1. Efficacy and safety analysis of tigecycline and polymyxin B in the treatment of carbapenem-resistant enterobacteriaceae pneumonia in critically ill patients
Xian ZHA ; Hua SHAO ; Dayu CHEN
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(2):154-163
AIM: To compare the efficacy and safety of tigecycline with polymyxin B in the treatment of carbapenem resistant enterobacteriaceae (CRE) pneumonia in critically ill patients. METHODS: A retrospective analysis was performed on the clinical data of patients with CRE pneumonia who received tigecycline or polymyxin B therapy from January 1, 2018 to Jun 30, 2023 in the Intensive Care Unit (ICU). Primary outcomes included the 28-day all-cause mortality and clinical cure rate within 28days. Secondary outcomes included the ICU mortality, in-hospital mortality, the length of hospital stay and ICU stay, microbial eradication, duration of mechanical ventilation. Independent predictors affecting 28-day clinical cure rate were tested using Cox regression analyses. RESULTS: A total of 83 eligible patients were included in the final analysis after propensity score matching, 54 in the tigecycline group and 29 in the polymyxin B group. The 28-day all-cause mortality was 31.5% (17/54) in the tigecycline group and 37.9% (11/29) in the polymyxin B group, the difference was not statistically significant (P=0.554); the clinical cure rate was 63% (34/ 54) in the tigecycline group, which was significantly higher than that of the polymyxin B group of 34.5% (10/29) (P = 0.013). There were no statistical differences between the two groups in terms of secondary outcomes. Multivariate logistic regression analysis found that the use of tigecycline was an independent predictor of the 28-day clinical cure rate (HR 2.083, 95%CI 1.018-4.263, P = 0.045). However, activated partial thromboplastin time (APTT) and prothrombin time (PT) were significantly prolonged in the tigecycline group compared with the polymyxin B group (P=0.047; P=0.027), and fibrinogen (FIB) was significantly decreased (P < 0.001) after drug administration. CONCLUSION: There was no significant difference in 28-day all-cause mortality between the tigecycline and polymyxin groups; tigecycline might be associated with a higher 28-day clinical cure rate compared with polymyxin B. It should be noted that tigecycline may increase the risk of coagulation abnormalities.
2.Preliminary construction of a measurement tool for atrial fibrillation patient's experience of catheter ablation
Ming-Li DU ; Song-Wen CHEN ; Li ZHU ; Xian-Feng YAO ; Lei YE ; Shao-Wen LIU
Fudan University Journal of Medical Sciences 2024;51(2):198-204
Objective To construct a measurement tool for atrial fibrillation(AF)patients'experience of catheter ablation,in order to provide quantifiable basis for improving the patients'perioperative experience.Methods From Jun 2022 to Apr 2023,literature analysis,qualitative research,Delphi expert consultation,and analytic hierarchy process were used to determine the content and weight of various indicators of the measurement tool.Results The enthusiasm of experts in 3 rounds was 100%.The authority coefficient of experts was 0.946,0.961 and 0.976.The Kendal harmony coefficients of the 2 and 3 rounds of expert consultation was 0.130 and 0.370(P<0.001).The final measurement tool included 46 items and 5 dimensions,including operational and technical quality experience,comfort management experience,information and communication experience,emotional support experience,service process and response experience.Conclusion The preliminary construction of measurement tool for AF patients'experience of catheter ablation,which were based on the features of specialty,could not only evaluate the patients'experience accurately,but also provide a basis for targeted improvement of medical and nursing service quality.
