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Objective:To explore the current status of the post competency evaluation index systems of Chinese general practitioners (GPs), and to summarize the post competency evaluation index systems of GPs in China.Methods:This study was a systematic review. We searched China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, China Science and Technology Journal Database (CQVIP), SinoMed, PubMed and other databases using "general practitioner" or "family doctor" or "standardized training for residents" or "post competency" or "evaluation system" or "core capability" or "assessment" or "evaluation" etc. as search terms and adding free words. The search was conducted from data establishment to October 2022. Literature screening and data extraction were carried out independently by 2 researchers using strict inclusion and exclusion criteria. The Ekman quality evaluation tool was used to evaluate the quality of the included literature. Excel was used to extract data information, including basic information of literatures, basic information of index systems and index content.Results:A total of 1 284 literatures were retrieved and 33 studies were included. A total of 15 research methods were used, and 28 (84.8%) applied 3 or more methods. There were 14 studies (42.4%) with good reliability and validity, and 17 studies (51.5%) with index weights. There were 12 applied theoretical bases, of which 20 studies (60.6%) used mature foreign competency models as a reference, 14 studies (42.4%) combined the job analysis and position requirements of GPs, and 11 studies (33.3%) interpreted policy documents. The content analysis method yielded 1 537 initial indicators, 1 268 indicators after eliminating repeated indicators, and 6 first-level indicators and 31 second-level indicators after combining and summarizing. Among the first-level indexes, "patient care" appeared most frequently (36.4% (462/1 268)); the secondary index with the highest frequency in this dimension was "master medical theoretical knowledge" followed by "community-oriented care ability" and "treatment and follow-up of common and frequently-occurring diseases"; the indicators "family-based care ability" and "human-centered care concept" reflected the characteristics of general medical practice. The frequency of "professional spirit and moral quality" (16.3%(207/1 268)), "clinical teaching and learning ability" (14.3%(181/1 268)) and "system-based practical ability"(11.1%(141/1 268)) ranked second, third and fourth among the first-level indicators respectively. The frequency of "basic public health service ability" (11.0%(139/1 268)) ranked the fifth, and the secondary indicator "health management of key community groups" reflected the concept of the whole life cycle of residents and the basic principle of continuity of care in general medicine. The frequency of "interpersonal and communication skills"(10.9%(138/1 268)) ranked sixth.Conclusions:There have been numerous researches on the post competency index evaluation system of GPs in China, but more research is still needed. There are many research methods with rich theoretical basis and Chinese characteristics. This study summarized the post competency evaluation index systems of GPs in China, generalized 6 first-level indicators and 31 second-level indicators that reflect the basic principles and characteristics of general medicine.
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The discovery of drug targets plays a crucial role in drug research. Accurate information of small molecule drug-protein interaction can be provided by label-free target discovery technology without any structural modification at the small molecule. So, the label-free drug target discovery technology had become the powerful tool to discover the targets of drugs. Due to the “multi-component and multi-target” characteristics of traditional Chinese medicines (TCMs), the research on its targets and mechanism had been restricted. Based on potential of the label-free target discovery technology in the research of TCMs, this paper summarized the label-free target discovery technology and its application in TCMs research. It will provide a reference for the discovery of targets of TCMs and a new view for promoting the modernization of TCMs.
