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ObjectiveTo investigate the role and possible mechanism of action of rhubarb decoction （RD） retention enema in improving inflammatory damage of brain tissue in a rat model of mild hepatic encephalopathy （MHE）. MethodsA total of 60 male Sprague-Dawley rats were divided into blank group （CON group with 6 rats） and chronic liver cirrhosis modeling group with 54 rats using the complete randomization method. After 12 weeks， 40 rats with successful modeling which were confirmed to meet the requirements for MHE model by the Morris water maze test were randomly divided into model group （MOD group）， lactulose group （LT group）， low-dose RD group （RD1 group）， middle-dose RD group （RD2 group）， and high-dose RD group （RD3 group）， with 8 rats in each group. The rats in the CON group and the MOD group were given retention enema with 2 mL of normal saline once a day； the rats in the LT group were given retention enema with 2 mL of lactulose at a dose of 22.5% once a day； the rats in the RD1， RD2， and RD3 groups were given retention enema with 2 mL RD at a dose of 2.5， 5.0， and 7.5 g/kg， respectively， once a day. After 10 days of treatment， the Morris water maze test was performed to analyze the spatial learning and memory abilities of rats. The rats were analyzed from the following aspects： behavioral status； the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） and the level of blood ammonia； pathological changes of liver tissue and brain tissue； the mRNA and protein expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （AKT）， and mammalian target of rapamycin （mTOR） in brain tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the MOD group， the RD1， RD2， and RD3 groups had a significantly shorter escape latency （all P<0.01）， significant reductions in the levels of ALT， AST， IL-1β， IL-6， TNF-α， and blood ammonia （all P<0.05）， significant alleviation of the degeneration， necrosis， and inflammation of hepatocytes and brain cells， and significant reductions in the mRNA and protein expression levels of PI3K， AKT， and mTOR in brain tissue （all P<0.05）， and the RD3 group had a better treatment outcome than the RD1 and RD2 groups. ConclusionRetention enema with RD can improve cognitive function and inflammatory damage of brain tissue in MHE rats， possibly by regulating the PI3K/AKT/mTOR signaling pathway.
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@#Objective To investigate the expression of α7 nicotinic acetylcholine receptor (α7 nAChR) in thymocytes of patients with myasthenia gravis (MG) and its effect on cytokine secretion and T cell proliferation. Methods Patients with MG who underwent expanded thoracoscopic thymectomy in the Comprehensive Diagnosis and Treatment Center of the Henan Provincial People’s Hospital from June 2021 to June 2022 were selected and allocated to a MG group. Patients who underwent partial thymectomy to expose the surgical field during the cardiac disease surgery from June 2021 to September 2022 in the Department of Adult Cardiac Surgery of Fuwai Huazhong Cardiovascular Hospital were selected as the control group. Thymic single cell suspensions were prepared from MG and control groups, and the expression of α7 nAChR in thymocytes of the two groups was detected by real-time polymerase chain reaction and Western blotting. Then CD3/CD28 monoclonal antibody coupled with magnetic beads was used to induce T cell activation, and the levels of cytokines interferon-gamma (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-6, IL-10, IL-17, and IL-21 in thymocytes of the two groups were detected by enzyme-linked immunosorbent assay (ELISA). The activated T cells of the MG group were divided into a blank control group, an α7 nAChR antagonist group, and an α7 nAChR agonist group according to different treatment methods. After 72 hours of culture, IFN-γ, TNF-α, IL-4, IL-6, IL-10, IL-17, and IL-21 expression levels in the culture supernatant were measured by ELISA. Afterwards, CD4-PE and CD8-APC antibodies were added, and the proliferation of T cell subsets was detected by flow cytometry. Results A total of 10 MG patients were collected, including 3 males and 7 females with an average age of 19.25±6.28 years; and 15 control patients were collected, including 6 males and 9 females with an average age of 26.18±6.77 years. Compared with the control group, the mRNA and protein levels of α7 nAChR in the thymocytes of MG group were decreased, and the expression levels of IFN-γ, TNF-α, IL-4, IL-6 and IL-21 in the supernatant were increased (P<0.05), but there was no statistical difference in the expression of IL-10 and IL-17 (P>0.05). The cell-culture experiment showed that compared with the blank control group, the levels of IFN-γ, TNF-α, IL-6 and IL-21 secreted by T cells in the α7 nAChR antagonist group were increased (P<0.05), while they were decreased in the α7 nAChR agonist group (P<0.05). There was no statistical difference in the secretion levels of IL-4, IL-10 or IL-17 among the three groups (P>0.05). CD4+ T and CD8+ T cells in the α7 nAChR agonist group were significantly less than those in the blank control group and α7 nAChR antagonist group (P<0.001), while they were significantly more in the α7 nAChR antagonist group than those in the blank control group (P<0.001). Conclusion The expression of α7 nAChR in thymocytes of MG patients is decreased, and α7 nAChR may be involved in the inflammatory response in thymocytes and thus in thymic function.
