1.Comparison of predictive accuracy and clinical applicability among four vancomycin individualized dosing tools
Shu CHEN ; Yanqin LU ; Yun SHEN ; Chang CAO ; Kunming PAN ; Xiaoyu LI ; Qianzhou LYU
China Pharmacy 2025;36(22):2822-2827
OBJECTIVE To compare the predictive accuracy and clinical applicability of four vancomycin individualized dosing tools (SmartDose, ClinCalc, Gulou, Pharmado) and provide a basis for rational clinical medication use. METHODS A retrospective cohort study was conducted, enrolling 479 adult patients who received vancomycin therapy and underwent steady-state trough concentration monitoring in Zhongshan Hospital, Fudan University (Xiamen Branch) from January 1, 2022, to June 30, 2024. The predictive accuracy of each tool was evaluated using indicators, such as mean error (ME), mean absolute error (MAE), mean percentage error (MPE), mean absolute percentage error (MAPE), the proportion of patients with an absolute percentage error (APE) of less than 30%, the 95% limits of agreement, and the overall relative percentage difference between predicted and measured values. Using indicators such as accessibility, patient management, and recommendation of multiple treatment options, the clinical panxso@163.com applicability of the tools for all patients was evaluated; using the discrepancy in accuracy between the predicted and actual measured blood drug concentrations as an indicator, the clinical applicability was assessed for patients in different renal function subgroups (hyperfunction, normal, mild impairment, moderate impairment, and severe impairment). RESULTS In terms of accuracy, SmartDose demonstrated the best overall performance with an MAPE of 46.40% and a proportion of APE <30% (46.56%). Bland-Altman analysis indicated that SmartDose had the smallest overall relative percentage difference (-7.25%), although the 95% limits of agreement were broad for all tools, with differences between the upper and lower limits exceeding 200%. In terms of applicability, all four dosing tools were freely accessible and demonstrated good availability; SmartDose and Pharmado provided the most comprehensive solutions, offering features such as patient management, multiple regimen recommendations, and drug concentration-time curve plotting. Stratified analysis based on renal function revealed that Pharmado showed optimal prediction for hyperfiltration patients (mean difference: 0.11 mg/L). SmartDose and ClinCalc showed relatively better performance in normal and mild renal impaiment (mean difference: 0.37, 0.51 mg/L and -1.13, -1.33 mg/L,respectively). SmartDose performed best in moderate renal impairment (mean difference: -2.60 mg/L). Pharmado and Gulou had smaller prediction biases in severe renal impairment (mean differences: 1.52 mg/L and -0.23 mg/L, respectively). CONCLUSIONS The four individualized dosing tools demonstrated limited accuracy in the initial prediction of vancomycin concentrations. Among them, SmartDose demonstrates the highest overall prediction accuracy and possesses comprehensive clinical management features. It is recommended that Pharmado be preferred for patients with renal hyperfiltration; SmartDose or ClinCalc can be used for patients with normal or mildly impaired renal function; SmartDose is recommended for patients with moderately impaired renal function; Pharmado or Gulou may be considered for patients with severely impaired renal function.
2.Effects of Tao Hong Si Wu decoction on circular RNA expression profiles in rats with middle cerebral artery occlusion
Chang-Yi FEI ; Li-Juan ZHANG ; Ni WANG ; Fu-Rui CHU ; Chao YU ; Su-Jun XUE ; Ling-Yu PAN ; Dai-Yin PENG ; Xian-Chun DUAN
Chinese Pharmacological Bulletin 2024;40(5):954-963
Aim To screen and study the effects of Tao Hong Si Wu decoction(THSWD)-mediated treat-ment on circular RNA(circRNA)expression profiles in rats with middle cerebral artery occlusion(MCAO),and investigate the possible roles and molecular mecha-nisms of THSWD.Methods Next-generation RNA sequencing was conducted to identify circRNA expres-sion profiles in MCAO rats after treatment with THSWD and compared with the MCAO model group and control group.Bioinformatics analysis was performed to predict the potential target microRNAs and mRNAs.Gene On-tology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses for the potential target mRNAs were applied to explore the potential roles of differentially expressed circRNAs.RT-qPCR was performed to verify circRNAs with significant differences in expression.Results We identified 87 significantly differentially expressed circRNAs between the MCAO group versus the control group,and 86 sig-nificantly differentially expressed circRNAs between the MCAO group versus the THSWD group.respective-ly.Among them,17 circRNAs induced by the MCAO model were reversed via treatment with THSWD.To demonstrate the roles of mRNAs targeted by DECs,the GO and KEGG databases were used.Further analysis revealed that five circRNAs may play important roles in the development of MCAO.Conclusions The com-prehensive expression profile of circRNAs in rats with middle cerebral artery occlusion after THSWD treat-ment is determined for the first time,suggesting that the therapeutic effect of THSWD on MCAO may be a-chieved by regulating the expression of circRNAs.
