1.A unicenter real-world study of the correlation factors for complete clinical response in idiopathic inflammatory myopathies
Zhanhong LAI ; Jiachen LI ; Zelin YUN ; Yonggang ZHANG ; Hao ZHANG ; Xiaoyan XING ; Miao SHAO ; Yue-Bo JIN ; Naidi WANG ; Yimin LI ; Yuhui LI ; Zhanguo LI
Journal of Peking University(Health Sciences) 2024;56(2):284-292
Objective:To investigate the correlation factors of complete clinical response in idiopathic inflammatory myopathies(IIMs)patients receiving conventional treatment.Methods:Patients diagnosed with IIMs hospitalized in Peking University People's Hospital from January 2000 to June 2023 were in-cluded.The correlation factors of complete clinical response to conventional treatment were identified by analyzing the clinical characteristics,laboratory features,peripheral blood lymphocytes,immunological indicators,and therapeutic drugs.Results:Among the 635 patients included,518 patients finished the follow-up,with an average time of 36.8 months.The total complete clinical response rate of IIMs was 50.0%(259/518).The complete clinical response rate of dermatomyositis(DM),anti-synthetase syn-drome(ASS)and immune-mediated necrotizing myopathy(IMNM)were 53.5%,48.9%and 39.0%,respectively.Fever(P=0.002)and rapid progressive interstitial lung disease(RP-ILD)(P=0.014)were observed much more frequently in non-complete clinical response group than in complete clinical re-sponse group.The aspartate transaminase(AST),lactate dehydrogenase(LDH),D-dimer,erythrocyte sedimentation rate(ESR),C-reaction protein(CRP)and serum ferritin were significantly higher in non-complete clinical response group as compared with complete clinical response group.As for the treat-ment,the percentage of glucocorticoid received and intravenous immunoglobin(IVIG)were significantly higher in non-complete clinical response group than in complete clinical response group.Risk factor analysis showed that IMNM subtype(P=0.007),interstitial lung disease(ILD)(P=0.001),eleva-ted AST(P=0.012),elevated serum ferritin(P=0.016)and decreased count of CD4+T cells in peripheral blood(P=0.004)might be the risk factors for IIMs non-complete clinical response.Conclu-sion:The total complete clinical response rate of IIMs is low,especially for IMNM subtype.More effec-tive intervention should be administered to patients with ILD,elevated AST,elevated serum ferritin or decreased count of CD4+T cells at disease onset.
2.Differentiation and Treatment of Co-morbidity of Osteoporosis and Knee Osteoarthritis based on the Concept of "Wei (痿) and Bi (痹) Unity"
Yushi CUI ; Hongfei WU ; Yun GAO ; Runmin LAI ; Xingping ZHANG ; Shuai ZHANG ; Mingyuan WANG ; Yamin LI
Journal of Traditional Chinese Medicine 2024;65(15):1565-1570
Osteoporosis and knee osteoarthritis often co-occur and are closely related in terms of epidemiology, clinical symptoms, pathogenesis and other aspects. Therefore, it is necessary to manage the co-morbidity and treat the two as a whole. Based on the overall relationship between wei (痿) and bi (痹) in TCM, it is believed that osteoporosis and knee osteoarthritis have marrow loss and bone atrophy as the core pathogenesis of co-morbidity, and microfractures as the central pathological link. The overall treatment is rooted in boosting kidney, supplementing marrow and strengthening the bones. According to the pathological manifestations of microfractures in the process of co-morbidity, and the different deficiency and excess characteristics of wei and bi, it can be divided into three types, "wei emerging with mild bi", "wei and bi progressing simultaneously", and "emphasis on both wei and bi", for treatment. In terms of "wei emerging with mild bi", that is the early stage of osteoporosis, the traditional Daoyin (导引) is the main therapy. For "wei and bi progressing simultaneously", it can be divided into three stages further, including the onset stage, remission stage, and recovery stage of knee pain, treated with Taohong Siwu Decoction (桃红四物汤), Bushen Huoxue Formula (补肾活血方) and self-made Bushen Qianggu Formula (补肾强骨方) as the main formula respectively. For "emphasis on both wei and bi", the proven formula, Qianggu Zhitong Formula (强骨止痛方), is taken as the main prescription.
