1.Anti-inflammatory mixture alleviates acute lung injury induced by sepsis in rats by modulating Beclin-1-mediated autophagy
Weilan LU ; Guoliang YAN ; Yifan SHEN ; Haitao LI ; Sai WU ; Tongrui WENG ; Rui ZHANG ; Yanwen HUO
Chinese Critical Care Medicine 2024;36(7):717-722
Objective:To investigate the protective effects of an anti-inflammatory mixture on acute lung injury (ALI) induced by sepsis in rats, as well as its possible mechanisms.Methods:A total of 40 Sprague-Dawley (SD) rats were randomly divided into the sham group, septic ALI model group (model group), 3-methyladenine (3-MA) control group, and anti-inflammatory mixture pretreatment group, with 10 rats in each group. Cecal ligation and perforation (CLP) was performed to reproduce a septic ALI model. The rats in the sham group only underwent opening and closing the abdomen without perforation and ligation. Both groups were given saline gavage and intraperitoneal injection for 3 consecutive days before surgery. The 3-MA control group was given intraperitoneal injection of saline and autophagy inhibitor 3-MA 15 mg/kg for 3 consecutive days before modeling. The anti-inflammatory mixture pretreatment group was given 8.8 mL/kg of anti-inflammatory mixture by gavage [the composition of anti-inflammatory mixture: rhubarb 15 g (after the next), coptis chinensis 15 g, baical skullcap root 12 g, magnoliae cortex 12 g, dahurian patrinia herb 30 g] and saline intraperitoneal injection for 3 consecutive days before modeling. The rats in each group were anesthetized 24 hours after surgery and died due to abdominal aortic blood collection. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum inflammatory cytokines interleukins (IL-1β and IL-6). Lung tissue was taken and then the bronchoalveolar lavage fluid (BALF) was collected, and the levels of IL-1β and IL-6 were detected by ELISA. Lung wet/dry weight (W/D) ratio was measured. After hematoxylin-eosin (HE) staining, the histopathological changes of the lungs were observed under light microscopy. Western blotting was used to detect the expression of autophagy markers microtubule-associated protein 1 light chain 3-Ⅱ/Ⅰ (LC3-Ⅱ/Ⅰ) and Beclin-1 protein in lung tissue. Autophagosomes in lung tissue were observed with transmission electron microscopy.Results:Compared with the sham group, the rats in the model group exhibited severe destruction of lung tissue structure, with significant infiltration of inflammatory cells, the lung W/D ratio and the levels of IL-1β and IL-6 in serum and BALF were significantly increased, the expressions of LC3-Ⅱ/Ⅰ and Beclin-1 protein were down-regulated, the autophagosomes were more. The rats in the 3-MA control group exhibited more severe lung tissue injury as compared with the model group, the lung W/D ratio and the levels of inflammatory cytokines in serum and BALF were further increased, the expressions of LC3-Ⅱ/Ⅰ and Beclin-1 protein still showed a decrease tendency as compared with the sham group, and the autophagosomes were less than that in the model group. Compared with the model group, the anti-inflammatory mixture pretreatment group showed milder lung tissue injury with a minimal amount of inflammatory cell infiltration, the lung W/D ratio was significantly reduced (7.07±1.02 vs. 11.33±1.85, P < 0.05), the levels of IL-1β and IL-6 in both serum and BALF were significantly decreased [IL-1β (ng/L): 26.04±3.86 vs. 40.83±5.46 in serum, 17.75±2.02 vs. 26.86±4.32 in BALF; IL-6 (ng/L): 91.28±10.15 vs. 129.44±13.05 in serum, 76.06±7.51 vs. 120.91±7.47 in BALF, all P < 0.05], and the ratio of LC3-Ⅱ/Ⅰ and Beclin-1 protein expression were significantly increased [LC3-Ⅱ/Ⅰ ratio: 1.23±0.02 vs. 0.60±0.02, Beclin-1 protein (Beclin-1/GAPDH): 2.37±0.33 vs. 0.62±0.05, both P < 0.05]. Furthermore, an increase in the number of autophagosomes was observed. Conclusion:The anti-inflammatory mixture improves lung injury in rats with sepsis induced by CLP and reduce inflammation levels, potentially through upregulation of Beclin-1-mediated autophagy.
