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OBJECTIVE To investigate the monitoring of tacrolimus blood concentration in patients with nephrotic syndrome （NS），and to establish a prediction model for tacrolimus blood concentration. METHODS Data from 509 concentration monitoring sessions of 166 NS patients using tacrolimus were collected from January 1， 2020 to August 31， 2023 in Zhongshan Hospital Affiliated to Xiamen University. The relationship of efficacy and adverse drug reaction（ADR） with blood concentration was analyzed. A multilayer perceptron （MLP） prediction model was established by using the blood concentration monitoring data of 302 times from 109 NS patients with genetic information， and then verified. RESULTS In terms of efficacy， the median blood concentration of tacrolimus in the non-remission group was 2.20 ng/mL， which was significantly lower than that in the partial remission group （4.00 ng/mL， P＜0.001） and the complete remission group （3.60 ng/mL， P＝0.002）. In terms of ADR， the median blood concentration of tacrolimus in the ADR group was 5.01 ng/mL， which was significantly higher than that in the non-ADR group （3.37 ng/mL） （P＝0.001）. According to the subgroup analysis of the receiver operating characteristic curve， when the blood concentration of tacrolimus was ≥6.65 ng/mL， patients were more likely to develop elevated blood creatinine [area under the curve （AUC） was 0.764， P＜0.001）； when the blood concentration of tacrolimus was ≥6.55 ng/mL， patients were more likely to develop blood glucose （AUC＝0.615， P＝ 0.005）. The established MLP prediction model has a loss function of 0.9， with an average absolute error of 0.279 5 ng/mL between the predicted and measured values. The determination coefficient of the validation scatter plot was 0.984， indicating an excellent predictive performance of the model. CONCLUSION Tacrolimus blood concentration has an impact on both efficacy and ADR in NS patients. The use of the MLP model for predicting blood concentration exhibits high accuracy with minimal error between predicted and measured values. The model can be used as an important tool in clinical individualized medication regimens.
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The immune system plays a pivotal role in the pathogenesis and progression of diseases. Lipid peroxidation, as a key effector molecule in the execution of ferroptosis, exerts critical effects on the functionality and survival of various immune cells and is involved in the pathological processes of multiple diseases. There is accumulating evidence suggesting the presence of ferroptosis in immune cells as well. Lipid peroxidation is closely associated with immune cell function. Accumulation of lipid peroxidation products in immune cells can lead to ferroptosis, directly impacting immune cell function. Non-immune cells, through lipid peroxidation-mediated cell death, release signaling molecules that regulate immune cell function. They jointly influence the body's homeostasis. This article provides a comprehensive review of the latest research progress on the regulatory role of lipid peroxidation in immune function. It analyzes the relationship between lipid peroxidation and immune cells, and provides a theoretical foundation for potential strategies targeting cellular lipid peroxidation and immunotherapy in the treatment of diseases.
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OBJECTIVE To system atically evaluate the efficacy and safety of immune checkpoint inhibitors （ICIs）versus routine second-line chemotherapy in the treatment of advanced esophageal cancer ，and to provide evidence-based reference for clinical medication. METHODS Randomized controlled trials （RCTs） about ICIs （trial group ） versus routine second-line chemotherapy （control group ） in the treatment of advanced esophageal cancer were searched from PubMed ，Embase，The Cochrane Library ，CNKI，Wanfang and VIP databases from the inception to August 1st，2021. After screening the literature and extracting data ，the risk of bias assessment tool recommended by Cochrane Systematic Evaluator Manual 5.1.0 was used to evaluate the quality of the included literature ，and RevMan 5.4.1 software was used for meta-analysis and sensitivity analysis. RESULTS A total of four studies were included ，involving 1 656 patients. Meta-analysis results showed that the overall survival of trial group was significantly longer than control group [HR ＝0.79，95％CI（0.71，0.88），P＜0.000 1]；the incidence of grade 3 or higher adverse events in trial group was significantly lower than control group [RR ＝0.42，95％CI（0.32，0.54），P＜0.000 01]. But there was no significant difference in progression-free survival [HR ＝0.95，95％ CI （0.75，1.21），P＝0.70] or objective remission rate [RR ＝1.72，95％CI（0.95，3.13），P＝0.07] between 2 groups. Results of subgroup analysis was performed according to the expression of programmed death ligand 1 showed that overall survival of patients with tumor proportion score （TPS）≥1％ in trial group was significantly longer than control group [HR ＝0.64，95％CI（0.51，0.79），P＜0.000 1]；there was no significant difference in overall survival of patients with TPS ＜1％ between 2 groups [HR ＝0.83，95％CI（0.67，1.02），P＝0.07]. The results of sensitivity analysis showed that except for the objective remission rate ，the conclusions of other indicators were robust. CONCLUSIONS Compared with routine second-line treatment ，ICIs can prolong overall survival and has good safety ，but shows no advantage in ） terms of progression-free survival and objective response rates.
