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OBJECTIVE@#To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification.@*METHODS@#Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway.@*RESULTS@#The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G1-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway.@*CONCLUSION@#Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.
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Humans , Proto-Oncogene Proteins c-akt/metabolism , Cell Proliferation , Matrix Metalloproteinase 9 , Molecular Docking Simulation , Cell Cycle , ErbB Receptors , Apoptosis , Colorectal Neoplasms/pathology , Cell Line, TumorABSTRACT
Fanconi anemia (FA) is an inheritable disorder that presents with bone marrow failure, developmental anomalies, and an increased susceptibility to cancer. The etiology of this condition stems from a genetic mutation that disrupts the proper repair of interstrand DNA cross-links (ICLs). The resultant dysregulation of the DNA damage response mechanism can induce genomic instability, thereby elevating the mutation rates and the likelihood of developing cancer. The FA pathway assumes a pivotal role in safeguarding genome stability through its involvement in the repair of DNA cross-links and the maintenance of overall genomic integrity. A mutation in the germ line of any of the genes responsible for encoding the FA protein results in the development of FA. The prevalence of aberrant FA gene expression in somatic cancer, coupled with the identification of a connection between FA pathway activation and resistance to chemotherapy, has solidified the correlation between the FA pathway and cancer. Consequently, targeted therapies that exploit FA pathway gene abnormalities are being progressively developed and implemented. This review critically examines the involvement of the FA protein in the repair of ICLs, the regulation of the FA signaling network, and its implications in cancer pathogenesis and prognosis. Additionally, it explores the potential utility of small-molecule inhibitors that target the FA pathway.
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In recent years， transcatheter arterial chemoembolization （TACE） has emerged as a common treatment modality for the treatment of hepatocellular carcinoma （HCC）. However， with the ongoing development of embolic agent techniques， the new advances in microspheres and nanoparticles have brought new hope for improving the efficacy and safety of TACE. This article reviews the latest advances and applications of microspheres and nanoparticles in TACE for HCC. First， this article introduces the background of TACE as a therapeutic approach and the emergence of microsphere and nanoparticle techniques， and then it describes the application of various types of microspheres and nanoparticles in TACE and discusses the requisite attributes of an ideal embolic agents. The article focuses on the advances in material science and engineering， as well as the clinical efficacy of drug-eluting microspheres and nanoparticles versus conventional TACE. Furthermore， it discusses the importance of radiological examination in TACE and summarizes the research advances in the radiopaque and magnetic resonance-visible embolic agents. This article also explores the future development directions and challenges of TACE. It also points out the combination of microspheres and nanoparticles with other treatment modalities， the application of personalized and precision medicine in TACE， and the potential regimen of TACE in clinical translation， and meanwhile， it raises the issues of ethics and regulation that need to be further discussed. It is believed that microspheres and nanoparticles have a potential effect in TACE， which provides a theoretical basis and technical support for innovating HCC treatment regimens and improving the prognosis of patients through TACE interventions.
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Objective@#To understand sleep quarity among primary and middle school students in Shenzhen City, so as to provide data support for sleeping quality improvement.@*Methods@#A survey was conducted among 8 742 children selected from two 12 year schools in Longhua District of Shenzhen City, by purposive sampling method from December 22, 2020 to January 15, 2021. The general information was investigated with the self designed questionnaire, and sleep disturbance was investigated and evaluated with the Sleep Disturbance Scale for Children (SDSC). And Chi square test was applied for data analysis.@*Results@#About 47.61 % of primary and middle school students in Shenzhen City reported sleep disturbance, 10.84% of students had moderate to severe sleep disturbance. The overall rate of sleep disturbance and moderate and to severe sleep disturbance among primary school students (48.03%, 10.04%), junior middle schools (45.89%, 11.30%), senior middle schools (52.61%, 16.83%) were found of statistically significant differences ( χ 2=8.89, 27.05, P <0.05). The time to fall asleep for primary school students, junior school students and senior school students at night during the study period were 22:00-23:00 (90.35%), 22:00-23:00 (62.37%), and 23:00-01:00 (61.44%), respectively, and the time to fall asleep of the different stages students were found of statistically significant differences ( χ 2=1 470.17, P <0.01). About 41.04% of students could fall asleep within 15 minutes and 50.57% could fall asleep within 15 to 30 minutes, and the differences in the latency for different stages students to fall asleep at night were of statistical significance ( χ 2=82.92, P <0.01); 8.03% of primary and middle school students had a night sleep time of over 9 hours, and 45.97 % had a night sleep time of 8-9 hours, and the differences in the night sleep time among different stages students were of statistical significance ( χ 2=1 292.86, P <0.01).@*Conclusions@#The main sleep problems among primary and secondary school students in Shenzhen City are insufficient sleep and poor sleep quality. The relevant departments should emphasize the sleep health education among children and their parents, so as to improve their sleep quality.