3.Alvianolic acid B exerts a protective effect on random skin flaps through autophagy mediated by activation of TFE3
Zhong-Bing HAN ; Hui-Wen YANG ; Hai-Zhou NIU ; Kuan-Kuan ZHANG ; Yang-Yang LIU ; Pan-Pan XU ; Ling-Ti KONG ; Chang-Chun ZHANG
Chinese Pharmacological Bulletin 2024;40(10):1912-1920
Aim To observe the role of salvianolic acid B(Sal B)in enhancing the survival of random skin flaps and to preliminarily explore its potential mecha-nisms.Methods The appearance,degree of edema,color and hair condition of the skin flap were evaluated seven days after operation.The vascular network and blood flow of random flaps were measured by laser Doppler flow measurement.HE staining was used to detect the growth of microvessels in random flaps.The expressions of VEGF and CD34 were detected by im-munohistochemistry,the expressions of RIPK1,2 and LC3 Ⅱ were detected by immunofluorescence,and the effects of autophagy related proteins and signaling path-ways were detected by Western blot.Results The ex-perimental results showed that Sal B induced autophagy in the random skin flaps,promoted angiogenesis,and reduced oxidative stress and necrotic apoptosis,signifi-cantly increasing the survival rate of the flaps.Immu-nohistochemistry,immunofluorescence staining,and Western blot confirmed that Sal B induced autophagy in the random skin flaps by activating TFE3 protein.Conclusion Sal B can promote autophagy in cells of random skin flaps and reduce their necrotic apoptosis by activating TFE3 protein.
4.Mechanism of artemisinin inhibiting malignant biological behavior of colorectal cancer cells stimulated by glucose
Yong-Na PAN ; Yue-Feng CHANG ; Jing-Jing GUO ; Yi-Li SUN ; Lan WEI ; Chun-Yan YANG ; Jin-Wang KANG
Journal of Regional Anatomy and Operative Surgery 2024;33(5):388-393
Objective To investigate the effect of artemisinin(ART)on the malignant biological behavior of colorectal cancer(CRC)cells stimulated by glucose and its mechanism.Methods The concentration gradients of 0,5,10,20,40 and 60 μmol/L of ART were used to treat the human colorectal cancer cell line SW480,and then the cell viability was detected by CCK-8.Cell apoptosis was detected by flow cytometry.Transwell was used to detect the cell migration and invasion.Western blot was used to detect the apoptosis,epithelial-mesenchymal transition(EMT)and Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)related proteins expression.Results Compared with the 0 μmol/L of ART,the viability of SW480 cells decreased under 5,10,20,40,60 μmol/L of ART treatment(P<0.05),and IC50 was 36.91 μmol/L.Therefore,the cells treated with 10,20 and 40 μmol/L of ART were as the low-dose,medium-dose and high-dose ART groups,the cells treated with 0 μmol/L of ART were as the control group,and the cells treated with 40 μmol/L of ART and 10 μmol/L of Coumermycin A1 were as the Coumermycin A1 group.Compared with the control group,the cell scratch wound healing rate,invasion ability,and expression levels of Bcl-2,N-cadherin,Vimentin,p-JAK2,and p-STAT3 in the low-dose ART group,the medium-dose ART group,and the high-dose ART group decreased obviously(P<0.05),while the apoptosis rate,and expression levels of Bax,Caspase-3 and E-cadherin increased(P<0.05).Compared with the high-dose ART group,the cell scratch wound healing rate,invasion ability,and expression levels of Bcl-2,N-cadherin,Vimentin,p-JAK2,and p-STAT3 in the Coumermycin A1 group increased obviously(P<0.05),while the apoptosis rate,and expression levels of Bax,Caspase-3 and E-cadherin decreased(P<0.05).Conclusion ART may inhibit the viability,migration,invasion and EMT of glucose-stimulated CRC cells and promote apoptosis by inhibiting the JAK2/STAT3 signaling pathway.