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Ferroptosis is a novel type of cell death, which is distinguished from the traditional cell death pathways such as apoptosis, proptosis, necrosis and autophagy in terms of morphology, biochemistry and genetics. The main features of ferroptosis are the iron accumulation and lipid peroxidation. The regulation mechanism of ferroptosis involves glutathione metabolism, lipid peroxidation reactions and iron metabolism, which are closely related to the pathological process of tumor, aging, neurodegenerative diseases, ischemia reperfusion injury, cardiovascular and cerebrovascular diseases, kidney injury, hepatic fibrosis and so on. How to effectively study the role of ferroptosis regulation mechanism in the treatment of diseases becomes the hot spot and focus of the ferroptosis research. In recent years, with the in-depth study of ferroptosis, the identification, confirmation and the mechanism of ferroptosis have been developed significantly and have come forth continuously, in the meantime, techniques based on the morphology, biochemistry, molecular biology and genetics have been widely applied in the detection of ferroptosis. In order to deepen readers' understanding of ferroptosis and its detection methods, this paper will mainly review the current research progress on the detection methods and their application in ferroptosis, summarize and discuss their advantages and disadvantages in the detection of ferroptosis, this knowledge are crucial for better understanding and studying the biological function of ferroptosis.
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In this study, chronic emotional stress-induced H1N1 influenza susceptibility model was employed to simulate the states of "emotional stagnation" and "liver fire invading lung", and the protective effect of Qinggan Xiefei Fang on viral pneumonia was investigated. Survival rate and morbidity rate of mice were observed within 21 days after H1N1 infection, the symptoms of viral pneumonia and the level of phospholipid peroxidation were detected in lungs of mice after 6-day infection. The experimental results showed that Qinggan Xiefei Fang could alleviate the decline of survival rate and morbidity rate of mice caused by chronic constraint stress loaded with H1N1, inhibit the replication of H1N1 and the production of inflammatory factors, reduce the level of phospholipid peroxidation, and improve the symptoms of pneumonia in mice. The results also showed that compound-target network of Qinggan Xiefei Fang contained 171 compounds and 260 corresponding targets involved in the signaling pathway of oxidative stress, inflammation and immunity. All the above results indicate that Qinggan Xiefei Fang protecting influenza virus pneumonia was related to the regulation of oxidative stress. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University, in compliance with the Institutional Animal Care Guidelines.
