidum).Methods The diagnosis and treatment process of a patient with PJI caused by C.avidum was summarized,and relevant literatures in the database were retrieved for review.Results A 65-year-old female patient with body mass index(BMI)of 31.1 kg/m2 underwent left humeral head prosthesis replacement surgery following a left proximal humerus fracture.Ten months after the surgery,the pa-tient exhibited poor wound healing and oozing,along with limited movement of the left shoulder joint,and was diag-nosed infection following shoulder arthroplasty.Patient underwent debridement of the infected lesion and removal of the prosthesis.The tissue,bone cement and prosthesis were cultured for C.avidum.Four literatures were re-trieved and screened,a total of 30 patients with PJI(28 cases hip joint infection and 2 cases shoulder joint infection)caused by C.avidum were reported through literature retrieval,and 78.6%(n=22)total hip arthroplasty(THA)surgeries were performed using direct anterior approach(DAA).The positive rate of preoperative joint fluid culture was 71.4%,29 cases underwent surgical combined with sensitive antimicrobials treatment.Except for one patient who had repeated infection and underwent three surgeries,other patients had a good prognosis.Conclusion PJI caused by C.avidum is mostly seen in THA patients who are obese and undergo DAA,with a few cases reported after shoulder arthroplasty.The high sensitivity of preoperative joint fluid culture provides an important basis for the development of surgical strategies and anti-infection protocols.
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@#Objective Loop mediated isothermal amplification(LAMP)was used to detect the distribution of pathogens in sputum samples,namely combined nucleic acid detection of respiratory pathogens(13 pairs),so as to provide provide reference for clinical accurate diagnosis and treatment.Methods A total of 1642 patients with lower respiratory tract infection admitted to Tongren City People's Hospital from January to December in 2022 were selected.Each patient collected sputum specimens/bronchoalveolar for detection by using LAMP(13 pairs).The detection of pathogenic bacteria in respiratory tract and the relationship with sex,age and season were analyzed.Results The overall detection rate of 13 respiratory pathogens was significantly higher in males than in females(P<0.01);In different age groups,the detection rates of Haemophilus influenzae and Streptococcus pneumoniae in patients aged 3-6,Mycoplasma pneumoniae in patients aged 6-18,and methicillin-resistant Staphylococcus aureus,Streptococcus maltophilus,and Klebsiella pneumoniae in patients aged over 60 were significantly higher than those in other groups(P<0.05);In different seasonal groups,Streptococcus pneumoniae and Chlamydia pneumoniae were more prevalent in spring,while Mycoplasma pneumoniae had the highest infection rate in autumn,and the differences were statistically significant(P<0.05).Conclusion LAMP can be used to detect the pathogen rapidly and provide the basis for clinical diagnosis and treatment.
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Objective@#To understand characteristics of men who have sex with men (MSM) who applied for HIV antibody self-testing reagents through "AIDS self-testing" column of a WeChat official account named "Dark Blue Public Health Center" in Tianjin City, so as to provide insights into exploring online modes of HIV antibody self-testing for MSM.@*Methods@#Data of MSM who were 18 years old or above, currently lived in Tianjin City, had sex with men in the past six months and applied for HIV antibody self-testing reagents through "AIDS self-testing" column from May 2018 to December 2022 were collected. Demographic characteristics, results return and positive findings were descriptively analyzed.@*Results@#Data of 2 064 MSM were collected, including 1 052 MSM aged 20 to 29 years (50.97%), 1 522 unmarried MSM (73.74%), 545 workers (26.41%), 1 385 MSM with college education or above (67.10%), and 315 MSM without testing for HIV antibody in the past (15.26%). A total of 6 470 self-testing reagents were applied, and 5 942 testing results were returned, with a return rate of 91.84%. There were 33.28% (687/2 064) of the applicants applying for 66.32% (4 291/6 470) reagents multiple times. There were 73 MSM with positive results, accounting for 1.23%.@*Conclusions@#The MSM applying for HIV antibody self-testing reagents through "AIDS self-testing" are mainly young and highly educated, including some who have never tested for HIV. However, attention should be paid to duplicate applications and the return rate should be increased.