5.Isolation,preservation,and biological characteristics analysis of a Listeria bacteriophage
Ling-Yun LIU ; Pan MAO ; Jin-Ni CHEN ; Ling-Ling LI ; Yan WANG ; Jing-Dong SONG ; Zheng-Hong CHEN ; Chang-Yun YE
Chinese Journal of Zoonoses 2024;40(5):435-441
The aim of our research was to obtain Listeria bacteriophages from food and related environments,and conduc-ted the analysis of the electron microscopic morphology,host range specificity,and biological characteristics of the purified phages.The double-layer agar method and the spot test were employed for the isolation and identification of a virulent Listeria phage named LMLPA5,with the isolated strain Listeria in-nocua Lin08 as the host.Phage morphology was observed by transmission electron microscope.The biological characteris-tics of the phage were assessed by determining their host range,optimal multiplicity of infection(MOI),one-step growth curve,and physicochemical stability.Additionally,the preservation efficacy of the phage at 4 ℃,-20 ℃,and-80 ℃ was explored.The phage LMLPA5 belongs to the family Myoviridae based on morphology,exhibiting clear and transparent plaques without halo surrounded.Strains of sever-al Listeria species and different serotypes strains of Listeria monocytogenes were susceptible to lysis by LMLPA5,indica-ting its broad-spectrum activity against Listeria monocytogenes.Optimal MOIs and single-step growth curve analyses revealed optimal MOIs of 0.1 and latent period of 10 minutes for LMLPA5,with average burst size at 95.2 PFU/cell.LMLPA5 was sensitive to high temperatures,and completely inactivated after exposure to 70 ℃ for 1 h,while the phage remained stable for over 32 hours ranging from 4 ℃ to 40 ℃.Within the pH range of 4 to 10,phage titer remained stable and completely inactiva-ted until 60 minutes of ultraviolet exposure.LMLPA5 displayed insensitivity to chloroform,confirming its non-enveloped phage morphology.The phages remained stable for over 8 months when store at 4 ℃ and-80 ℃.The biological characteristics and lysis capacity of phage LMLPA5 were elucidated in this study,which provide the basis for further application.
6.Rituximab based treatment in pediatric Epsstain Bar Virus associated lymphocyte proliferative diseases after aplastic anemia with haplo-identical transplantation:a prospective single centre study
Feng ZHANG ; Guanhua HU ; Pan SUO ; Zhengli XU ; Lu BAI ; Huifang WANG ; Shanyamei HUANG ; Lanping XU ; Yingjun CHANG ; Xiaohui ZHANG ; Xiaojun HUANG ; Yifei CHENG
Chinese Journal of Hematology 2024;45(7):678-682
Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorders (PTLD) are one of the most severe complications after hematopoietic stem cell transplantation (HSCT). This study includes 31 cases of aplastic anemia (AA) patients who developed PTLD after haploidentical transplantation, summarizing their clinical characteristics and categorizing them into either rituximab monotherapy group or combination therapy group based on whether their condition improved by 1 log after a single dose of rituximab. The incidence of PTLD after HSCT in children with AA was 10.16%, and the incidence of PTLD in patients with age >10 years was significantly increased ( χ2=11.336, P=0.010). Of the 31 patients, 27 were clinically diagnosed and 4 were pathologically confirmed. Finally, 15 patients were classified into the rituximab treatment group and 15 patients into the combination treatment groups. Finally three patients died, and the 2-year overall survival rate was (89.7±5.6) %. Standard pre-treatment protocols and EBV reactivation are risk factors affecting the prognosis of PTLD. There was no statistically significant difference in the impact of the two treatment schemes on prognosis.