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In this study, according to TCM theory of "liver qi stagnation forming fire", emotional stress mice model was employed to evaluate the protective effects of Qingre Xiaoyanning on herpes simplex virus type 1 (HSV-1) induced reactivation. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University, in compliance with the Institutional Animal Care Guidelines. BALB/c mice were divided into six groups, including mock group, HSV-1 latency group, HSV-1 reactivation group (HSV-1 latency + stress), low (0.658 g·kg-1·day-1) and high dose (1.316 g·kg-1·day-1) of Qingre Xiaoyanning groups and positive control group (acyclovir, 0.206 g·kg-1·day-1). Except for the normal group and HSV-1 latency group, all mice in other groups received a daily 12-h restraint stress for 4 days. After 7-day treatment of drugs, body weight and recurrent eye infections of mice were recorded. Brain tissues were harvested to monitor HSV-1 antigen distribution by immunohistochemical staining and detect virus titer by plaque assay. In the meantime, the mRNA and protein levels of infected cell polypeptide (ICP27) and glycoprotein B (gB) in the brain tissues were detected by RT-PCR and Western blot, respectively. The level of 4-hydroxynonenal (4-HNE) and expressions of ferroptosis-related proteins were measured by Western blot. The evaluation of malondialdehyde (MDA) content in the brain tissues was conducted by MDA assay commercial kit. The results showed that Qingre Xiaoyanning significantly retarded the decline of body weight of mice induced by HSV-1 reactivation, reduced the activation rate of HSV-1 and recurrent eye infections, declined virus titer of HSV-1, down-regulated gene and protein expressions of ICP27 and gB, and hindered the distribution of HSV-1 antigen in the brain of mice. Meanwhile, Qingre Xiaoyanning also decreased the protein expression of ferroptosis-related proteins, including DMT1, TFR1 and ALOX15 in the brain tissue of HSV-1 reactivated mice. The levels of lipid peroxidation products, 4-HNE and MDA, were also reduced by Qingre Xiaoyanning treatment. All the above results indicate that Qingre Xiaoyanning significantly inhibited HSV-1 reactivation by restraint stress, which might be related to the regulation of ferroptosis. Our findings provide a theoretical basis for the application of "clearing liver-fire" TCM on treatmenting HSV-1 reactivation-related symptoms.
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In this study, emotional stress-induced herpes simplex virus type 1(HSV-1) susceptibility model was employed to simu-late the pathological state of " depression-induced liver fire", and the protection effect of Qingre Xiaoyanning(QX) in clearing liver fire was investigated. BALB/c mice were randomly divided into a normal group, a HSV-1 group, a restraint stress + HSV-1 group,low-(0. 658 g·kg~(-1)) and high-dose(1. 316 g·kg~(-1)) QX groups, and an acyclovir group. Except for the normal group and the HSV-1 group, the mice in other groups received daily restraint stress for 6 h from day 3 of medication. On day 9 of medication, mice were anesthetized by isoflurane and infected intranasally with HSV-1. Survival rate, weight change, encephalitis symptoms, and eye injury of mice were recorded for 14 d after virus infection. Hematoxylin-eosin(HE) staining and immunohistochemical staining were used to detect pathological changes and HSV-1 antigen distribution. Plaque assay was performed to detect the titer of HSV-1. The protein ex-pression of ICP27 in the mouse brain was detected by Western blot. The experimental results showed that QX could increase the survival rate of HSV-1-infected mice loaded with emotional stress(P<0. 001), reduce the titer of HSV-1 in the mouse brain(P<0. 01), relieve brain inflammation(P<0. 05) and eye injury(P<0. 05), down-regulate the expression of ICP27 related to HSV-1(P<0. 05), and decrease the distribution of HSV-1 antigen in the mouse brain. The results demonstrated that QX significantly reduced the susceptibility to HSV-1 induced by emotional stress, which is expected to provide a theoretical basis for the treatment and preven-tion of HSV-1 infection and promote the clinical development and application of Chinese medicine effective in clearing liver fire.
