OBJECTIVE To establish a method for simultaneous determination of 7 anti-tumor drugs （irinotecan， capecitabine， paclitaxel， docetaxel， tamoxifen， letrozole and methotrexate） in human plasma and apply it to the clinic. METHODS After precipitating with a methanol-acetonitrile mixture （1∶ 1， V/V） containing 0.1% formic acid， liquid chromatography-tandem mass spectrometry （LC-MS/MS） was used to determine the plasma concentration， using deuterium isotopes of each analyte as internal standards. The chromatography was performed on the Agilent Eclipse Plus C18 column with a gradient elution of water （containing 0.1% formic acid+0.04% 5 mmol/L ammonium formate） as mobile phase A and acetonitrile （containing 0.1% formic acid） as mobile phase B. The flow rate was 0.6 mL/min， and the column temperature was set at 40 ℃ . The sample size was 10 μL， and the analysis lasted for 5.5 min. Electrospray ionization was used in positive and negative ion mode， and multiple reaction monitoring mode was used. The ion pairs used for quantitative analysis were m/z 587.1→167.1 （irinotecan）， m/z 360.1→244.1 （capecitabine）， m/z 876.4→308.0 （paclitaxel）， m/z 830.3→304.2 （docetaxel）， m/z 372.1→129.1 （tamoxifen）， m/z 284.1→242.1 （letrozole）， and m/z 455.0→ 308.0 （methotrexate）. A total of 97 patients with malignant tumors in our hospital were selected to measure the plasma concentrations of 7 anti-tumor drugs using the above method. RESULTS The linear ranges of irinotecan， capecitabine， paclitaxel， docetaxel， tamoxifen， letrozole and methotrexate were 2-1 000 ng/mL （r＝0.994 3）， 20-10 000 ng/mL （r＝0.997 5）， 2-1 000 ng/mL （r＝0.997 9）， 1-500 ng/mL （r＝0.995 8）， 1-500 ng/mL （r＝0.995 2）， 1-500 ng/mL （r＝0.996 4）， 10-5 000 （r＝0.997 7）， respectively. The quantitative lower limits were 2， 20， 2， 1， 1， 1 and 10 ng/mL； RSDs of intra-assay precision were 0.08%-14.86% （n＝6）. RSDs of inter-batch precision were 1.51%-11.55% （n＝3）， and the accuracies were 89.17%-114.93% （n＝6）. The matrix effects ranged from 89.89%-119.74% （n＝6）. RSDs of the stability tests were 1.98%-14.88% （n＝6）. The results of E-mail：hangpengzhou@163.com clinical application showed， the average plasma concentrations of irinotecan， capecitabine， paclitaxel and docetaxel were 704.09， 909.40， 36.45， 150.43 ng/mL， respectively. The values of the coefficient of variation were 25.24%， 62.65%， 122.69%， and 92.27%. CONCLUSIONS The established LC-MS/MS method is simple and rapid， and can be used for the simultaneous determination of 7 commonly used anti-tumor drugs in the plasma of patients with malignancy.

Chronic heart failure （CHF） is the final stage of cardiovascular diseases. It is a complex syndrome， with dyspnea and edema as the main clinical manifestations， and it is characterized by complex disease conditions， difficult cure， and high mortality. Ferroptosis， a new type of programmed cell death， is different from other types of programmed cell death. Ferroptosis is iron-dependent， accompanied by lipid peroxide accumulation and mitochondrial shrinkage， becoming a hot research topic. Studies have confirmed that ferroptosis plays a key role in the occurrence and development of CHF. The regulation of ferroptosis may become a potential target for the treatment of CHF in the future. The theory of Qi deficiency and stagnation refers to the pathological state of original Qi deficiency and abnormal transportation and distribution of Qi， blood， and body fluid， which has guiding significance for revealing the pathogenesis evolution of some chronic diseases. We believe that Qi deficiency and stagnation is a summary of the pathogenesis of ferroptosis in CHF. Deficiency of Qi （heart Qi） is the root cause of CHF， and stagnation （phlegm turbidity and blood stasis） is the branch of this disease. The two influence each other in a vicious circle to promote the development of this disease. Traditional Chinese medicine （TCM） plays an important role in the treatment of CHF， improving the prognosis and quality of life of CHF patients. This paper explores the correlation between the theory of Qi deficiency and stagnation and the mechanism of ferroptosis in CHF. Furthermore， this paper reviews the mechanism of Chinese medicines and compound prescriptions in preventing and treating CHF by regulating ferroptosis according to the principles of replenishing Qi and dredging to remove stagnation， aiming to provide new ideas and methods for the treatment of CHF with TCM.

