Objective To evaluate the effect of LifePort combined with polymyxin B in preventing donor-derived infections caused by preservation solution contamination. Methods Clinical data of 110 kidney transplant recipients were retrospectively analyzed. According to the decontamination status of preservation solution, the recipients were divided into the decontamination group (n=62) and the non-decontamination group (n=48). The general data of the two groups were compared, and the preventive effect of polymyxin B on possible donor-derived infections (p-DDI) was analyzed, especially infections associated with multidrug-resistant Gram-negative bacteria (MDR GNB). Results There were no statistically significant differences in baseline data (gender, age, preservation solution contamination status, etc.) between the decontamination group and the non-decontamination group (all P > 0.05). The overall contamination rate of preservation solution was 80.0%, and 68 contaminated samples were with single microorganism and 20 with multiple microorganisms. Coagulase-negative staphylococci, Enterococcus and Klebsiella pneumoniae were the most common microorganisms in the positive samples. Fifteen cases of preservation solution were contaminated by MDR GNB, including 10 cases in the non-decontamination group and 5 cases in the decontamination group, with no statistically significant difference between the two groups (P = 0.053). Postoperative infection-related events occurred in 69 recipients, including 39 cases in the non-decontamination group and 30 cases in the decontamination group, with the incidence rate in the non-decontamination group significantly higher than that in the decontamination group (P < 0.001). Only 10 cases of infections were identified as p-DDI, all of which were positive for preservation solution culture, including 8 cases in the non-decontamination group and 2 cases in the decontamination group (P < 0.05). There were 5 cases of p-DDI related to MDR GNB in the non-decontamination group, while no such cases occurred in the decontamination group (P < 0.05). No adverse reactions related to polymyxin B were observed, and no recipient death or renal allograft dysfunction occurred in either group. Conclusions Adding polymyxin B to the preservation fluid during hypothermic machine perfusion with LifePort before renal transplantation may reduce p-DDI and its potential adverse consequences.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

ObjectiveTo explore the molecular mechanism implicated in the treatment of primary myelofibrosis （PMF） using Chinese medicinal herbs （CMH） by bioinformatics and molecular dynamics. MethodsData mining was performed to find the high-frequency CMH in treating PMF between the year of 1985 and 2024 by searching CNKI， Chinese Science and Technology Journal Database （CCD）， and China Academic Journal Database （CSPD）. TCMSP， SwissTargetPrediction and related reports were used to collect the main active ingredients of high-frequency CMH and their targets. The PMF datasets GSE44426 and GSE124281 were downloaded from GEO database， and R software was used for data normalization and differentially expressed genes （DEGs） screening. Key module hub genes were obtained by weighted gene co-expression network analysis （WGCNA） analysis. The common intersection genes of active ingredient targets， DEGs and key module hub genes of CMH were selected， and the target network was generated using Cytoscape 3.9.2 software. The core target network was generated by topological analysis， while key pathways were selected by GO and KEGG pathway enrichment analysis， and protein interaction relationships were obtained from the String database， so as to construct drug-ingredient-target network and protein interaction network （PPI） relationship diagrams. Discovery Studio 2020 software was used to perform molecular docking， and the GROMACS program was used to perform molecular dynamics simulation. ResultsA total of 21 prescriptions were collected involving 121 herbs. There were 9 herbs with a frequency ≥10 times， which were Danshen （Radix et Rhizoma Salviae Miltiorrhizae）， Huangqi （Radix Astragali）， Baizhu （Rhizoma Atractylodis Macrocephalae）， Danggui （Radix Angelicae Sinensis）， Dangshen （Radix Codonopsis）， Gancao （Radix et Rhizoma Glycyrrhizae）， Baishao （Radix Paeoniae Alba）， Fuling （Poria） and Shudihuang （Radix Rehmanniae Praeparata） from high- to low-frequency. A total of 98 active ingredients and 1125 potential targets were obtained from 9 high-frequency CMH. GSE44426 and GSE124281 data sets screened out 24 gene samples， including 14 of the healthy control group and 10 of the PMF group， and identified 319 DEGs between the two groups， including 122 up-regulated genes and 197 down-regulated genes. WGCNA screened out 24 co-expression module genes and found that the five modules closely related to the onset of PMF were MEpink， MEdarkred， MEblack， MEgrey， and MEturquoise， involving 7112 key module hub genes. The GO and KEGG enrichment analyses indicated that lipids and the atherosclerosis pathways were mainly involved in the mechanism of above high-frequency CMH in treating PMF， which included six hub protein targets： HSP90AA1， HSP90AB1， SRC， MAPK1， IL1B and IL10. From the drug-ingredient-target network， seven active ingredients of CMH targeting at these six hub targets were found， including verbascoside， verbascos isoflavone， kaempferol， luteolin， naringenin， quercetin and pachymic acid. The molecular docking and molecular dynamics analyses showed that the key CMH were Shudihuang， Huangqi， Baishao， Danshen， Gancao and Fuling， and among the seven active ingredients， calycosin had the highest binding affinity with HSP90AB1. ConclusionThe main CMH for the treatment of PMF may be Shudihuang， Huangqi， Baishao， Danshen， Gancao and Fuling， and the active ingredients include verbascoside， verbascos isoflavones， kaempferol， luteolin， naringenin， quercetin and pachymic acid. The relevant targets are HSP90AA1， HSP90AB1， SRC， MAPK1， IL-10， and IL-1β， and the most critical pathways are lipid and atherosclerosis pathways.