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Animals , Mice , Capsules , Herpes Simplex , Herpesvirus 1, Human , Mice, Inbred BALB C , Psychological DistressABSTRACT
Objective To observe the effectiveness and safety of Linggui Zhugan Decoction in the treatment of metabolic syndrome(MS) induced by antipsychotics.Methods Sixty MS patients were enrolled who also matched the diagnostic criteria for phlegm stagnation type.These 60 patients who were treated in the Second Affiliated Hospital of Xinxiang Medical University were randomly divided into the observation group and control group,each group included 30 patients.The patients in the observation group were given the treatment of Linggui Zhugan Decoction in addition to antipsychotic treatment,while the patients in the control group were only given antipsychotic treatment.After two weeks or four weeks of treatment,the levels of triglyceride (TG),high density lipoprotein (HDL),fasting plasma glucose,insulin,C-peptide and insulin resistance index (HOMA-IR) were compared between the two groups before and after treatment.Results After two weeks or four weeks treatment,the levels of TG,fasting plasma glucose,insulin,C-peptide and HOMA-IR significantly increased and that of HDL decreased significantly in the control group patients compared with those before treatment (P ＜ 0.05),while the results in the observation group were opposite (P ＜ 0.05).In the control group patients,the levels of insulin,HOMA-IR and C-peptide after four weeks treatment were significantly higher than those after two weeks treatment (P ＜ 0.05).However,in the observation group patients,the levels of insulin,HOMA-IR and C-peptide after four weeks treatment were significantly lower than those after two weeks treatment (P ＜ 0.05).Compared with the control group,after two weeks or four weeks treatment the levels of TG,fasting plasma glucose,insulin,C-peptide and HOMA-IR decreased significantly in the observation group patients and that of HDL increased significantly (P ＜ 0.05).The treatment emergent symptom scale score of the observation group was lower than that of the control group at the end of four weeks (P ＜ 0.05).Conclusion Linggui Zhugan Dcoction can improve MS caused by antipsychotics and has good safety.
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OBJECTIVE:To provide reference for promoting clinical rational use of Aidi injection. METHODS:Some inpa-tient records that used Aidi injection in our hospital from Jan. to Jun. 2015 were randomly selected and statistically reviewed by us-ing Excel(2011 edition) in aspects of gender,age,tumor location,usage and dosage,solvents usage,treatment course,adverse reactions,etc. RESULTS:In the 125 patients who used Aidi injection,male was more than female,with average age of 58.4 years;the tumor location of 66 patients (52.80%) was consistent with the indications in instructions;treatment course of 30 pa-tients(24.00%)was consistent with the instructions;all solvent types were consistent with the instruction recommendation,while only 6 patients(4.80%)showed consistence in solvent usage and instructions;122 patients(97.60%)showed consistence in single dosage and instructions;7 patients had adverse reactions,mainly rash and gastrointestinal reactions. CONCLUSIONS:The use of Aidi injection in our hospital shows off-label drug use,non-standardized treatment course and inappropriate solvent usage. Physi-cians,clinical pharmacists and relevant departments should further strengthen the rational use,medical advice comments,supervi-sion and management of Aidi injection in the hospital to promote the rational drug use.
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OBJECTIVE:To investigate blood concentration monitoring data,therapeutic efficacy,toxic reaction and combi-nation of tacrolimus in patients with Allo-HSCT,and to provide reference for clinical application of tacrolimus. METHODS:The blood concentration of tacrolimus in 16 inpatients were monitored with EMIT 3 months after Allo-HSCT. The occurrence of Graft-versus-Host disease(GVHD),ADR and drug combination were analyzed and discussed. RESULTS:A large individual dif-ferences were found in blood concentration of tacrolimus. When blood concentration 20 ng/ml,the occurrence of diabetes,kidney damage and other side effects seems increased. Tacrolimus had a good effect on treatment and prevention of GVHD,and could have an interaction with other drugs. CONCLUSIONS:Blood concentration monitoring of tacrolimus plays an important role on the prevention and treatment of GVHD,and the decrease of side effects such as diabetes and neurotoxicity. The satisfactory blood concentration is 8-20 ng/ml,when there seems a smaller possibility of GVHD and ADR 3 months after Allo-HSCT.