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@#Objective To exploring the effectiveness of perioperative application of new surgical clinical classification and staging for myasthenia gravis (MG) in reducing the incidence of postoperative myasthenic crisis (MC). Methods The clinical data of patients with generalized MG admitted to the Comprehensive Treatment Center for Myasthenia Gravis of Henan Provincial People’s Hospital from January 2018 to June 2022 were retrospectively analyzed, who were scored with myasthenia gravis-activities of daily living (MG-ADL) score and quantification of the myasthenia gravis (QMG) score at the first visit, 1 day before surgery, and 3 days after surgery. The patients were divided into a group A (typeⅡ) and a group B (typeⅢ+Ⅳ+Ⅴ) by the new surgical clinical classification and staging of MG according to the disease progression process, and all patients underwent expanded thoracoscopic thymus (tumor) resection after medication and other interventions to control symptoms in remission or stability. The incidence of MC and the efficiency rate after surgery were analyzed. The normal distribution method and percentile method were used to calculate the unilateral 95% reference range of the QMG score and MG-ADL score. Results Finally 126 patients were enrolled, including 62 males and 64 females, aged 13-71 years, with an average age of 46.00±13.00 years. There were 95 patients in the group A and 31 patients in the group B, and the differences of the preoperative baseline data between the two groups were not statistically significant (P>0.05). The incidence of postoperative MC was 1.05% (1/95) in the group A and 3.23%(1/31) in the group B (P>0.05). The effective one-sided 95% reference range of the QMG score and MG-ADL score 1 day before surgery was 0-7.75 and 0-5.00, and there was no postoperative death in both groups. Conclusion The new surgical clinical classification and staging of MG can guide the timing of surgery, which can benefit patients undergoing surgery for MG and greatly reduce the incidence of postoperative MC.
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Objective:To compare and analyze the technical success rate and safety between computed tomography(CT)-percutaneous radiological gastrostomy (PRG) and percutaneous endoscopic gastrostomy (PEG).Methods:From January 2017 to January 2022, at the First Affiliated Hospital of Zhengzhou University, the data of 76 patients who underwent gastrostomy due to inability to eat orally were collected, including 38 patients in PEG group and 38 patients in CT-PRG group. Surgical outcomes and complications were compared between the PEG and CT-PRG groups. Surgical outcomes included technical success rate, operation time, postoperative body mass index and hospital stay; while complications included minor complications (such as perifistula infection, granulation tissue proliferation, leakage, pneumoperitoneum, fistula tube obstruction, fistula tube detachment and persistent pain) and serious complications (such as bleeding, peritonitis, colonic perforation and death within 30 d). Independent sample t test, chi-square test, and Fisher exact probability test were used for statistical analysis. Results:The technical success rate of CT-PRG group was higher than that of the PEG group (100.0%, 38/38 vs. 78.9%, 30/38), and the operation time was shorter than that of the PEG group ((17.16±8.52) min vs. (29.33±16.22) min), and the differences were statistically significant ( χ2=1.19, t=2.36; P=0.038 and 0.011). There were no significant differences in postoperative body mass index ((16.29±3.56) kg/m 2 vs. (16.12±3.17) kg/m 2) and hospital stay ((4.13±1.26) d vs. (3.52±1.13) d) between PEG group and CT-PRG group (both P>0.05). The incidence of minor complications in the PEG group was 42.1% (16/38), including 6 cases of perifistulal infection, 1 case of leakage, 5 cases of fistula tube obstruction, 1 case of fistula tube detachment, and 3 cases of persistent pain. The incidence of serious complications was 5.3% (2/38), including 1 case of bleeding and 1 case of colonic perforation. The incidence of minor complications in the CT-PRG group was 39.5% (15/38), including 5 cases of perifistula infection, 1 case of granulation tissue proliferation, 3 cases of pneumoperitoneum, 3 cases of fistula tube obstruction, 2 cases of fistula tube detachment, and 1 case of persistent pain. The incidence of serious complications was 0. There was no significant difference in the incidence of minor complications between the PEG group and the CT-PRG group ( P>0.05), while the incidence of serious complications in the CT-PRG group was lower than that of the PEG group, and the difference was statistically significant (Fisher exact probability test, P=0.043). Conclusion:PEG is a safe and effective method of gastrostomy, but for patients with esophageal obstruction, CT-PRG can be an effective supplement to PEG.
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Recent studies have found that the brain-gut-microbiome axis(BGMA)is closely related to the occurrence and development of Alzheimer's disease(AD). BGMA can affect AD in various aspects such as neuro-immune regulation and intestinal microflora, and is a potential new target for the treatment of AD.The "Sanjiao" acupuncture method is proposed by professor Han Jingxian, a famous Chinese medicine practitioner, based on his theory of "dysfunction of Qi activity of Sanjiao leads to aging" , and has been widely used in the treatment of AD and other age-related diseases in clinical practice.This article reviews the theory of "dysfunction of Qi activity of Sanjiao leads to aging" and the relationship between the "Sanjiao" acupuncture method and BGMA, with the hope that the "San Jiao" acupuncture method can become a new target for treatment of AD in the future.
