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OBJECTIVE@#To screen the active components from Fuzheng Huayu Recipe (FZHY) and redesign a new recipe composed of the active components, and validate the effect of active components formulation from FZHY against liver fibrosis.@*METHODS@#Thirty-two components from FZHY were evaluated for their activities against liver fibrosis respectively, with 6 kinds of cell models in vitro, including oxidative stressed hepatocyte in L-02, hypoxia injured/proliferative hepatic sinusoidal endothelial cells in SK-HEP-1 and human hepatic sinusoidal endothelial cells (HHSEC), and activated hepatic stellate cell in LX-2. The comprehensive activity of each component against liver fibrosis was scored according to the role of original herbs in FZHY and cell functions in fibrogenesis. Totally 7 active components were selected and combined with equal proportion to form a novel active components formulation (ACF). The efficacy of ACF on liver fibrosis were evaluated on activation of LX-2 and proliferation of HHSEC in vitro and in liver fibrosis model mice induced by dimethylnitrosamine (DMN). Totally 72 mice were divided into 6 groups using a random number table, including normal, high-dose ACF control (20 µ mol/L × 7 components/kg body weight), model, low-, medium-, high-dose ACF groups (5, 10, 20 µ mol/L × 7 components/kg body weight, respectively). Hematoxylin eosin and Sirius red stainings were used to observe inflammation and fibrosis change of liver tissue; scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were utilized to observe the effect of ACF on ultrastructure of hepatic sinusoids.@*RESULTS@#Fifteen components from FZHY showed higher scores for their activity on against liver fibrosis. Among them, 7 components including tanshinone II A, salvianolic acid B, cordycepin, amygdalin, quercetin, protopanaxatriol, and schizandrin B were recombined with equal proportions to form ACF. ACF at 1,2, 4 µ mol/L showed strong inhibitory effects on activation of LX-2 and proliferation of HHSEC in vitro (all P<0.01). Compared with the model group, ACF attenuated liver collagen deposition, improved sinusoidal capillarization in a dose-dependent manner (all P<0.05).@*CONCLUSION@#ACF exerts a satisfactory effect against experimental liver fibrosis and attenuates sinusoidal capillarization, which warrant a further research and development for herbal components formulation on liver fibrosis.
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Animals , Body Weight , Drugs, Chinese Herbal/adverse effects , Endothelial Cells , Liver , Liver Cirrhosis/drug therapy , MiceABSTRACT
RNA binding protein (RBP) plays a key role in gene regulation and participate in RNA translation, modification, splicing, transport and other important biological processes. Studies have shown that abnormal expression of RBP is associated with a variety of diseases. The Musashi (Msi) family of mammals is an evolutionarily conserved and powerful RBP, whose members Msi1 and Msi2 play important roles in the regulation of stem cell activity and tumor development. The Msi family members regulate a variety of biological processes by binding and regulating mRNA translation, stability and downstream cell signaling pathways, and among them, Msi2 is closely related to embryonic growth and development, maintenance of tumor stem cells and development of hematological tumors. Accumulating evidence has shown that Msi2 also plays a crucial role in the development of solid tumors, mainly by affecting the proliferation, invasion, metastasis and drug resistance of tumors, involving Wnt/β-catenin, TGF-β/SMAD3, Akt/mTOR, JAK/STAT, Numb and their related signaling pathways (Notch, p53, and Hedgehog pathway). Preclinical studies of Msi2 gene as a therapeutic target for tumor have achieved preliminary results. This review summarizes the molecular structure, physiological function, role of Msi2 in the development and progression of various solid tumors and the signaling pathways involved.
Subject(s)
Animals , Hedgehog Proteins , Mammals/metabolism , Neoplasms/genetics , Neoplastic Stem Cells , RNA-Binding Proteins/metabolism , Signal TransductionABSTRACT
Objective: To analyze the characteristics of heart rate variability (HRV) in patients with vestibular migraine (VM) and to explore its possible mechanism. Methods: Forty-eight patients with VM [17 males and 31 females, age (36.2±9.2) years], 44 patients with migraine [15 males and 29 females, age (34.4±9.0) years], and 30 patients with health check-ups during the same period [12 males and 18 females, age (34.6±6.5) years old] were selected as study subjects. Ambulatory ECG monitoring was performed in all subjects, and the HRV characteristics of each group were analyzed from both daytime and nighttime time phases. Time domain parameters were analyzed: standard deviation of normal to normal (SDNN), root mean square of successive differences (RMSSD), and percentage of normal to normal intervals differing by more than 50 ms (pNN50). The parameters in the frequency domain were analyzed: high frequency power (HF), low frequency power (LF), and the ratio of low frequency to high frequency power (LF/HF). Statistical analysis of the data was performed using SPSS 26.0 software. Results: At night, RMSSD (F=6.694) and HF (F=9.434) were lower in the VM and migraine groups compared to the control group, while LF/HF (F=16.049) and LF (F=9.434) were elevated compared to the control group, with statistically significant differences (P<0.05 or P<0.01), while LF was significantly elevated in the VM group compared to the migraine group, with a statistically significant (P<0.05). On the daytime measurements, mainly LF was elevated in the vestibular migraine group compared with the control group, while RMSSD was decreased compared with the control group, with statistically significant differences (P<0.05). Conclusion: Autonomic dysfunction characterized by sympathetic hyperfunction and vagal hypofunction is present in VM patients and is more pronounced at night. In addition, the degree of autonomic dysfunction may be more pronounced in VM patients than in migraine patients.