7.Comparison of outcomes of laparotomic and minimally invasive radical hysterectomy in women with early-stage cervical cancer
Shu-Han CHANG ; Kuan-Gen HUANG ; Lan-Yan YANG ; Yu-Bin PAN ; Chyong-Huey LAI ; Hung-Hsueh CHOU
Journal of Gynecologic Oncology 2024;35(5):e60-
Objective:
This study compared the outcomes of laparotomic radical hysterectomy (LRH) and minimally invasive radical hysterectomy (MISRH) in patients with early-stage cervical cancer.
Methods:
The clinical data of patients with early-stage cervical cancer who underwent LRH or MISRH (laparoscopic/robotic) at Chang Gung Memorial Hospital, Linkou Branch, from 2002 to 2017 were retrospectively reviewed. The surgical safety (operation time, blood loss, blood transfusion rate, length of postoperative stay, and perioperative complications), overall survival (OS), disease-free survival (DFS), and recurrence pattern were analyzed. Propensity score matching (PSM) at a 3:1 ratio was performed to balance prognostic variables.
Results:
Of the 760 patients (entire cohort), 614 underwent LRH and 146 underwent MISRH.After PSM, 394 and 140 patients were included in the LRH and MISRH groups, respectively.The 5-year OS rate was significantly lower in the MISRH group than in the LRH group (85.6% vs. 93.2%, p=0.043), and the 5-year DFS rate (p=0.21) did not differ significantly. After PSM, the 5-year OS rates did not differ significantly between the MISRH and LRH groups (87.1% vs. 92.1%, p=0.393). The MISRH group had a significantly shorter operation time (p<0.001), lower intraoperative blood loss (p<0.001), lower blood transfusion rate (p<0.001), and shorter postoperative stay (p<0.001) but a significantly higher rate of intraoperative bladder injury (p<0.001) than the LRH group.
Conclusion
After PSM, MISRH is associated with nonsignificantly lower OS but a significantly higher risk of intraoperative urological complications than LRH.
8.Histopathological changes in secondary visual cortex and enhanced calcium activity in neurons being involved in microwave radiation-induced anxiety-like behavior
Zhihua FENG ; Ting PAN ; Ganghua HE ; Chenxu CHANG ; Zhilin CUI ; Meiying YANG ; Yanhui HAO ; Fengsong LIU ; Yang LI ; Hongyan ZUO
Chinese Journal of Radiological Medicine and Protection 2024;44(6):464-471
Objective:To clarify the effects of microwave radiation on anxiety-like behavior, the histomorphology of the secondary visual cortex, and calcium activity in neurons.Methods:36 C57BL/6N mice were selected and divided into control group and microwave radiation group according to the random number table method. In the simple behavioral testing, there were 8 mice in the control group and 7 mice in the radiation group. Combining fiber optic recording with behavioral experiments, there were 8 mice in the control group and 7 mice in the radiation group. Hematoxylin-eosin (HE) staining was conducted with 3 mice in each group. A high-power microwave simulated source in the X-band with a center frequency of 9.875 GHz and an average power density of 12 mW/cm 2 was used to irradiate the mice for 15 minutes, establishing a microwave radiation animal model. Then, anxiety-like behavior changes in the radiation group were identified using the open-field and elevated plus maze (EPM) tests. The effects of microwave radiation on the histomorphology of the secondary visual cortex were investigated using HE staining and optical microscopy. Based on the genetically encoded calcium imaging technique, as well as optical fiber recording combined with behavioral paradigms in the open field and the EPM, the changes of calcium activity in neurons in the V2M region of the secondary visual cortex were detected. Results:Compared to the control group, the radiation group showed a significant decrease in the frequency of exploring the central region of the open field and the open arm of the EPM ( t = 2.24, 3.10, P < 0.05). Furthermore, the radiation group exhibited the degeneration and apoptosis of some neurons in the secondary visual cortex, primarily manifested as pyknosis and deep staining, cell body shrinkage, and the slightly widening of perivascular space. Fiber optic recordings and behavioral experiments indicated that compared to the control group, mice in the radiation group exhibited significantly increased calcium activities in neurons of the secondary visual cortex when exploring the central region of the open field ( t = -2.75, P < 0.05) or the open arm of the EPM ( t = -2.77, -3.41, P < 0.05) compared to those before radiation after microwave exposure. Conclusions:Microwave radiation can induce anxiety-like behaviors and histopathological changes in the secondary visual cortex. Increased calcium activity in neurons of the secondary visual cortex is proved to be an important mechanism underlying the changes in anxiety-like behavior due to microwave radiation.
