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Objective:To investigate the clinical characteristics and treatment of Beh?et′s disease complicated with cardiac valve involvement.Methods:We searched the wanfang medical database and Medline database to reviewed the domestic and foreign literature reports on cardiac Beh?et′s disease and analyzed their clinical features and therapeutic strategies. Chi-squared test was used for data analysis.Results:It was shown that Beh?et′s disease with cardiac valve involvement mainly affect men. The male to female ratio was 3.86∶1 in China and 2.50∶1 in foreign patients( χ2=1.32, P=0.251). The preoperative diagnosis rate was not high(60.3% in China, 57.1% abroad) ( χ2=0.13, P=0.716). Aortic valve and perivalvular lesions were the most common involved sites, of which aortic regurgitation was the most frequenty occurred, followed by mitral valve lesions. Glucocorticoids was still the main means treatment for medical(93/235 in China, 28/420 abroad), cyclophosphamide was more widely used in China(28/235), azathioprine was more widely used in foreign countries (12/42). Aortic replacement (AVR) was the mainly surgical approach, followed by artificial aortic valve replacement and left ventricular outflow tract plasty (Bentall).The incidence of postoperative perivalvular leakage or valve prolapse was higher with AVR than with Bentall(AVR 76.3%/Bentall 21.8% at home, χ2=32.60, P<0.001, AVR 71.4%/Bentall 0 abroad, χ2=13.84, P<0.001). Conclusions:Cardiac valve involvement is a severe complication of Beh?et′s disease. Heart involvement are more common, and the preoperative diagnosis rate is lower in China. The incidence of perivalve leakage (PVL) or valve prolapse (PD) after operation is higher with AVR than with Bentall surgery.The Bentall operation could improve prognosis and the postoperative complications abroad are lower than domestic.
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Objective:To explore the value of multiparametric ultrasonography consisting of gray-scale ultrasound(US), color Doppler flow imaging (CDFI), real-time strain elastography(RTE), and contrast-enhanced ultrasound(CEUS) in the differential diagnosis of testicular lesions.Methods:Forty patients (40 lesions) detected by ultrasonography examination at the Ultrasound Medical Center of Lanzhou University Second Hospital from June 2020 to June 2022 were retrospectively analyzed, and further the CDFI, CEUS and RTE were performed. The presence of vascularization in the lesion was determined by CDFI and CEUS, avascular lesions were defined as benign, vascularization lesions were defined as malignant. The lesion tissue elasticity was assessed by real-time strain elastography, tissue stiffness was encoded as red(soft), green(intermediate), and blue(hard), and the hard lesions were defined as malignant, soft lesions were defined as benign. All lesions were subjected to pathological histologic examination after surgical resection or puncture biopsy as a reference standard. The correct classification rate, sensitivity, specificity and likelihood ratio of the multiparametric ultrasonography imaging for the diagnosis of benign and malignant testicular lesions were analyzed by ROC.Results:Of 40 testicular lesions, 24 (60.0%) were benign and 16 (40.0%) were malignant. The sensitivity of CDFI, CEUS and RTE in the diagnosis of testicular lesions was 0.875, 1.000 and 1.000, and the specificity was 0.833, 0.750 and 0.708, respectively. The correct classification rate was 85.0%, 85.0% and 82.5%, and the positive likelihood ratio was 5.24, 4.00 and 4.42, respectively. AUC was 0.781, 0.802, 0.771, respectively. By combining RTE and CDFI, a sensitivity of 1.000 and specificity of 0.875 and correct classification rate of 92.8% and positive likelihood ratio of 8.00 and AUC of 0.915 ( P<0.001) were achieved in differentiating testicular lesions. And combining RTE and CEUS, achieved sensitivity of 1.000 and specificity of 0.917 and correct classification rate of 95.0% and positive likelihood ratio of 12.0 and AUC of 0.958( P<0.001). Conclusions:Multiparametric US is of great value in the differential diagnosis of benign and malignant testicular lesions.