Subject(s)
Adult , Female , Heart Rate/physiology , Humans , Male , Middle Aged , Migraine Disorders , VertigoABSTRACT
Objective:To observe the changes of corneal curvature and ocular surface after congenital ptosis.Methods:A total of 188 patients with congenital blepharoptosis were treated with frontal muscle flap suspension, levator eyelid muscle shortening and fixation, and levator aponeurosis according to different conditions. The postoperative correction effect, corneal curvature, and ocular surface changes were observed.Results:There was no significant difference in the good correction rate among the three methods ( P>0.05). The corneal curvature at 3 months after operation was lower than that before operation and 7 days after operation ( P<0.05). The fluorescein staining score at 7 days after operation was higher than that before operation and 3 months after operation ( F=2 910.05, P<0.05). The tear film rupture time at 7 days after operation was significantly shorter than that before operation and 3 months after operation ( F=758.12, P<0.05). There was no significant difference in tear secretion test before operation, 7 days after operation and 3 months after operation ( P>0.05). The conjunctival congestion score at 3 months after operation was lower than that at 7 days after operation, and the incidence of meibomian gland dysfunction and abnormal eyelash angle at 3 months after operation was lower than that at 7 days after operation ( t=113.56, χ 2=11.02, 11.46, P<0.05). 3 months after operation, the average diopters of 3 mm and 5 mm were higher than those before operation ( t=12.35, 15.19, P<0.05). Conclusions:Frontal muscle suspension, levator eyelid muscle shortening and fixation, and levator aponeurosis are effective in treating congenital blepharoptosis, and can effectively improve the ocular surface and corneal curvature. Clinically, the appropriate one can be selected according to the condition of the child correction method.
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Objective:To evaluate the application value of left ventricular pressure-strain loop (PSL) in patients with rheumatoid arthritis (RA) by the PSL.Methods:From April 2020 to June 2021, 75 RA patients(case group) and 35 healthy physical examination person(control group) were selected from the Affiliated Hospital of Inner Mongolia Medical University.According to the disease activity scores 28(DAS28) joint disease range of activity score, the patients were divided into low range of activity group (16 cases), medium range of activity group (35 cases) and high range of activity group (24 cases). Echocardiographic examinations were performed on all patients, conventional ultrasound data were collected and the left ventricular PSL technology was used to analyze the myocardial work parameters, including global work index (GWI), global constructive work (GCW), global waste work (GWW) and global work efficiency (GWE). The mean values of myocardial work index (MWI), constructive work (CW), waste work (WW) and work efficiency (WE) were calculated. The differences of myocardial work parameters between the case groups and the control group were compared, and the correlation analysis of myocardial work parameters with global longitudinal strain of left ventricle(LVGLS), left ventricular ejection fraction(LVEF) and DAS28 scores were conducted.Results:①There were no statistically significant differences of clinical data between each case group and the control group (all P>0.05). ②Compared with the control group and low disease activity group, the LVGLS of medium and high disease activity groups decreased obviously (all P<0.05). ③The GWI and GCW of the medium and high disease activity groups were significantly lower than those of the control group (all P<0.05), and there were no statistically significant differences of GWW and GWE between the case groups and the control group (all P>0.05). The mid-segment MWI, apical MWI and CW of the medium and high disease activity case groups, and the mid-segment CW of the medium disease activity case group were lower than those of the control group (all P<0.05). ④In the case group, GWI, GCW and LVEF were significantly and positively correlated ( rs1=0.253, P=0.008; rs2=0.261, P=0.024), and were significantly negatively correlated with LVGLS ( rs1=-0.525, P<0.001; rs2=0.455, P<0.001). There were no significant correlations between myocardial work parameters and DAS28 score (all P>0.05). Conclusions:PSL can early reflect to the impaired cardiac function of RA patients with moderate and high disease activity, and provide a new imaging method for clinical evaluation of the cardiac function of patients.