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The medical records of 108 inpatients treated with vancomycin and norvancomycinin were collected and analyzed retrospectively.And 78.7% of all cases were used for therapy and 21.3% for prevention.The pathologic examination submission rate was 88.9% ( n=96 ).The drug utilization index ( DUI) of norvancomycin was 0.95 and vancomycin 0.92.The proportion of combination use was 86.1%and a maximum of 3 antibiotics were used.There were 6.5% cases of doubtful adverse drug reaction.The inpatient uses of vancomycin and norvancomycin are basically rational.Indications should be mastered strictly.Empirical and prophylactic uses should be minimized to prevent and delay drug resistance strain from spreading and prolong effectiveness.Necessary therapeutic drug monitoring is required.
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OBJECTIVE:To establish a HPLC method for the determination of oxymatrine(OMT)and matrine(MT)in dog plasma.METHODS:Plasma protein was precipitated with perchloric acid;OMT and MT were extracted with dichloromethane under strong base condition and then plasma levels of OMT and MT were determined by HPLC.RESULTS:The linear ranges of OMT and MT were 0.2～ 15? g? mL-1 and 0.1～ 5? g? mL-1,respectively,and the detection limits of OMT and MT were 20ng? mL-1.The absolute recoveries,relative recoveries,intra-day and inter-day precisions of OMT and MT were all in line with the standards.CONCLUSION:The method is simple,accurate and sensitive yet with little interference,and it is applicable for the determination of OMT and MT in plasma,the studying of the pharmacokinetics,the transformation process and the metabolic pathway of OMT in vivo,furthermore,it serves as guidance for the development of new OMT preparations.
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OBJECTIVE:To analyze the postoperative application of anti-infective agents in patients undergoing stem cell transplantation. METHODS:The application of anti-infective agents in 30 patients undergoing stem cell transplantation in the pretreatment period and after operation in our hospital from 2003 to 2008 were analyzed in respect of etiology inspection,the cost of anti-infective agents,utilization frequency(cases/times),duration of medication,DDDs,DUI,drug combination and its rationality. RESULTS:The infection was found in 26 cases after operation,accounting for 86.67%. Pathogens were found out in 11 cases. The total cost of anti-infective agents was 327 598.23 yuan. The DUI of 7 kinds of top 10 anti-infective agents in terms of DDDs were less than 1 and that of other 3 were more than 1. In terms of drug combination,two-drug consisted of 73.08%(38 cases/times), three-drug 25.00%(13 cases/times)and four-drug 1.92%(1 cases/times). CONCLUSION:The postoperative application of anti-infective agents in patients undergoing stem cell transplantation in our hospital is rational on the whole.
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OBJECTIVE:To explore the clinical role of two-hour(C2)of CsA in allogeneic hematopoietic stem cell transplantation.METHODS:The whole blood CsA concentration of 9 patients of C0 and 12 of C2 were determined by FPIA method . RESULTS: The satisfactory immunosuppressive concentration was found as follow: C0 was 200～400 ?g?L-1and C2 was 500～700 ?g?L-1.Both C0 and C2 could predict the acute rejection and side-effects,but C2 is more effective.CONCLUSION:The factors that affect the whole blood concentration of CsA were complex. CsA blood concentration monitoring can be used to guide rational use of CsA,but C2 is more effective than C0.
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OBJECTIVE:To analyze the drug use in the inpatients undergoing allogenic stem cell transplantation.METHODS:The drug use in 24 inpatients undergoing allogenic stem cell transplantation from 2004 to 2007 were analyzed retrospectively in respect of drug variety and drug cost etc.RESULTS:The average drug cost for the inpatients undergoing stem cell transplantation was(66 418.56?24 381.73)yuan,comprising 61.69% of the total cost of hospitalization.The top 20 drugs in terms of consumption sum were mainly drugs for immune system,drugs affecting hematological and hematopoietic system and anti-tumor drugs etc.The top 20 drugs in terms of DDDs were mainly immunosuppressants,anti-tumor drugs and adjunctive drugs,with DUI ≤1 for the majority of the drugs.CONCLUSION:The drug use in the inpatients undergoing allogenic stem cell transplantation in our hospital was rational on the whole.