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Objective:To construct the evaluation index system of "early clinical contact" education of undergraduate medical students, and to provide guidance for the evaluation of "early clinical contact" education in medical teaching.Methods:The evaluation index system of "early clinical contact" education of undergraduate medical students was constructed by literature research, Delphi expert consultation and analytic hierarchy process, and the weight of each index was determined. Excel 2010 and SPSS 25.0 were used to make data entry and statistical analysis.Results:The enthusiasm of experts in the two rounds of expert consultation were 100.00%(26/26) and 96.15%(25/26) respectively, the expert authority coefficients were 0.900 and 0.920, and the coordination coefficients were 0.255 and 0.175 respectively ( P < 0.05). The evaluation index system included 4 first-class indexes, 12 second-class indexes and 47 third-class indexes. Conclusion:The index system has high scientificity and reliability. After further verification, it can be used as an evaluation tool for the teaching quality of "early clinical contact" education of undergraduate medical students.
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Objective:To explore the effect of early clinical clerkship training in the early exposure to clinical practice of eight-year program medical students.Methods:Experimental control method was used in this study. A total of 120 eight-year program medical students in the third year of Batch 2014 to 2016 from the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were selected as the research objects. The students of each grade were randomly selected by computer and divided into experimental group and control group, with 20 students in each group. Before early clinical exposure, the experimental group received 16 class hours of early clinical clerkship training, while the control group did not receive early clinical clerkship training. After the early clinical exposure, the clinical diagnosis and treatment ability of the two groups of students was compared. SPSS 24.0 software was used for t test. Results:The scores of medical history inquiry of experimental group and control group were [(17.45±1.96) points and (15.95±1.93) points; (18.30±1.03) points and (16.75±1.86) points; (17.95±1.36) points and (16.40±1.60) points, respectively]. The physical examination scores were [(17.75±1.65) points and (16.05±1.64) points; (17.85±1.18) points and (16.80±1.47) points; (18.25±1.16) points and (16.85±1.63) points, respectively]. The clinical judgment scores were [(18.15±1.42) points and (16.35±2.41) points; (18.20±1.24) points and (16.65±1.53) points; (18.35±1.35) points and (16.25±1.83) points, respectively]. Diagnosis and treatment scheme scores were [(17.15±1.57) points and (14.55±2.56) points; (17.30±1.42) points and (15.90±1.48) points; (17.80±1.06) points and (16.35±1.87) points, respectively]. The scores of communication skills were [(17.95±1.15) points and (17.00±1.19) points; (18.55±0.83) points and (17.45±1.50) points; (18.45±1.00) points and (17.45±1.23) points, respectively], with statistically significant differences (all P<0.05). Conclusion:The application of early clinical clerkship training in the early exposure to clinical practice of eight-year program medical students can improve the quality of students' clerkship.
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ObjectiveTo establish a rat model of hyperuricemia （HUA）， to study the effect of Liqing granules on lowering serum uric acid， and to evaluate its safety . MethodsMale SD rats were randomly divided into solvent control group and model group according to their body weight. For the model group， serum uric acid （SUA） was determined after 7 days of intra-gastric administration of potassium oxyazinate. The model group were randomly divided into model control group， positive control group， and low， medium， high dose group based on SUA level. Each group from the model group continued to receive potassium oxyazinate in the morning. The animals in the model groups received 0.5% CMC-Na， 10 mg·kg-1 benzbromarone （Doses by body weight） and Liqing granules 0.6， 1.2， 2.4 g·kg-1 （Doses by body weight）， respectively in the afternoon. 0.5% CMC-Na suspension with the same volume was given both in the morning and afternoon for the solvent control group. Levels of SUA， creatinine （CREA）， alanine aminotransferase （ALT） and aspartate transaminase （AST） were determined after 32 and 45 days administration of the test substance. ResultsSUA of the model group was （218±23） μmol·L-1 after 7 days of modeling， which was significantly higher than that of the solvent control group （P<0.001）. After 32 days administration of the test substance， SUA didn’t significantly decrease in each dose group （P>0.05）. CREA in the medium and high dose groups significantly decreased （P<0.05）. After 45 days administration of the test substance， SUA in each dose group was significantly decreased （P<0.001）， but CREA， ALT， and AST were not significantly different in each dose group in comparison with the model control group （P>0.05）. ConclusionLiqing granules can assist in lowering blood serum uric acid in the rat HUA model， and no damage to liver and kidney function is found.