3.Endo-beta-N-acetylglucosaminidase: Possible Functions and Mechanisms
Xin-Rong LU ; Yong-Liang TONG ; Wei-Li KONG ; Lin ZOU ; Dan-Feng SHEN ; Shao-Xian LÜ ; Rui-Jie LIU ; Shao-Xing ZHANG ; Yu-Xin ZHANG ; Lin-Lin HOU ; Gui-Qin SUN ; Li CHEN
Progress in Biochemistry and Biophysics 2024;51(5):985-999
Endo-beta-N-acetylglucosaminidase (ENGase) is widely distributed in various organisms. The first reported ENGase activity was detected in Diplococcus pneumoniae in 1971. The protein (Endo D) was purified and its peptide sequence was determined in 1974. Three ENGases (Endo F1-F3) were discovered in Flavobacterium meningosepticum from 1982 to 1993. After that, the activity was detected from different species of bacteria, yeast, fungal, plant, mice, human, etc. Multiple ENGases were detected in some species, such as Arabidopsis thaliana and Trichoderma atroviride. The first preliminary crystallographic analysis of ENGase was conducted in 1994. But to date, only a few ENGases structures have been obtained, and the structure of human ENGase is still missing. The currently identified ENGases were distributed in the GH18 or GH85 families in Carbohydrate-Active enZyme (CAZy) database. GH18 ENGase only has hydrolytic activity, but GH85 ENGase has both hydrolytic and transglycosylation activity. Although ENGases of the two families have similar (β/α)8-TIM barrel structures, the active sites are slightly different. ENGase is an effective tool for glycan detection andglycan editing. Biochemically, ENGase can specifically hydrolyze β‑1,4 glycosidic bond between the twoN-acetylglucosamines (GlcNAc) on core pentasaccharide presented on glycopeptides and/or glycoproteins. Different ENGases may have different substrate specificity. The hydrolysis products are oligosaccharide chains and a GlcNAc or glycopeptides or glycoproteins with a GlcNAc. Conditionally, it can use the two products to produce a new glycopeptides or glycoprotein. Although ENGase is a common presentation in cell, its biological function remains unclear. Accumulated evidences demonstrated that ENGase is a none essential gene for living and a key regulator for differentiation. No ENGase gene was detected in the genomes of Saccharomyces cerevisiae and three other yeast species. Its expression was extremely low in lung. As glycoproteins are not produced by prokaryotic cells, a role for nutrition and/or microbial-host interaction was predicted for bacterium produced enzymes. In the embryonic lethality phenotype of the Ngly1-deficient mice can be partially rescued by Engase knockout, suggesting down regulation of Engase might be a solution for stress induced adaptation. Potential impacts of ENGase regulation on health and disease were presented. Rabeprazole, a drug used for stomach pain as a proton inhibitor, was identified as an inhibitor for ENGase. ENGases have been applied in vitro to produce antibodies with a designated glycan. The two step reactions were achieved by a pair of ENGase dominated for hydrolysis of substrate glycoprotein and synthesis of new glycoprotein with a free glycan of designed structure, respectively. In addition, ENGase was also been used in cell surface glycan editing. New application scenarios and new detection methods for glycobiological engineering are quickly opened up by the two functions of ENGase, especially in antibody remodeling and antibody drug conjugates. The discovery, distribution, structure property, enzymatic characteristics and recent researches in topical model organisms of ENGase were reviewed in this paper. Possible biological functions and mechanisms of ENGase, including differentiation, digestion of glycoproteins for nutrition and stress responding were hypothesised. In addition, the role of ENGase in glycan editing and synthetic biology was discussed. We hope this paper may provide insights for ENGase research and lay a solid foundation for applied and translational glycomics.