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Objective:To exploring the correlation between the expression levels of microRNA-124 (miR-124), miR-146a, and miR-326 in serum of patients with gestational hypothyroidism and thyroid function and adverse pregnancy outcomes.Methods:Patients who came to our hospital for gestational hypothyroidism treatment from Jun. 2017 to Jun. 2019 were selected as the observation group ( n=121), while the control group was pregnant women who came to our hospital for normal pregnancy during the same period ( n=120). Quantitative real time PCR (RT-qPCR) was used to detect the serum expression levels of miR-124, miR-146a, and miR-326. The serum thyroid hormone (TSH), free triiodothyronine (FT3), free T4 (FT4), thyroid peroxidase antibody (TPOAb), thyroid hormone receptor antibodies (TRAb) were compared. The levels of thyroid microsomal antibody (TMAb) and anti-thyroid autoantibodies (TGAb) were different. Spearman and Pearson correlation analysis were used to explore the correlation between the expression of miR-124, miR-146a and miR-326 and the indicators of thyroid hormone. Chi-square was used to examine the correlation between the levels of miR-124, miR-146a and miR-326 and adverse pregnancy outcomes after treatment. Results:Compared with the control group of healthy pregnant women, the observation group showed an upregulation of miR-146a (0.98 ± 0.12 vs 2.71 ± 0.34) and miR-326 (1.09 ± 0.22 vs 2.11 ± 0.32) serum expression, while the expression of miR-124 was down regulated (1.46 ± 0.23 vs 0.56 ± 0.10), with statistically significant differences ( P<0.05). The TSH, TGAb, TRAb, TMAb, and TPOAb in the observation group were higher than those in the control group, while FT3 and FT4 were lower than those in the control group ( P<0.05). After treatment, FT4, TGAb and TPOAb levels were significantly different between miR-124, miR-146a and miR-326 high expression groups and low expression groups ( P < 0.05). The expression level of miR-124 was significantly positively correlated with FT3 and FT4, and significantly negatively correlated with TSH, TGAb, TRAb, TMAb and TPOAb, while the expression level of miR-146a and miR-326 was significantly negatively correlated with FT3 and FT4. It was positively correlated with TSH, TGAb, TRAb, TMAb and TPOAb ( P < 0.05) . Conclusion:MiR-124, miR-146a, and miR-326 can be used as predictive factors for the efficacy evaluation of gestational hypothyroidism and adverse pregnancy outcomes.
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There is a variety of gut microbiota in human body, which is closely associated with the health and disease. Normal gut microbiota can produce colonization resistance to pathogens. Antibiotics can affect the composition of gut microbiota and change the intestinal microenvironment, resulting in intestinal microecological disorders, which in turn cause intestinal pathogenic infections and other diseases. In this paper, the concept of intestinal microecology, the mechanism of intestinal colonization resistance, the effect of antibiotics on intestinal microecology, and the treatment methods were reviewed, aiming to provide the information for the rational use of antibiotics and the development of more effective treatment methods to maintain the stability of intestinal microecology.
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The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC50 = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC50 = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 ( 5) and AZD5099 ( 6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 ( 6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.
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The Sepsis Coagulopathy Asahi Recombinant LE Thrombomodulin (SCARLET) trial has many defects, and thus cannot be the terminator of recombinant thrombomodulin (rTM). On the contrary, it provides sufficient evidence for further research. Based on analysis focusing on the failure of SCARLET and several previous anticoagulant studies, it is most important for new studies to grasp the following two points: (1) The enrolled cases should have sufficient disease severity and a clear standard for disseminated intravascular coagulation; (2) Heparin should not be used in combination with the investigated drugs. Multiple post-hoc analyses show that no combination of heparin will not increase the risk of thromboembolism. In fact, the combination of heparin can mask the true efficacy of the investigated drug. Due to the complexity of sepsis treatment and the limitations of clinical studies, the results of all treatment studies should be repeatedly verified, rather than be determined at one stroke. Some research conclusions contrary to disease physiology, pharmacology and clinical practice may be deceptive, and should be cautious rather than be simply accepted. On the other hand, the dissenting voices in the "consensus" scene are often well discussed by the authors and should be highly valued.
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Humans , Anticoagulants/therapeutic use , Thrombomodulin/therapeutic use , Blood Coagulation Disorders , Disseminated Intravascular Coagulation/drug therapy , Sepsis/drug therapy , Heparin/therapeutic use , Recombinant ProteinsABSTRACT
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among urban and rural residents in China, and elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for ASCVD. Considering the increasing burden of ASCVD, lipid management is of the utmost importance. In recent years, research on blood lipids has made breakthroughs around the world, hence a revision of China guidelines for lipid management is imperative, especially since the target lipid levels in the general population vary in respect to the risk of ASCVD. The level of LDL-C, which can be regarded as appropriate in a population without frisk factors, can be considered abnormal in people at high risk of developing ASCVD. As a result, the "Guidelines for the prevention and treatment of dyslipidemia" were adapted into the "China Guidelines for Lipid Management" (henceforth referred to as the new guidelines) by an Experts' committee after careful deliberation. The new guidelines still recommend LDL-C as the primary target for lipid control, with CVD risk stratification to determine its target value. These guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle, be used as an initial line of treatment, followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as necessary. The new guidelines provide guidance for lipid management across various age groups, from children to the elderly. The aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice.