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【Objective:】 To explore the relationship between the moral courage of nurses in Intensive Care Unit (ICU) and the hospital ethical climate, and to provide a theoretical basis for enhancing the moral courage of ICU nurses. 【Methods:】 A total of 468 ICU nurses from 8 tertiary A hospitals in Shaanxi Province were selected as the subjects by convenience sampling method, and the General Information Form, Hospital Ethical Climate Survey, and Nurses’ Moral Courage Scale were used for the questionnaire survey. 【Results:】 A total of 468 questionnaires were distributed and 463 valid questionnaires were returned, with an effective recovery rate of 98.93%. The score of hospital ethical climate for ICU nurses was (100.69±19.76), and the score of moral courage was (83.67±15.48). There was a positive correlation between hospital ethical climate and moral courage (r=0.866, P<0.001). Hierarchical multiple regression analysis showed that hospital ethical climate entered the influencing factor model of ICU nurses’ moral courage, which can independently explain 57% of the variation in ICU nurses’ moral courage. 【Conclusion:】 The moral courage of ICU nurses was at a medium level, and positively correlated with the hospital ethical climate, that is, the better the hospital ethical climate perceived by ICU nurses, the higher their level of moral courage. Nursing managers should focus on deepening the hospital ethical climate, and enhance the level of hospital ethical climate through scientific methods to promote the improvement of ICU nurses’ moral courage.
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Iron overload cardiomyopathy (IOC) is a type of cardiac dysfunction caused by several factors resulting in iron overload in the myocardium. Two major causes of IOC include hereditary hemochromatosis and transfusion-dependent anemia. IOC significantly reduces long-term survival of patients. Since IOC is a rare disease in Asian populations that also lacks etiology-specific manifestations, early diagnoses in clinical practice are challenging. Two groups of patients with high risk of IOC should be further investigated: those who present heart failure of unknown origin will be screened for iron overload followed by confirmation of IOC; and those who have high risk of iron overload or an established diagnosis will be monitored for the development of IOC. Serum ferritin is recommended as the first-line screening test for iron overload, while cardiac magnetic resonance T2* should be used to confirm iron overload in the myocardium. Phlebotomy and iron chelating agents can effectively remove the extra iron from the body, preventing IOC, as well as reverse the disease at an early stage and slow down its progession. Timely diagnosis and treatment is critical in improving the prognosis of patients with IOC. Therefore, this review aims to help clinicians to understand IOC in multiple dimensions including pathogenesis, clinical manifestations, diagnostic methods and treatment choices.
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Background@#To date, consistent data have not been reported on the association between serum amyloid A (SAA) levels and type 2 diabetes mellitus (T2DM). The purpose of this study was to systematically summarize their relationship. @*Methods@#Databases including PubMed, Cochrane Library, Embase, Web of Science, and MEDLINE were searched until August 2021. Cross-sectional and case-control studies were included. @*Results@#Twenty-one studies with 1,780 cases and 2,070 controls were identified. SAA levels were significantly higher in T2DM patients than in healthy groups (standardized mean difference [SMD], 0.68; 95% confidence interval [CI], 0.39 to 0.98). A subgroup analysis showed that the mean age of participants and the continent that participants were from were related to differences in SAA levels between cases and controls. Furthermore, in T2DM patients, SAA levels were positively associated with body mass index (r=0.34; 95% CI, 0.03 to 0.66), triglycerides (r=0.12; 95% CI, 0.01 to 0.24), fasting plasma glucose (r=0.26; 95% CI, 0.07 to 0.45), hemoglobin A1c (r=0.24; 95% CI, 0.16 to 0.33), homeostasis model assessment for insulin resistance (r=0.22; 95% CI, 0.10 to 0.34), C-reactive protein (r=0.77; 95% CI, 0.62 to 0.91), and interleukin-6 (r=0.42; 95% CI, 0.31 to 0.54), but negatively linked with highdensity lipoprotein cholesterol (r=–0.23; 95% CI, –0.44 to –0.03). @*Conclusion@#The meta-analysis suggests that high SAA levels may be associated with the presence of T2DM, as well as lipid metabolism homeostasis and the inflammatory response.