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Chronic pancreatitis (CP) is a progressive and irreversible fibroinflammatory disorder, accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota. Recently, accumulating evidence has supported a correlation between gut dysbiosis and CP development. However, whether gut microbiota dysbiosis contributes to CP pathogenesis remains unclear. Herein, an experimental CP was induced by repeated high-dose caerulein injections. The broad-spectrum antibiotics (ABX) and ABX targeting Gram-positive (G+) or Gram-negative bacteria (G-) were applied to explore the specific roles of these bacteria. Gut dysbiosis was observed in both mice and in CP patients, which was accompanied by a sharply reduced abundance for short-chain fatty acids (SCFAs)-producers, especially G+ bacteria. Broad-spectrum ABX exacerbated the severity of CP, as evidenced by aggravated pancreatic fibrosis and gut dysbiosis, especially the depletion of SCFAs-producing G+ bacteria. Additionally, depletion of SCFAs-producing G+ bacteria rather than G- bacteria intensified CP progression independent of TLR4, which was attenuated by supplementation with exogenous SCFAs. Finally, SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype switching. The study supports a critical role for SCFAs-producing G+ bacteria in CP. Therefore, modulation of dietary-derived SCFAs or G+ SCFAs-producing bacteria may be considered a novel interventive approach for the management of CP.
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Objective@#To investigate the detection of HIV/AIDS cases in medical institutions in Tianjin Municipality from 2005 to 2021, so as to provide insights into optimization of HIV antibody testing strategies in medical institutions.@*Methods@#All data pertaining to individuals receiving HIV antibody tests in medical institutions in Tianjin Municipality from 2005 to 2021 were collected from the information systems in medical institutions and the HIV/AIDS Prevention and Control Information System of Chinese Disease Prevention and Control Information System. The positive rate of HIV antibody and epidemiological characteristics of HIV/AIDS cases in medical institutions were analyzed.@*Results@#The number of HIV antibody tests increased from 86 102 person-times in 2005 to 1 369 345 person-times in 2021 in medical institutions in Tianjin Municipality, with annual increase by 18.88%. The positive rate of HIV antibody increased from 2.44/104 to 2.85/104 (P<0.05), with annual increase by 2.79/104. Both the proportion of the number of HIV antibody tests and the number of HIV/AIDS cases detected by medical institutions in the whole city appeared a tendency towards a rise (P<0.05). A high positive rate of HIV antibody was seen in sexually transmitted disease clinics (53.69/104) and other testing services (12.25/104), and the highest positive rate of HIV antibody was seen in individuals at ages of 20 to 39 years (5.40/104), while the positive rate of HIV antibody was higher in men (5.84/104) than in women (0.53/104) (P<0.05). A total of 3 610 HIV/AIDS cases were detected in medical institutions in Tianjin Municipality from 2005 to 2021, with a median age of 38 (interquartile range, 24) years. Of all HIV/AIDS patients, there were 3 277 men (90.78%), and men who have sex with men was the predominant transmission route (63.46%), while the proportion of late identification of HIV/AIDS cases was 65.60%. In addition, the proportion of timely detection for the first CD4+T lymphocyte count testing increased from 23.81% in 2005 to 71.54% in 2021 (P<0.05).@*Conclusions@#The number of HIV antibody tests and positive rate of HIV antibody appeared a tendency towards a rise in medical institutions in Tianjin Municipality from 2005 to 2021. The HIV/AIDS cases were predominantly identified in sexually transmitted disease clinics and other testing services, and were predominantly men.
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Familial hypercholesterolemia (FH) is an autosomal dominant inherited disease caused by abnormal lipoprotein metabolism. Patients with FH have a significantly increased risk of coronary artery disease (CAD) due to long-term exposure to high levels of low-density lipoprotein (LDL). The diagnosis of FH relies heavily on gene detection, and examination of LDL receptor (LDLR) function is of great significance in its treatment. This review summarizes the current advances in the screening, diagnosis, and treatment of FH and functional analysis of LDLR gene mutations.