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Long noncoding RNAs (lncRNAs) play a critical role in the regulation of atherosclerosis. Here, we investigated the role of the lncRNA growth arrest-specific 5 (lncR-GAS5) in atherogenesis. We found that the enforced expression of lncR-GAS5 contributed to the development of atherosclerosis, which presented as increased plaque size and reduced collagen content. Moreover, impaired autophagy was observed, as shown by a decreased LC3II/LC3I protein ratio and an elevated P62 level in lncR-GAS5-overexpressing human aortic endothelial cells. By contrast, lncR-GAS5 knockdown promoted autophagy. Moreover, serine/arginine-rich splicing factor 10 (SRSF10) knockdown increased the LC3II/LC3I ratio and decreased the P62 level, thus enhancing the formation of autophagic vacuoles, autolysosomes, and autophagosomes. Mechanistically, lncR-GAS5 regulated the downstream splicing factor SRSF10 to impair autophagy in the endothelium, which was reversed by the knockdown of SRSF10. Further results revealed that overexpression of the lncR-GAS5-targeted gene miR-193-5p promoted autophagy and autophagic vacuole accumulation by repressing its direct target gene, SRSF10. Notably, miR-193-5p overexpression decreased plaque size and increased collagen content. Altogether, these findings demonstrate that lncR-GAS5 partially contributes to atherogenesis and plaque instability by impairing endothelial autophagy. In conclusion, lncR-GAS5 overexpression arrested endothelial autophagy through the miR-193-5p/SRSF10 signaling pathway. Thus, miR-193-5p/SRSF10 may serve as a novel treatment target for atherosclerosis.
Subject(s)
Humans , Atherosclerosis/genetics , Autophagy/genetics , Cell Cycle Proteins/metabolism , Endothelial Cells/metabolism , Endothelium/metabolism , MicroRNAs/metabolism , Repressor Proteins/metabolism , RNA Splicing Factors , Serine-Arginine Splicing Factors/genetics , RNA, Long Noncoding/metabolismABSTRACT
Tuberculosis (TB) is one of the deadly diseases caused by Mycobacterium tuberculosis (Mtb), which presents a significant public health challenge. Treatment of TB relies on the combination of several anti-TB drugs to create shorter and safer regimens. Therefore, new anti-TB agents working by different mechanisms are urgently needed. FtsZ, a tubulin-like protein with GTPase activity, forms a dynamic Z-ring in cell division. Most of FtsZ inhibitors are designed to inhibit GTPase activity. In Mtb, the function of Z-ring is modulated by SepF, a FtsZ binding protein. The FtsZ/SepF interaction is essential for FtsZ bundling and localization at the site of division. Here, we established a yeast two-hybrid based screening system to identify inhibitors of FtsZ/SepF interaction in M. tuberculosis. Using this system, we found compound T0349 showing strong anti-Mtb activity but with low toxicity to other bacteria strains and mice. Moreover, we have demonstrated that T0349 binds specifically to SepF to block FtsZ/SepF interaction by GST pull-down, fluorescence polarization (FP), surface plasmon resonance (SPR) and CRISPRi knockdown assays. Furthermore, T0349 can inhibit bacterial cell division by inducing filamentation and abnormal septum. Our data demonstrated that FtsZ/SepF interaction is a promising anti-TB drug target for identifying agents with novel mechanisms.
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[This corrects the article DOI: 10.1016/j.apsb.2023.01.022.].
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An adult female patient of internal nuclear inclusion disease(NIID)with a major clinical manifestation of decreased intelligence and recurrent disturbance of consciousness was followed up for nearly 4 years.In particular,the evolution of the video-electroencephalogram(VEEG),the auxiliary diagnosis of VEEG,and the prediction value of VEEG for clinical outcome were summarized.We found that(1)the background rhythm in NIID patients evolved with the progression of the disease;(2)electroencephalogram reactivity could predict the outcome of NIID coma;(3)VEEG helped to determine whether the consciousness disturbance caused by NIID was due to non-convulsive status epilepticus,This case provides a new idea to explore the application of VEEG in NIID.
