Objective To mine the adverse drug event(ADE)signals of minocycline,to provide a reference for clinical drug safety.Methods The reporting odds ratio(ROR)method,proportional report ratio(PRR)method,the Medicines and Healthcare Products Regulatory Agency(MHRA)method,and Bayesian confidence propagation neural network(BCPNN)method were used to analyze the ADE reports of minocycline based on U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)registration data from first quarter 2004 to fourth quarter 2023,and the signal distribution,signal intensity,gender and age differences,and mortality based on standard MedDRA query(SMQ)were analyzed.Results A total of 16 871 ADE cases of minocycline were screened,and 364 positive ADE signals were mapped to 27 system organ classification(SOC),the most involved SOC were systemic diseases and various reactions at the administration site,skin and subcutaneous tissue diseases,various neurological diseases,etc,and the strong signals with the higher number of ADE cases were drug reaction with eosinophilia and systemic symptoms(DRESS),polyarteritis nodosa and idiopathic intracranial hypertension,and compared to other drugs,the proportion of women with idiopathic intracranial hypertension caused by minocycline was higher(P＜0.05).At the same time,29 cases of ADE in children under 8 years old were obtained,involving 10 SOC,206 deaths and 1 046 associated ADE-related cases,and there were 1 565 cases of hypersensitivity ADE,and 88 PT signals under the hypersensitivity SMQ.Among them,DRESS,urticaria,anti-neutral cytoplasm antibody-positive vasculitis,and facial edema were reported in high numbers and with strong signals.Conclusion The risk of hypersensitivity events and autoimmune diseases should be vigilant in the clinical use of minocycline,and ophthalmic monitoring could be performed especially in female patients if necessary.Attention should be paid to ADE collection and monitoring of minocycline in children under 8 years old.

Objective To rapidly evaluate the effectiveness,safety and economy of edaravone in treating acute ischemic stroke(AIS),and to provide the evidence-based basis for clinical decision-making.Methods PubMed,Embase,Web of Science,Cochrane Library,CNKI and WanFang Data databases and the official website of health technology assessment(HTA)agency were electronically searched to collect HTA reports,systematic reviews/Meta-analysis and pharmacoeconomic studies of edaravone in the treatment of AIS from the inception to October 1,2024.Two reviewers independently screened the literature,extracted data,evaluated the quality,summarized the results,and qualitatively described and analyzed the results.Results A total of 12 literature were included,involving 9 systematic reviews/Meta-analysis and 3 pharmacoeconomic studies.In terms of efficacy,edaravone alone or in combination with conventional therapy(alteplase,ozagrel)increased efficiency,improved short-term neurological deficit scores and improved patients'ability to perform activities of daily living compared with placebo or conventional therapy(alteplase,ozagrel)(P＜0.05).There was no significant difference in the incidence of adverse reactions between edaravone and placebo,routine treatment,or other neuroprotectants(P＞0.05).Combined with alteplase,it could reduce the incidence of intracranial hemorrhage compared to alteplase alone(P＜0.05),with no statistically significant difference in all-cause mortality(P＜0.05).Pharmacoeconomic studies showed that,edaravone does not have a cost-effectiveness advantage in the short term,but it may have a cost-effectiveness advantage from limited long-term studies.Conclusion Edaravone is effective and safe in the treatment of AIS,but there is limited research evidence and the conclusion still needs to be confirmed by further studies and clinical trials,and the economics need to be further evaluated.

Objective To evaluate the clinical value of single-pill combination(SPC)of perindopril and amlodipine for the treatment of hypertension and provide reference for the selection and rational use in medical institutions.Methods A comprehensive clinical evaluation index system was established based on literature research and expert demonstration.Therefore,the safety,effectiveness,economy,innovation,suitability and accessibility of drugs were analyzed qualitatively and quantitatively.Results A total of 12 studies reported the outcome of perindopril and amlodipine SPC,including efficacy and safety.Perindopril amlodipine SPC was safe,and there was no significant difference in the incidence of adverse events during treatment compared with monotherapy,monotherapy combination or other antihypertensive SPC.In terms of effectiveness,perindopril and amlodipine SPC had clear antihypertensive effect,which could significantly reduce systolic blood pressure,diastolic blood pressure,pulse pressure difference and heart rate,and the blood pressure compliance rate of perindopril and amlodipine SPC was better than that of amlodipine or perindopril monotherapy group.Compared with other depressurized SPCs,it showed better or non-inferior effect.Perindopril amlodipine SPC,as a patented drug,has good innovation,high patient compliance,and has been included in China's medical insurance catalog,but the current medical institutions have a low supply rate,and drug prices and affordability are still at a relatively high level.Conclusion Perindopril amlodipine SPC has significant advantages in safety,effectiveness,suitability and innovation,but its economy and accessibility still need to be improved.