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Objective:To explore the clinical efficacy of CT-guided 125I seed implantation in patients with oligometastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) activating mutations (EGFRm+ ) without progression after first-line EGFR-tyrosine kinase inhibitors (TKIs) treatment. Methods:From January 2015 to January 2019, 89 eligible patients (38 males, 51 females; age: (62±11) years) in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. They were divided into 2 groups according to different treatment methods. The 125I seeds were implanted for oligometastatic lesions and/or primary tumors without progression after first-line EGFR-TKIs therapy in local consolidation treatment group (Group A, n=32). The maintenance treatment group (Group B, n=57) only received EGFR-TKIs until disease progression. The progression-free survival (PFS) and overall survival (OS) of the 2 groups were estimated by Kaplan-Meier curves, and were compared by using log-rank test. Complications in Group A were observed. Results:The follow-up time of the group A and group B were 36.5(31.0, 43.3) months and 30.0(24.0, 35.0) months respectively. The median PFS and OS in group A were 15.0(95% CI: 12.8-17.2 ) months and 37.0(95% CI: 33.9-40.1) months, both of which were significantly longer than those in group B (12.0(95% CI: 10.9-13.1) months and 31.0(95% CI: 28.9-33.1) months; χ2 values: 8.80, 7.15, P values: 0.003, 0.007). In Group A, the total incidence of complications in CT-guided 125I seed implantation was 21.9%(7/32), and the common complications and adverse events were pneumothorax and hemoptysis. Only 1 patient underwent chest tube insertion, and the rest were treated with conservative treatment. No operation related death occurred. Conclusion:CT-guided 125I seed implantation is safe and feasible for patients with EGFRm+ oligometastatic NSCLC without progression after first-line EGFR-TKIs treatment, and can prolong the PFS and OS of patients.
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Objective:To investigate the expression and clinical significance of somatostatin receptor 2 (SSTR2), a disintegrin and metalloproteinase-12 (ADAM-12), and friend leukemia virus integration-1 (FLI-1) in small cell lung cancer tissue.Methods:Eighty-two patients with small cell lung cancer who received treatment in Haiyang People's Hospital from January 2020 to January 2021 were included in this study. All patients underwent radical surgical resection. Small cell lung cancer tissues and adjacent tissues more than 2 cm from the edge of cancer tissues were harvested. The positive expression rates of SSTR2, ADAM-12, and FLI-1 in cancer tissues and adjacent tissues were determined by immunohistochemistry. The relationship between SSTR2, ADAM-12, FLI-1, and clinical characteristics were analyzed. The 1-year survival rate of patients with small cell lung cancer was calculated.Results:The positive rates of SSTR2, ADAM-12, and FLI-1 in small cell lung cancer tissue were 79.27% (65/82), 76.83% (63/82), and 78.05% (64/82), respectively, which were significantly higher than 19.51% (16/82), 17.07% (14/82), 20.73% (17/82) in the adjacent tissue ( χ2 = 58.57, 58.78, 53.90, all P < 0.05). SSTR2, ADAM-12, and FLI-1 were positively associated with lymph node metastasis, clinical stage, tissue invasion, tumor size, and histological grade (all P < 0.05). After controlling for gender, age, and others, SSTR2, ADAM-12, and FLI-1 were associated with lymph node metastasis, clinical stage, tissue invasion, tumor size, and histological grade (all P < 0.05). All patients were followed up for 1 year. Six patients were lost to follow-up. The 1-year survival rate of 76 patients with small cell lung cancer was 67.11% (51/76). The survival rate of patients with positive SSTR2, ADAM-12, and FLI-1 expression were lower than that of patients with negative SSTR2, ADAM-12, and FLI-1 expression ( χ2 = 3.93, 6.43, 7.52, all P < 0.05). Conclusion:SSTR2, ADAM-12, and FLI-1 are highly expressed in small cell lung cancer tissue. Combined detection of SSTR2, ADAM-12, and FLI-1 is conducive to the prognosis and evaluation of small cell lung cancer in patients. This study is innovative and scientific.