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Microfluidic liver and kidney chips have become preferred model carriers in recent years for new drug development， pharmacological and toxicological research， mechanism exploration， and disease model construction. In the context of the USA. Food and Drug Administration allowing the use of in vitro model data as a substitute for animal model data in new drug applications when animal disease models are difficult to construct， microfluidic chips have received widespread attention due to their high throughput， ability to highly mimic biological characteristics of living organisms， convenient evaluation of drug toxicity in normal or pathological states with repeated dosing， real-time induction and monitoring of culture processes， and real-time data acquisition and analysis. In toxicology research， liver and kidney chips can construct in vitro models suitable for the pharmacological and toxicological detection of different substances by combining 2D monocultures and co-cultures from different species sources， 3D cultures， spheroids/organoid cells， precision-cut liver and kidney slices， immortalized cell lines， or sandwich-cultured cell lines. This model maximally simulates or retains the organ function and in vivo microenvironment of the liver and kidney， including specific physiological tissue structures， multicellular interactions/crosstalk， and multi-organ coordination/feedback， to obtain results similar to or the same as in vivo experimental data， reducing interspecies differences. At the same time， it greatly reduces the use of experimental animals and lowers costs. Microfluidic technology provides necessary shear force microenvironments for the cultivation of contents and solves problems encountered in the cultivation process of liver and kidney chips， such as insufficient tissue oxygen supply， nutrient deficiencies， and accumulation of metabolites， leading to cell apoptosis and even tissue necrosis fibrosis， which make it difficult to maintain long-term structure and function. This article reviewed the application of microfluidic technology combined with liver and kidney chips in Chinese medicine toxicology research. By summarizing the development of microfluidic technology， liver chips， kidney chips， and providing application examples of microfluidic liver and kidney chips in Chinese medicine toxicology research， combined with the characteristics of Chinese medicine administration， the article explored the advantages and future development directions of their application in the field of Chinese medicine toxicology research.
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OBJECTIVE To study protective effect and potential mechanism of Modified yupingfeng nasal spray （YPF+） on nasal mucosal injury in allergic rhinitis （AR） model rats. METHODS AR model was induced by ovalbumin （OVA） and randomly divided into model group， YPF+group （50 µg/side，twice a day）， positive control group （Mometasone furoate aqueous nasal spray， 50 µg/side，once a day）； the blank group was set up， with 10 rats in each group. Administration groups were given relevant medicine， and blank group and model group were given equivalent normal saline for consecutive 4 weeks. Thirty minutes after last medication， the behavioral scores of rats were recorded， and the pathological changes of their nasal mucosa tissue were observed. The level of reactive oxygen species （ROS） in nasal mucosa tissue was detected. The protein and mRNA expressions of nucleotide- binding oligomerization domain-like receptor protein 3 （NLRP3），caspase-1，gasdermin D （GSDMD） were detected； the contents of interleukin-1β （IL-1β） and IL-18 in serum were also determined. RESULTS Compared with blank group， in model group， the nasal mucosa tissue structure was disordered， inflammatory cells infiltrated seriously， and lamina propria vascular dilation was visible； its behavioral score and pathological score， the level of ROS， protein and mRNA expressions of NLRP3， caspase-1 and GSDMD， serum contents of IL-1β and IL-18 in nasal mucosa tissue were increased significantly （P＜0.05）. Compared with model group， the symptoms of nasal mucosal injury in rats of each drug group were improved to varying degrees， and the above indicators were significantly reduced （P＜0.05）. CONCLUSIONS YPF+ may improve nasal mucosal injury of rats， relieve AR symptoms such as sneezing， itchy nose， runny nose， the mechanism of which may be associated with reducing the production of ROS in nasal mucosa and downregulating NLRP3/caspase-1/ GSDMD pathway.
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Cryoablation (CRA) and microwave ablation (MWA) are two main local treatments for hepatocellular carcinoma (HCC). However, which one is more curative and suitable for combining with immunotherapy is still controversial. Herein, CRA induced higher tumoral PD-L1 expression and more T cells infiltration, but less PD-L1highCD11b+ myeloid cells infiltration than MWA in HCC. Furthermore, CRA had better curative effect than MWA for anti-PD-L1 combination therapy in mouse models. Mechanistically, anti-PD-L1 antibody facilitated infiltration of CD8+ T cells by enhancing the secretion of CXCL9 from cDC1 cells after CRA therapy. On the other hand, anti-PD-L1 antibody promoted the infiltration of NK cells to eliminate PD-L1highCD11b+ myeloid cells by antibody-dependent cell-mediated cytotoxicity (ADCC) effect after CRA therapy. Both aspects relieved the immunosuppressive microenvironment after CRA therapy. Notably, the wild-type PD-L1 Avelumab (Bavencio), compared to the mutant PD-L1 atezolizumab (Tecentriq), was better at inducing the ADCC effect to target PD-L1highCD11b+ myeloid cells. Collectively, our study uncovered the novel insights that CRA showed superior curative effect than MWA in combining with anti-PD-L1 antibody by strengthening CTL/NK cell immune responses, which provided a strong rationale for combining CRA and PD-L1 blockade in the clinical treatment for HCC.