With the widespread adoption of technologies such as diagnostic imaging, interventional medicine, radiotherapy, and nuclear medicine, a growing number of people are exposed to low-dose ionizing radiation. Currently, the biological effects of low-dose radiation remain unclear, necessitating the identification of sensitive and specific biomarkers for risk assessment and health monitoring of such exposure. In this paper, we review the latest research progress in low-dose ionizing radiation biomarkers from the five perspectives of cytogenetics, DNA damage, transcriptome, proteome, and metabolomics. This review aims to provide a theoretical basis for the study of the biological effects of low-dose radiation.

ObjectiveTo observe the effect of Coptidis Rhizoma and Ophiopogonis Radix on renal tissue injury and epidermal growth factor receptor （EGFR）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in rats with diabetic nephropathy （DN） and explore its possible mechanism of delaying DN. MethodThirty-six male Wistar rats were randomly divided into a normal group （6 rats） and a model group （30 rats）. The model group was fed with a high-fat and high-sugar diet combined with streptozotocin （STZ） to establish a rat model of type 2 diabetes. After the successful preparation of the model， the rats were randomly divided into the model group， low， medium， and high dose groups of Coptidis Rhizoma and Ophiopogonis Radix （100， 200， 400 mg·kg^-1）， and metformin group （200 mg·kg^-1）. After administration， the levels of fasting blood glucose （FBG）， 24 h urine protein （24 h-UTP）， creatinine （SCr）， urea nitrogen （BUN）， and uric acid （UA） were detected. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathological changes of renal tissue in rats. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were used to detect the related protein expression of EGFR， PI3K， and Akt and their mRNA expression levels in the renal tissue of rats in each group. ResultsCompared with the normal group， the levels of FBG， SCr， BUN， UA， 24 h-UTP， and kidney index in the model group were significantly increased （P<0.01）， most renal tubular epithelial cells were necrotic， and the content of collagen in glomeruli was significantly increased （P<0.01）. Compared with the model group， the above indexes of rats in each administration group were improved to varying degrees. The FBG， SCr， BUN， UA， 24 h-UTP， and kidney index of rats in each dose group and metformin group were significantly decreased （P<0.01， P<0.05）. The necrosis degree of renal tubular epithelial cells was reduced， and the fibrosis area was decreased （P<0.01）. There related protein and mRNA expressions of EGFR， PI3K， and Akt were significantly increased （P<0.05， P<0.01）. ConclusionCoptidis Rhizoma and Ophiopogonis Radix can alleviate renal tissue injury in rats with DN， and their mechanism may be related to the regulation of the EGFR/PI3K/Akt signaling pathway.