2.Effects of acupuncture and moxibustion on UHRF1 and DNMT1 in ectopic endometrium of rats with endometriosis
Mingyang LI ; Yanwen WANG ; Yanting SHAO ; Yichun SUN ; Jiawei HU ; Yuan GAO ; Yuran LI ; Chuting WU ; Chunyan ZHANG
Journal of Acupuncture and Tuina Science 2024;22(3):204-213
Objective:To observe the effects of acupuncture and moxibustion on ubiquitin-like containing PHD and RING finger domains 1(UHRF1)and DNA methyltransferase 1(DNMT1)in ectopic endometrium of rats with endometriosis(EMS). Methods:Forty Sprague-Dawley rats were randomly divided into a sham operation group with 10 rats and a model-building group with 30 rats according to body mass.EMS rat models were established in the model-building group and then were divided into a model group,an acupuncture and moxibustion group,and a progesterone group,with 10 rats in each group.All rats were fixed by a fixator.The sham operation group and the model group were given normal saline by gavage.The acupuncture and moxibustion group received acupuncture at Xuehai(SP10)and Sanyinjiao(SP6),moxibustion at Guanyuan(CV4),and gavage of normal saline.The progesterone group was given the mixed liquid made of dydrogesterone and normal saline by gavage.After 28 d of treatments,the three diameters(length,width,and height)of EMS rats'ectopic cysts were measured,the cyst volumes were calculated,the volumes before intervention were subtracted,and the difference values were used to evaluate the growth of ectopic cysts.UHRF1 and DNMT1 mRNA and protein levels in normal endometrium,eutopic endometrium,and ectopic endometrium were detected by real-time polymerase chain reaction and immunohistochemistry. Results:There was no significant difference in the ectopic cyst volume difference between the acupuncture and moxibustion group and the progesterone group(P>0.05),but they were smaller than that of the model group(P<0.05).The levels of UHRF1 and DNMT1 mRNA and protein in the ectopic endometrium of the model group were lower than those in the normal endometrium(P<0.05).The levels of DNMT1 mRNA and UHRF1 protein in the eutopic endometrium of the model group were lower than those in the normal endometrium(P<0.05).The levels of UHRF1 mRNA and protein and the level of DNMT1 protein in the ectopic endometrium of the acupuncture and moxibustion group were higher than those in the model group(P<0.05),and the level of UHRF1 mRNA was higher than that in the progesterone group(P<0.05).The level of DNMT1 mRNA in the eutopic endometrium of the acupuncture and moxibustion group was higher than that in the model group(P<0.05).The levels of UHRF1 and DNMT1 mRNA and protein in the acupuncture and moxibustion group were insignificantly different from those in the normal endometrium(P>0.05). Conclusion:Acupuncture and moxibustion may up-regulate the levels of UHRF1 mRNA and UHRF1 and DNMT1 proteins in the ectopic endometrium to the normal level so as to reduce the volume of ectopic cysts and cure EMS in rats.
3.Effect of Different Antitumor Regimens on Incidence and Severity of Corona Virus Disease 2019 Pneumonia in Lung Cancer Patients: A Single-center Retrospective Study.
Wanjun LU ; Jiawen LV ; Qin WANG ; Yanwen YAO ; Dong WANG ; Jiayan CHEN ; Guannan WU ; Xiaoling GU ; Huijuan LI ; Yajuan CHEN ; Hedong HAN ; Tangfeng LV ; Yong SONG ; Ping ZHAN
Chinese Journal of Lung Cancer 2023;26(6):429-438
BACKGROUND:
Studies have shown that the incidence and severity of corona virus disease 2019 (COVID-19) in patients with lung cancer are higher than those in healthy people. At present, the main anti-tumor treatments for lung cancer include surgery, immunotherapy, chemotherapy, radiotherapy, targeted therapy and anti-angiogenesis therapy. While the effects of different anti-tumor treatments on the occurrence and severity of COVID-19 pneumonia are not uniform. Therefore, we aimed to describe clinical characteristics and antitumor therapy of patients with lung cancer and COVID-19 pneumonia, and examined risk factors for severity in this population.