3.Research status of atezolizumab combined with bevacizumab plus chemotherapy for the treatment of advanced non-small cell lung cancer
Hou-Yun LAI ; Yan LIANG ; Feng LI ; Jin ZHOU ; Yan CHEN ; Yi-Xin WANG
The Chinese Journal of Clinical Pharmacology 2024;40(17):2591-2595
Immunotherapy had completely changed the treatment for patients with advanced non-small cell lung cancer.However,due to its low response rate as a monotherapy,many patients had not been able to benefit from the treatment.The combination of immunotherapy with anti-angiogenic drugs and chemotherapy might have helped to address this issue,and the regimen of atezolizumab with bevacizumab,carboplatin,and paclitaxel(ABCP)had been approved as a first-line treatment for advanced metastatic non-small cell lung cancer,holding great potential for application.This review had summarized the antitumor mechanisms of the ABCP regimen,had concluded the current status of its clinical application for different subgroups and treatment sequences,the safety and cost-effectiveness of the regimen,as well as the possibilities for alternative drug choices within the ABCP regimen and the development of new drugs,providing a reference for the personalized application of the ABCP regimen in patients with non-small cell lung cancer.
4.Mapping Dissolved Gases Distribution in Lake Water Using Shipborne Membrane Inlet Mass Spectrometry
Han WANG ; Chang-Jie LIU ; Hai-Yun SONG ; You-Jiang LIU ; Chi-Lai CHEN
Chinese Journal of Analytical Chemistry 2024;52(7):937-944
As global average carbon dioxide concentrations steadily rise,the frequency,intensity,and duration of cyanobacterial blooms in aquatic ecosystems are increasing annually.This phenomenon presents a significant threat to the overall health of global ecosystems and has garnered worldwide attention.In this study,an online detection of small-molecule dissolved gas concentrations in lake using a home-made membrane inlet mass spectrometer was conducted.Comparative water samples analyses demonstrated that the developed mass spectrometer instrument effectively discriminated between different water samples based on its dissolved gas detection capabilities.Online survey revealed that the concentrations of dissolved O2 and dissolved CO2 were 0.24 mmol/L and 1.31 μmol/L,respectively,in areas without cyanobacterial coverage.In areas with cyanobacterial coverage,their concentrations were 0.21 mmol/L and 0.92 μmol/L,respectively.In areas where cyanobacteria were densely collected,the dissolved CO2 content rose rapidly,while the dissolved O2 content decreased rapidly.This result revealed that large-scale cyanobacterial blooms exacerbated CO2 emissions,and during such blooms,lakes acted as sources of CO2,emitting substantial amounts into the atmosphere,thereby contributing to adverse impacts on global climate change.Furthermore,extensive cyanobacterial blooms led to a rapid decrease in dissolved O2 levels,resulting in O2 depletion and the mortality of fish and benthic invertebrates.The research highlighted the significance of the ratio of content of O2 and CO2 as a crucial indicator for cyanobacterial monitoring,with a smaller ratio indicating higher cyanobacterial content.Moreover,changes in turbidity and variations in the ratio of O2 and CO2 exhibited strong consistency.Large-scale algal blooms increased water turbidity,which posed a threat to the survival of aquatic organisms.This study provided a technological means for online detection of dissolved gases in water,offering essential references for water quality assessment,ecological evaluation,and particularly,for early prevention,mid-term management,and post-treatment effectiveness assessment of cyanobacterial blooms.