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Alanine-serine-cysteine transporter 2 (ASCT2) is reported to participate in the progression of tumors and metabolic diseases. It is also considered to play a crucial role in the glutamate-glutamine shuttle of neuroglial network. However, it remains unclear the involvement of ASCT2 in neurological diseases such as Parkinson's disease (PD). In this study, we demonstrated that high expression of ASCT2 in the plasma samples of PD patients and the midbrain of MPTP mouse models is positively correlated with dyskinesia. We further illustrated that ASCT2 expressed in astrocytes rather than neurons significantly upregulated in response to either MPP+ or LPS/ATP challenge. Genetic ablation of astrocytic ASCT2 alleviated the neuroinflammation and rescued dopaminergic (DA) neuron damage in PD models in vitro and in vivo. Notably, the binding of ASCT2 to NLRP3 aggravates astrocytic inflammasome-triggered neuroinflammation. Then a panel of 2513 FDA-approved drugs were performed via virtual molecular screening based on the target ASCT2 and we succeed in getting the drug talniflumate. It is validated talniflumate impedes astrocytic inflammation and prevents degeneration of DA neurons in PD models. Collectively, these findings reveal the role of astrocytic ASCT2 in the pathogenesis of PD, broaden the therapeutic strategy and provide a promising candidate drug for PD treatment.
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The high incidence of unplanned readmission of postoperative patients with gynecologic malignancies not only seriously affects the quality of life of patients, but also increases the medical burden. This paper reviews the current situation, common causes, relevant factors and insights of unplanned readmission of postoperative gynecologic malignancy patients, and further explores the unplanned readmission of postoperative gynecologic malignancy patients in China by drawing on existing foreign studies and combining them with the actual situation in China, with the aim of providing a basis for clinical health care professionals to develop targeted intervention plans, so as to effectively reduce the unplanned readmission of postoperative gynecologic malignancy patients.
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Objective:To analyze the research hotspots and trends in the field of Traditional Chinese Medicine (TCM) for cervical cancer at home and abroad in recent 30 years through visualization method.Methods:By setting "cervical cancer" and "TCM" as the research subjects, the articles were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, and Web of Science Core database (WoS) from January 1, 1992 to January 1, 2022. Citespace 5.8 R3 software was used to conduct visual analysis on the authors, institutions and keywords included in the articles.Results:A total of 1 123 Chinese articles and 573 English articles were included. The number of articles issued showed a gradual upward trend; the author with the largest number of Chinese publications was Jin Zhe, and the author with the largest number of English publications was Chen Guo. The institution with the largest number of Chinese publications was Beijing University of Chinese Medicine; the institution with the largest number of English publications was Chinese Academy of Medical Sciences. Keywords co-occurrence of the top 3 Chinese keywords in the network frequency (excluding the search words) were "cervical erosion", "urinary retention" and "Yunnan Baiyao"; English keywords were "HeLa cell", "bibliometric", and "information monitoring system". Chinese keywords formed 11 clusters and 25 emergent words; English keywords formed 9 clusters and 17 emergent words.Conclusions:The research content in the field of TCM of cervical cancer about knowledge map in the past 30 years at home and abroad is rich. TCM can play the role of antagonizing human papillomavirus, enhancing immune function, regulating TCM constitution, improving quality of life and so on. At present, the research hotspot is the mechanism exploration of cervical cancer and the curative effect research of clinical complications, and the research trend is clinical curative effect research.