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Objective:To investigate the clinical characteristics of choledocholithiasis com-bined with periampullary diverticulum and influencing factor for difficult cannulation of endoscopic retrograde cholangiopancreatography (ERCP).Methods:The retrospective case-control study was conducted. The clinical data of 1 920 patients who underwent ERCP for choledocholithiasis in 15 medical centers, including the First Hospital of Lanzhou University, et al, from July 2015 to December 2017 were collected. There were 915 males and 1 005 females, aged (63±16)years. Of 1 920 patients, there were 228 cases with periampullary diverticulum and 1 692 cases without periampullary diverticulum. Observation indicators: (1) clinical characteristics of patients with choledocholithiasis; (2) intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis; (3) influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Logistic regression model was used for univariate and multivariate analyses. Results:(1) Clinical characteristics of patients with choledocholithiasis. Age, body mass index, cases with complications as chronic obstructive pulmonary disease, diameter of common bile duct, cases with diameter of common bile duct as <8 mm, 8?12 mm, >12 mm, diameter of stone, cases with number of stones as single and multiple were (69±12)years, (23.3±3.0)kg/m 2, 16, (14±4)mm, 11, 95, 122, (12±4)mm, 89, 139 in patients with choledocholithiasis combined with periampullary diverticulum, versus (62±16)years, (23.8±2.8)kg/m 2, 67, (12±4)mm, 159, 892, 641, (10±4)mm, 817, 875 in patients with choledocholithiasis not combined with periampullary diver-ticulum, showing significant differences in the above indicators between the two groups ( t=?7.55, 2.45, χ2=4.54, t=?4.92, Z=4.66, t=?7.31, χ2=6.90, P<0.05). (2) Intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis. The balloon expansion diameter, cases with intraoperative bleeding, cases with hemorrhage management of submucosal injection, hemostatic clip, spray hemostasis, electrocoagulation hemostasis and other treatment, cases with endoscopic plastic stent placement, cases with endoscopic nasal bile duct drainage, cases with mechanical lithotripsy, cases with stone complete clearing, cases with difficult cannulation, cases with delayed intubation, cases undergoing >5 times of cannulation attempts, cannulation time, X-ray exposure time, operation time were 10.0(range, 8.5?12.0)mm, 56, 6, 5, 43, 1, 1, 52, 177, 67, 201, 74, 38, 74, (7.4±3.1)minutes, (6±3)minutes, (46±19)minutes in patients with choledocholithiasis combined with periampullary diverticulum, versus 9.0(range, 8.0?11.0)mm, 243, 35, 14, 109, 73, 12, 230, 1 457, 167, 1 565, 395, 171, 395, (6.6±2.9)minutes, (6±5)minutes, (41±17)minutes in patients with choledocholithiasis not combined with periampullary diverticulum, showing significant differences in the above indicators between the two groups ( Z=6.31, χ2=15.90, 26.02, 13.61, 11.40, 71.51, 5.12, 9.04, 8.92, 9.04, t=?3.89, 2.67, ?3.61, P<0.05). (3) Influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Results of multivariate analysis showed total bilirubin >30 umol/L, number of stones >1, combined with periampullary diverticulum were indepen-dent risk factors for difficult cannulation in patients with periampullary diverticulum who underwent ERCP for choledocholithiasis ( odds ratio=1.31, 1.48, 1.44, 95% confidence interval as 1.06?1.61, 1.20?1.84, 1.06?1.95, P<0.05). Results of further analysis showed that, of 1 920 patients undergoing ERCP for choledocholithiasis, the incidence of postoperative pancreatitis was 17.271%(81/469) and 8.132%(118/1 451) in the 469 cases with difficult cannulation and 1 451 cases without difficult cannula-tion, respectively, showing a significant difference between them ( χ2=31.86, P<0.05). In the 1 692 patients with choledocholithiasis not combined with periampullary diverticulum, the incidence of postopera-tive pancreatitis was 17.722%(70/395) and 8.250%(107/1 297) in 395 cases with difficult cannula-tion and 1 297 cases without difficult cannulation, respectively, showing a significant difference between them ( χ2=29.00, P<0.05). In the 228 patients with choledocholithiasis combined with peri-ampullary diverticulum, the incidence of postoperative pancreatitis was 14.865%(11/74) and 7.143%(11/154) in 74 cases with difficult cannulation and 154 cases without difficult cannulation, respectively, showing no significant difference between them ( χ2=3.42, P>0.05). Conclusions:Compared with patients with choledocholithiasis not combined with periampullary divertioulum, periampullary divertioulum often occurs in choledocholithiasis patients of elderly and low body mass index. The proportion of chronic obstructive pulmonary disease is high in choledocholithiasis patients with periampullary diverticulum, and the diameter of stone is large, the number of stone is more in these patients. Combined with periampullary diverticulum will increase the difficult of cannulation and the ratio of patient with mechanical lithotripsy, and reduce the ratio of patient with stone complete clearing without increasing postoperative complications of choledocholithiasis patients undergoing ERCP. Total bilirubin >30 μmol/L, number of stones >1, combined with periampullary diverticulum are independent risk factors for difficult cannulation in patients of periampullary diverticulum who underwent ERCP for choledocholithiasis.