9. Effects of Tao Hong Si Wu decoction on IncRNA expression in rats with occlusion of middle cerebral artery
Li-Juan ZHANG ; Chang-Yi FEI ; Chao YU ; Su-Jun XUE ; Yu-Meng LI ; Jing-Jing LI ; Ling-Yu PAN ; Xian-Chun DUAN ; Li-Juan ZHANG ; Chang-Yi FEI ; Chao YU ; Su-Jun XUE ; Yu-Meng LI ; Jing-Jing LI ; Xian-Chun DUAN ; Dai-Yin PENG ; Xian-Chun DUAN ; Dai-Yin PENG
Chinese Pharmacological Bulletin 2024;40(3):582-591
Aim To screen and study the expression of long non-coding RNA (IncRNA) in rats with middle cerebral artery occlusion (MCAO) with MCAO treated with Tao Hong Si Wu decoction (THSWD) and determine the possible molecular mechanism of THSWD in treating MCAO rats. Methods Three cerebral hemisphere tissue were obtained from the control group, MCAO group and MCAO + THSWD group. RNA sequencing technology was used to identify IncRNA gene expression in the three groups. THSWD-regulated IncRNA genes were identified, and then a THSWD-regu-lated IncRNA-mRNA network was constructed. MCODE plug-in units were used to identify the modules of IncRNA-mRNA networks. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) were used to analyze the enriched biological functions and signaling pathways. Cis- and trans-regulatory genes for THSWD-regulated IncRNAs were identified. Reverse transcription real-time quantitative pol-ymerase chain reaction (RT-qPCR) was used to verify IncRNAs. Molecular docking was used to identify IncRNA-mRNA network targets and pathway-associated proteins. Results In MCAO rats, THSWD regulated a total of 302 IncRNAs. Bioinformatics analysis suggested that some core IncRNAs might play an important role in the treatment of MCAO rats with THSWD, and we further found that THSWD might also treat MCAO rats through multiple pathways such as IncRNA-mRNA network and network-enriched complement and coagulation cascades. The results of molecular docking showed that the active compounds gallic acid and a-mygdalin of THSWD had a certain binding ability to protein targets. Conclusions THSWD can protect the brain injury of MCAO rats through IncRNA, which may provide new insights for the treatment of ischemic stroke with THSWD.
10.Echo-guiding percutaneous aortic stent implantation for coarctation of the aortic: A case report
Junke CHANG ; Peijian WEI ; Yaoxing LU ; Fengwen ZHANG ; Fang FANG ; Chuangshi WANG ; Shouzheng WANG ; Wenbin OUYANG ; Junyi WAN ; Xiangbin PAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(02):325-328
Currently, transcatheter intervention has emerged as a first-line treatment for coarctation of the aortic. Due to the radiation exposure associated with catheter interventional therapy, there are numerous restrictions, which harms both patients and medical personnel and is dependent on sizable radiation apparatus. Here, we report for the first time a case of echo-guiding percutaneous aortic stent implantation for a 27 years female patient of reproductive age. After discharge, the patient's aortic coarctation pressure decreased to 18 mm Hg, and the surgical results were satisfactory.

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