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Arsenic, a naturally occurring metal-like chemical element, is one of the 10 chemicals of major public concerns listed by the World Health Organization as harmful to the environment and human health. It can enter the human body through breathing, intaking food, drinking water, skin exposure, and other ways, and long-term exposure to arsenic can cause cancer of multiple organs and impaired function of multiple systems. Epigenetic mechanisms play an important role in arsenic-induced health effects, and research suggested that the carcinogenicity of arsenic may be associated with epigenetic changes. Previous studies focused on the effects of arsenic on DNA methylation modification. In recent years, research showed that 5-hydroxymethylcytosine (5-hmC), an intermediate of active demethylation of DNA, can act as a sensitive epigenetic mark and play a crucial role as a "bridge" between arsenic exposure and health effects. Based on the latest research progress on the role of DNA hydroxymethylation in the health effects associated with arsenic exposure, this article briefly described the relationship between the health effects of arsenic exposure and DNA hydroxymethylation, summarized the possible mechanisms of DNA hydroxymethylation in the health effects associated with arsenic exposure, and provided a scientific basis for preventing and treating the health effects associated with arsenic exposure.
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OBJECTIVE To explore the mechanism of Zadi-5 pill in improving myocardial ischemia-reperfusion injury （MIRI）. METHODS The targets and pathways of potential effects of Zadi-5 pill improving MIRI were screened based on the network pharmacology. Seventy-two rats were randomly divided into model group， sham operation group， Danshen group [Compound danshen dripping pills 80 mg/（kg·d）] and Zadi-5 pill high-dose， medium-dose and low-dose groups [1.6， 0.8， 0.4 g/（kg·d）]， with 12 rats in each group. The rats in each group were given corresponding drugs intragastrically， once a day， for 14 consecutive days. After the last administration， MIRI model was established by ligating the anterior descending branch of left coronary artery in rats， while rats in the sham operation group were threaded without ligation. The contents of creatine kinase （CK）， lactate dehydrogenase （LDH）， aspartate transaminase （AST）， cardiac troponin T （CTn-T）， apoptotic rate of cardiomyocyte， phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， B-cell lymphoma-2 （Bcl-2）， Bcl-2 related X protein （Bax） and caspase-3 in myocardial tissue were detected in each group after modeling； the morphological changes of myocardial tissue were observed. RESULTS A total of 177 active ingredients and 220 targets of Zadi-5 pill were obtained， including 51 targets involved in improving myocardial ischemia； the core target of Zadi-5 pill improving MIRI was AKT1， including PI3K-Akt， endoplasmic reticulum and hypoxia-inducible factor-1. Compared with model group， the contents of CK， LDH， AST and CTn-T， the apoptotic rate of cardiomyocyte as well as the protein expressions of caspase-3 and Bax were significantly decreased in Danshen group and Zadi-5 pill high-dose group （P＜0.05 or P＜0.01）， while the protein expressions of PI3K， Akt and Bcl-2 in myocardial tissue were significantly increased （P＜0.05 or P＜0.01）， respectively； the myocardial histopathological changes were significantly improved. The above indicators were improved to varying degrees in Zadi-5 pill low-dose and medium-dose groups， too. CONCLUSIONS Zadi-5 pill may inhibit apoptosis by activating the PI3K-Akt signaling pathway， thus playing a role in improving MIRI.