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Objective:To analyze the rule of acupoint selection for acupuncture in relieving postoperative pain based on data mining technology.Methods:Articles about acupuncture for postoperative pain were retrieved from CNKI, SinoMed, VIP, Wanfang, PubMed, Embase and Web of Science databases from establishment to June 6, 2022. Excel 2019 and SPSS Modeler 18.0 software were used to establish acupoints database and conduct the data analysis.Results:Totally 308 articles were obtained, involving 317 acupuncture prescriptions and 173 acupoints. Acupoints of bladder meridian, stomach meridian, large intestine meridian and spleen meridian were used frequently. Zusanli (ST 36), Hegu (LI 4) and Neiguan (PC 6) were high-frequency acupoints with a frequency of ≥50 times. Five-shu acupoint was often selected in specific acupoints. The common sites for acupuncture to relieve postoperative pain were abdomen, perianal, lumbar back and knee. Zusanli (ST 36), Neiguan (PC 6) and other acupoints were commonly used for abdominal postoperative pain, and the most commonly used combination was "Zusanli (ST 36)-Neiguan (PC 6)"; Chengshan (BL 57), Changqiang (GV 1) and other acupoints were often used for perianal postoperative pain, and "Chengshan (BL 57)-Changqiang (GV 1)" was highly correlated combination; Shenshu (BL 23) and Huantiao (GB 30) were commonly used for postoperative pain in the lumbar and back region, and acupoints with high correlation were "Ashi acupoint-Huantiao (GB 30)" and "Shenshu (BL 23)-Huantiao (GB 30)"; Xuehai (SP10) and Liangqiu (ST 34) were commonly used for postoperative pain of knee, and their compatibility had a high correlation.Conclusion:Acupuncture therapy for relieving postoperative pain often selects Yang meridians acupoints, and follows the principle of distal-proximal points combination and acupoint selection along meridians, and pays attention to the use of specific acupoints.
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OBJECTIVE To investigate the efficacy and safety of different doses of zinc in the treatment of diarrhea in children， and to provide a reference for clinical safe and rational drug use. METHODS Retrieved from PubMed， Cochrane Library， Embase database， randomized controlled trials about zinc （zinc group） versus placebo or conventional treatment （control group） in the treatment of diarrhea in children were collected from the inception to October 2022. Then， the quality of the included literature was evaluated by the Cochrane Handbook 6.0， and meta-analysis and sensitivity analysis were performed by RevMan 5.3 software. RESULTS Finally， 25 RCTs were included， with a total of 8 618 children. The results of meta-analysis showed that in terms of duration of diarrhea， in zinc ＜20 mg group， the zinc group was significantly shorter than the control group [SMD＝ －0.39， 95%CI（－0.71， －0.08）， P＝0.01]， but in subgroups of ＜6 months old， there was no significant difference between the two groups [SMD＝0.01， 95%CI（－0.10， 0.11）， P＝0.88]. In zinc 20 mg group， the zinc group was significantly shorter than the control group [SMD＝－0.52， 95%CI（－0.80， －0.23）， P＝0.000 3]. In zinc ＞20 mg group， the zinc group was significantly shorter than the control group [SMD＝－0.83， 95%CI（－1.39， －0.27）， P＝0.004]. In zinc ＞10 mg （age ≤12 months） or zinc ＞ 20 mg （age ＞12 months） group （short for “constant dose group”）， the zinc group was significantly shorter than the control group [SMD＝－0.16， 95%CI（－0.27， －0.06）， P＝ 0.003]. In the aspect of diarrhea rate after 7 days of treatment，there was no significant difference in the diarrhea rate after 7 E-mail：lihuiying@etyy.cn days of treatment between the zinc group and the control group： in zinc ＜20 mg group[OR＝1.28，95%CI （0.96，1.70），P＝0.09]， in zinc 20 mg group [OR＝0.40， 95%CI （0.15，1.01），P＝ 0.05]， in constant dose group [OR＝0.64， 95%CI （0.28， 1.44）， P＝0.28]. In terms of vomiting rate， in zinc ＜20 mg group， the vomiting rate of zinc group was significantly higher than that of the control group [OR＝2.13， 95%CI （1.68， 2.70）， P＜0.001]； in constant dose group， vomiting rate of zinc group was significantly higher than that of the control group [OR＝1.84， 95%CI （1.44， 2.34）， P＜0.001]. CONCLUSIONS Zinc can significantly shorten the duration of diarrhea in children（6 months and above）， but low doses can increase the risk of vomiting， which should be taken attention in clinical.