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OBJECTIVES@#To study the clinical effect and adverse drug reactions of different doses of glucocorticoid (GC) in the treatment of children with recurrence of steroid-sensitive nephrotic syndrome (SSNS).@*METHODS@#A total of 67 children who were hospitalized and diagnosed with SSNS recurrence in the Department of Nephrology, Children's Hospital, Capital Institute of Pediatrics, from November 2017 to December 2019 were enrolled. They were randomly divided into a moderate-dose GC group (32 children) and a full-dose GC group (35 children). The two groups were compared in terms of urinary protein clearance, recurrence rate within 6 months, and incidence rate of GC-associated adverse reactions.@*RESULTS@#There was no significant difference in the urinary protein clearance rate between the moderate-dose GC and full-dose GC groups (91% vs 94%, P>0.05). There was also no significant difference in the recurrence rate within 6 months between the two groups (41% vs 36%, P>0.05). At 6 months of follow-up, compared with the full-dose GC group, the moderate-dose GC group had a significantly lower cumulative dose of prednisone [(87±18) mg/kg vs (98±16) mg/kg, P=0.039] and a significantly lower proportion of children with an abnormal increase in body weight (6% vs 33%, P=0.045). The logistic regression analysis showed that prednisone dose ≥10 mg/alternate day at enrollment was a risk factor for recurrence within 6 months in children with SSNS (P=0.018).@*CONCLUSIONS@#For children with SSNS recurrence, moderate-dose GC has similar effects to full-dose GC in the remission induction rate and the recurrence rate within 6 months, with a lower cumulative dose and fewer GC-associated adverse reactions within 6 months than full-dose GC.
Subject(s)
Child , Humans , Glucocorticoids/therapeutic use , Nephrotic Syndrome/drug therapy , Prednisone/adverse effects , Prospective Studies , Remission InductionABSTRACT
OBJECTIVE@#To investigate the mechanism of the in vitro toxicity of doxycycline to myeloma cell line H929 and also the possible pathway involved its toxicity.@*METHODS@#Myeloma cell line H929 was treated with DOX, MEK inhibitor U0126 or RAS agonist ML-098, either alone or in combination. Then, the expression of p-MEK, caspase-3, caspase-9 and c-Jun in H929 were used to detected by Western blot; the cells proliferation and apoptosis were detected by CCK-8 assay and flow cytometry, respectively.@*RESULTS@#DOX significantly increased the levels of cleaved caspase-3 and caspase-9, and down-regulated the level of p-MEK in H929 (P<0.05). MEK antagonist U0126 significantly increased the levels of cleaved caspase-3 and caspase-9, and down-regulated the level of p-MEK (P<0.05). After Dox combined with ML-098 treatment of H929 cells, the apoptosis rate of H929 cells was lower than that of DOX alone treatment group(P<0.05). Compared with DOX alone treatment group, the expressions of p-MEK and p-ERK1/2 in DOX+ML-098 combined treatment group were increased, and the levels of cleaved caspase-3,9 in H929 cells were decreased (P<0.05). The levels of c-Jun mRNA and protein increased in H929 when treated by DOX alone (P<0.05).@*CONCLUSION@#DOX can induce apoptosis of H929 via intrinsic apoptosis pathway, and MEK/ERK pathway and c-Jun possibly play a role in this process.