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Objective@#To identify epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma based on 18 F-fluorodeoxyglucose (FDG) PET/CT radiomics and clinical features and to distinguish EGFR exon 19 deletion (19 del) and exon 21 L858R missense (21 L858R) mutations using FDG PET/CT radiomics. @*Materials and Methods@#We retrospectively analyzed 179 patients with lung adenocarcinoma. They were randomly assigned to training (n = 125) and testing (n = 54) cohorts in a 7:3 ratio. A total of 2632 radiomics features were extracted from the tumor region of interest from the PET (1316) and CT (1316) images. Six PET/CT radiomics features that remained after the feature selection step were used to calculate the radiomics model score (rad-score). Subsequently, a combined clinical and radiomics model was constructed based on sex, smoking history, tumor diameter, and rad-score. The performance of the combined model in identifying EGFR mutations was assessed using a receiver operating characteristic (ROC) curve. Furthermore, in a subsample of 99 patients, a PET/CT radiomics model for distinguishing 19 del and 21 L858R EGFR mutational subtypes was established, and its performance was evaluated. @*Results@#The area under the ROC curve (AUROC) and accuracy of the combined clinical and PET/CT radiomics models were 0.882 and 81.6%, respectively, in the training cohort and 0.837 and 74.1%, respectively, in the testing cohort. The AUROC and accuracy of the radiomics model for distinguishing between 19 del and 21 L858R EGFR mutational subtypes were 0.708 and 66.7%, respectively, in the training cohort and 0.652 and 56.7%, respectively, in the testing cohort. @*Conclusion@#The combined clinical and PET/CT radiomics model could identify the EGFR mutational status in lung adenocarcinoma with moderate accuracy. However, distinguishing between EGFR 19 del and 21 L858R mutational subtypes was more challenging using PET/CT radiomics.
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OBJECTIVE To interpret the revision of the in dicators o f pharmaceutical administration in National Tertiary Public Hospitals Performance Evaluation Operational Manual （2022 edition）[hereinafter referred to as the Mannual（2022 edition）]，and to provide reference for the implementation of a new round of performance appraisal in tertiary public hospitals. METHODS The contents and revision details of the indicators of pharmaceutical administration in the Mannual（2022 edition）were described briefly，and the revised contents were interpreted and relevant suggestions were put forward. RESULTS & CONCLUSIONS The Manual（2022 edition）continued the scope of performance evaluation ，indicators’structure and sequence in the Manual（2020 edition），which focused on rational drug use and drug cost control. The Manual （2022 edition） placed more emphasis on strengthening the provision and use of essential medicines and selected drugs in the centralized drug procurement ，and further reducing the burden of medical costs in patients. It is suggested that tertiary public hospitals scientifically set indicators for the use of essential medicines ，selected drugs in the centralized drug procurement ，auxiliary drugs and antibacterial drugs in clinical departments，and improve relevant incentive mechanisms and performance assessment systems ；strengthen the interpretation of policies about essential medicines and drug centralized procurement ，as well as the training of rational drug use ；optimize in-hospital drug catalog and formulary ；formulate medication standards ，strengthen prescription review ，rational medication review and assessment ；establish and improve the drug use monitoring and evaluation and early warning system so as to standardize clinical drug use behavior by information technology ；strengthen the use of essential drugs and centrally purchase selected drugs on the basis of ensuring rationality ；control the unreasonable gradually reduce the increase in average drug costs.
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Objective:To investigate the application of radiotherapy and the basic situation of teaching and scientific research in Xinjiang.Methods:A unified questionnaire was adopted, distributed and collected by mail, instant messaging software and telephone. The basic situation of all radiotherapy affiliations in the whole region was counted.Results:The questionnaire coverage rate was 100% with a recovery rate of 100%. In 2020, 17 affiliations operated radiotherapy in Xinjiang, including 23 linear accelerators, 1 cobalt-60 therapeutic machine, 3 gamma knives, 6 post-installed therapeutic machines, 13 special analogue positioning machines, 46 treatment planning systems, and 103 sets of radiotherapy quality control equipment. It was estimated that the number of radiotherapy equipment for one million people in the whole region was approximately 0.84. In Xinjiang, 359 radiotherapy personnel were registered, including 220 physicians, 49 physicists and 90 technicians. A total of 1 270 beds were available, with an average daily treatment volume of approximately 1 255 person-times. From 2016 to 2021, 17 affiliations have undertaken 9 National Natural Science Foundation of China and 49 provincial and ministerial projects. Nineteen doctoral degrees and 87 master′s degrees were accredited. These affiliations participated in the publication of 25 articles in Chinese Journal of Radiation Oncology, of which 18 were published as the first authors and/or corresponding authors.Conclusions:The radiotherapy work in Xinjiang has developed rapidly in recent years, but there is still a certain gap with the national average level. At the same time, several problems still exist in the whole region, such as regional differences, unbalanced allocation of radiotherapy resources and scientific research and teaching resources, which need further improvement.