Background Under the background of global warming, research on association between ambient temperature and risk of injury is needed. Objective To examine the effect of temperature on injury in Bao'an district, Shenzhen and identify the sensitive population, thereby providing a scientific basis for formulating prevention and control strategies and measures of injury. Methods The injury reports from the Injury Surveillance System and the meteorological data of Bao'an District between 2018 to 2022 were collected. The meteorological data were sourced from the fifth generation of the European Centre for Medium-Range Weather Forecasts (ECMWF) land reanalysis data. Based on time-stratified case-crossover design, conditional logistic regression combined with distributed lag nonlinear model was used to evaluate the exposure-response association between ambient temperature and injury. The stratified analyses were further conducted by gender, age, and causes of injury. Results A total of 156205 injury cases were collected from the injury surveillance sentinel hospitals in Bao'an District of Shenzhen from 2018 to 2022, and the median of daily average temperature during the same period was 20.0 ℃. The exposure-response curve showed that the risk of injury was positively correlated with temperature. The linearized analysis revealed that each 1°C increase in temperature was associated with a 1.05% (95%CI: 0.68%, 1.42%) rise in injury risk (ER). Notably, the effect was greater in females (ER=1.31%, 95%CI: 0.67%, 1.94%) than males (ER=0.92%, 95%CI: 0.47%, 1.37%). Among age groups, adults ＞60 years faced the highest risk (ER=1.91%, 95%CI: −0.36%, 4.24%). The top three temperature-associated injury risks were sharp instrument injuries (ER=2.19%, 95%CI: 1.16%, 3.22%), animal injuries (ER=1.71%, 95%CI: 0.86%, 2.56%), and blunt injuries (ER=071%, 95%CI: −0.08%, 1.51%). The impact of temperature on unintentional injuries (ER=1.11%, 95%CI: 0.72%, 1.49%) was higher than that on intentional injuries (ER=0.43%, 95%CI: −0.85%, 1.72%). Severe injuries (ER=2.20%, 95%CI: −3.09%, 7.77%) were more affected by temperature than mild injuries (ER=1.00%, 95%CI: 0.58%, 1.43%) and moderate injuries (ER=1.15%, 95%CI: 0.42%, 1.89%). Conclusion The increase in ambient temperature associates with injury occurrence, and the impact of temperature exhibits obvious heterogeneity among different populations, indicating that targeted intervention measures should be taken for different populations and types of injuries.

Guided by the theory of turbid pathogen disturbing clarity， this paper holds that the pathogenesis of otolith disorders involves the failure of clear yang to ascend and the internal generation of phlegm-turbidity as the initiating factors. The clinical manifestations are characterized by the intermingling of phlegm and fluid， as well as the disturbance between turbid and clear substances， while the root lies in spleen-kidney deficiency and depletion of primordial qi. Treatment strategies are formulated according to the different stages of the disease： in the acute phase， therapy focuses on warming and resolving phlegm-fluid retention， using a modified combination of Linggui Zhugan Decoction （苓桂术甘汤） and Zexie Decoction （泽泻汤）； in the residual phase， the approach shifts to tonifying qi and uplifting clear yang， with a modified combination of Shengxian Decoction （升陷汤） and Shengmai Power （生脉散）； in the consolidation phase， therapy aims to tonify the kidney and replenish essence， employing a modified version of Qiju Dihuang Pill （杞菊地黄丸）.