Objective:To construct the enteral nutrition nursing scheme of ICU patients with abdominal hypertension based on internal abdominal pressure classification, and provide reference for effectively preventing enteral nutrition intolerance of ICU patients with abdominal hypertension.Methods:According to the "6S" evidence pyramid model, searched from top to bottom for relevant literature on enteral nutrition support for ICU patients with abdominal hypertension in databases such as BMJ Best Practice, Cochrane Library, Guidelines International Network, Medlive, UpToDate, PubMed, Ovid, Web of Science, Embase, China National Knowledge Infrastructure, VIP, Wanfang Medicine, Chinese Biomedical Literature. Developed an enteral nutrition care plan for ICU patients with abdominal hypertension based on intra-abdominal pressure grading, with a search date from database establishment to January 25, 2023. The Delphi expert letter consultation method was used to conduct two rounds of letter consultation with 20 experts to solicit expert opinions and determine the intervention plan.Results:The age of 20 experts was (43.75 ± 5.28) years old, with a working experience of (22.00 ± 6.98) years. The effective recovery rates of the two rounds of Delphi expert correspondence questionnaires were 100%(20/20), the expert judgment basis coefficients were 0.945 and 0.970, the familiarity coefficients were 0.865 and 0.895, and the authority coefficients were 0.905 and 0.932, respectively. Kendall coordination coefficient of importance of the first, second and third level items in the two rounds of expert correspondence were 0.100, 0.093, 0.098 and 0.200, 0.165, 0.119. The Kendall coordination coefficients of operability for the first, second and third level items were 0.117, 0.130, 0.115 and 0.200, 0.184, 0.154, respectively. Finally, an enteral nutrition nursing scheme for patients with abdominal hypertension in ICU was formed, which included 5 primary items, 30 secondary items and 51 tertiary items.Conclusions:The Delphi method in this study has a high degree of authority and enthusiasm of experts, and a good degree of coordination of expert opinions. The established enteral nutrition nursing scheme for ICU patients with abdominal hypertension based on intra-abdominal pressure classification is reliable and scientific, and can provide reference for clinical nursing practice of enteral nutrition for ICU patients with abdominal hypertension.

Heart failure is a severe manifestation or advanced stage of various heart diseases,with high mortality and readmission rates.The 2024 guidelines for the diagnosis and treatment of heart failure,which are on the 2018 guidelines,combined with new evidence and China's national conditions,provide a comprehensive and systematic description and recommendation on the classification,diagnosis,prevention,treatment,comorbidity,and management of heart failure.This article reviewed the update of the therapeutic drugs section.

Objective To rapidly evaluate the efficacy,safety and economics of empagliflozin in the treatment of type 2 diabetes mellitus(T2DM)and to provide evidence-based medical evidence for clinical decision.Methods PubMed,Embase,the Cochrane Library,CNKI,Wangfang,VIP database and major health technology assessment(HTA)websites were searched from the construction of the databases to Nov 30th,2022.Two researchers independently screened,extracted the data,evaluated the quality and analyzed the results according to inclusion and exclusion criteria.Results A total of 23 literatures were included,including 3 HTA reports,10 systematic review/Meta-analyses and 10 pharmacoeconomic studies.The results of efficacy showed that empagliflozin reduced HbA1c,blood pressure,body weight and all-cause mortality compared with the control group.Safety studies showed that empagliflozin was generally well tolerated,and significantly reduced MACEs and the relative risk of the renal primary outcomes,but increased the risk of genital infections and electrolyte abnormality compared with placebo and other oral antidiabetic drugs.The economic evaluation results showed that empagliflozin was more cost-effective in high risk patients with comorbid cardiovascular or kidney disease.Conclusion Empagliflozin is effective and safe in the treatment of T2DM,but the pharmacoeconomic studies focusing on chinese populations are urgently needed.