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Chemotherapy-induced complications, particularly lethal cardiovascular diseases, pose significant challenges for cancer survivors. The intertwined adverse effects, brought by cancer and its complication, further complicate anticancer therapy and lead to diminished clinical outcomes. Simple supplementation of cardioprotective agents falls short in addressing these challenges. Developing bi-functional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events simultaneously. Drug repurposing was naturally endowed with co-therapeutic potential of two indications, implying a unique chance in the development of bi-functional agents. Herein, we further proposed a novel "trilogy of drug repurposing" strategy that comprises function-based, target-focused, and scaffold-driven repurposing approaches, aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional agent. Through function-based repurposing, a cardioprotective agent, carvedilol (CAR), was identified as a potential neddylation inhibitor to suppress lung cancer growth. Employing target-focused SAR studies and scaffold-driven drug design, we synthesized 44 CAR derivatives to achieve a balance between anticancer and cardioprotection. Remarkably, optimal derivative 43 displayed promising bi-functional effects, especially in various self-established heart failure mice models with and without tumor-bearing. Collectively, the present study validated the practicability of the "trilogy of drug repurposing" strategy in the development of bi-functional co-therapy agents.
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SUMMARY OBJECTIVE: The aim of this study was to evaluate the clinical efficacy of crisaborole ointment in the treatment of vulvar leukoplakia. METHODS: A prospective, randomized controlled clinical trial was conducted, and a total of 100 patients with vulvar leukoplakia were divided into the observation group (n=50) treated with crisaborole ointment and the control group (n=50) treated with vitamin E. The symptom improvement and vulvar leukoplakia score after 2 weeks of treatment were analyzed, and the clinical efficacy of vulvar leukoplakia was evaluated by referring to the Guidelines for Clinical Research of New Drugs of Traditional Chinese Medicine (2018 Edition). RESULTS: After 2 weeks of treatment, the overall score of lesions in the observation group decreased, and the total treatment efficiency of patients in the observation group was 92% (46/50), which was significantly higher than that of 52% (26/50) in the control group P<0.05). CONCLUSION: Crisaborole ointment can effectively treat vulvar leukoplakia, improving the symptoms and pathological changes of the vulvar skin.
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@#Objective To systematically evaluate the risk factors for postoperative pulmonary infection in patients with esophageal cancer. Methods CNKI, Wangfang Data, VIP, CBM, PubMed, EMbase, The Cochrane Library were searched from inception to January 2021 to collect case-control studies, cohort studies and cross-sectional studies about risk factors for postoperative pulmonary infection in patients with esophageal cancer. Two researchers independently conducted literature screening, data extraction and quality assessment. RevMan 5.3 software and Stata 15.0 software were used for meta-analysis. Results A total of 20 articles were included, covering 5 409 patients of esophageal cancer. The quality score of included studies was 6-8 points. Meta-analysis results showed that age (MD=1.99, 95%CI 0.10 to 3.88, P=0.04), age≥60 years (OR=2.68, 95%CI 1.46 to 4.91, P=0.001), smoking history (OR=2.41, 95%CI 1.77 to 3.28, P<0.001), diabetes (OR=2.30, 95%CI 1.90 to 2.77, P<0.001), chronic obstructive pulmonary disease (OR=3.69, 95%CI 2.09 to 6.52, P<0.001), pulmonary disease (OR=2.22, 95%CI 1.16 to 4.26, P=0.02), thoracotomy (OR=1.77, 95%CI 1.32 to 2.37, P<0.001), operation time (MD=14.08, 95%CI 9.64 to 18.52, P<0.001), operation time>4 h (OR=3.09, 95%CI 1.46 to 6.55, P=0.003), single lung ventilation (OR=3.46, 95%CI 1.61 to 7.44, P=0.001), recurrent laryngeal nerve injury (OR=5.66, 95%CI 1.63 to 19.71, P=0.006), and no use of patient-controlled epidural analgesia (PCEA) (OR=2.81, 95%CI 1.71 to 4.61, P<0.001) were risk factors for postoperative pulmonary infection in patients with esophageal cancer. Conclusion The existing evidence shows that age, age≥60 years, smoking history, diabetes, chronic obstructive pulmonary disease, pulmonary disease, thoracotomy, operation time, operation time>4 h, single lung ventilation, recurrent laryngeal nerve injury, and no use of PCEA are risk factors for postoperative pulmonary infection in patients with esophageal cancer. Due to the limitation of the quantity and quality of included literature, the conclusion of this study still needs to be confirmed by more high-quality studies.