4.Downregulation of MUC1 Inhibits Proliferation and Promotes Apoptosis by Inactivating NF-κB Signaling Pathway in Human Nasopharyngeal Carcinoma
Shou-Wu WU ; Shao-Kun LIN ; Zhong-Zhu NIAN ; Xin-Wen WANG ; Wei-Nian LIN ; Li-Ming ZHUANG ; Zhi-Sheng WU ; Zhi-Wei HUANG ; A-Min WANG ; Ni-Li GAO ; Jia-Wen CHEN ; Wen-Ting YUAN ; Kai-Xian LU ; Jun LIAO
Progress in Biochemistry and Biophysics 2024;51(9):2182-2193
ObjectiveTo investigate the effect of mucin 1 (MUC1) on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) and its regulatory mechanism. MethodsThe 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital. The expression of MUC1 was measured by real-time quantitative PCR (qPCR) in the patients with PNC. The 5-8F and HNE1 cells were transfected with siRNA control (si-control) or siRNA targeting MUC1 (si-MUC1). Cell proliferation was analyzed by cell counting kit-8 and colony formation assay, and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells. The qPCR and ELISA were executed to analyze the levels of TNF-α and IL-6. Western blot was performed to measure the expression of MUC1, NF-кB and apoptosis-related proteins (Bax and Bcl-2). ResultsThe expression of MUC1 was up-regulated in the NPC tissues, and NPC patients with the high MUC1 expression were inclined to EBV infection, growth and metastasis of NPC. Loss of MUC1 restrained malignant features, including the proliferation and apoptosis, downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells. ConclusionDownregulation of MUC1 restrained biological characteristics of malignancy, including cell proliferation and apoptosis, by inactivating NF-κB signaling pathway in NPC.
5.Coronary artery perforation after using shockwave balloon during percutaneous coronary intervention treatment:a case report
Chen-Ji XU ; Fei LI ; Fa ZHENG ; Bin ZHANG ; Feng-Xia QU ; Jian-Meng WANG ; Ya-Qun ZHOU ; Xian-Liang LI ; Song-Tao WANG ; Yan SHAO ; Chang-Hong LU
Chinese Journal of Interventional Cardiology 2024;32(7):405-408
Coronary perforation is when a contrast agent or blood flows outside a blood vessel through a tear in a coronary artery.In this case,we reported a case of percutaneous coronary intervention for coronary calcified lesions,which led to iatrogenic coronary perforation and cardiac tamponade after the use of Shockwave balloon to treat intracoronary calcified nodules,and the management of PCI-related CAP was systematically reviewed through the literature.
6.Research progress of PPAR-γ regulating brain cholesterol metabolism to clear β-amyloid protein to improve Alzheimer's disease
Xue-Qing DUAN ; Shao-Feng WANG ; Xian-Yu CHEN ; Yan-Wei HAO ; Jia-Xin LI ; Li LI ; Shi-Jun XU ; Bin LI
Chinese Pharmacological Bulletin 2024;40(11):2005-2009
Peroxisome proliferator-activated receptor gamma(PPAR-γ)is a member of the ligand-activated nuclear tran-scription factor superfamily.Activated PPAR-γ is involved in the regulation of many central nervous system(CNS)events,and is involved in cholesterol metabolism by inducing or inhibi-ting a series of gene pathways,thereby inhibiting the deposition of β-amyloid protein(Aβ).It plays an important neuroprotec-tive role in Alzheimer's disease(AD),improves memory and cognition in AD,and is a potential target for AD.Drug develop-ment aimed at restoring cholesterol homeostasis may be a poten-tial strategy to counteract AD.By analyzing the distribution and structure of PPAR-γ,focusing on the biological correlation be-tween PPAR-γ-mediated cholesterol metabolism and AD,this paper describes the mechanism regulation of PPAR-γ on key proteins,genes and their corresponding molecules,providing a new reference for the treatment of AD.
7.Targeting mitochondria:a vital therapeutic strategy for ischemic stroke
Li-Yuan MA ; Si-Yin CHEN ; Shao-Ping YIN ; Kai-Pei LUO ; Xian-Li MENG ; Lu YANG
Chinese Pharmacological Bulletin 2024;40(11):2025-2030
Ischemic stroke(IS)is a devastating neurological disease commonly around the world.Although modern medicine has recognized the confined mechanisms in the pathological process of cerebral ischemia,it has never been enough for the treatment of IS.Recent studies have confirmed the vital role of mitochondrial dysfunction in neuronal injury after cerebral ische-mia,thereby exerting a potential target for prevention and treat-ment of IS.Herein,we review the main molecular mechanisms of neuronal injury and death by mitochondrial dyshomeostasis under the condition of ischemia/hypoxia,especially mitochon-drial permeability transition pore opening,oxidative stress and apoptotic signaling.Given remodeling of mitochondrial function as a new idea for the management of IS,some emerging strate-gies containing mitochondrial antioxidant,mitophagy regulation and mitochondrial transfer also raise concern in this paper.