Objective:To explore the prognostic value of baseline 18F-FDG PET/CT metabolic parameters in locally advanced cervical cancer (LACC) after concurrent chemoradiotherapy (CCRT). Methods:From September 2015 to October 2021, the clinical data of 180 LACC patients (age: 22-76 years) who underwent 18F-FDG PET/CT before CCRT at Affiliated Cancer Hospital of Shandong First Medical University were analyzed retrospectively. The metabolic tumor volume (MTV), total lesion glycolysis (TLG), SUV max, and SUV mean were computed by using the margin threshold of 42%SUV max. The optimal threshold for predicting progression-free survival (PFS) was obtained by ROC curve analysis. The Kaplan-Meier method was applied for survival analysis, and the log-rank test was applied to compare the survival rate between groups. Multivariate Cox proportional hazard regression was used to analyze progression for PFS. Results:The median follow-up was 19.1 months, and 54 patients (30.0%, 54/180) suffered from disease progression. ROC curve analysis showed that the optimal cut-off value of MTV was 31.145 ml, with the AUC of 0.641. Para-aortic lymph node (PALN) metastasis had the highest AUC value (0.589) among the clinical factors, followed by International Federation of Gynecology and Obstetrics (FIGO) stage (0.581). The 1-year PFS rates of patients with MTV<31.145 ml ( n=88) and MTV≥31.145 ml ( n=92) were 80.68% and 59.78%, respectively ( χ2=13.72, P<0.001). Multivariate Cox analysis demonstrated that pathological type (hazard ratio ( HR)=3.075, 95% CI: 1.370-6.901, P=0.006), FIGO stage ( HR=1.955, 95% CI: 1.031-3.707, P=0.040), PALN metastasis ( HR=2.136, 95% CI: 1.202-3.796, P=0.010) and MTV ( HR=2.449, 95% CI: 1.341-4.471, P=0.004) were the significant predictors for PFS. Conclusions:Pathological type, FIGO stage, PALN metastasis and MTV are independent prognostic risk factors for PFS. MTV as the baseline 18F-FDG PET/CT metabolic parameter, can realize prognostic stratification analysis.

OBJECTIVE To explore the effects of letrozole combined with methylprednisolone on clinical outcomes， ovarian reserve function， serum sex hormones， and safety in infertile patients with polycystic ovary syndrome resistant to clomiphene. METHODS The clinical data of 78 infertile patients with polycystic ovary syndrome resistant to clomiphene in the Department of Gynecology of Qingdao Central Hospital from February 2021 to January 2022 was analyzed retrospectively， and all patients were divided into control group （42 cases） and observation group （36 cases） based on the treatment methods. The control group took letrozole 5 mg/d orally on the 5th to 9th day of the menstrual cycle. Vaginal ultrasound was used to monitor the development of the endometrium and follicles； estradiol valerate was used to correct endometrial thickness， and measures such as inducing ovulation with follicle-stimulating hormone were taken to promote pregnancy. On the basis of treatment in the control group， the observation group began taking methylprednisolone orally at a dose of 4 mg/d starting from the third day of natural menstruation or withdrawal bleeding. Both groups were treated for 6 menstrual cycles. The ovulation and pregnancy within one year， serum levels of sex hormones [estradiol （E2）， luteinizing hormone （LH）， follicle-stimulating hormone （FSH）， testosterone] and anti-Müllerian hormone （AMH）， ovulation indicators （follicle growth time， the number of ovulations， and the number of dominant follicles）， and the occurrence of adverse drug reactions were compared between the two groups. RESULTS After treatment， the biochemical pregnancy rate （72.22%） and clinical pregnancy rate （47.22%） of the observation group were significantly higher than those of control group （47.62%， 19.05%）； the serum levels of E2， LH， FSH， testosterone and AMH were significantly lower than the control group； the follicle growth time was significantly shorter than the control group； the number of ovulation and dominant follicles were significantly higher than the control group （P＜0.05）. There was no statistically significant difference in ovulation rate （94.44% vs. 83.33%） and total incidence of adverse drug reactions （8.33% vs. 9.52%） between the observation group and the control group （P＞0.05）. CONCLUSIONS Compared with letrozole alone， the combination of letrozole and methylprednisolone can significantly improve the pregnancy rate， the sex hormone levels and ovarian reserve function in infertile patients with polycystic ovary syndrome resistant to clomiphene， with high safety profiles.