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ObjectiveTo investigate the clinical efficacy and safety of Qihuang Jianpi Zishen granules in the treatment of cardiac involvement in systemic lupus erythematosus （SLE）. MethodA total of 62 SLE patients with cardiac involvement treated in the Department of Rheumatology and Immunology， the First Affiliated Hospital of Anhui University of Chinese Medicine from June 2021 to December 2022 were randomized into control and observation groups （n=31）. The control group was treated with methylprednisolone tablets and hydroxychloroquine sulfate tablets， and the observation group with Qihuang Jianpi Zishen granules on the basis of the therapy in the control group. After 12 weeks of treatment， the two groups were compared in terms of the therapeutic effect， cardiac function indicators ［left atrial end-diastolic diameter （LADd）， left ventricular end-diastolic diameter （LVDd）， left ventricular posterior wall thickness （LVPWTd）， peak blood flow velocity in early diastolic period （peak E）， peak blood flow velocity in late diastolic period （peak A）， E/A ratio， stroke volume （SV）， left ventricular ejection fraction （LVEF）， left ventricular short axis shortening rate （LVFS）， and B-type natriuretic peptide （BNP）］， vascular damage indicators ［nitric oxide （NO）， endothelin-1 （ET-1）， vascular endothelial growth factor （VEGF）， and homocysteine （Hcy）］， inflammation indicators ［erythrocyte sedimentation rate （ESR） and hypersensitive C-reactive protein （Hs-CRP）］， anti-double-stranded DNA （dsDNA） antibodies， disease activity index （SLEDAI） score， mitigation of symptoms and signs， and occurrence of adverse reactions. ResultThe total response rate in the observation group was 87.09%， which was higher than that （67.74%） in the control group （P<0.01）， and the incidence of adverse reactions had no significant difference between the two groups. After treatment， the control group showed lowered LVDd， LVPWTd， BNP， ET-1， VEGF， and Hcy （P<0.05） and increased E peak， E/A ratio， SV， LVEF， and LVFS （P<0.05）. In the observation group， LADd， LVDd， LVPWTd， peak A， BNP， NO， ET-1， VEGF， and Hcy decreased （P<0.05）， while peak E， E/A ratio， SV， LVEF and LVFS increased （P<0.05） after treatment. The treatment in both groups decreased the scores of palpitation， chest tightness， dyspnea， and edema （P<0.05）， reduced ESR， Hs-CRP， ds-DNA， and SLEDAI （P<0.05）. After treatment， the observation group had lower LADd， LVDd， LVPWTd， peak A， BNP， and scores of palpation， chest tightness， dyspnea， and edema （P<0.05） and higher peak E， E/A ratio， SV， LVEF， and LVFS （P<0.05） than the control group. In addition， the observation group had lower NO， ET-1， VEGF， Hcy， ESR， Hs-CRP， ds-DNA， and SLEDAI than the control group （P<0.05）. ConclusionQihuang Jianpi Zishen granules combined with hydroxychloroquine sulfate and methylprednisolone can improve multiple indicators and mitigate the symptoms and signs of SLE patients with cardiac involvement， demonstrating a clinical application value.