METHODS:
From December 1, 2022 to February 15, 2023, a retrospective study was conducted in 217 patients diagnosed with COVID-19 and pathologically confirmed lung cancer in the Jinling Hospital. We collected data about patients' clinical features, antitumor treatment regimen within 6 months, and the diagnosis and treatment of COVID-19. Risk factors for occurrence and severity of COVID-19 pneumonia were identified by univariable and multivariable Logistic regression models.
RESULTS:
(1) Among the 217 patients included, 51 (23.5%) developed COVID-19 pneumonia, of which 42 (82.4%) were classified as medium and 9 (17.6%) were classified as severe; (2) Univariate and multivariate analysis revealed overweight (OR=2.405, 95%CI: 1.095-5.286) and intrapulmonary focal radiotherapy (OR=2.977, 95%CI: 1.071-8.274) are risk factors for increasing occurrence of COVID-19 pneumonia, while other therapies are not; (3) Chronic obstructive pulmonary disease (COPD) history (OR=7.600, 95%CI: 1.430-40.387) was more likely to develop severe pneumonia and anti-tumor therapies such as intrapulmonary focal radiotherapy, chemotherapy, targeted therapy and immunotherapy did not increase severity.
CONCLUSIONS
Intrapulmonary focal radiation therapy within 6 months increased the incidence of COVID-19 pneumonia, but did not increase the severity. However, there was no safety concern for chemotherapy, targeted therapy, surgery and immunotherapy.
Humans
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COVID-19
;
Retrospective Studies
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Lung Neoplasms/drug therapy*
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Incidence
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Pneumonia/etiology*
4.Study on Myocardial Lymphangiogenesis Disorder in Dilated Cardiomyopathy Mice Induced by Doxorubicin and the Protective Mechanism of Kuoxin Decoction
Yidan DONG ; Mengjiao MA ; Longping PENG ; Maolin ZHOU ; Qianqian LIANG ; Qiong WU ; Yanwen WANG ; Youhua WANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(10):3293-3303
Objective To observe the dynamic changes of cardiac lymphangiogenesis in Doxorubicin(DOX)-induced dilated cardiomyopathy(DCM)model mice,and to study the the protective mechanism of Kuoxin Decoction.Methods The DCM mouse model was established by intraperitoneal injection of DOX,and the dynamic observation was performed every week.On this basis,60 C57BL/6 mice were randomly divided into 6 groups(n=10):control group,Model group,L-KXD,M-KXD and H-KXD groups and Captopril group.After successful modeling,the KXD and the positive control drug Captopril were administered continuously for 28 days.Echocardiography was used to detect cardiac function in mice,HE staining and Masson staining were used to observe pathological and morphological changes of the heart,Whole-mount immunofluorescent staining was used to detect the expression of LYVE-1 and Podoplanin in epicardial lymphatic vessels,Western blot was used to detect the expression of VEGFR-3 protein,and qPCR was used to detect the expression of VEGFR-3 mRNA.Results DCM mice induced by DOX showed significant cardiac function decline from the third week(DOX:15 mg·kg-1,P<0.05),and significant ventricular remodeling at the fifth week(DOX:15 mg·kg-1,P<0.01);The lymphatic vessel area of the mouse heart decreased significantly from the fourth week(DOX:20 mg·kg-1,P<0.0001),and the expression of VEGFR-3 decreased significantly from the third week(DOX:15 mg·kg-1,P<0.01).Conclusion KXD can improve ventricular remodeling and cardiac function in DOX-induced DCM mice,promote cardiac lymphangiogenesis,and upregulate the expression of VEGFR-3 at protein and mRNA levels,with a better effect than captopril.DOX-induced cardiac lymphangiogenesis in DCM mice leads to severe myocardial fibrosis and weakened cardiac function,which gradually worsens with the accumulation of modeling time and dose.KXD can promote cardiac lymphangiogenesis and improve cardiac function in DOX-induced DCM mice.The mechanism may be related to the up-regulation of VEGFR-3 expression.