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Objective:To analyze the prognostic factors of patients with locally advanced nasopharyngeal carcinoma after treatment, to develop and validate the prognostic Nomogram model.Methods:From July 2010 to June 2017, 317 patients with nasopharyngeal carcinoma who were treated with definitive intensity modulated radiation therapy were selected. The regression method of least absolute shrinkage and selection operator (LASSO) was used for univariate screening, and Cox multivariate regression analysis was performed. The prognostic Nomogram model was constructed for locally advanced nasopharyngeal carcinoma patients. C-index, calibration curve, Net Reclassification Index (NRI), integrated discrimination improvement (IDI) were used to validate and evaluate the model between Nomogram and TNM staging system. The risk evaluated through nomogram was stratified by decision tree algorithm, and the survival rate was calculated by Kaplan-Meier method and compared by Log-rank test.Results:T stage, N stage, LDH, GTVnd and pre-treated plasma EBV-DNA copy (EBV-DNA) were correlated with total survival (OS). All the above factors were included in prognostic Nomogram model, and C-index was 0.784 (95% CI: 0.736-0.831, P<0.01). The calibration curve showed that the OS probability predicted by Nomogram model was in good agreement with the actual OS, and the result were verified in the validation cohort. Furthermore, the accuracy of the Nomogram model for OS predicting was superior to AJCC 8 th version staging system judged by NRI and IDI. According to the Nomogram score, patients can be divided into four subgroups with different risk by decision tree algorithm. K-M survival curve showed that the difference of OS between different groups was statistically significant ( χ2=113.21, P<0.01), and patients in high-risk group can benefit from induction chemotherapy combined with concurrent chemoradiotherapy in survival. Conclusions:The Nomogram model established by our research group can provide information on diagnosis, treatment and prognosis evaluation for locally advanced nasopharyngeal carcinoma patients in this area.
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Objective:To investigate the application status of the practice evidence of falls prevention in elderly inpatients in Chinese comprehensive tertiary hospitals.Methods:Using a self-designed questionnaire based on the practice evidence of falls prevention in elderly inpatients to investigate the application status of that in 81 Chinese comprehensive tertiary hospitals.Results:93.83% (76/81) of the investigated hospitals had a falls screen in the admission assessment of elderly inpatients, and 49.38% (40/81) of the surveyed hospitals used Morse Falls Scale to screen. At the same time, 62.96%(51/81) of the hospitals had falls assessment of elderly inpatients, while only 25.93%-40.74% of the hospitals included the fear of falls, urinary incontinence, footwear, as well as foot problems in the falls screen or assessment. In addition, the implementation rate of falls prevention was 12.35%-79.01% in the hospitals surveyed, and only 60.49% (49/81) of the hospitals had individualized falls prevention intervention. Furthermore, the falls prevention participation rate of primary nurses and doctors, as well as patients′ care was higher than 80.00%, but that of pharmacists, rehabilitation therapists and physiotherapists was only between 12.35% to 24.69%.Conclusions:Hospitals should take the characteristics of environment and elderly inpatients in the hospital into consideration to choose the risk factors which should be included in the falls screen/assessment, as well as select the appropriate screen/assessment tools. Meanwhile, hospitals should culture and encourage the right workers′ participation to build a multidisciplinary team for falls assessment and intervention to achieve the goal of falls and falls injuries prevention with the evidence.
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Objective:To explore the clinical characteristics and susceptibility factors for bloodstream infections (BSI) of Enterococcus faecium in children, thus providing guidance for clinical prevention and treatment. Methods:Clinical data of 18 children with BSI of Enterococcus faecium treated in the West China Second University Hospital, Sichuan University from January 2011 to October 2019 were collected.Their underlying diseases, predisposing factors, clinical information, etiological data, treatment and prognosis were retrospectively analyzed. Results:Sixteen of 18 children (88.9%) with BSI of Enterococcus faecium had underlying diseases, including intestinal diseases or intestinal surgery, preterm infants, hematological diseases, congenital heart disease, biliary atresia and urinary system malformations.Seventeen of 18 children (94.4%) had predisposing factors, including broad-spectrum antibiotics exposure, Intensive Care Unit (ICU) admission, central venous catheterization, malnutrition, abdominal distension or intestinal infection, granulopenia or agranulocyte, mechanical ventilation.The underlying diseases and susceptible factors varied with the age of patients.The most common predisposing factors of all-aged patients with BSI of Enterococcus faecium were broad-spectrum antibiotics exposure (76.5%) and central venous catheterization (52.9%). In patients with single infection of Enterococcus faecium, their C-reactive protein (CRP) was normal or slightly elevated and no children died.The incidences of respiratory failure, shock and severe sepsis in patients with single infection of Enterococcus faecium were 16.6%, 0% and 8.3% respectively, which were 33.3%, 33.3% and 66.7% respectively in 6 children (33.3%) with mixed infections, and one died.Vancomycin-resistant strains were not found, and Vancomycin treatment was effective that quickly relieved clinical symptoms. Conclusions:(1)Most of children with BSI of Enterococcus faecium have underlying diseases and susceptible factors.The most common predisposing factors of all-aged patients with BSI of Enterococcus faecium are broad-spectrum antibiotics exposure and central venous catheterization.(2)The pathogenicity of Enterococcus faecium is low, and the clinical manifestations of BSI are atypical.(3)There is a high rate of mixed infections of Enterococcus faecium, and the severity and mortality of the mixed infected children are much higher than those with single infection.(4)No Vancomycin-resistant strains are found, and vancomycin treatment is effective that quickly relieves clinical symptoms.(5)Rational use of antibiotics and strict management of central venous cathete-rization are the most important preventive measures.