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Objective:To investigate the expression levels of peripheral blood lymphocytes in patients with high-grade squamous intraepithelial lesions (HSIL) of the cervix and early cervical cancer, and to analyze their correlation with the clinicopathological characteristics of cervical cancer.Methods:The clinical data of 65 patients with HSIL and 78 patients with early cervical cancer (2018 International Federation of Gynecology and Obstetrics stage ≤ stage Ⅱ A) treated in Shanxi Province Cancer Hospital from October 2020 to November 2021 were retrospectively analyzed, and 31 healthy people undergoing physical examination during the same period were treated as the healthy control group. The expressions of CD3 + T cells, CD4 + T cells, CD8 + T cells, NK cells, NK/T cells and other immune cells in fasting peripheral blood of the patients were detected by using flow cytometry. Results:The expression levels of CD3 + T cells, CD4 + T cells, CD4 +/CD8 + and NK cells were 71±8, 39±7, 1.5±0.5, 16±7, respectively in HSIL group, and 73±9, 41±9, 1.5±0.6, 16±9, respectively in early cervical cancer group, which were lower than those in the healthy control group (76±9, 45±10, 2.0±1.3, 20±7) (all P < 0.05). The expression levels of CD8 + T cells was 28±7, 29±8, respectively in HSIL group and early cervical cancer group, which were higher than those in the healthy control group (24±7) (all P < 0.05). The expression level of total B cells in early cervical cancer group was lower than that in healthy control group (10±4 vs.12±3, P < 0.05). The expression level of CD3 + T cells in peripheral blood of early cervical cancer patients with tumor diameter >4 cm and nerve/vascular invasion was 71±10 and 72±8, which was lower than that of patients with tumor diameter 2-4 cm, ≤2 cm and without nerve/vascular invasion (72±8, 75±8, 78±7); the expression level of CD8 + T cell was 32±8 and 35±4, which was higher than that of patients with tumor diameter 2-4 cm, ≤2 cm, and without nerve/vascular invasion (28±8, 28±7, 29±8) (all P < 0.05). The levels of CD3 + T cells and total B cells were negatively correlated with the tumor diameter (all P < 0.05), while the level of CD8 + T cells was positively correlated with tumor diameter ( P < 0.05); the levels of CD3 + T cells and NK cells were negatively correlated with nerve/vascular invasion (all P < 0.05). Conclusions:The immune function of the body starts to change in the early progression of cervical cancer, and is related to the tumor diameter and nerve/vascular invasion of cervical cancer.
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Objective:To construct future-oriented theoretical management model for medical quality and patient safety.Methods:Procedure grounded theory was applied to code data including 30 expert interview records from July 2021 to June 2022 and the qualitative analysis results of 71 core literatures in Chinese and English, and then the theoretical model was constructed.Results:After three-level coding, 555 reference points, 249 initial concepts, 41 categories, 27 main categories and 7 core categories related to medical quality and safety management were sorted out, and the theoretical model of SQ (I-SPORT) matrix for medical quality and safety management was constructed. This model extended the traditional dimension in quality and safety management.Conclusions:Regarding medical quality and safety management, on one hand, should focus on the systematic improvement of structure, process, results, reengineering, education and training in terms of management functions; on the other hand, it is necessary to improve the organization, employees, resources, technology and tools, and patient experience in terms of management elements.
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Objective:To systematically construct the foreign medical quality and safety management model by searching the English literature related to medical quality and safety management, so as to provide reference for improving the level of medical quality and safety management in China.Methods:The Web of Science database was used as the data source, the English literature related to medical quality and safety management in foreign countries was screened following the PRISMA guidelines, and the content of the screened literature was analyzed using qualitative text analysis based on the Structure Process System Outcome (SPSO) theoretical model.Results:In this study, a total of 37 articles were screened, 5 first-level themes of structure, process, system, outcome and continuous quality improvement were identified, 16 second-level themes were found, and their functional relationships were established. A theoretical model of the SPSO-Extension (SPSO-E) for medical quality and safety management was constructed, added new elements of the external environment, organizational outcome and employee outcome, and refined the continuous quality improvement into three segments of quality checking, problem handling and quality consolidation.Conclusions:In order to improve medical quality and safety management in China, the internal management model of the hospital should be dynamically adjusted according to the changes of external environment, and the result dimension should pay attention to the improvement of organization′s operational effectiveness and the physiological and psychological aspects of the staff. The final management results have a feedback effect on the hospital′s resource allocation, service delivery, organizational arrangements and cultural construction, promoting continuous improvement and enhancement of the hospital′s quality.