5.Clinical analysis of Chlamydia psittaci pneumonia in the elderly
Lihong HU ; Yanwen ZHENG ; Jianhua CAO ; Li LIN ; Yongcheng LI ; Haiyan WU
Chinese Journal of General Practitioners 2022;21(8):737-742
Objective:To analyze the clinical characteristics of Chlamydia psittaci pneumonia in the elderly, and factor related to the disease severity. Methods:Clinical data of 32 elderly patients with Chlamydia pneumoniae pneumonia admitted in the First People′s Hospital of Xiaoshan District from January 2019 to January 2021 were retrospectively analyzed. The patients were diagnosed by the second generation sequencing using bronchoalveolar lavage fluid (BALF) samples. There were 17 patients in moderate group and 15 patients in severe group; the liver function, muscle enzymes, imaging and lymphocyte subsets of the two groups were compared. Results:There were no significant differences in the age, gender and basic diseases, bird contact history, flaccid fever and dry cough symptoms between two groups, while there were significant differences in mental symptoms and gastrointestinal symptoms between the two groups ( P=0.032, 0.018). There were significant differences in ALT , AST, LDH , CK , CK-MB, CRP, BNP , troponin-T and PCT between the two groups (all P<0.001). The increase of leukocytes was not significant in both groups. The moderate group was dominated by single lobe involvement, while the severe group was dominated by multi lobe involvement and pleural effusion ( P=0.043, 0.015, 0.023). The total lymphocytes, T lymphocytes, CD4 + T cells, CD8 + T cells, CD4 +/CD8 + ratio, NK cells, B cells, CD4 +CD8 + double positive T cells decreased in both groups, while those in the severe group decrease more markedly ( P<0.05). CD4 -CD8 - double negative T cells were higher in the severe group than those in the moderate group ( P<0.001). CD4 +/CD8 + ratio and CD4 -CD8 - double negative T cells were correlated with severity index PSI and CURB-65 ( P<0.05). Conclusions:The liver function, muscle enzyme, lymphocyte immune function in patients with Chlamydia psittaci pneumonia are impaired, which were more markedly in severe patients. The multileaf infiltration and increased procalcitonin may indicate the severe pneumonia. CD4 +/CD8 + ratio and CD4 -CD8 - double negative T cells are correlated with the severity of pneumonia.
6.Discovery of a new nosiheptide-producing strain and its fermentation optimization for nosiheptide production
Qihang SUN ; Yuncong XU ; Lingrui WU ; Jiale RONG ; Yanwen WANG ; Yudan CAO ; Chen LUO ; Xuri WU
Journal of China Pharmaceutical University 2022;53(6):725-733
Nosiheptide is a typical thiopeptide antibiotic displaying potent activity toward various drug-resistant strains of Gram-positive pathogens.Although nosiheptide lacks in vivo activity, and good water-solubility with a series of uncontrollable analogues, which may limit its clinical application, glycosylated analogues may overcome problem of low activity and may improve its druggability.In search of novel glycosylated nosiheptide producers, we applied a genome mining strategy that identified Actinoalloteichus sp.AHMU CJ021 that contains all genes required.However, despite the presence of a predicted glycosyltransferase, glycosylated derivatives of nosiheptide were not detected, after following one strain many compounds (OSMAC) strategy and heterologous expression of a regulatory protein NocP.Nevertheless, nosiheptide produced by this strain was remarkably pure, and further experiments were conducted to improve its production by optimization of the culture medium.Under optimal conditions, 58.73 mg/L nosiheptide was produced, representing an almost 6-fold improvement compared to the original fermentation medium.Therefore, we consider Actinoalloteichus sp.AHMU CJ021 a suitable potential candidate for industrial production of nosiheptide, which provides the basis for solving the problem of nosiheptide structural analogues.