Objective To explore the predictive value of pulse pressure variation(PPV),stroke volume variation(SVV)and their changing values after tidal volume increase from 6 mL/kg to 8 mL/kg predicted body weight(PBW)on the volumetric responsiveness in the patients with acute respiratory distress syndrome(ARDS).Methods A prospective study was conducted.Twenty-three ARDS patients with acute circulatory failure treated in the intensive care unit(ICU)of this hospital from January 2021 to December 2022 were se-lected.The indicators such as PPV,SVV and cardiac index were recorded at the tidal volume of 6 mL/kg PBW,1 min after tidal volume challenge(tidal volume instantly increased to 8 mL/kg PBW),the tidal volume re-reduced to 6 mL/kg PBW,and after fluid bolus(FB),respectively.The cardiac index increase(ΔCI)≥15％served as the volumetric responsiveness positive when the tidal volume was re-reduced to 6 mL/kg PBW and after giving FB.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of PPV,SVV and their changing values for the volumetric responsiveness after the tidal volume increase from 6 mL/kg to 8 mL/kg PBW.Results A total of 42 measurements were performed in 23 patients.Among them,24 set of measurements were volumetric responsiveness positive(group R),and 18 set of measurements were volumetric responsiveness negative(group NR).The absolute values(ΔPPV6-8,ΔSVV6-8)and percentage(％ΔPPV6-8,％ΔSVV6-8)of PPV and SVV in tidal volume increase from 6 mL/kg to 8 mL/kg PBW had statisti-cal differences between the two groups(P＜0.05).ΔPPV6-8 and ΔSVV6-8 could predict the volumetric respon-siveness in the patients with ARDS.The area under the ROC curve(AUC)and its 95％CI were 0.92(0.84-1.00)and 0.90(0.81-0.99),and the optimal cut off values were 2.5％and 3.5％,respectively.When the tid-al volume was 6 mL/kg PBW,the PPV,SVV and central venous pressure(CVP)could not effectively predict the volumetric responsiveness in the patients with ARDS.Conclusion The efficiency of PPV or SVV changing values after tidal volume challenge for predicting the volumetric responsiveness of ARDS patients during low tidal volume ventilation is superior to PPV and SVV.

OBJECTIVE To identify and classify the chemical components and components absorbed into blood of Sishen Pills u-sing ultra-high performance liquid chromatography-quadrupole-orbitrap high resolution mass spectrometry.METHODS SD rats were divided into blank group and drug administration group.The rats in drug administration group were given water extract of Sishen Pills formula intragastrically,and blank and drug-containing plasma were collected respectively.A Hypersil GOLD VANQUISH column(2.1 mm×100 mm,1.9 μm)was used,with 0.1%formic acid water acetonitrile as the mobile phase,gradient elution,volume flow rate of 0.3 mL·min-1,and column temperature of 35℃.Electrospray ion source(ESI)with positive and negative ion scanning mode was used for chromatographic separation and mass spectrometry data acquisition.The chemical components of Sishen Pills were identi-fied by comparing the exact molecular mass,fragment ion information and relative retention time with the map of reference substance,matching with the self-established database and combining with literature reports.On this basis,the components absorbed into blood of Sishen Pills were analyzed by comparing the blank plasma and drug-containing plasma.RESULTS A total of 181 chemical compo-nents were identified from Sishen Pills,mainly including flavonoids,alkaloids,lignans and other components.A total of 49 prototype blood components were identified from the plasma samples,mainly including flavonoids,alkaloids and other components.CONCLU-SION A variety of chemical components in Sishen Pills and drug-containing plasma are comprehensively,accurately and quickly i-dentified,and all of them are assigned to the various medicinal materials in the prescription.This study provides reference for the qual-ity control,basic research on medicinal effect materials and clinical application of Sishen Pills.

Objective:To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis.Methods:This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924 th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results:Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m 2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions:The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.