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Formononetin is a kind of plant isoflavones extracted from medicinal herbs such as Trifolium pratense，Astragalus membranaceus and Spatholobi Caulis have shown that formononetin has strong anti-tumor biological activity，and can be used as an anti-tumor drug in the treatment of various malignant tumors. Many studies so far have shown that formononetin can inhibit cell proliferation，induce cell apoptosis，inhibit cell migration and invasion，and induce cell cycle arrest on tumors through a variety of molecular mechanisms and pathways. These antitumor activities can be observed in cells of various tumors such as breast cancer，colorectal cancer，prostate cancer，bladder cancer and lung cancer in trials and animal models. Examples of these effects include triggering the generation of reactive oxygen species （ROS），regulating phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin（PI3K/Akt/mTOR） and Mitogen-activated protein kinases（MAPK） signaling pathways，inhibiting the activation of tyrosine kinase（JAK1 and JAK2 ）and nonreceptor tyrosine kinase（c-Src），and regulating cytokeratin 19（CK19），matrix metalloproteinases（MMP），microRNA-21（miR-21），lamin A/C antibody（Lamin A/C），expression of Cyclin D1 and Cyclin E1. In addition， the anti-tumor effects of formononetin derivatives were reviewed in this paper. By modifying the chemical structure of formononetin，many related derivatives have been obtained. Experimental results have shown that some derivatives of formononetin have stronger anti-tumor activity and lower cytotoxicity，but the related molecular mechanism of action still needs to be explored further in-depth. In conclusion，formononetin and its derivatives may become potential anti-tumor drugs.
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Uterine leiomyoma （UL）， the most common benign tumor of the reproductive system in women of childbearing age， is characterized by clinical symptoms such as increased menstrual flow， prolonged menstrual period， breast tenderness，backache， lower abdominal pain and mass in the lower abdomen. With the continuous progress of modern society， the age of women's marriage and childbirth is gradually pushed back， which to a certain extent has led to an increase in the probability of modern women suffering from UL. Relevant literature shows that the incidence of UL is about 70%， and 25%-50% of the patients have clinical symptoms， seriously endangering women's physical health. The prevention and treatment of UL by modern medicine is currently limited to two aspects： drug control of estrogen and progesterone levels and surgical removal. Traditional Chinese medicine（TCM）has shown obvious advantages in improving the clinical symptoms of UL patients， with very broad application prospects as it can regulate body's Qi and blood on the basis of syndrome differentiation， treatment and overall concepts. Lichongtang， as a famous TCM prescription for replenishing Qi， activating blood and removing blood stasis， was created by ZHANG Xi-chun， a famous Chinese medicine doctor in the Qing dynasty， and recorded in the Records of Tradition Chinese and Western Medicine in Combination. It is widely used in the field of gynecological diseases in clinical practice. Studies have shown that Lichongtang is effective in treating UL. Clinical observations show that Lichongtang can significantly relieve the clinical symptoms of UL patients such as prolonged menstrual period， dysmenorrhea， waist and abdomen swelling and irregular vaginal bleeding， with the characteristics of stable curative effect， high safety， less side effect and low recurrence rate. The experimental results show that Lichongtang has a comprehensive regulatory effect on UL through inhibiting the proliferation of UL cells and inducing apoptosis， reducing serum estrogen and progesterone level， regulating the apoptosis pathway of tumor cells， and promoting the degradation of extracellular matrix（ECM）. After retrieval in PubMed， CNKI and other databases， the authors made a review by summarizing the theories， clinical efficacy and action mechanisms of Lichongtang in the treatment of UL， in order to provide reference for the follow-up in-depth study of pharmacological mechanism of Lichongtang and its further clinical application and promotion.