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Objective:To find the preferences of nursing staff when they provide " Internet + nursing service" for elderly patients.Methods:By means of the discrete choice experiment, a questionnaire was designed to investigate the preferences of nursing staff when they provide " Internet + nursing services" for elderly patients. In-service nursing staff from 8 medical and health institutions in Ningbo city and Wenzhou city were selected by random sampling, for an online questionnaire survey conducted from May to June 2022. The preferences of nursing staff on their service income, service content, service distance, service continuity and residence status of elderly patients when providing " Internet + nursing service" were analyzed by mixed logit regression.Results:A total of 420 valid questionnaires were collected. Compared to 50 yuan/order, nursing staff preferred to a price of 150 yuan/order ( β= 1.22, P<0.001) nursing services; Compared to specialized nursing services, nursing staff preferred to the routine care ( β= 0.86, P<0.001) and health promotion ( β= 0.86, P<0.05) service; Compared to<5 km, nursing staff were unwilling to provide nursing services for elderly patients at distances of 5-10 km and 11-15 km ( β=-0.66, P<0.05; β=-0.95, P<0.001) ; Compared to 1-2 visits per month, nursing staff preferred not to provide continuing care services ( β=-0.70, P<0.05); Compared to homestay with the patient family, nursing staff preferred to provide nursing services for elderly patients residing in nursing homes ( β= 1.21, P<0.001) . Conclusions:Considering the preference of nursing staff tend to provide " Internet + nursing service" for the elderly patients with services featuring appropriate price, non-specialist care, close distance, low continuity (moderate intensity used as the reference) and security assurance for practice.
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Objective:To discuss the procedure for correction of inverted nipple using tiny incision with primary breast ducts reserved.Methods:A total of 35 patients (63 sides) with primary inverted nipples from January 2006 to March 2019 were reviewed retrospectively. Tiny radial incisions were made on the areola around the base of the inverted nipple which had been pulled out. Without skin removed, shorten fiber bundles which caused nipple inverted were totally cut and released. While the primary breast ducts were preserved, purse-string suture was taken around the base of the nipple. The nipple protector was prepared by ourselves, and the nipple was pulled and suspended for 2-6 months.Results:Sixty-three sides of 35 patients with inverted nipples were successfully corrected by this minimally invasive surgery. There was no nipple necrosis. One patient developed mild swelling 3 weeks after operation, and the swelling subsided after symptomatic anti-inflammatory treatment. The average follow-up period was 39 months. After removing the nipple protector, 2 sides (2/63) had a certain degree of recurrence. The rest of the nipples had ideal shape, no obvious scar, good nipple feeling, and retained the possibility of lactation.Conclusions:The procedure for correction of inverted nipple using tiny incision with primary breast ducts reserved has advantages of minimal invasion, safety, less pain, while retaining the possibility of lactation in the future. The clinical effect is satisfactory. It is especially suitable for the correction of type Ⅰ and type Ⅱ inverted nipples.
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Objective:To explore the innovation mode of independent transformation-oriented science and technology research program approval by medical new research & development (R&D) institution.Methods:Through analyzing the program layout, funds, review experts, undertaking units, chief experts and interdisciplinarity to summarize the experiences of the independent transformation-oriented municipal program approval by Haihe laboratory of Cell Ecosystem in 2022.Results:As a new medical R&D institution, which vigorously constructed by Tianjin, Haihe laboratory of Cell Ecosystem has carried out the practice of the independent transformation-oriented municipal program through the measures of layout of full-chain transformation, conducting transformation-oriented review, gathering high-level research talents, and emphasizing interdisciplinarity.Conclusions:The experiences of Haihe laboratory of Cell Ecosystem make significance for medical new R&D institutions to explore and cultivate scientific research program with transformation potential and to promote the transformation of scientific and technological achievements, which are powerful factors for new R&D institutions to play a role of pilot and provide important support to scientific and technological innovation and transformation.