7.Application of fibular flap with partial continuous periosteum and cortex in hip preservation surgery for femoral head necrosis
Mingfei HE ; Yanwen LEI ; Zhongming HUANG ; Chuanghao YU ; Yi LUO ; Xiang WU ; Zengyang GAO ; Jingliang ZHANG
Chinese Journal of Microsurgery 2021;44(6):625-628
Objective:To investigate the short-term clinical effect of using fibular flap with preserving the continuity of fibula in hip preservation surgery for femoral head necrosis.Methods:From September, 2017 to November, 2020, 13 cases of femoral head necrosis were repaired with fibular flap. The fibular flaps were cut with an improved method for preserving the continuity of the fibular cortex, and the donor sites were sutured directly. The fibuls were inserted into the femoral heads with single or double segment folding support. Autogenous iliac crest combined with platelet-rich plasma(PRP) was used for impaction of bone grafting in femoral head, and the fibular flaps were anastomosed with 1 artery and 2 veins. All follow-up data were obtained, including bone union by X-ray and CT as well as the functional recovery of the hip joint and donor site. Statistical analysis was performed. P<0.05 was considered statistically significant. Results:The followed-up time ranged from 6 to 23 months. The fibular bones were significantly thicker and the incisions healed well at the donor sites. There was neither abnormal sensation in toes, dorsal foot, and lateral of the leg, nor significant influence on foot function. The hip joint activities were normal. The outcome was proved to be remarkable according to the Harris score(from 58.9±10.6 points before surgery to 81.7±10.6 points after surgery), the difference was statistically significant ( P<0.05) . Conclusion:The method of the improved fibular flap in hip preservation surgery is beneficial to the repair and reconstruction of the necrotic femoral head since the donor area is less traumatic, and a satisfactory clinical effect can be obtained.
8.The value of textural analysis based on dynamic contrast-enhanced-MRI in predicting IDH genetic phenotypes of high-grade gliomas
Haitao LU ; Wei XING ; Yanwen ZHANG ; Bo DONG ; Ruhong WU ; Zhengzhang GU
Chinese Journal of Radiology 2020;54(5):450-455
Objective:To investigate the value of dynamic contrast-enhanced(DCE)-MRI based textural analysis in differentiating IDH mutated high-grade gliomas from IDH gene wild types.Methods:Twenty-nine patients with high grade gliomas collected from April 2016 to December 2019 in First People's Hospital of Changzhou were assessed retrospectively, including 10 patients with IDH mutation and 19 patients with IDH gene wild type. All patients underwent DCE, conventional plain and enhanced MR scanning. Omni Kinetics software was used to perform DCE-MRI data processing, volume transfer constant (K trans), ratio constant of tracer refluxing from tissue to plasma (Kep), extravascular extracellular space per unit volume of tissue (Ve), blood plasma volume (Vp) and area under the gadolinium concentration-time curve (AUC) were obtained. Five commonly used textural features, including Energy, Entropy, Inertia, Correlation, and Inver Difference Moment (IDM), were generated based on gray-level co-occurrence matrices. The independent samples t test (normal distributionand equal variance) or Mann-Whitney rank sum test (abnormal distribution or unequal variance) was used to compare the differences in textural features of DCE-MRI parameters between IDH mutated group and IDH gene wild type group. Receiver operating characteristic (ROC) curves were used to evaluate the efficiency of textural features of DCE-MRI parameters in differentiating IDH mutated high-grade gliomas from IDH gene wild types for statistically significant textural features. Results:Entropy of K trans and Ve for IDH mutated group were 5.368±1.458 and 6.698±1.081, respectively; while the corresponding values were 7.334±1.385 and 8.213±1.320 for IDH gene wild type group, respectively. The difference between the two groups was statistically significant ( t values were-3.570, -3.113, P values were 0.001, 0.004, respectively). Inverse difference moment of K trans and Ve for IDH mutated group were 0.567±0.147 and 0.417±0.106, respectively; while for IDH gene wild type group, the values were 0.393±0.119 and 0.296±0.101, respectively. The difference between the two groups was statistically significant ( t values were 3.452, 3.014, P values were 0.002, 0.006, respectively). In all textural features, the area under the ROC curve of entropy of K trans was the largest (0.874), and the sensitivity was the highest (100%), and the specificity of IDM of Ve was the highest (94.7%). Conclusion:Textural analysis of DCE-MRI can help to differentiate IDH mutated high-grade gliomas from IDH gene wild types.