Subject(s)
Humans , Apoptosis , Caspase 3 , Caspase 9/pharmacology , Cell Line, Tumor , Cell Proliferation , Doxycycline/pharmacology , Mitogen-Activated Protein Kinase Kinases/pharmacology , Multiple MyelomaABSTRACT
OBJECTIVE@#To investigate the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in multiple myeloma (MM) patients, and analyze the effect of doxycycline (DOX) on the expression of MMP-2 and MMP-9 in MM cells.@*METHODS@#The peripheral blood and bone marrow samples of MM patients were collected, and the patients were divided into three groups: newly diagnosed group, remission group and relapsed/refractory group, while the peripheral blood samples of 34 health people and the bone marrow samples of 17 IDA patients were selected as normal control and control group. The levels of MMP-2 and MMP-9 were detected by ELISA. The protein levels of MMP-2 and MMP-9 in H929 cells treated by different concentrations of DOX were analyzed by Western blot. After H929 cells was treated by Akt inhibitor MK-2206 2HCl in combination with DOX, Western blot was used to detect the levels of MMP-2 and MMP-9.@*RESULTS@#The levels of MMP-2 and MMP-9 in newly diagnosed MM patients were higher than those in control (P<0.05), while for the patients in the remission group were decreased, but still higher than those in control. The levels of MMP-2 and MMP-9 were increased again for the patients in relapsed/refractory group, and showed no significant difference as compared with those in newly diagnosed group. The levels of MMP-2 and MMP-9 could be inhibited by 10 mg/L and 15 mg/L DOX treated by H929 cell. The protein levels of MMP-2 and MMP-9 showed no altered in H929 cells treated by 5 nmol/L MK-2206 2HCl alone. DOX exerted more profound inhibitory effect to MMP-2 and MMP-9 expression in H929 cells when Akt inhibitor MK-2206 2HCl was combined with DOX.@*CONCLUSION@#The levels of MMP-2 and MMP-9 are increased in MM patients and related to the disease status of MM. DOX can inhibit the expression of MMP-2 and MMP-9 in MM cells, and antagonizing its activation of Akt signaling pathway can further enhance the inhibitory effect.
Subject(s)
Humans , Doxycycline/pharmacology , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Multiple Myeloma/metabolism , Proto-Oncogene Proteins c-aktABSTRACT
To explore the effectiveness and safety of a Chinese medicinal decoction Wuwei Xiaodu Drink (WWXDD) in inhibiting chronic osteomyelitis via regulatory T cells signaling. The effective constitutes of WWXDD and osteomyelitis related genes were screened. Target proteins were cross-validated using the Venny database. GO function and KEGG pathway analysis were performed for target proteins, while pharmacological network was constructed. The bone properties were analyzed by HE staining and the concentrations of immune factors were measured by ELISA. The expression of CTLA-4 and Foxp3 mRNA and STAT5, p-STAT5, CTLA-4 and Foxp3 protein were detected using Real-time PCR and Western blot, respectively. FACS was used to analyze the percentages of cells. A total of 117 genes overlapped between 785 target genes of the active compounds of WWXDD and 912 osteomyelitis related genes. Inflammation-related genes, including IL-6, TNFα, IL-1β and IL-2 showed high connection degree in the drug-compound-disease-target network. GO function and KEGG pathway analysis revealed that 117 intersection genes mainly enriched in virus infection related pathways, immune related pathways and chemokine signaling pathway. Furthermore, the development of chronic osteomyelitis was suppressed in model rats after treatment with WWXDD. Meanwhile, the concentrations of IL-2 and CD4+CD25+Foxp3 Treg percentages together with the levels of p-STAT5, CTLA-4 and Foxp3 were also down-regulated. Furthermore, IL-2 and WWXDD drug-containing serum exhibited opposite effects on regulating IL-2, IL-10, TGF-β1, Foxp3, CTLA4 and STAT5. In addition, a STAT5 phosphorylation inhibitor suppressed the expression of Foxp3 and CTLA-4. WWXDD can treat chronic osteomyelitis through suppressing the main regulating factors of Tregs and interfere its immunodepression. Our results bring a new solution for chronic osteomyelitis.