Emergence agitation （EA） is a common complication after general anesthesia， especially in children and adolescents. Remifentanil， as a short-acting μ-receptor agonist， has become an important drug for the prevention and treatment of EA due to its rapid recovery and low risk of respiratory depression. This article reviews the mechanism of action and clinical research progress of remifentanil in the prevention and treatment of EA. Its mechanism of action involves the inhibition of pain signals mediated by traditional μ-receptor activation and potential new mechanism based on neural-endocrine-immune network， including regulation of microglial inflammatory pathways， and the modulation of cytokines and chemokines，etc. Clinical studies have shown that remifentanil can significantly shorten the recovery time， reduce the incidence of EA， and further optimize the analgesic effect and recovery quality by combining with other drugs （such as local anesthetics， sedatives， and opioid drugs）. Future research should further explore the mechanism of action of remifentanil， optimize clinical treatment strategies， and conduct large- scale clinical trials to standardize the drug use plan， while paying attention to its long-term effects and the development of multimodal treatment plans to promote the further development of EA prevention and treatment plans.

Objective To explore the efficiency improvement in segmenting neural network with the application of Transformer + U-Net artificial intelligence (AI) and modeling with the application of Python scripts in three-dimensional (3D) printing brachytherapy. Methods A Transformer + U-Net AI neural network model was constructed, and Adam optimizer was used to ensure rapid gradient descent. Computed tomography or magnetic resonance imaging data of patients were standardized and processed as self-made data sets. The training set was used to train AI and the optimal result weight parameters were saved. The test set was used to evaluate the AI ability. Python programming language was used to write an automated script to obtain the output segmentation image and convert it to the STL file for import. The source applicator and needle could be automatically modeled. The time of automatic segmentation and modeling and the time of manual segmentation and modeling were entered by two people, and the difference was verified by paired t-test. Results Dice similarity coefficient (DSC), mean intersection over union (MIOU), and Hausdorff distance (HD95) were used for evaluation. DSC was 0.9341, MIOU was 0.8762, and mean HD95 was 2.516. The mean time of manual segmentation was 1187 s, and the mean time of AI segmentation was 145 s (P < 0.01). The mean time of manual modeling was 321 s, and the mean time of modeling with Python automated scripts was 18 s (P < 0.01). Conclusion The application of Transformer + U-Net automatic segmentation and Python automated scripts can effectively improve work efficiency in the 3D printing brachytherapy for cervical cancer.

Background::Growth retardation is a common complication of chronic kidney disease in children, which can be partially relieved after renal transplantation. This study aimed to develop and validate a predictive model for growth patterns of children with end-stage renal disease (ESRD) after kidney transplantation using machine learning algorithms based on genomic and clinical variables.Methods::A retrospective cohort of 110 children who received kidney transplants between May 2013 and September 2021 at the First Affiliated Hospital of Zhengzhou University were recruited for whole-exome sequencing (WES), and another 39 children who underwent transplant from October 2021 to March 2022 were enrolled for external validation. Based on previous studies, we comprehensively collected 729 height-related single-nucleotide polymorphisms (SNPs) in exon regions. Seven machine learning algorithms and 10-fold cross-validation analysis were employed for model construction.Results::The 110 children were divided into two groups according to change in height-for-age Z-score. After univariate analysis, age and 19 SNPs were incorporated into the model and validated. The random forest model showed the best prediction efficacy with an accuracy of 0.8125 and an area under curve (AUC) of 0.924, and also performed well in the external validation cohort (accuracy, 0.7949; AUC, 0.796). Conclusions::A model with good performance for predicting post-transplant growth patterns in children based on SNPs and clinical variables was constructed and validated using machine learning algorithms. The model is expected to guide clinicians in the management of children after renal transplantation, including the use of growth hormone, glucocorticoid withdrawal, and nutritional supplementation, to alleviate growth retardation in children with ESRD.