9.Construction of pressure injury information system for patients with surgery based on chain-type process
Qingye HU ; Xiaorong WU ; Yanwen QIN ; Yan YANG ; Huiqin XI ; Xinnan QIN ; Yajun ZHANG
Chinese Journal of Modern Nursing 2018;24(25):3016-3021
Objective To explore how to optimize management process of pressure injury for surgery patients by applying information system.Methods We built an integrated surgery patients pressure injury management information system based on chain-type process along with controlling key links and realizing monitoring in a whole process and many links for surgery patients from be hospitalized to leave hospital.This research took the surgery patients pressure injury chain-type process as a breakthrough and selected 1240 patients as subjects in experimental operating room.A total of 578 patients were in control group in May 2016 before implementing information system and 662 patients were in observation group in May 2017 after implementing information system.We compared the qualified rate of pressure injury assessment,accuracy rate of screen for patients with high-risk pressure injury and being with pressure injury,accordance rate of description in skin condition during transportation and handover,the incidence of pressure injury in hospital and surgery patients in the first stage,the second stage and above.Results The qualified rate of pressure injury assessment,accuracy rate of screen for patients with high-risk pressure injury,accordance rate of description in skin condition during transportation and handover of observation group was 99.24%,100%and 100.00%significantly higher than those of control group(P< 0.05).The incidence of pressure injury in hospital and in the first stage of surgery patients was 2.95%and 2.65%in observation group with significant differences compared with those in control group(6.51%,5.82%)(P< 0.05).Conclusions The integrated surgery patients pressure injury management information system based on chain-type process realizes a full,continuous,accurate,dynamic evaluation and monitoring for patients' skin.It can effectively improve the nursing quality of pressure injury and is convenientfor managers to carry out a continuous improvement.
10.Ag-Solid-Phase Extraction-Programmed Temperature Vaporization-Gas Chromatography for Analysis of Mineral Oil-Saturated Hydrocarbons in Commercial Chocolates
Bingning LI ; Lingling LIU ; Zhenxia ZHANG ; Yanwen WU
Chinese Journal of Analytical Chemistry 2017;45(4):514-520
An offline silver-impregnated silica gel solid-phase extraction (Ag-SPE) approach combined with a programmed temperature vaporization-gas chromatography-flame ionization detector (PTV-GC-FID) was proposed for routine analysis of mineral oil saturated hydrocarbons (MOSH) in chocolates. The MOSH in chocolates were extracted by n-hexane and 1 mL of extract was purified by offline Ag-SPE column. The SPE columns packed with 0.3% Ag-activated silica gel were used to separate MOSH from triglycerides and olefins in chocolates. The eluent of MOSH fraction was only 5 mL and then concentrated to 0.2 mL through nitrogen blowing with little evaporation loss. The PTV parameters were as follows: the initial temperature was set at 45℃ and held for 1 min (split ratio was 200∶1), then warmed up to 360℃ at linear gradient of 250℃ minSymbolm_1 and held for 27 min (split valve was closed for 2 min followed by split ratio of 100∶1). The GC injection volume was 40 μL. The GC column was heated from 35℃ (3 min) to 350℃ at 25℃/min, and then raised to 370℃ (10 min) at 5℃/min. The flow rate of the carrier gas was 1.3 mL/min (and pressure was 60 kPa), FID temperature was set at 380℃. The limit of quantification (LOQ) and the recoveries of the method were 0.5 mg/kg and 84.9%-108.6%, respectively, with the relative standard deviations (RSD) of 0.2%-1.5%. Twenty-five commercial chocolate samples were analyzed with the proposed method, and it was found that the MOSH in three samples were not detected, and the concentrations of MOSH in other 22 samples were 1.09-8.15 mg/kg (the concentrations of MOSH with C16-C35 component were 0.56-4.43 mg/kg). The results suggested that it was necessary to routinely detect mineral oil contamination in chocolates for food safety.

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