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Objective:To explore the relationship between the level of mindfulness, illness uncertainty, negative coping style and fear of recurrence in patients after radical resection of gastric cancer, and to understand the internal mechanism of how mindfulness affects the fear of recurrence.Methods:This was a cross sectional survey. From January 2019 to March 2021, the convenience sampling method was used to select 227 patients undergoing radical gastric cancer surgery in the Affiliated Hospital of Naval Medial University of Chinese PLA as the research objects. The general information questionnaire, Mindfulness Attention and Awareness Scale, Fear of Disease Progression Simplified Scale, Mishel′s Illness Uncertainty Scale and Simplified Coping Style Questionnaire were used for questionnaire surveys. The relationship between the level of mindfulness, illness uncertainty, negative coping style and fear of recurrence was explored and the model was tested.Results:The returned questionnaires were 207 with a recovery rate of 91.19%(207/227). Pearson correlation analysis showed that the level of mindfulness was negatively correlated with illness uncertainty, negative coping style, and fear of recurrence ( r=-0.176, -0.269, -0.480, all P<0.01). Illness uncertainty, negative coping styles were positively correlated with fear of recurrence ( r=0.433, 0.420, both P<0.01). The mediation model test showed that mindfulness had a significant direct effect on fear of relapse (effect value was -0.220), illness uncertainty and negative coping styles had significant partial mediating effect between mindfulness level and fear of recurrence (effect value were -0.036, -0.030). And the chain mediating effect of illness uncertainty and negative coping style was also significant (effect value was -0.006). Conclusions:The level of mindfulness can not only have a direct impact on the fear of recurrence in patients after radical gastrectomy, but also indirectly affect the fear of recurrence through the chain mediating effect of illness uncertainty, negative coping style, and disease uncertainty→negative coping style.
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The treatment concept and standardization of primary surgery for patients with differentiated thyroid cancer vary among different regions and different treatment centers in the same region, resulting in different reoperation rates for patients. Intraoperative experience, preoperative evaluation, surgical approach, and procedure may all influence the success rate of reoperation. In order to reduce the risk of surgery and complications, reoperation should be treated standardized, while combining the current diagnosis and treatment techniques to provide individualized treatment options for reoperation patients, under the premise of ensuring efficacy, to broaden the indications of surgery, make large incisions into small incisions, and change traditional open surgery into minimally invasive surgery, improve the quality of life of patients and confidence in coping with social stress. This paper will summarize the main content of preoperative assessment at the time of reoperation in patients with differentiated thyroid cancer, analyze the notes and rationally developing a surgical plan for patients, in the hope of attracting the same emphasis and normalizing the reoperation treatment, so as to achieve reoperation of the tumor R0 resection.
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From the perspective of market classification of Cnidii Fructus, this paper revealed the scientific connotation of evaluating the quality grade of Cnidii Fructus by its appearance traits. Thirty batches of Cnidii Fructus in different grades were selected as the research objects. The canonical correlation analysis and principal component analysis(PCA) were used to explore the measurement values of 15 appearance traits and intrinsic content indexes. The results of correlation analysis showed that except the aspect ratio, the 5 appearance trait indexes(length, width, 1 000-grain weight, broken grain weight proportion, and chroma) and 9 internal content indexes(the content of moisture, total ash, acid insoluble ash, osthole, imperatorin, 5-methoxy psoralen, isopimpinellin, xanthotoxin, and xanthotol) showed significant correlation to varying degrees. In addition, there was a significant positive correlation between the first typical variable U_1 composed of appearance traits and the first typical variable V_1 composed of internal content indexes(CR_1=0.963, P<0.01). The results of PCA showed that the classification results of appearance traits for 30 batches of Cnidii Fructus were consistent with the actual information of the samples. Under the same analysis conditions, 30 batches of Cnidii Fructus were reclassified by 9 groups of internal content indexes, and the analysis results were consistent. From the classification standard of the appearance traits of the system study, the statistical results of 6 appearance traits of Cnidii Fructus showed a correlation with grades. There was a good correlation between the appearance and the internal content of Cnidii Fructus, and the appearance quality effectively predicted the level of the internal content. There is a certain scientific basis for the quality classification of Cnidii Fructus by main appearance traits. Appearance classification can replace quality grading to realize the "quality evaluation through morphological identification" of Cnidii Fructus.
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Frutas , Fenotipo , Análisis de Componente Principal , Grupos de PoblaciónRESUMEN
Most hematological tumors have high-grade malignancy and low cure rate, requiring new molecular markers for detection and evaluation. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently closed-loop structures, which participate in gene transcription and translation by binding to microRNAs and proteins. In recent years, with the deepening research on circRNAs, circRNAs have been found to play an important role in hematological malignancies. In this review, the latest research progress on the function and molecular mechanism of circRNAs in hematological malignancies was systematically summarized, and it was found that circRNAs may be potential new biomarkers and therapeutic targets in hematological malignancies.