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Humans , Hyperlipoproteinemia Type II/therapy , Coronary Artery Disease , Lipoproteins, LDL , Mutationالملخص
ObjectiveTo study the effect and underlying mechanism of Stemona tuberosa alkaloids on the proliferation and apoptosis of human non-small cell lung cancer NCI-H460 cells. MethodNon-small cell lung cancer NCI-H460 cells were divided into a blank group and S. tuberosa alkaloids groups (50, 100, 150, 200, and 250 mg·L-1). The effect of S. tuberosa alkaloids on the proliferation of human NCI-H460 cells was observed by thiazolyl blue tetrazolium bromide (MTT) assay and colony formation assay. Cell apoptosis was observed by Hoechst 33258 staining and flow cytometry. Real-time fluorescence-based polymerase chain reaction (Real-time PCR) was used to detect the effect of S. tuberosa alkaloids on the mRNA expression of cysteinyl aspartate-specific protease 3 (Caspase-3), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and epidermal growth factor receptor (EGFR). The protein expression levels of Caspase-3, Bax, Bcl-2, protein kinase B (Akt), phosphorylated (p-)Akt, EGFR, c-Jun N-terminal kinase (JNK), p-JNK, p38 mitogen-activated protein kinase (p38 MAPK), and p-p38 MAPK were measured by Western blot. ResultCompared with the blank group, the S. tuberosa alkaloids groups showed increased inhibition rate on cell proliferation (P<0.01), reduced number of cell clones formed and the rate of cell clonal formation (P<0.05, P<0.01), and increased karyopyknosis, cytoplasmic aggregation, and cell apoptosis rate (P<0.01). The S. tuberosa alkaloids groups at 100, 150, 200, and 250 mg·L-1 showed increased Caspase-3 mRNA expression (P<0.05), decreased EGFR mRNA expression (P<0.05, P<0.01), up-regulated protein expression of Caspase-3 and p-JNK (P<0.01), and down-regulated protein expression of EGFR and p-Akt (P<0.05, P<0.01). Additionally, compared with the blank group, the S. tuberosa alkaloids groups showed increased expression of Bax mRNA (P<0.01), decreased expression of Bcl-2 mRNA (P<0.01), up-regulated protein expression of Bax and p-p38 MAPK (P<0.01), and down-regulated protein expression of Bcl-2 (P<0.01). ConclusionsS. tuberosa alkaloids can inhibit proliferation and induce apoptosis of human non-small cell lung cancer NCI-H460 cells, and the mechanism may be related to the inhibition of EGFR protein expression and phosphorylation of Akt protein, as well as the activation of the JNK/p38 MAPK signaling pathway.
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ObjectiveTo analyze the differential components in water extract of Chuanxiong Rhizoma before and after processing with wine, and to explore the molecular mechanism of Chuanxiong Rhizoma processed with wine in enhancing anti-cerebral ischemia injury. MethodUltra high performance liquid chromatography tandem quadrupole orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was used to qualitatively analyze the main chemical components in water extract of Chuanxiong Rhizoma based on the spectral information of compound, comparison of reference substance and references. The chemical pattern recognition method was used to screen the differential components of Chuanxiong Rhizoma before and after processing. Based on these differential components, the potential targets of differential components were predicted by online databases, and the related targets of cerebral ischemia were searched. Cytoscape 3.6.0 was used to establish the network diagram of differential components-action targets-diseases of Chuanxiong Rhizoma processed with wine. The protein-protein interaction (PPI) network of intersection targets was constructed by STRING 11.5. The potential targets of differential components against cerebral ischemia were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis through DAVID 6.8. At the same time, the chemical compounds with high relative content and increased peak area after wine processing were docked with their corresponding targets to verify the mechanism of enhanced effect after wine processing. ResultA total of 71 chemical components were identified from Chuanxiong Rhizoma, 34 differential components and 603 potential targets were screened out. At the same time, a total of 769 disease targets and 60 intersection targets were obtained. Seven key targets were identified through PPI network analysis, including JUN, signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase 3 (MAPK3), interleukin-1β (IL-1β), vascular endothelial growth factor A (VEGFA), Caspase-3 (CASP3) and mtrix metalloproteinase 9 (MMP9). Tumor necrosis factor (TNF) signaling pathway was the main differential signaling pathway. The results of molecular docking showed that differential components (senkyunolide K, senkyunolide F, 3-n-butylphthalide, Z,Z′-6,8′,7,3′-diligustilide, ferulic acid and Z-ligustilide) and corresponding targets had good binding activities. ConclusionThe synergistic mechanism of Chuanxiong Rhizoma processed with wine may be related to the enhanced inhibitory effect of inflammatory reaction.