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Objective:To study the effect and mechanism of Zuoguiwan on the autophagy of cells in the skin during the development of congenital kidney-deficient mice， and to explore the application value of kidney tonifying and essence filling method in abnormal growth and development. Method:36 rats with a 2∶1 ratio of male to female were paired， and the pregnant rats were stimulated by combined stress method to build a model of congenital kidney-deficient rats. According to different treatment methods， the pregnant rats were divided into the control group， the kidney-deficient group， and the Zuoguiwan low and high dose groups （2， 8 g·kg<sup>-1</sup>）. The control group was given normal saline without modeling. Kidney deficiency group was modeled before intragastric administration of normal saline. Zuoguiwan small dose and high dose groups received intragastric administration of Zuoguiwan suspension. 21 days after the birth of mice， the back skin was taken to observe the skin microstructure and morphology of the mice by HE staining and detect the thickness of dermis and epidermis. The gene and protein expression levels of Wingless3a and <italic>β</italic>-catenin in the skin of neonatal rats were measured by Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Double immunofluorescence assay was used to detect the skin autophagy indicators Microtubule-associated protein light chain 3 （LC3）and Sequestosome 1 （SQSTM1-p62）. Result:In the control group， the skin layers were clear and the structure was normal， in the kidney deficiency group， the collagen arrangement in the dermis was loose， the skin composition in Zuoguiwan low and high dose groups was basically normal. Compared with the control group， the epidermal layer of the kidney deficiency group was thickened and the dermis was thinned （<italic>P</italic><0.05）. Compared with the kidney deficiency group， the thickness changes of epidermal layer and dermis layer were significantly restored in Zuoguiwan low and high dose groups （<italic>P</italic><0.05）. Compared with the control group， the expression of Wnt3a and <italic>β</italic>-catenin protein and gene in the kidney deficiency group significantly decreased （<italic>P</italic><0.05）. Compared with the kidney deficiency group， Wnt3a and <italic>β</italic>-catenin protein and gene expression increased in Zuoguiwan low and high dose groups （<italic>P</italic><0.05）. At the same time， immunofluorescence assay showed that compared with the control group， the expression of LC3 was up-regulated and the expression of SQSTM1-p62 was down-regulated in the kidney deficiency group， while Zuoguiwan could reverse such abnormal expression （<italic>P</italic><0.05）. Conclusion:Zuoguiwan can down-regulate the autophagy level of skin cells and improve the abnormal skin development of congenital renal deficiency by increasing the expression of Wnt3a and <italic>β</italic>-catenin protein and gene in the skin of neonatal rats.
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Objective:To explore the effect of Bushen Tongluo prescription （BSTLP） on the synaptic plasticity of hippocampal neurons in vascular dementia （VD） model rats and its mechanism. Method:SD male rats of SPF grade were selected. The rat model of VD was established by permanent bilateral ligation of the common carotid artery several times. The model rats were randomly divided into a model group， an insulin-like growth factor-1 （IGF-1， 20 μg·kg<sup>-1</sup>） group， high-dose （3 g·kg<sup>-1</sup>）， medium-dose （1.5 g·kg<sup>-1</sup>）， and low-dose （0.75 g·kg<sup>-1</sup>） BSTLP groups. A sham operation group was also set. Drugs were administered to rats by gavage once a day for four weeks. The model group and the sham operation group received the same volume of normal saline. After the last administration， all the rats were detected for spatial learning and memory by the Morris water maze. The apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase （TdT） dUTP nick-end labeling （TUNEL） assay. The changes in synaptic morphological structure and the number of dendritic spines in hippocampal neurons were detected by Golgi's method. The expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， mammalian target of rapamycin （mTOR）， synaptophysin （SYP）， and amyloid precursor protein （APP） in hippocampal neurons were detected by Western blot. Result:Compared with the sham operation group， the model group showed prolonged escape latency， lengthened swimming distance， dwindled the number of times for the platform crossing after platform removal （<italic>P</italic><0.05）， increased apoptotic cells （<italic>P</italic><0.05）， declining synaptic dendritic spines （<italic>P</italic><0.05）， down-regulated expression levels of PI3K， Akt， mTOR， and SYP proteins， and up-regulated expression level of APP protein in hippocampal neurons （<italic>P</italic><0.05）. Compared with the model group， the BSTLP groups and the IGF-1 group showed shortened escape latency and swimming distance， increased number of times for the platform crossing after platform removal （<italic>P</italic><0.05），declining apoptotic cells （<italic>P</italic><0.05）， up-regulated expression levels of PI3K， Akt， mTOR， and SYP proteins， and down-regulated expression level of APP protein in hippocampal neurons （<italic>P</italic><0.05）. Compared with the IGF-1 group， the high-dose BSTLP group showed no significant difference in the escape latency， swimming distance， the number of times for the platform crossing after platform removal， apoptotic cells， synaptic dendritic spines， and expression levels of PI3K， Akt， mTOR， SYP， and APP proteins in hippocampal neurons. However， the differences were significant in the medium-dose and low-dose BSTLP groups （<italic>P</italic><0.05）. Conclusion:BSTLP can improve the learning and memory of rats with VD. The mechanism is presumedly related to the activation of thePI3K/Akt/mTOR pathway and improvement of synaptic plasticity of hippocampal neurons.