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Humanos , ARN Circular , MicroARNs/genética , Neoplasias , Neoplasias Hematológicas/genética , BiomarcadoresRESUMEN
AIM: By analyzing the effect of gambogenic acid (GNA) on the mRNA expression profile of melanoma xenograft model mice, the possible mechanism of GNA in the treatment of melanoma was explored. METHODS: The inhibitory effect of GNA on melanoma cells was studied by measuring the cell survival rate by MTT method in vitro and observing the cell morphology under an inverted microscope. In the in vivo experiment, the effect of GNA on the growth of xenografted tumors in melanoma mice was observed by comparing the results of HE (hematoxylin-eosin) staining and immunohistochemistry (Ki-67), and the tumor weight and tumor weight ratio were recorded. RNA-seq sequencing technology was used to sequence the GNA medium-dose group and the model group, and the screened mRNAs were analyzed by GO and KEGG, and finally the screening results of differentially expressed genes were verified by real-time quantitative fluorescent PCR. RESULTS: After different doses of GNA acted on the melanoma mouse model, a large area of necrosis occurred in the tumor tissue of the model mouse, and the tumor growth was significantly inhibited. A total of 36 differentially expressed mRNAs were identified by mRNA sequencing, of which 30 were up-regulated and 6 were down-regulated. The possible functions of the mRNAs were predicted according to the genomic adjacency analyzed by GO and KEGG. The expression of the selected differential mRNAs was further verified by real-time quantitative PCR technology. The results showed that the mRNA expressions of Cidec, Ces1d, Mylk4, and Igkv9-123 were up-regulated, and the mRNA expressions of Ryr3 and Hapln1 were down-regulated. CONCLUSION: GNA can inhibit the proliferation of melanoma cells in vitro and in vivo, and its mechanism is related to the regulation of cytokine-cytokine receptor interaction, NF-κB, MAPK, and other pathways of mRNA expression.
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Aim To investigate the effect of XNST and its monomeric components on the barrier structure and tight junction protein expression of brain microvascular endothelial cells damaged by oxygen glucose deprivation/reoxygenation (OGD/R) and the possible mechanism. Methods The mouse brain microvascular endothelial cell line bEnd. 3 was inoculated in the upper layer of the Transwell chamber to establish an OGD/R damage model, and the effect of the drug on the integrity of the endothelial cell barrier was investigated by the transmembrane resistance value and fluorescein-so-dium transmittance. Claudin-5 immunofluorescence staining was used to observe the changes of tight junction structure between endothelial cells. RT-PCR and Western blot were employed to detect mRNA and protein expression levels of tightly linked proteins Claudin-5 , Occludin, ZO-1. Western blot was applied to detect the expression levels of MAPKs (JNK, p38, ERK) , I kappa B a, I kappa B kinase phosphorylated protein expression, and Western blot and immunofluorescence were utilized to detect NF-K.B/p65 nucleation expression. Results XNST and its three monomers could significantly increase endothelial cell resistance and de- crease fluorescein-sodium transmittance. Claudin-5 fluorescence staining showed that the tight junction between cells in the model group was significantly damaged , while XNST and its monomer components could significantly improve its tight structure. RT-PCR and Western blot results showed that it could significantly upregulate the expression of mRNA and protein of Claudin-5, Occludin and ZO-1, and further study on the mechanism showed that XNST and its monomer components could significantly inhibit the phosphoryla-tion of JNK, p38 and ERK, inhibit the phosphorylation of I kappa B a and I kappa B kinases, and significantly inhibit the nuclear translocation of NF-KB/p65. Conclusion Both XNST and its monomeric components can exert cerebroprotective effects by increasing the tight junction structure between cells to promote barrier integrity, and the mechanism may be related to inhibition of NF-kB and MAPKs signaling pathway activation.
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OBJECTIVE@#To investigate the effects of the pre-shock state on the mortality of patients with sepsis.@*METHODS@#We enrolled patients with sepsis admitted to the medical intensive care unit of a tertiary care university hospital. These patients were then classified into three groups: sepsis, pre-shock state, and septic shock. The primary outcome was the 28-day mortality rate. The secondary outcomes were the 90-day, 180-day, and 1-year mortality rates.@*RESULTS@#A total of 303 patients (groups: sepsis 135 [44.6%]), pre-shock state (93 [30.7%]), and septic shock (75 [24.8%]) completed the 1-year follow-up. The mortality rates at 28 days, 90 days, and 180 days and 1 year were significantly higher in the pre-shock state group than those of the sepsis group, but significantly lower than those in the septic shock group, especially among older patients. When compared with the pre-shock state group, the sepsis group had significantly lower mortality risks at 28 days, 90 days, and 180 days and 1 year, whereas the sepsis shock group had higher mortality risks at these time points.@*CONCLUSION@#The mortality rates of patients in the pre-shock state were notably different from those of patients with sepsis or septic shock. The introduction of a modified sepsis severity classification, which includes sepsis, pre-shock state, and septic shock, could offer valuable additional prognostic information.