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Aim To target the key proteins of TLR4 signaling pathway to sereen the compounds of Blumea baisamifera ( L.) DC.in order to explore the anti-in- flammatorv active components and the mechanism of action of key proteins targeting TLR4 signaling pathway in Blumea balsamifera( L.) DC.Methods The effects of ergosterol peroxide ( EP) on cell activity, LPS in¬duced inflammatory factor secretion and NF-kB related protein expression were detected by MTT, EL1SA, Western blot and Subcellular Structural Localization.Results The results showed EP, (3-sitosterol, 16- kaurene, carosterol, luteolin, ergosterol, hyperin and genkwa had more optimal interconnection score.EP (2.3 x 10"5 ~ 9.3 x 10 5 mol • L"1) inhibited the degradation and phosphorylation of inflammatory pro¬tein IkB and phosphorylation of NF-kB p65 down¬stream of TLR4 signaling pathway induced by LPS in BAW264.7 cells,and further inhibit the entrv of NF-kB p65 into the nucleus, thus inhibiting the secretion of cytokines IL-lp and 1L-6.Conclusions The antiin¬flammatory components of Blumea balsamifera ( L.) DC are identified by molecular docking technology and ac-tivity detection technique, and the anti-inflammatory action anrl mechanism of EP as active substances are e- luci dated.
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Objective: To investigate the sonographic features of primary thyroid lymphoma (PTL) and to evaluate the clinical significance of ultrasound-guided core needle biopsy (US-CNB) in PTL. Methods: A total of 24 patients with suspected PTL in Sir Run Run Shaw Hospital from January 2013 to June 2018 were analyzed retrospectively. All cases were confirmed by pathology, of them 23 patients received US-CNB and 1 patient chose operation without US-CNB, including 5 males and 19 females, aged from 39 to 75 years old. The effectiveness and safety of 23 patients with US-CNB were evaluated, and the sonographic features of 20 patients with PTL diagnosed by pathology were analyzed. Descriptive statistical methods were used in the study. Results: In the 23 patients with suspected PTL underwent US-CNB, 18 patients were diagnosed as PTL, 4 patients were respectively diagnosed as subacute thyroiditis, anaplastic carcinoma, Hashimoto's thyroiditis, and fibro thyroiditis, and the another patient was hard to diagnose by US-CNB and then was diagnosed as PTL by surgical biopsy. The success rate of US-CNB for diagnosis of PTL was 18/19, and no severe complications occurred in the patients with US-CNB. The other case was diagnosed as PTL by surgical biopsy without US-CNB. Sonographic features of 20 cases with PTL (18 cases diagnosed by US-CNB and 2 cases by surgery or surgery biopsy) were as follows: (1) Most nodules had irregular shapes and unsmooth margins; (2) Hypoechoic or markedly hypoechoic nodules with honeycombed or cord structures were observed in most cases; (3) Calcification was rare; (4) Multiple lesions were common; (5) Abundant intralesional vascularization was commonly observed; (6) Most cases had intensification of posterior acoustic enhancement; (7) Thyroid gland enlargement or with irregular shape; and (8) PTL often accompanied with lymph nodes enlargement in lateral neck or central region. Conclusion: PTL has certain sonographic features, with assistance of US-CNB, more accurate diagnosis of PTL can be obtained.