5.Effect of Yaobitong Capsules Combined with Fu's Subcutaneous Needling on Lumbar Range of Motion and Surface Electromyography of Trunk Extensors in Patients with Lumbar Disc Herniation
Yun-Yao CHEN ; Guo-Shu WANG ; Xiu-Juan LAI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(5):1174-1180
Objective To investigate the effect of Yaobitong Capsules combined with Fu's subcutaneous needling on lumbar range of motion and surface electromyography of trunk extensors in patients with lumbar disc herniation(LDH).Methods A total of 80 patients with LDH of blood stasis type were randomly divided into the study group and the control group,with 40 cases in each group.The control group was treated with Yaobitong Capsules orally,and the study group was given Fu's subcutaneous needling combined with Yaobitong Capsules orally.The course of treatment for the two groups covered 2 weeks.The changes of lumbar range of motion,pain visual analogue scale(VAS)score,improved Chinese Oswestry Disability Index(ODI)score,Roland-Morris Disability Questionnaire(RMDQ)score and surface electromyography of trunk extensors in the two groups before and after treatment were observed.After treatment,the clinical efficacy of the two groups was evaluated.Results(1)After 2 weeks of treatment,the total effective rate of the study group was 97.50%(39/40),and that of the control group was 80.00%(32/40).The intergroup comparison(tested by chi-square test)showed that the clinical efficacy of the study group was significantly superior to that of the control group(P<0.05).(2)After treatment,the range of motion of lumbar flexion,extension and rotation in the two groups was significantly improved compared with that before treatment(P<0.05),and the improvement of lumbar range of motion in the study group was significantly superior to that in the control group(P<0.05 or P<0.01).(3)After treatment,the lumbar function scores of ODI score and RMDQ score in the two groups were significantly lower than those before treatment(P<0.05),and the decrease of ODI score and RMDQ score in the study group was significantly superior to that in the control group(P<0.01).(4)The pain VAS scores of the study group after one week,2 weeks and one month of treatment and the pain VAS scores of the control group after 2 weeks and one month of treatment were significantly lower than those before treatment(P<0.05),and the decrease of pain VAS scores of the study group after one week,2 weeks and one month of treatment was significantly superior to that of the control group(P<0.01).(5)After treatment,the parameters of surface electromyography of trunk extensors such as integrated electromyographic value(IEMG)and mean power frequency(MPF)in the two groups were obviously increased compared with those before treatment(P<0.05),and the increase of MPF and IEMG in the study group was significantly superior to that of the control group(P<0.01).Conclusion Yaobitong Capsules combined with Fu's subcutaneous needling can significantly enhance the curative effect of LDH patients,alleviate the lumbar range of motion,improve the surface electromyography of trunk extensors,and relieve muscle fatigue and pain symptoms.
6.Pretreatment and analysis techniques development of TKIs in biological samples for pharmacokinetic studies and therapeutic drug monitoring
Chen LAN ; Zhang YUAN ; Zhang YI-XIN ; Wang WEI-LAI ; Sun DE-MEI ; Li PENG-YUN ; Feng XUE-SONG ; Tan YUE
Journal of Pharmaceutical Analysis 2024;14(4):439-459
Tyrosine kinase inhibitors(TKIs)have emerged as the first-line small molecule drugs in many cancer therapies,exerting their effects by impeding aberrant cell growth and proliferation through the mod-ulation of tyrosine kinase-mediated signaling pathways.However,there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites,which may render patients with compromised immune function susceptible to diverse infections despite receiving theo-retically efficacious anticancer treatments,alongside other potential side effects or adverse reactions.Therefore,an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods,clinical pharmacokinetics,and therapeutic drug monitoring of different TKIs.This paper provides a comprehensive overview of the advancements in pretreatment methods,such as protein precipitation(PPT),liquid-liquid extraction(LLE),solid-phase extraction(SPE),micro-SPE(p-SPE),magnetic SPE(MSPE),and vortex-assisted dispersive SPE(VA-DSPE)achieved since 2017.It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography(HPLC)and high-resolution mass spectrometry(HRMS)methods,capillary electro-phoresis(CE),gas chromatography(GC),supercritical fluid chromatography(SFC)procedures,surface plasmon resonance(SPR)assays as well as novel nanoprobes-based biosensing techniques.In addition,a comparison is made between the advantages and disadvantages of different approaches while pre-senting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.
7.Study on improvement effect of Danggui Shaoyao San on edema in rats with nephrotic syndrome and its mechanism
Xiao-Wen MA ; Sheng-Nan FAN ; Zai-Ping XU ; Qing-Zhen XIANG ; Zi-Hua XUAN ; Yun-Lai WANG ; Fan XU
Chinese Pharmacological Bulletin 2024;40(6):1172-1178
Aim To explore the effect of Danggui Shaoyao San on edema in rats with nephrotic syndrome and the underlying mechanism.Methods Rats were randomly divided into control group,model group,Danggui Shaoyao San group(17.2 g·kg-1·d-1),losartan group(30 mg·kg-1·d-1)and tolvaptan group(3 mg·kg-1·d-1).The rat model of nephrot-ic syndrome was established by tail vein injection of adriamycin.After four weeks of treatment,the levels of renal function and 24 h urinary protein were detected.The distribution of aquaporin 2(AQP2)and pS256-AQP2 in renal tissue was detected by immunohisto-chemistry.The levels of plasma arginine vasopressin(AVP)and angiotensin Ⅱ(Ang Ⅱ)were measured by radioimmunoassay.The expressions of renal AQP2,pS256-AQP2,angiotensin type 1 receptor(AT1R),arginine vasopressin receptor 2(V2R)protein and mRNA were measured by Western blot and RT-PCR,respectively.Results The three drugs could improve renal function,reduce proteinuria,decrease plasma AVP and Ang Ⅱ levels,and down-regulate AQP2 and pS256-AQP2 protein and mRNA expression in model rats.Danggui Shaoyao San and tolvaptan were more ef-fective than losartan in reducing plasma AVP levels.Conclusions Danggui Shaoyao San may regulate the expression of AQP2 by reducing the levels of AVP and Ang Ⅱ,and improve the edema of nephrotic syndrome rats.