8.Refractory fever of unknown origin: analysis of clinical characteristics of patients with trisomy 8 syndrome and autoimmune diseases
Wenxin CHEN ; Zhangyufan HE ; Yiting TANG ; Qianqian LIU ; Xian ZHOU ; Lingyun SHAO ; Wenhong ZHANG ; Yan GAO
Chinese Journal of Infectious Diseases 2024;42(10):597-601
Objective:To conduct a thorough analysis of the clinical characteristics in patients with trisomy 8 syndrome and autoimmune diseases, and to provide a new perspective on the diagnosis and management of the fever of unknown origin (FUO).Methods:Patients who were admitted to Huashan Hospital, Fudan University between July 1st, 2021 and May 1st, 2024 for FUO and subsequently diagnosed with trisomy 8 syndrome with autoimmune diseases were included. In this retrospective cohort study, patients were divided into infection and non-infection group according to the etiological evidence, and the clinical characteristics and treatments were collected and compared between the two groups. Statistical analysis was performed using the Mann-Whitney U test. Results:Among the nine enrolled patients, one case was associated with Behet syndrome (BD) without myelodysplastic syndrome (MDS) and without co-occurring infection, eight cases were associated with MDS, among which six cases had both BD and MDS, one case had allergic pneumonia, and one case had rheumatoid arthritis. Six MDS cases had infections. The C-reactive protein (CRP) level in the infection group was significantly higher than that in the non-infection group(72.39(14.62, 132.70) mg/L vs 3.68(2.30, 10.09) mg/L; Z=1.00, P=0.048). There were no statistically significant differences in other inflammatory markers (such as white blood cell count, platelet count, erythrocyte sedimentation rate, ferritin, and neutrophil CD64 index) between the infection and non-infection groups (all P>0.05). In the infection group, one had bacterial infection, five had fungal infections, including two cases of disseminated aspergillosis, one case of mixed bacterial, fungal, and viral infections, one case of mucormycosis combined with Enterococcus faecalis infection, and one case of pulmonary aspergillosis combined with disseminated Mycobacterium abscessus infection. Among the nine patients, eight patients received immunosuppressive treatment centered on the glucocorticoids and (or) thalidomide, and all six infected patients received the above immunosuppressive treatment based on the anti-infection therapy. Eight of the nine cases were stable and followed up regularly, while one case died due to worsening of illness. Conclusions:Autoimmune diseases associated with trisomy 8 syndrome is rare. In addition to anti-infection treatment, glucocorticoids, thalidomide or other immunosuppressive drugs should be administrated to suppress the inflammatory response in patients with co-infection, and the disease could be well controlled.