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Adult , Aged , Female , Humans , Male , Middle Aged , Biopsy, Large-Core Needle , Image-Guided Biopsy , Lymphoma/diagnostic imaging , Retrospective Studies , Thyroid Gland , Thyroid Neoplasms/diagnostic imaging , Thyroid Nodule , Ultrasonography, Interventionalالملخص
OBJECTIVES@#Long non-coding RNA (lncRNA) has become a key epigenetic regulator that regulates gene expression and affects a variety of biological processes. LncRNA plays an important role in the occurrence and development of rheumatoid arthritis (RA). The study on lncRNA in peripheral blood cells of RA patients has been reported. However, there is no study on autophagy regulation by lncRNA in RA patients. This study aims to provide a new direction for the diagnosis and treatment of RA via screening the changes of lncRNAs in RA fibroblast-like synoviocytes (RA-FLSs) before and after autophagy and finding the key lncRNAs targeting RA-FLSs autophagy.@*METHODS@#Synovial tissues of 6 RA patients after knee and hip joint surgery were obtained, and RA-FLSs were cultured to the 5th generation for further experiments (tissue culture method). After treatment with mTOR inhibitor PP242, the expression of LC3-II was detected by Western blotting. Total RNAs of 3 cases of RA-FLSs before and after treatment with mTOR inhibitor PP242 were extracted by TRIzol and screened by Agilent Human ceRNA Microarray 2019 (4×180 K, design ID: 086188) chip. The lncRNAs with significantly changed expression levels were selected (difference multiple≥2.0, @*RESULTS@#RA-FLSs were successfully isolated and cultured from the synovial tissues of the patient's knee or hip joint. After 6 RA-FLSs were treated with PP242, the expression level of autophagy marker protein LC3-II was increased (@*CONCLUSIONS@#Differentially expressed lncRNAs in RA-FLSs have been identified with microarray analysis. In RA, differential expression of lncRNAs is involved in the autophagy of RA-FLSs. The underlying mechanisms based on bioinformatics analysis include regulating the secretion of cytokines, such as IL-6, TGF-β, TNF-α and IL-17, participating in the immune cell differentiation, such as Th17, Th1, Th2 cells and osteoclasts, as well as regulating the autophagy pathway, MAPK, FoxO, and other signaling pathways. It has been verified that the expression of ENST0000584721.1 is up-regulated and ENST0000615939.1 is down-regulated after autophagy of RA FLSs, which provides a good experimental basis for further study on the mechanism of lncRNA in RA-FLSs autophagy.
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Humans , Arthritis, Rheumatoid/genetics , Autophagy/genetics , Cell Proliferation , Cells, Cultured , Fibroblasts , RNA, Long Noncoding/genetics , Reproducibility of Results , Synoviocytesالملخص
Objective:To explore the value of multi-parametric MRI for thyroid gland in differentiating benign and malignant thyroid nodules.Methods:From December 2018 to May 2020, 78 patients with 91 post-surgically pathologically confirmed thyroid nodules were enrolled in Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. For each patient, the following MRI findings were obtained including the nodules′ location, size, shape, margin, signal intensity, cystic change, degree and pattern of contrast enhancement, involvement of surrounding structure, and ADC values. The time-intensity curve (TIC) were plotted and subtyped based on dynamic contrast enhancement MRI. The MRI findings between the benign and malignant thyroid nodules were compared using Mann-Whitney U test, χ 2 test or Fisher exact test. Multiple logistic regression analysis was used to select independent predictive variables and build a combined model, and the ROC curve was used to evaluate the diagnostic performance of each MRI finding and the combined model. Results:Between the benign and malignant thyroid nodules, the significant differences were found in size, shape, margin, presence of cystic changes, T 1WI signal intensity, ADC value, enhancement homogeneity, TIC subtypes and presence of thyroid capsule involvement ( P<0.05). Multivariate logistic analysis showed that ill-defined margin (OR=77.61), no presence of cystic changes (OR=36.11) and difference between TIC subtypes (OR=83.41) were independent predictive variables, and the area under the ROC curve (AUC) was 0.879, 0.788, and 0.751, respectively. The AUC, sensitivity and specificity of the combined model were 0.977, 0.986, and 0.904, respectively. Conclusions:Thyroid multi-parametric MRI derived findings can be used for the differential diagnosis of benign and malignant nodules. Combined with the independent risk factors with ill-defined margin, no presence of cystic changes, TIC of type plateau or washout, the diagnostic model has a higher diagnostic efficiency.