8.Experimental study on concentration selection of immunohistochemical antibodies for retinal endoplasmic reticulum stress
Xiao-Hong CHEN ; Wan-Jiao LIANG ; Shi-Shu HUANG ; Yan SUN ; Xin LUO ; Lu LAI ; Zhao-Sheng CHI ; Mei-Zhu CHEN ; Yun-Peng WANG ; Wei-Ming YAN
International Eye Science 2023;23(1):32-38
AIM: To explore the optimal concentration of endoplasmic reticulum stress immunohistochemical(IHC)staining antibody in mouse retinitis pigmentosa(RP)model, which provides the corresponding index detection method for studying the pathogenesis and intervention measures of RP.METHODS: Clean male C57BL/6J mice were intraperitoneally injected with N-methyl-N-nitrosourea(MNU, 60mg/kg)to prepare RP mouse model. Electroretinogram(ERG)and hematoxylin-eosin(HE)staining were performed on 7d after modeling to verify the successful modeling. The expression of endoplasmic reticulum stress-related proteins(IRE1, ATF6, PERK, GRP78, Caspase-12)was detected by IHC staining.RESULTS: The following proteins, including IRE1, ATF6, PERK, GRP78 and Caspase-12, were positively expressed in retina of RP mouse. The optimal concentrations of the above proteins were as follows: IRE1 antibody concentration was 1:1000, ATF6 antibody concentration was 1:500 and 1:1000(with no difference in positive expression, P>0.05), PERK antibody concentration was 1:1500, GRP78 antibody concentration was 1:200 and Caspase-12 antibody concentration was 1:100, the proteins were well expressed at the above concentrations, and the positive expressions of corresponding proteins were different from those of other antibody concentrations(P<0.05).CONCLUSION: The optimal concentrations for IHC staining in different proteins of mouse RP models were as follows: the concentrations of endoplasmic reticulum stress-related protein antibodies were 1:1000 in IRE1, 1:500 and 1:1000 in ATF6, 1:1500 in PERK, 1:200 in GRP78, and 1:100 in Caspase-12.
9.Research progress on the mechanism of ferroptosis in ocular disease associated with retinal pigment epithelial cell injury
International Eye Science 2023;23(1):75-78
Ferroptosis is a newly identified programmed cell death characterized by lipid peroxidation and iron accumulation. In recent years, with the proposal of the concept of ferroptosis as well as the deepening of its mechanism research, great breakthroughs have been made in the exploration of the pathogenesis of ocular diseases related to the function decline of retinal pigment epithelium cells(RPECs), such as age-related macular degeneration(AMD), retinitis pigmentosa(RP)and diabetic retinopathy(DR). This article reviews the basic concept of ferroptosis, the main mechanism of ferroptosis in RPECs and the role of ferroptosis regulation in the development of RPECs-related ocular diseases, hoping to provide references for the study of the pathogenesis of RPECs-related ocular diseases.
10.Research progress of tight junction between retinal pigment epithelium cells and its disruption in the pathogenesis of age-related macular degeneration
International Eye Science 2023;23(2):232-235
Age-related macular degeneration(AMD)is a common eye disease causing irreversible visual impairment in the elderly. The tight junction(TJ)between retinal pigment epithelium cells(RPECs)is an important structural unit of the outer blood retinal barrier(oBRB). The TJ is defective in the pathogenesis of AMD, which in turn promotes the destruction of oBRB and accelerates the occurrence and progression of AMD. In this paper, the roles of TJ and TJ protein in maintaining oBRB function, TJ protein abnormality and oBRB destruction in the pathogenesis of AMD were reviewed, aiming to provide new ideas for the treatment of AMD.

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