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Objective:To investigate the mechanism of Shugan Bushen Yulin decoction in inhibiting voltage-dependent anion-selective channel protein 2 （VDAC2） gene methylation， affecting sperm mitochondrial function， and improving sperm motility through the cyclic adenosine monophosphate/protein kinase A （cAMP/PKA） pathway. Method:Forty male SD rats were randomly divided into the blank group， model group， high- and low-dose Shugan Bushen Yulin decoction groups， and L-carnitine group， with eight rats in each group. Adenine （0.05 g·kg<sup>-1</sup>） was administered by gavage for 14 d for inducing oligospermia and asthenospermia. Rats in the Shugan Bushen Yulin decoction groups were treated with intragastric administration of 32.4， 8.1 g·kg<sup>-1 </sup>Shugan Bushen Yulin decoction， respectively， while those in the L-carnitine group received 0.27 g·kg<sup>-1</sup> L-carnitine by gavage. Following the measurement of sperm motility using an automatic sperm analyzer， the pathological changes in testicular tissue were observed by hematoxylin-eosin （HE） staining. Sperm mitochondrial membrane potential was detected by flow cytometry. The expression of VDAC2 in the testicular tissue was determined by immunofluorescence assay. Real-time polymerase chain reaction （Real-time PCR） was conducted for detecting VDAC2 mRNA expression in testicular tissue. The methylation of VDAC2 gene was examined using bisulfite sequencing. The cAMP expression in testicular tissue was detected by enzyme-linked immunosorbent assay （ELISA）， and the PKA protein expression in testicular tissue by Western blot. Result:Compared with the blank group， the model group exhibited significantly decreased sperm density and motility （<italic>P</italic><0.01）， increased mitochondrial membrane potential （<italic>P</italic><0.01）， down-regulated VDAC2 mRNA and protein expression， PKA protein expression， and cAMP content in testicular tissue （<italic>P</italic><0.01）， and elevated VDAC2 gene methylation （<italic>P</italic><0.01）. Compared with the model group， L-carnitine and Shugan Bushen Yulin decoction at the high and low doses all remarkably increased the sperm density and motility and mitochondrial membrane potential （<italic>P</italic><0.01）， up-regulated VDAC2 mRNA and protein expression， PKA protein expression， and cAMP content in the testicular tissue （<italic>P</italic><0.01）， and lowered the methylation of VDAC2 in testicular tissue （<italic>P</italic><0.01）. The comparison with the L-carnitine group showed that the sperm density and motility and mitochondrial membrane potential in the low-dose Shugan Bushen Yulin decoction group declined significantly （<italic>P</italic><0.01）. The VDAC2 mRNA and protein expression， PKA protein expression， and cAMP content in the testicular tissue were significantly down-regulated （<italic>P</italic><0.01）， while the methylation of VDAC2 was significantly enhanced （<italic>P</italic><0.01）. Conclusion:Shugan Bushen Yulint decoction may inhibit VDAC2 gene methylation， increase VDAC2 expression， regulate cAMP/PKA pathway， and change mitochondrial membrane potential to enhance the sperm motility.
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Objective@#To understand school physician in primary and secondary schools in Yichang City, Hubei Province from 2019 to 2020, and to provide a reference for strengthening the school physician team in primary and secondary schools.@*Methods@#149 and 102 primary and secondary schools from 6 municipal districts in Yichang City, Hubei Province, were randomly selected in November 2019 and November 2020, respectively, and were administered by questionnaire survey.@*Results@#The proportion of school physicians increased from 39.6% in 2019 to 65.7% in 2020. In the past two years, the equipment rate of school physician in both central and fringe urban areas increased, especially the fringe urban areas, number of school physician increased from 38 to 96. A total of 93 and 141 school physicians were selected to pariticipate in questionaire survey in 2019 and 2020 respectively. The survey showed that more than 90% of school physicians in primary and secondary schools in Yichang received training, and 74.5% had college education level. However, most of them lack professional qualification and medical background.@*Conclusion@#School physician of primary and secondary of Yichang is well development over the past two years, and the proportion substantially increased. However, there is still room for improvement in the quantity and quality of school physicians, and professional qualification needs to be improved. More attention should be paid to the marginal urban areas to achieve a balance between quantity and quality.