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Objective To investigate the intestinal mucosal barrier function protective effect of ulinastatin in sepsis rats and its effect on Wnt/β-catenin signaling pathway. Methods One hundred SD rats were randomly divided into control group, sepsis group, ulinastatin group, XAV939+ulinastatin group and lithium chloride( LiCl) +ulinastatin group. The classical cecal ligation was used to duplicate sepsis model, and the jejunal mucosal injury was evaluated. The levels of inflammatory factors interleukin (IL)-6 and tumor necrosis factor(TNF)-α were detected by ELISA, and the expressions of β-catenin and cyclin D1 were detected by Real-time PCR and Western blotting. We also observed the effect of the Wnt signal pathway blockage by XAV939 or Wnt signal pathway activator by LiCl on ulinastatin protection of intestinal mucosa and proteins related to the Wnt signal pathway. Results The levels of IL-6, TNF-α and intestinal mucosal injury in the sepsis group were significantly higher than those in the ulinastatin group. The mRNA and protein expression levels of β- catenin and cyclin D1 in the sepsis group were significantly higher than those in the control group (P<0.05), After ulinastatin treatment, the expression levels of β-catenin and cyclin D1 mRNA and protein were significantly decreased, and the difference was significant (P<0.05). Compared with the ulinastatin group, combined treatment with XAV939 promoted the protective effect of ulinastatin on the intestinal mucosa of rats, and the protein expression of β-catenin and cyclin D1 was reduced (P<0.05). Combined treatment with LiCl weakened the protective effect of ulinastatin on the intestinal mucosa of rats, and the protein expression of β-catenin and cyclin D1 was increased (P<0.05). Conclusion Ulinastatin may inhibit the Wnt signaling pathway by down-regulating the expression of β-catenin, reduce the expression of inflammatory factors IL-6 and TNF-α, thereby promote repairing the intestinal mucosal barrier function damage.
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BACKGROUND: To investigate the thalamic neurotransmitters and functional connections in the development of chronic constriction injury (CCI)-induced neuropathic pain. METHODS: The paw withdrawal threshold was measured by mechanical stimulation the right hind paw with the von frey hair in the rats of CCI-induced neuropathic pain. The N-acetylaspartate (NAA) and Glutamate (Glu) in thalamus were detected by magnetic resonance spectrum (MRS) process. The thalamic functional connectivity with other brain regions was scanned by functional magnetic resonance image (fMRI). RESULTS: The paw withdrawal threshold of the ipsilateral side showed a noticeable decline during the pathological process. Increased concentrations of Glu and decreased levels of NAA in the thalamus were significantly correlated with mechanical allodynia in the neuropathic pain states. The thalamic regional homogeneity (ReHo) decreased during the process of neuropathic pain. The functional connectivity among the thalamus with the insula and somatosensory cortex were significantly increased at different time points (7, 14, 21 days) after CCI surgery. CONCLUSION: Our study suggests that dynamic changes in thalamic NAA and Glu levels contribute to the thalamic functional connection hyper-excitation during CCI-induced neuropathic pain. Enhanced thalamus-insula functional connection might have a significant effect on the occurrence of neuropathic pain.
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Animals , Rats , Thalamus/metabolism , Wounds and Injuries/physiopathology , Neurotransmitter Agents/metabolism , Neuralgia , Thalamus/physiopathology , Aspartic Acid/analogs & derivatives , Aspartic Acid/metabolism , Glutamic Acid/metabolism , Constriction , Hyperalgesiaالملخص
Cognitive impairment in children with benign childhood epilepsy with centrotemporal spikes (BECT) has complex etiologies and is closely associated abnormal neural networks. Multimodal magnetic resonance imaging of brain structure and function is a powerful tool for studying abnormal neural networks of cognitive impairment in epilepsy and can explore the pathogenesis of cognitive impairment in epilepsy at the level of brain structure and function by analyzing the imaging features of brain structure and function. This article reviews the research advances in multimodal magnetic resonance for cognitive impairment in children with BECT.