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Animals ; Cell Differentiation ; Embryo, Mammalian/metabolism* ; Embryonic Development ; Mice ; Pluripotent Stem Cells/metabolism* ; RNA, Messenger/genetics* ; RNA, Ribosomal ; RNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism* ; Zygote/metabolism*

Extraskeletal Ewing sarcoma is a rare event, and extraskeletal Ewing sarcoma of the thyroid gland is even rarer. It has non-specific clinical manifestation and difficulty in early diagnosis. The diagnosis mainly depends on histology and immunohistochemistry. It possesses the features of high malignancy, high rate of local recurrence, and distant metastasis. Currently, the aggressive multimodal treatment contains surgery, chemotherapy, and radiotherapy. This study presented a case of extraskeletal Ewing sarcoma arising in the thyroid gland of a 30-year-old woman, who presented with supraclavicular mass and sense of dysphagia obstruction in Department of Otolaryngology, Head and Neck Surgery, Second Xiangya Hospital, Central South University in 2018. Imaging studies demonstrated a cystic-solid mass in inferior of the left leaf of thyroid gland and in the posterior of the trachea and esophagus. The patient underwent localized tumor resection. The pathological diagnosis revealed that it was a small round cell tumor, and the immunohistochemistry results were considered to be extraskeletal Ewing sarcoma. Subsequently, the patient was given chemotherapy and local radiation therapy. There was no evidence of tumor recurrence or metastasis.
Adult ; Combined Modality Therapy ; Female ; Humans ; Immunohistochemistry ; Neoplasm Recurrence, Local ; Sarcoma, Ewing/therapy* ; Thyroid Gland

Objective:To investigate the influence of preoperative thyroid dysfunction on the 30-day postoperative mortality and complications in elderly patients with hip fracture.Methods:A retrospective analysis was conducted of the 349 elderly patients with hip fracture who had been admitted to Department of Orthopedic Trauma, Beijing Luhe Hospital Affiliated to Capital Medical University from January 2018 to December 2019. They were 108 males and 241 females, with an average age of 76.3 years (from 60 to 104 years). There were 190 femoral intertrochanteric fractures and 159 femoral neck fractures. By the preoperative level of thyroid function, the patients were divided into a normal function group of 290 cases and a dysfunction group of 59 cases. The 2 groups were compared in terms of hospital stay, mortality and incidence of complications within 30 days postoperation.Results:In this cohort, the rate of 30-day postoperative mortality was 3.4%(12/349) and the incidence of 30-day postoperative complications 14.6%(51/349). The 2 groups were comparable because there was no significant difference between them in the preoperative general data except for the preoperative comorbidity of coronary heart disease ( P>0.05). In the dysfunction group, the hospital stay averaged (10.2±6.9) d, the rate of 30-d postoperative mortality 1.7%(1/59) and the incidence of 30-day postoperative complications 16.9%(10/59), which were insignificantly different from those in the normal function group [(10.7±7.5) d, 3.8%(11/290) and 14.1%(41/290), respectively] ( P> 0.05). Conclusion:Since preoperative thyroid dysfunction does not affect the 30-day postoperative mortality and postoperative complications in the elderly patients with hip fracture but no definite thyroid disease, routine thyroid function screening is not recommended for them.

Objective: To analyze the expression of tight junction protein 3(claudin-3) in colorectal cancer and its relationship with the development, metastasis and prognosis of colorectal cancer. Methods: From February 2013 to February 2015, 78 patients with colorectal cancer operated in the People's Hospital of Sanmen County were selected in this study.The tissues of colorectal cancer and adjacent tissues were collected and claudin-3 expression was detected.The relationship between claudin-3 and clinicopathological features of colorectal cancer was analyzed. Results: The positive rate of claudin-3 in cancer tissues(83.33%) was higher than that in paracancerous tissues(48.72%), and the difference was statistically significant(χ²=20.832, P<0.01). The positive rate of claudin-3 in the poorly differentiated group(100.00%) was significantly higher than that in the well-differentiated group(85.71%) and the well-differentiated group(52.63%)(χ²=19.209, P<0.01). The claudin-3 positive rate with lymphatic metastasis(97.30%) was higher than that without lymphatic metastasis(70.73%), and the difference was statistically significant(χ²=9.882, P<0.01). The claudin-3 positive rate in patients with less than 3 years of survival (91.11%) was higher than that in patients with more than 3 years of survival(72.73%)(χ²=4.633, P<0.05). Conclusion The expression of claudin-3 is related to the occurrence, development and lymphatic metastasis of colorectal cancer, and can predict the prognosis of the patients.