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Animals , Rats , Forkhead Transcription Factors/metabolism , Interleukin-2/metabolism , Osteomyelitis/metabolism , STAT5 Transcription Factor/metabolism , Signal Transduction , T-Lymphocytes, RegulatoryABSTRACT
@#Objective （ ） To explore the application value of bone suppression imaging BSI in the diagnosis of occupational （ pneumoconiosis） Methods - pneumoconiosis hereinafter referred to as " " . A total of 330 chest films of high kV digital （ ） radiograph DR of patients with suspected pneumoconiosis were selected by convenient sampling method. BSI is applied to the ， ， ， ， chest films and the differences of small opacity shape small opacity aggregation the number of large opacity lung areas small （ ）， opacity profusion and diagnostic stage of pneumoconiosis were analyzed by simple DR reading DR group simple BSI reading （ ） （ ） Results BSI group and DR and BSI combined reading combined group . There was no significant difference in the distribution of small shadows and the detection rate of small shadows aggregation and large shadows in pneumoconiosis among （ P ） ， the three film reading methods all >0.05 . For the concentration distribution of each lung area there was statistically （P< ）， significant difference between the DR group and the BSI group 0.05 but there was no statistically significant difference ， （ P ） between the DR group and the combined group and between the BSI group and the combined group all >0.05 . The results of ， consistency analysis showed that the DR group and the BSI group and the DR group and the combined group had high （ ， P< consistency in the judgment of small shadow intensity in the lung region both weighted Kappa coefficient were 0.75 all ） 0.01 . There was a high consistency between BSI group and DR group and combined group and DR group in the diagnosis of （ ， ， P< ） ， pneumoconiosis stage weighted Kappa coefficient were 0.77 0.79 all 0.01 . Compared with the DR group the diagnostic ， rate of pneumoconiosis stage Ⅰwas significantly reduced and the diagnostic rate of pneumoconiosis stage Ⅱ was significantly （ P< ） ， increased in the BSI group and the combined group all 0.01 . However there was no significant difference in the diagnosticrate of pneumoconiosis stage Ⅲ >0.05 . Both the BSI reading and DR and BSI combined reading can improve ， the display of pneumoconiosis lesions to varying degrees and therefore can improve the diagnosis of pneumoconiosis. In ， addition the identification and diagnosis of pneumoconiosis lesions in the BSI reading is comparable to that in the combined ， group which has a good application value in the diagnosis of pneumoconiosis.
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Combination products face unique R&D, manufacturing, clinical, and regulatory challenges compared to individual devices, drugs, or biological products. Based on the interpretation of the relevant policies and the latest principles of combination products, this paper expounds the FDA's guidance, application trends, and application strategies for the pre-market pathways of combination products, with a view to providing relevant information for Chinese researchers and manufacturers when they start to entry the United States market.
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Commerce , Consumer Product Safety , Direct-to-Consumer Advertising , United States , United States Food and Drug AdministrationABSTRACT
OBJECTIVE@#To observe the effect of wheat-grain moxibustion at "Dazhui" (GV 14) on the expressions of Beclin-1 and GRP78 in spinal dorsal horn in rats with cervical spondylotic radiculopathy (CSR), and to explore the possible analgesic mechanism of wheat-grain moxibustion for CSR.@*METHODS@#A total of 48 SD rats were randomly divided into a sham operation group, a model group, a wheat-grain moxibustion group and a wheat-grain moxibustion+3-MA group, 12 rats in each group. The CSR model was prepared by spinal cord insertion method. Three days after modeling, the rats in the model group were intraperitoneally injected with 1 mL of 0.9% sodium chloride solution; the rats in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14, 6 cones per time) on the basis of the model group; the rats in the wheat-grain moxibustion+3-MA group were intraperitoneally injected with 3-MA solution and wheat-grain moxibustion at "Dazhui" (GV 14, 6 cones per time). The three groups were intervened for 7 days, once a day. The gait score and mechanical pain threshold were observed before treatment and 7 days into treatment; after the treatment, the expressions of mRNA and protein of Beclin-1 in spinal dorsal horn were detected by real-time fluorescence quantitative PCR and immunohistochemistry; the expression of GRP78 protein in spinal dorsal horn was detected by Western blot method; the autophagosomes and ultrastructure in spinal dorsal horn neurons were observed by electron microscope.@*RESULTS@#After the treatment, compared with the sham operation group, in the model group, the gait score was increased and the mechanical pain threshold was decreased (P<0.01), and the expression of GRP78 protein in spinal dorsal horn was increased (P<0.01). Compared with the model group and the wheat-grain moxibustion+3-MA group, in the wheat-grain moxibustion group, the gait score was decreased and mechanical pain threshold was increased (P<0.01), and the expression of GRP78 protein in spinal dorsal horn was decreased, and the expressions of mRNA and protein of Beclin-1 were increased (P<0.01). Under electron microscope, the ultrastructure of spinal dorsal horn neurons in the wheat-grain moxibustion group was not significantly damaged, and its structure was basically close to normal, and the number of autophagosomes was more than the other three groups.@*CONCLUSION@#Wheat-grain moxibustion at "Dazhui" (GV 14) has analgesic effect on CSR rats. The mechanism may be related to moderately up-regulate the expression of Beclin-1, enhance autophagy and reduce endoplasmic reticulum stress.