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Humanos , Choque Séptico , Estudios Retrospectivos , Sepsis , Hospitalización , UniversidadesRESUMEN
Wu Liande’s spirit was formed during the development of modern public health in China. It is a unity of the spirit of patriotism, humanitarianism, scientific exploration, and dedication, and a valuable resource and vivid textbook for medical students to carry out professional spirit education. Promoting Wu Liande’s spirit in the new era is not only conducive to inspiring the patriotism of medical students, bravely undertaking the mission of the times, and devoting themselves to the cause of human health, but also conducive to guiding medical students to refine benevolence and skill, and fulfill the sacred oath of medical students. To cultivate the professional spirit of medical students with Wu Liande’s spirit, it is necessary to achieve the "integration of specialized courses and ideological and political education" , promote the collaborative development of ideological and political courses and curriculum ideological and political education, innovate teaching methods and use modern information technology to empower Wu Liande’s spirit to be visualized and expressed, and take discipline practice as the starting point to expand the new path of professional spirit practice education for medical students.
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Ginsenoside Rg_3, an active component of traditional Chinese medicine(TCM), was used as the substitute for cholesterol as the membrane material to prepare the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin and paclitaxel. The effect of the prepared drug-loading liposomes on triple-negative breast cancer in vitro was evaluated. Liposomes were prepared with the thin film hydration method, and the preparation process was optimized by single factor experiments. The physicochemical properties(e.g., particle size, Zeta potential, and stability) of the liposomes were characterized. The release behaviors of drugs in different media(pH 5.0 and pH 7.4) were evaluated. The antitumor activities of the liposomes were determined by CCK-8 on MDA-MB-231 and 4T1 cells. The cell scratch test was carried out to evaluate the effect of the liposomes on the migration of MDA-MB-231 and 4T1 cells. Further, the targeting ability of liposomes and the mechanism of lysosome escape were investigated. Finally, H9c2 cells were used to evaluate the potential cardiotoxicity of the preparation. The liposomes prepared were spheroid, with uniform particle size distribution, the ave-rage particle size of(107.81±0.01) nm, and the Zeta potential of(2.78±0.66) mV. The encapsulation efficiency of dihydroartemisinin and paclitaxel was 57.76%±1.38% and 99.66%±0.07%, respectively, and the total drug loading was 4.46%±0.71%. The accumulated release of dihydroartemisinin and paclitaxel from the liposomes at pH 5.0 was better than that at pH 7.4, and the liposomes could be stored at low temperature for seven days with good stability. Twenty-four hours after administration, the inhibition rates of the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin(70 μmol·L~(-1)) and paclitaxel on MDA-MB-231 and 4T1 cells were higher than those of the positive control(adriamycin) and free drugs(P<0.01). Compared with free drugs, liposomes inhibited the migration of MDA-MB-231 and 4T1 cells(P<0.05). Liposomes demonstrated active targeting and lysosome escape. In particular, liposomes showed lower toxicity to H9c2 cells than free drugs(P<0.05), which indicated that the preparation had the potential to reduce cardiotoxicity. The findings prove that ginsenoside Rg_3 characterized by the combination of drug and excipient is an ideal substitute for lipids in liposomes and promoted the development of innovative TCM drugs for treating cancer.
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Humanos , Paclitaxel/farmacología , Liposomas/química , Ginsenósidos/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Cardiotoxicidad/tratamiento farmacológico , Línea Celular TumoralRESUMEN
OBJECTIVE@#This study aimed to evaluate the clinical benefits of a vancomycin dosage strategy based on a serum trough concentration model in elderly patients.@*METHODS@#This prospective single-center, open-label, randomized controlled trial categorized 66 elderly patients with severe pneumonia into study and control groups. The control group received vancomycin using a regimen decided by the attending physician. Meanwhile, the study group received individualized vancomycin therapy with a dosing strategy based on a serum trough concentration model. The primary endpoint was the proportion of patients with serum trough concentrations reaching the target values. The secondary endpoints were clinical response, vancomycin treatment duration, and vancomycin-associated acute kidney injury (VA-AKI) occurrence.@*RESULTS@#All patients were at least 60 years old (median age = 81 years). The proportion of patients with target trough concentration achievement (≥ 15 mg/L) with the initial vancomycin regimen was significantly higher in the study group compared to the control group (75.8% vs. 42.4%, P = 0.006). Forty-five patients (68.2%) achieved clinical success, the median duration of vancomycin therapy was 10.0 days, and VA-AKI occurred in eight patients (12.1%). However, there were no significant differences in these parameters between the two groups. The model for predicting vancomycin trough concentrations was upgraded to: serum trough concentration (mg/L) = 17.194 - 0.104 × creatinine clearance rate (mL/min) + 0.313 × vancomycin daily dose [(mg/(kg∙d)].@*CONCLUSION@#A vancomycin dosage strategy based on a serum trough concentration model can improve the proportion of patients achieving target trough concentrations in elderly patients with severe pneumonia.