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Child , Humans , Brain , Cognitive Dysfunction , Epilepsy, Rolandic , Magnetic Resonance Spectroscopyالملخص
OBJECTIVE@#Lung-toxin Dispelling Formula No. 1, referred to as Respiratory Detox Shot (RDS), was developed based on a classical prescription of traditional Chinese medicine (TCM) and the theoretical understanding of herbal properties within TCM. Therapeutic benefits of using RDS for both disease control and prevention, in the effort to contain the coronavirus disease 2019 (COVID-19), have been shown. However, the biochemically active constituents of RDS and their mechanisms of action are still unclear. The goal of the present study is to clarify the material foundation and action mechanism of RDS.@*METHODS@#To conduct an analysis of RDS, an integrative analytical platform was constructed, including target prediction, protein-protein interaction (PPI) network, and cluster analysis; further, the hub genes involved in the disease-related pathways were identified, and the their corresponding compounds were used for in vitro validation of molecular docking predictions. The presence of these validated compounds was also measured in samples of the RDS formula to quantify the abundance of the biochemically active constituents. In our network pharmacological study, a total of 26 bioinformatic programs and databases were used, and six networks, covering the entire Zang-fu viscera, were constructed to comprehensively analyze the intricate connections among the compounds-targets-disease pathways-meridians of RDS.@*RESULTS@#For all 1071 known chemical constituents of the nine ingredients in RDS, identified from established TCM databases, 157 passed drug-likeness screening and led to 339 predicted targets in the constituent-target network. Forty-two hub genes with core regulatory effects were extracted from the PPI network, and 134 compounds and 29 crucial disease pathways were implicated in the target-constituent-disease network. Twelve disease pathways attributed to the Lung-Large Intestine meridians, with six and five attributed to the Kidney-Urinary Bladder and Stomach-Spleen meridians, respectively. One-hundred and eighteen candidate constituents showed a high binding affinity with SARS-coronavirus-2 3-chymotrypsin-like protease (3CL), as indicated by molecular docking using computational pattern recognition. The in vitro activity of 22 chemical constituents of RDS was validated using the 3CL inhibition assay. Finally, using liquid chromatography mass spectrometry in data-independent analysis mode, the presence of seven out of these 22 constituents was confirmed and validated in an aqueous decoction of RDS, using reference standards in both non-targeted and targeted approaches.@*CONCLUSION@#RDS acts primarily in the Lung-Large Intestine, Kidney-Urinary Bladder and Stomach-Spleen meridians, with other Zang-fu viscera strategically covered by all nine ingredients. In the context of TCM meridian theory, the multiple components and targets of RDS contribute to RDS's dual effects of health-strengthening and pathogen-eliminating. This results in general therapeutic effects for early COVID-19 control and prevention.
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Humans , Antiviral Agents , Chemistry , Therapeutic Uses , Betacoronavirus , Chemistry , Coronavirus Infections , Drug Therapy , Virology , Cysteine Endopeptidases , Chemistry , Drugs, Chinese Herbal , Chemistry , Therapeutic Uses , Mass Spectrometry , Medicine, Chinese Traditional , Molecular Docking Simulation , Pandemics , Pneumonia, Viral , Drug Therapy , Virology , Protein Interaction Maps , Viral Nonstructural Proteins , Chemistryالملخص
@#This study aimed to observe the therapeutic effect and mechanism of Jinshuibao tablet on acute renal injury induced by cisplatin. Acute renal injury models in SD rats were induced separately by single intraperitoneal injection of cisplatin(5 mg/kg)and intravenous injection for 5 consecutive days at a dosage of 2 mg/kg per day. The renal function and renal histopathological changes were observed in rat acute renal injury models after prevention and treatment with Jinshuibao tablet, respectively. The content of tumor necrosis factor(TNF-α)and reactive oxygen species(ROS), the activity of Caspase 3 and the expression of t-p38, p-p38, Bax and Bcl-2 in the kidneys were detected. The results showed that preventive and therapeutic administration of Jinshuibao tablets could both significantly inhibit the increase of the blood urea nitrogen(BUN)and creatinine(CRE), increase the creatinine clearance rate, reduce the contents of TNF-α and ROS, and decrease the activity of Caspase 3 in acute renal injury models induced by cisplatin. The renal histopathological results showed that Jinshuibao tablets could significantly reduce renal histopathology scores, ameliorate renal tubule degeneration and inflammatory infiltration. Western blot results showed that Jinshuibao tablets could significantly decrease the expression of t-p38 and p-p38, while increasing the Bcl-2/Bax ratio in the kidneys. These results suggested that preventive and therapeutic administration of Jinshuibao tablets could both improve renal function and pathological changes of renal tissue, which might be related to the inhibition of TNF-α and the ROS-p38 MAPK-Caspase3 pathway and thus inhibition of apoptosis.