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Objective: To investigate the effect and possible mechanism of Y-box-binding protein 1 (YB-1) on sorafenib resistance in hepatoma cells. Methods: Lentiviral vectors with YB-1 overexpression and knockdown were constructed, respectively, to stimulate human hepatoma cell lines (HepG2 and Huh7) alone or in combination with sorafenib.The overexpression part of the experiment was divided into four groups: overexpression control group (Lv-NC), YB-1 overexpression group (Lv-YB-1), overexpression control combined with sorafenib resistance group (Lv-NC+sorafenib), YB-1 overexpression combined with sorafenib resistance group (Lv-YB-1 + sorafenib). The knockdown part of the experiment was also divided into four groups: knockdown control group (Lv-shNC), YB-1 knockdown group (Lv-shYB-1), knockdown control combined with sorafenib resistance group (Lv-shNC + sorafenib), YB-1 knockdown combined with sorafenib resistance group (Lv-shYB-1 + sorafenib). The occurrence of cell apoptosis was detected by TUNEL. The protein expression levels of phosphorylated (p)-ERK and ERK, key proteins in the extracellular regulatory protein kinase (ERK) signaling pathway, were detected by Western blot and quantified by ImageJ software. Subcutaneous tumorigenesis experiments were performed in nude mice. The effect of YB-1 on the efficacy of sorafenib was verified in vivo. The comparison between the two sets of data was carried out by an independent sample t-test. One-way ANOVA was used for comparisons between the three groups of data above. Results: Sorafenib had accelerated the occurrence of apoptosis in hepatoma cells, while YB-1 overexpression had inhibited cell apoptosis, and at the same time also inhibited the apoptosis-accelerating impact of sorafenib. On the contrary, YB-1 knockdown accelerated cell apoptosis and amplified the induction effect of sorafenib on apoptosis. Furthermore, sorafenib resistance had down-regulated p-ERK levels (HepG2: Lv-NC 0.685 ± 0.143, Lv-NC + sorafenib 0.315 ± 0.168, P < 0.05; Huh7: Lv-NC 0.576 ± 0.078, Lv-NC + sorafenib 0.150 ± 0.131, P < 0.01), whereas YB-1 overexpression had inhibited sorafenib resistance p-ERK reduction (HepG2: Lv-NC + sorafenib 0.315 ± 0.168, Lv-YB-1 + sorafenib 0.688 ± 0.042, P < 0.05; Huh7: Lv-NC + sorafenib 0.150 ± 0.131, Lv-YB-1 + sorafenib 0.553 ± 0.041, P < 0.05). YB-1 knockdown further increased sorafenib-induced p-ERK downregulation (HepG2: Lv-shNC + sorafenib 0.911 ± 0.252, Lv-shYB-1 + sorafenib 0.500 ± 0.201, P < 0.05; Huh7: Lv-shNC + sorafenib 0.577 ± 0.082, Lv-shYB-1 + sorafenib 0.350 ± 0.143, P < 0.05), which was further verified in naked mice (Lv-shNC + sorafenib 0.812 ± 0.279, Lv-shYB-1 + sorafenib 0.352 ± 0.109, P < 0.05). Conclusion: YB-1 mediates the occurrence of sorafenib resistance via the ERK signaling pathway in hepatoma cells.
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Humans , Animals , Mice , Cell Line, Tumor , Sorafenib/pharmacology , Drug Resistance, Neoplasm , Y-Box-Binding Protein 1/metabolism , Carcinoma, Hepatocellular/metabolism , MAP Kinase Signaling System , Mice, NudeABSTRACT
Since the application of biomedical nanotechnology in the field of drug delivery breathes new life into the research and development of high-end innovative agents, a substantial number of novel nano-drug delivery systems (nano-DDSs) have been successively developed and applied in the clinical practice. Among them, small molecule pure drug and prodrug-based nanoassemblies have grasped great attention, owing to the facile fabrication, ultrahigh drug loading and feasible industrial production. Herein, we provide an overview on the latest updates of small-molecule nanoassemblies. Firstly, the self-assembled prodrug-based nano-DDSs are introduced, including nanoassemblies formed by amphiphilic monomeric prodrugs, hydrophobic monomeric prodrugs and dimer monomeric prodrugs. Then, the recent advances on nanoassemblies of small molecule pure chemical drugs and biological drugs are presented. Furthermore, carrier-free small-molecule hybrid nanoassemblies of pure drugs and/or prodrugs are summarized and analyzed. Finally, the rational design, application prospects and clinical challenges of small-molecule self-assembled nano-DDSs are discussed and highlighted. This review aims to provide scientific reference for constructing the next generation of nanomedicines.