9.Analysis of the current status of cancer incidence and mortality in Yunnan province in 2020
Maosen CHEN ; Yang CHEN ; Qingping SHI ; Ying SHAO ; Xian TANG ; Siying REN ; Hongmei WEN
Practical Oncology Journal 2024;38(5):283-288
Objective This study aimed to analyze the current epidemic situation of cancer in Yunnan province in 2020,and to provide theoretical basis for the prevention and treatment of cancer in Yunnan province.Methods The data on the incidence and mortality of cancer were collected from 129 cancer registration areas in Yunnan province in 2020.A total of 89 counties(cities,dis-tricts)that met the quality control standards were included in this analysis.Among them,there were 16 in urban areas,covering a pop-ulation of 7,593,622(24.16%),and 73 in rural areas,covering a population of 23,838,542(75.84%).The number of malignant tumor cases,deaths,the crude incidence and China age-standardized incidence(China Standardized Incidence),the crude mortality and China age-standardized mortality(China Standardized Mortality),the cumulative incidence and mortality from 0 to 74 years old,as well as the order of cancer incidence and death were statistical analyzed.Results In 2020,66,719 new cases of cancer were re-ported from 89 tumor registration areas in Yunnan province,with a crude rate of 212.26/100,000 and the China age-standardized in-cidence of 150.33/100,000;The reported number of deaths from cancer was 39,251,with a crude mortality of 124.88/100,000 and the China age-standardized mortality of 82.45/100,000.The incidence and mortality of cancer were higher in men than those in fe-male,and higher in rural than those in urban areas.According to the crude incidence rate and crude mortality,the top 5 cancers with the highest crude incidence were lung cancer,female breast cancer,colo-rectum cancer,liver cancer and thyroid cancer,and the top 5 cancers with the highest crude mortality were lung cancer,liver cancer,colo-rectum cancer,stomach cancer and female breast cancer.Conclusion Lung cancer,liver cancer,colo-rectum cancer and female breast cancer are still the key cancers for prevention and con-trol in Yunnan province.The incidence of thyroid cancer is relatively high,and there are significant differences in the incidence and mortality of cancer between urban and rural areas and between sexes.The corresponding cancer prevention should be carried out ac-cording to the current epidemic situation of cancer in Yunnan province.
10.Analysis of the incidence and mortality of cervical cancer in cancer registration areas of Yunnan province in 2020 and the trend from 2012 to 2020
Maosen CHEN ; Hongmei WEN ; Qingping SHI ; Ying SHAO ; Xian TANG ; Siying REN ; Yang CHEN
Practical Oncology Journal 2024;38(6):355-360
Objective This study aimed to analyze the incidence and mortality of cervical cancer in tumor registration areas of Yunnan province in 2020,as well as the trend of incidence and mortality from 2012 to 2020,in order to provide a basis for the pre-vention and treatment of cervical cancer in Yunnan province.Methods The data of cervical cancer incidence and mortality were col-lected and sorted out in tumor registration areas of Yunnan province from 2012 to 2020.The crude incidence,crude mortality,age-standardized incidence rate by World standard population(ASIRW)(referred to the World standard incidence),age-standardized mortality rate by World standard population(ASMRW)(referred to the World standard mortality)and other indicators of cervical canc-er in 2020 were statistically analyzed according to the urban and rural areas.The annual percent change(APC)was used to evaluate the changing trend of cervical cancer incidence and mortality from 2012 to 2020,and the GM(1,1)model was used to predict the crude incidence and ASIRW from 2021 to 2025.Results In 2020,there were 2426 new cases of cervical cancer in tumor registration area of Yunnan province,ranking fifth in the incidence of female malignant tumors.The crude incidence and ASIRW were 15.83/100,000 and 11.16/100,000,respectively.There were 831 deaths from cervical cancer,ranking sixth deaths of female malignant tumors.The crude mortality and ASMRW were 5.42/100,000 and 3.52/100,000,respectively.ASIRW was higher in rural areas(11.86/100,000)than that in urban areas(9.11/100,000).ASMRW was slightly higher in urban areas(3.63/100,000)than that in rural areas(3.48/100,000).The age-specific incidence of cervical cancer increased rapidly after the age of 20,and reached a peak in the 55-59 age group;The age-specific mortality of cervical cancer increased rapidly after the age of 35,reaching a peak in the 75-79 age group.ASIRW of cervical cancer in Yunnan province from 2012 to 2020 showed a downward trend with annual changes(APC=-7.54%,95%CI:-13.19%--1.53%),and the trend change was statistically significant(P<0.05).The prediction of the GM(1,1)model showed that the crude incidence and ASIRW of cervical cancer in Yunnan province would continue to decline from 2021 to 2025.Conclusion The incidence and mortality of cervical cancer are relatively low in Yunnan province,but it is still a common malignant tumor in women.The incidence of cervical cancer in Yunnan province is showing a trend of becoming younger,and rural women are the key population for prevention and treatment.

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