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Objective:To investigate the prognostic value of absolute lymphocyte count (ALC) and neutrophil-lymphocyte ratio (NLR), macrophage-lymphocyte ratio (MLR) and platelet-lymphocyte ratio (PLR) before treatment in patients with locally advanced cervical cancer (LACC).Methods:A total of 175 patients newly-diagnosed with LACC admitted to Cancer Hospital affiliated to Xinjiang Medical University from August 2016 to October 2019 were enrolled in this study. Complete clinical data and ALC before treatment were recorded and NLR, MLR and PLR were calculated. Multivariate Cox′s proportional hazard regression model was used to analyze the prognostic factors of patients with LACC.Results:The progress-free survival (PFS) of LACC patients in the NLR reduction group (<3.34) and MLR reduction group (<0.315) were significantly higher than those in the NLR and MLR elevation groups (both P<0.05). The overall survival (OS) of LACC patients in the ALC elevation group (≥1.375 × 10 9/L) and the PLR reduction group (<160.575) were significantly higher compared with those in the ALC reduction group and PLR elevation group (both P<0.05). Univariate analysis showed that EQD 2Gy, the equivalent dose of HR-CTV, was an important prognostic factor of PFS in patients with LACC ( P=0.030). Multivariate Cox′s regression analysis demonstrated that FIGO staging ( HR=2.339, 95% CI 1.22-4.48, P=0.010) and concurrent chemoradiotherapy ( HR=0.213, 95% CI 0.11-0.43, P<0.001) were the independent predicators of PFS in patients with LACC. However, concurrent chemoradiotherapy ( HR=0.229, 95% CI 0.07-0.81, P=0.023) and MLR ( HR=4.933, 95% CI 1.39-17.54, P=0.014) before treatment were the independent predictors of OS in patients with LACC. Conclusions:Patients with locally advanced cervical cancer can benefit from concurrent chemoradiotherapy. HR-CTV EQD 2Gy is a critical prognostic factor of PFS in patients with LACC. The increase of MLR before treatment is an independent prognostic factor of OS in LACC patients.
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Objective:To Studythe extracellular matrix metalloproteinase inducer (CD147) changes in patients with systemic lupus erythematosus (SLE), and to study thecorrelation of CD147 level and athero-sclerosis in SLE.Methods:Eighty patients with SLE in total were divided into intimal thickening group, (24 cases, group A) and normal intimal group (56 cases, group B) according to carotid intimamedia thickness (IMT) checked by carotid ultrasonography. In addition, their age, bodymass index, blood pressure, seral total cholesterol (TC), high density liptein cholestero (HDL-C), low density lipoprotein cholestero (LDL-C), triglyceride (TG), urinary protein quantitative test(24 h), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anticardiolipin antibody, serum creatinine level, course of the disease, and treatment regimens were collected. Thirty-five healthy people were set as the control group (group C). The levels of serum CD147 were measured by enzyme-linked immuno sorbent assay (ELISA) in 3 groups. The correlation between the serum CD147 level of SLE patients and atherosclerosis was analyzed. The statistical analysis was carried out with independent t-test, chi-square test, analysis of variance, Spearman correlation and Logistic regression. Results:① Levels of serum CD147 in group A [ (238±30) pg/ml] were significantly higher than those in group B [(198±30) pg/ml] and group C [(150±26) pg/ml, F=67.908, P<0.01]. ② Body mass index, hypertensive ratio,total blood cholesterol,urine protein quantitative test (24 h), systemic lupus erythematosus disease activity index (SLEDAI), serum CD147 index in group A were significantly higher than those in group B ( P<0.05). ③ In Logistic regression analysis, serum CD147 [ OR (95% CI)=1.039(1.014, 1.065), P<0.05], urine protein quantitative (24 h) [ OR (95% CI)=2.598(1.033, 6.534), P<0.05] were independently relevant factors affecting carotid artery IMT. Conclusion:Serum CD147 is an independent risk factor for carotid intimamedia thickness in SLE patients.
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The protein tyrosine phosphatase Src homology phosphotyrosyl phosphatase 2 (SHP2) is implicated in various cancers, and targeting SHP2 has become a promising therapeutic approach. We herein described a robust cross-validation high-throughput screening protocol that combined the fluorescence-based enzyme assay and the conformation-dependent thermal shift assay for the discovery of SHP2 inhibitors. The established method can effectively exclude the false positive SHP2 inhibitors with fluorescence interference and was also successfully employed to identify new protein tyrosine phosphatase domain of SHP2 (SHP2-PTP) and allosteric inhibitors. Of note, this protocol showed potential for identifying SHP2 inhibitors against cancer-associated SHP2 mutation SHP2-E76A. After initial screening of our in-house compound library (∼2300 compounds), we identified 4 new SHP2-PTP inhibitors (0.17% hit rate) and 28 novel allosteric SHP2 inhibitors (1.22% hit rate), of which SYK-85 and WS-635 effectively inhibited SHP2-PTP (SYK-85: IC