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Objective:In the era of precision medicine, there is an urgent need for a preclinical evaluation method with a high cost-benefit ratio to improve the effectiveness and value of clinical trials.Methods:Taking clinical needs and scientific research purposes as the starting point, the platform focused on four aspects of project management, information retrieval, quality control, and practical application, and introduced in detail the management practice of building a patient-derived xenograft model platform system.Results:With the support of the institutional system, quality control system, and information system, the patient-derived xenograft model platform was formed with standardization as the core. With the assistance of this platform and scientific research management, as of December 2021, there are 48 animal models of patient-derived xenograft in the database. In total of 6 SCI scientific and technological articles were published using these animal models, with a total impact factor of 36.77 (the highest single article was 7.333). In total of 6 direct industrial projects, 6 clinical trial-related projects, and 4 NSFC projects were approved with a total research fund of 1.5 million yuan.Conclusions:Continuous construction and improvement of the existing platform will help promote the development of basic research translation and clinical research in the field of oncology, and accelerate the development of new oncological diagnosis and treatment models, thereby benefiting more patients.
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Objective:As a newly emerging thing, the construction and operation management of research wards are still being explored. According to the previous practice, this study summarized and shared the key points of a demonstration research ward in Beijing, and provided a reference for the development of domestic research wards.Methods:Focusing on improving the efficiency and quality of clinical research, this article summarizes and shares the experience of research ward construction. In addition, this study explores how to maintain the high-quality sustainable development of research wards from the aspects of improving core competence, system construction, and talent training.Results:Professional teams, innovative operation modes, as well as intelligence and informatization could improve the quality of clinical research. Besides, the improvement of core competence, talent training, and policy support ensure sustainable development of research wards.Conclusions:As clinical research platforms, the development paths of research wards need to be clarified further. The standardized construction and sustainable development of research wards can effectively improve clinical research capability and promote the transformation of scientific achievements.
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Objective:To explore the association between serum high density lipoprotein subtype 3 cholesterol (HDL3-C) levels and the severity and in-stent restenosis of patients with coronary artery disease.Methods:124 patients with coronary artery diseases and 62 healthy controls were included in this clinical case-control retrospective study. Participants were hospitalized from November 2020 to November 2021 at Jinling Hospital, Medical School of Nanjing University were enrolled. Patients with coronary artery disease were as follows: 28 patients with acute coronary syndrome and 96 patients with stable coronary heart disease. Serum HDL3-C levels as well as total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were determined. According to the coronary artery angiography results of all patients at the time of admission, Gensini scores were calculated and patients were divided into in-stent restenosis group ( n=22), no in-stent stenosis group ( n=23) and non-stent implantation group ( n=79). The correlation between HDL3-C levels and other parameters was analyzed by Pearson or Spearman correlation analyses. Multivariate Logistic regression analyses were used to determine the impact of HDL3-C on the in-stent restenosis of coronary artery diseases. Results:Compared with controls, serum levels of HDL3-C and HDL-C were significantly decreased in patients with coronary artery diseases (all P<0.05). There was a significantly negative correlation between HDL3-C levels and Gensini scores ( r=-0.201, P=0.043). Among patients with coronary artery disease, serum levels of HDL3C, TC and TG in the in-stent restenosis group were significantly lower than in no in-stent stenosis group as well as than in the non-stent implantation group (all P<0.05). Multivariate Logistic regression analyses showed that after adjusting for age, sex, lipid-lowering drugs and TC, TG, LDLC parameters, HDL3-C ( OR=0.885, 95% CI 0.791-0.990, P=0.033) and HDL-C ( OR=0.018, 95% CI 0.001-0.426, P=0.013) levels were both independently associated with the occurrence of coronary artery disease; only HDL3-C levels (no in-stent stenosis group as the reference: OR=0.833, 95% CI 0.698-0.994, P=0.042; non-stent implantation group as the reference: OR=0.812, 95% CI 0.685-0.963, P=0.017) were independently associated with the presence of in-stent restenosis ( P<0.05). Conclusions:Serum HDL3-C levels are decreased in patients with coronary artery disease, especially in patients with in-stent restenosis. HDL3-C levels are associated with the severity of coronary artery lesions and the presence of in-stent restenosis of coronary arteries.