Subject(s)
Animals , Rats , Beclin-1/genetics , Endoplasmic Reticulum Chaperone BiP , Moxibustion , RNA, Messenger , Radiculopathy/therapy , Rats, Sprague-Dawley , Spinal Cord , Spinal Cord Dorsal Horn , Spondylosis , Triticum/geneticsABSTRACT
In this study, a novel oral drug delivery system based on linolenic acid-modified chitosan (CS-LA) micelle was developed to improve the oral bioavailability of doxorubicin (DOX), which was proven by its in vivo intestinal absorption in rats. The DOX-loaded CS-LA micelles (CS-LA@DOX) were prepared by the dialysis method. The synthesized micelle material was identified by proton nuclear magnetic resonance spectroscopy (1H-NMR) and Fourier transform infrared spectroscopy (FT-IR). A series of the micelle properties, including particle size distribution, zeta potential, encapsulation efficiency (EE), drug loading (DL), micromorphology, polymorphy, and critical micelle concentration (CMC) were characterized or tested. The in vitro release of micelles was observed by the dialysis method, and the absorption-promoting effect of micelles was investigated by intestinal circulation experiments in rats. The animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Guilin Medical University. The results of 1H-NMR and FT-IR showed that CS and LA were covalently bound via an amide linkage. The DOX encapsulated in the micelle core was in an amorphous state. The as-prepared micelles in the transmission electron microscope (TEM) image showed regular spherical shapes and uniform sizes with a series of excellent characteristics including (119.2 ± 2.1) nm of mean particle size [polymer dispersity index (PDI), 0.190 ± 0.08], +12.1 mV of zeta potential, (70.23 ± 0.74) % of EE, (8.77 ± 0.02) % of DL and 51.75 μg·mL-1 of CMC. Compared with the reference, DOX hydrochloride, the proposed micelle drug delivery system showed an obvious sustained-release effect in vitro release; and enhanced drug absorption in the small intestine of rats.
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Objective: We evaluated the safety and efficacy of lipoprotein apheresis (LA) in patients with familial hypercholesterolemia (FH) who can't reach low-density lipoprotein cholesterol(LDL-C) target goals with the maximal tolerated dose of lipid-lowering agents. Methods: This was a retrospective cross-sectional study. Between February 2015 and November 2019, patients with FH who were admitted in Fuwai hospital and treated with LA were consecutively enrolled. Based on intensive lipid-lowering agents, these patients received LA by double filtration plasma pheresis (DFPP) method. The changes of lipid levels such as LDL-C and lipoprotein(a)[Lp(a)] were compared before and after LA treatment, and the changes of immunoglobulin (Ig) concentration and LA-related adverse effects were also discussed. Results: A total of 115 patients with FH were enrolled in this study, of which 8 cases were homozygous FH and 107 cases were heterozygous FH. The age was (43.9±12.2) years and there were 75 (65.2%) males, and 108 (93.8%) with coronary artery disease. For pre-and immediately after LA treatment, the LDL-C was (5.20±2.94) mmol/L vs. (1.83±1.08) mmol/L, Lp(a) concentration was 428.70(177.00, 829.50)mg/L vs. 148.90(75.90, 317.00) mg/L (P<0.001), with a decrease of 64.2% and 59.8% respectively. The levels of IgG and IgA measured 1 day after LA treatment were both in the normal range and IgM concentration was below the reference value, the reductions of which were 15.1%, 25.0% and 58.7% respectively (P<0.001). Six patients had mild symptoms of nausea, hypotension dyspnea and palpitation, the symptoms were relieved by symptomatic treatment. Conclusion: For patients with FH who do not achieve LDL-C target goal with the maximal tolerated lipid-lowering agents, especially those with elevated Lp(a) levels, LA, which can significantly further reduce LDL-C and Lp(a) levels, is an effective and safe option.