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OBJECTIVE@#To analyze the distribution and drug resistance of pathogens in oral mucositis associated with chemotherapy in hospitalized patients with malignant hematopathy, so as to provide scientific evidences for rational selection of antibiotics and infection prevention and control.@*METHODS@#From July 2020 to June 2022, 167 patients with malignant hematopathy were treated with chemical drugs in the Department of Hematology, Hainan Hospital, and secretions from oral mucosal infected wounds were collected. VITEK2 COMPECT automatic microbial identification system (BioMerieux, France) and bacterial susceptibility card (BioMerieux) were used for bacterial identification and drug susceptibility tests.@*RESULTS@#A total of 352 strains of pathogens were isolated from 167 patients, among which 220 strains of Gram-positive bacteria, 118 strains of Gram-negative bacteria and 14 strains of fungi, accounted for 62.50%, 33.52% and 3.98%, respectively. The Gram-positive bacteria was mainly Staphylococcus and Streptococcus, while Gram-negative bacteria was mainly Klebsiella and Proteus. The resistance of main Gram-positive bacteria to vancomycin, ciprofloxacin and gentamicin was low, and the resistance to penicillin, cefuroxime, ampicillin, cefotaxime, erythromycin and levofloxacin was high. The main Gram-negative bacteria had low resistance to gentamicin, imipenem and penicillin, but high resistance to levofloxacin, cefotaxime, cefuroxime, ampicillin and vancomycin. The clinical data of oral mucositis patients with oral ulcer (severe) and without oral ulcer (mild) were compared, and it was found that there were statistically significant differences in poor oral hygiene, diabetes, sleep duration less than 8 hours per night between two groups (P<0.05).@*CONCLUSION@#Gram-positive bacteria is the main pathogen of oral mucositis in patients with malignant hematopathy after chemotherapy. It is sensitive to glycopeptide antibiotics and aminoglycosides antibiotics. Poor oral hygiene, diabetes and sleep duration less than 8 hours per night are risk factors for oral mucositis with oral ulcer (severe).
Subject(s)
Humans , Vancomycin/therapeutic use , Cefuroxime , Levofloxacin , Oral Ulcer/drug therapy , Drug Resistance, Bacterial , Anti-Bacterial Agents/adverse effects , Ampicillin , Penicillins , Cefotaxime , Gram-Positive Bacteria , Gram-Negative Bacteria , Gentamicins , Stomatitis/drug therapyABSTRACT
OBJECTIVE@#To explore the effect of dichloromethane extraction phase of ethanol extract from stem of Patrinia scabiosaefolia Fisch.(DPSS) on proliferation and differentiation of K562 cells and its related mechanism.@*METHODS@#MTT assay was used to detect the effects of DPSS at 0, 25, 50, 100 and 200 μg/ml on the proliferation of K562 cells at 24, 48 and 72 hours. Flow cytometry was used to analyze the changes of cell cycle and apoptosis at 24 and 48 hours. Wright-Giemsa staining was used to observe the morphological changes of K562 cells. The cell surface antigens CD33 and CD11b were detected by flow cytometry.@*RESULTS@#The proliferation of K562 cells treated with different concentrations of DPSS was inhibited in a time-dose dependent manner (r=-0.96). Cell cycle analysis showed that with the increase of DPSS concentration, cells in G2/M phase increased (r=0.88), and cells were blocked in G2/M phase. Flow cytometry results showed that with the apoptosis rate of K562 cells was the highest when treated with 200 μg/ml DPSS for 48 h. Morphological observation showed that the K562 cell body increased, the amount of cytoplasm increased, the ratio of nucleus to cytoplasm decreased, and the nuclear chromatin was rough after DPSS treatment. Cell differentiation antigen, CD33 and CD11b, were positively expressed after treated with DPSS.@*CONCLUSION@#DPSS can induce apoptosis through cell cycle arrest, inhibit the proliferation of K562 cells, and induce K562 cells to differentiate into monocytes, which has a potential anti-leukemia effect.