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Objective:To analyze the clinical and laboratory characteristics of acute myeloid leukemia (AML) patients with NPM1 mutation, and to explore the prognostic factors.Methods:A total of 77 AML patients with NPM1 gene mutation admitted to Hebei Yanda Ludaopei Hospital from May 1st 2012 to December 31st 2021 were enrolled in the study, including 34 male and 43 female patients. The median age was 40 (3, 68) years old. Patients were selected and divided into 4 groups according to the morphological FAB classification. There were 29 cases (37.7%) of M1 type, 13 cases (16.9%) of M2 type, 23 cases (29.9%) of M4 type, and 12 cases (15.5%) of M5 type. The clinical characteristics, bone marrow/peripheral blood cell morphology, immunophenotype, cytogenetics, molecular biology and overall survival of different groups were retrospectively analyzed, and the risk factors affecting the prognosis of AML were also explored. Cox multivariate regression was used to analyze the clinical influencing factors of survival and prognosis.Results:The white blood cell counts were highest in M4 and M5 patients and lowest in M2 patients, while no significant difference in the red blood cell, hemoglobin, and platelet counts( P>0.05). Morphologically, there were significant differences in the percentage of blasts and blasts with cup-like nuclei on bone marrow (BM) and peripheral blood (PB). The proportion of blasts in BM and PB was the highest in M1 and the lowest in M2 ( P<0.001). The positive rate of blasts with cup-like nuclei was the highest in M1 and the lowest in M5 of BM ( P<0.001), while the highest in M2 and the lowest in M5 of PB ( P=0.006). The scores of myeloperoxidase and chloroacetate esterase were all the highest in M1 and the lowest in M5 ( P<0.001, 0.001, respectively). In terms of molecular biology, the occurence rate of blasts combined with DNMT3A mutation was the highest in M4 and the lowest in M2 ( P=0.044), while those combined with FLT3-ITD mutation was the highest in M4 and the lowest in M5 ( P=0.002). In immunophenotype, there were significant differences in the expression positivities of seven antigens including HLA-DR, CD56, CD11c, CD15, CD14, CD96 and cMPO ( P<0.05). Multivariate COX regression analysis showed that no recurrence after treatment ( P<0.001), complete remission after treatment ( P=0.015) and transplantation ( P<0.001) were correlated with overall survival (OS). No recurrence after treatment ( P=0.033), transplantation ( P=0.027), no mutation of FLT3-ITD ( P=0.040), and hemoglobin concentration ( P=0.023) were associated with relapse-free survival (RFS). Survival analysis by Kaplan-Meier curve showed that there was no significant difference in survival time between the M1, M2, M4 and M5 groups in OS and RFS. Conclusion:There were significant differences in the white blood count, the percentage of blasts and blasts with cup-like nuclear morphology, cytochemical staining (MPO integration, CE integration and percentage of NAS-DCE), gene mutation (DNMT3A and FLT3-ITD) and immunophenotypes (HLA-DR, CD56, CD11c, CD15, CD14, CD96 and cMPO) between the four groups. The multivariate analysis revealed that no recurrence after treatment and transplantation were independent prognostic factors in NPM1 mut AML patients. On the other hand, FLT3-ITD mutation and hemoglobin concentration were associated with RFS and complete remission after treatment was associated with OS in the entire NPM1 mut cohort.