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@#【Objective】To evaluate the protective effect of Scutellarin(SCU)on type II diabetes-induced disorder of testes and show the mechanism of Scutellarin′s action.【Method】We divided 24 Wistar rats equally into 3 groups:control group,diabetes group and diabetes + SCU group. We used streptozotocin and high-fat diet to establish type Ⅱ diabetic rat model on Wistar rat. Haematoxylin and eosin staining were used to evaluate the testicular morphologic changes. Immunohistochemical staining was used to measure the expression level of vascular endothelial growth factor(VEGF)in testes. Oxidative stress in testes and epididymis was tested by fluorescence spectrophotometer and enzyme linked immunosorbent assay(ELISA). The blood flow rate in testicular vessels was measured by Doppler. 【Results】 Our results showed that hyperglycemia induced morphologic impairments in testes of rats, higher concentrations of Malondialdehyde(MDA) and ROS in testes and epididymis, lower testicular blood flow rate, while administration of Scutellarin could significantly inhibit these damages(DCF:12.93 vs. 7.63 mg/min ;MDA:2.37 vs. 1.48 mg/min ;testicular blood flow rate:110.0 vs. 210.2 mm/s;P < 0.05).【Conclusion】Our data suggest that SCU has the potential to reverse male reproductive disorder in diabetes by reducing the concentrations of ROS and improving. microcirculatory disturbances.
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Rhinacanthus nasutus is the shrubs of Acanthacesa of Rhinacanthus nasutus. It has been used as traditional Zhuang medicine for thousands of years, with antipyretic and alexipharmic, antibacterial and anti-inflammatory, antiasthmatic and expectorant effects. Modern pharmacological studies have shown that R. nasutus has been used for treatment of various diseases, including pneumonia, gastritis and hepatitis. In addition, naphthoquinone esters isolated from this plant exhibits antitumor, antiviral, antifungal, and immunomodulatory activities, with a high application value. Scholars at home and abroad have isolated a variety of compounds from R. nasutus, including 20 naphthoquinones, organic acids, lignans, alkaloids and other structural types of components. Among them, naphthoquinones have a variety of biological activities. Up to now, there are no systematic and comprehensive report on the chemical constituents and pharmacological effects of naphthoquinones. In this review, we summarized the chemical constituents of naphthoquinones with pharmacological activity, finding that R. nasutus and naphthoquinones have a great potential to be developed as a traditional Chinese medicine for tumors, diabetes, nonalcoholic fatty liver, which can provide an important scientific basis for defining the pharmacodynamic basis of the pharmacological activities and a reference for further research and comprehensive utilization of Zhuang medicine of Rhinacanthus nasutus.
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In order to study the transcriptional differences of Citrus medica var. sarcodactylis at different developmental stages, we explored the genes regulating the biosynthesis of the effective components. In this study, Illumina Hiseq 4 000 high-throughput sequencing technology was used to sequence the transcriptome of C. medica var. sarcodactylis at different developmental stages, 121 235 unigenes were obtained with an average length of 2 434 bp, 3 379 different genes were obtained using DESeq screening, which mainly connected to biological processes such as signal transmission, biological regulation, and metabolic processes, and enriched in metabolic pathways such as starch, sucrose metabolism, phenylpropanoid biosynthesis, and flavonoid biosynthesis. Further dynamic comparison of biosynthesis related genes of active ingredients: the expression levels of PAL, CHI, CYP75B1, ZDS, 4CL and FLS gradually increased as the fruit turned from green to yellow; the expressions of COMT, F3H and CYP73A increased at first and then decreased; CCR, HCT and HRP were down-regulated whereas up-regulated. This study provides references for further excavation of key genes in the biosynthesis of active components, as well as biopathway analysis of active components for C. medica var. sarcodactylis.