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Humanos , Anciano , Anciano de 80 o más Años , Persona de Mediana Edad , Vancomicina/uso terapéutico , Antibacterianos/uso terapéutico , Estudios Prospectivos , Estudios Retrospectivos , Lesión Renal Aguda/tratamiento farmacológico , Neumonía/tratamiento farmacológicoRESUMEN
OBJECTIVE@#To observe the clinical effect of bloodletting at auricular dorsal vein combined with auricular point sticking on menstrual migraine (MM) of qi stagnation and blood stasis, and explore its possible mechanism.@*METHODS@#A total of 102 cases of MM with qi stagnation and blood stasis were randomly divided into an observation group (51 cases, 3 cases dropped off) and a control group (51 cases, 2 cases dropped off). The patients in the observation group were treated with bloodletting at auricular dorsal vein combined with auricular point sticking. The bloodletting was performed at vein at upper 1/3 of the dorsalis near the ear helix; the auricular point sticking was performed at Pizhixia (AT4), Neifenmi (CO18), Jiaogan (AH6a), Nie (AT2), Zhen (AT3), Shenmen (TF4) and Yidan (CO11). The auricular points of both ears were alternate used. From 7 days before the onset of menstruation, bloodletting at auricular dorsal vein was given once every 7 days, 3 times were taken as a course of treatment, and 1 course of treatment was given; the auricular point sticking was given once every 3 days, and 6 times of treatment were given. The patients in the control group were treated with oral administration of flunarizine hydrochloride capsules. From 7 days before the onset of menstruation, flunarizine hydrochloride was given 2 capsules per time, once a day for 3 weeks. The menstrual headache index and visual analogue scale (VAS) score of the two groups were observed before treatment, one menstrual cycle into treatment and the first and the second menstrual cycle after treatment; the migraine-specific quality of life questionnaire (MSQ) score and the serum levels of estradiol (E2) and 5-hydroxytryptamine (5-HT) were compared before treatment and one menstrual cycle into treatment; the clinical efficacy was evaluated at one menstrual cycle into treatment.@*RESULTS@#Compared before treatment, the menstrual headache index and VAS scores were reduced at one menstrual cycle into treatment and the first and second menstrual cycle after treatment in the two groups (P<0.05), and those in the observation group were lower than the control group (P<0.05). Compared before treatment, the MSQ scores and the serum levels of E2 and 5-HT in the two groups were increased at one menstrual cycle into treatment (P<0.05), and those in the observation group were higher than the control group (P<0.05). The total effective rate was 95.8% (46/48) in the observation group, which was higher than 73.5% (36/49) in the control group (P<0.05).@*CONCLUSION@#Bloodletting at auricular dorsal vein combined with auricular point sticking could relieve headache intensity, improve the quality of life in patients with MM of qi stagnation and blood stasis, which may be achieved by raising the serum levels of E2 and 5-HT to improve the level of hormone in the body.
Asunto(s)
Femenino , Humanos , Acupuntura Auricular , Venodisección , Serotonina , Cápsulas , Flunarizina , Qi , Calidad de Vida , Trastornos Migrañosos/tratamiento farmacológico , Cefalea/terapia , Resultado del Tratamiento , Puntos de AcupunturaRESUMEN
Coronary heart disease (CHD) and stroke are the most well-known cardiovascular diseases, which share many common pathological basis. Yindan Xinnaotong soft capsule (YDXNT) is a commonly used Chinese patent medicine in the treatment of stroke and CHD. However, its action of mechanism of co-treatment for stroke and CHD is still unclear. The aim of this study was to explore the common mechanism of YDXNT in co-treatment of CHD and stroke using network pharmacology, experimental verification and molecular docking. An integrated literature mining and databases of IPA, ETCM, HERB, Swiss Target Prediction, OMIM and GeneCards were used to screen and predict active ingredients and potential targets of YDXNT in co-treatment of CHD and stroke. The protein-protein interaction network, GO analysis and pathway analysis were analyzed by IPA software. The effect of YDXNT on core targets was verified by immunofluorescence. UPLC-QTOF/MS and molecular docking were used to screen and predict the main active constituents of YDXNT and their interactions with core targets. A total of 151 potential targets are predicted for YDXNT in co-treatment of CHD and stroke. Hypoxia-inducible factor-1α (HIF1α)-matrix metalloproteinase-9 (MMP9)-mediated HIF1α signaling pathway serves as one of the common mechanisms. YDXNT could reduce the increase of mitochondrial fluorescence intensity and the protein expression of HIF1α and MMP9 in HL-1 and HA induced by oxygen and glucose deprivation/reperfusion (OGD/R) in a dose-dependent manner. Baicalin may be the material basis for treating stroke and CHD with YDXNT. In conclusion, the HIF1α signaling pathway is one of the common key mechanisms of YDXNT in the co-treatment of stroke and CHD. The study provides support and basis for the in-depth scientific connotation of the traditional Chinese medicine theory of "same treatment to different diseases".