Objective:To explore the clinical characteristics of pediatric kidney transplant recipients reinfected with SARS-CoV-2.Method:The relevant clinical data were retrospectively reviewed for 191 pediatric kidney transplant recipients at a single center. Based upon whether or not there was a reinfection of SARS-CoV-2, they were assigned into two groups of single infection (group A, 127 cases) and reinfection (group B, 64 cases). Baseline profiles, clinical symptoms, diagnostic and therapeutic strategies, markers of disease progression, immune status, respiratory support modalities, comorbidities and transplantation-related data were collected for comparing the inter-group differences during primary infection and between two infections in reinfected group.Result:As compared with group A, group B recipients had a higher proportion of age <12 years (71.9% vs 54.3%) ,unvaccinated (81.2% vs 66.1%) and such symptoms as high fever (34.4% vs 12.6% ), dry cough (43.8% vs 23.6% ) and chest tightness (14.1% vs 3.9 %) during primary infection (all P<0.05). During primary infection, the levels of IL-6 and CRP were higher in group B than in group A and inter-group difference was statistically significant (both P<0.01). The levels of IL-6 ( P<0.01), CRP ( P<0.01) and PCT ( P= 0.023) were lower in group B during reinfection than those during primary infection and the difference was statistically significant. During primary infection, the counts of CD3+, CD4+, CD8+, NK and B lymphocyte of group B were lower than those of group A. And inter-group differences were statistically significant (all P<0.01). During reinfection, the levels of CD3+, CD4+, CD8+, NK and B lymphocyte counts of group B spiked as compared with those of group A during primary infection and the differences were statistically significant (all P<0.01). The levels of SCr and UA in group B differed insignificantly before and after primary infection with SARS-CoV-2. However, the differences before and after reinfection were statistically significant (both P<0.01) . Conclusion:Symptomatic and immunocompromised pediatric KT recipients during primary infection with SARS-CoV-2 are more prone to reinfection during subsequent epidemics. Though mildly symptomatic, reinfection may exacerbate impairments of graft kidney function in pediatric KT recipients.

Objective:To explore the characteristic pathological manifestations of non-HLA antibodies after kidney transplantation (KT) and examine the differences of MFT values of non-HLA antibodies in different pathological manifestations.Methods:The study was conducted on KT recipients at the First Affiliated Hospital of Zhengzhou University from February 2021 to June 2023 with unexplained elevated serum creatinine. Patients undergoing pathological puncture and concurrent HLA antibody testing were included, focusing on those with DSA (MFI>4 000) and non-HLA antibody negativity. According to the detection results of non-HLA and HLA antibodies, they were assigned into two groups of non-HLA antibody positive (45 cases) and HLA-DSA positive (28 cases). Both non-HLA and HLA antibodies were detected by luminex single antigen microbeads, χ2, t or Mann-Whitney U nonparametric tests were utilized for examining the inter-group differences in pathological manifestations. The recipients with positive non-HLA antibodies were grouped according to the differential pathological features[microvascular inflammation group (22 cases) and non-microvascular inflammation group (23 cases), interstitial fibrosis group (39 cases) and non-interstitial fibrosis (9 cases) ]. MFI values of non-HLA antibodies were standardized and heat map was generated with R language ComplexHeatmap package. The differences of response values of non-HLA antibodies with different pathological manifestations were examined by rank-sum test. Results:The positive rates of microvascular inflammation were 48.9% (22/45) and 82.1% (23/28) in HLA-DSA positive and non-HLA antibody positive groups with statistical significance ( χ2=8.073, P=0.006). The positive rates of interstitial fibrosis in two groups were 80.8% (36/45) and 53.6% (15/28) and the difference was statistically significant ( χ2=5.726, P=0.021). The relative levels of anti-arachnotoxin receptor 1 (Latrophilin 1, LPHN1), keratin 8 (KRT8), keratin 18 (KRT18) and Sjogren's syndrome antigen B (SSB) were higher in microvascular inflammation group than those in non-microvascular inflammation group. The differences were statistically significant [559.50 (262.00, 801.25) vs 285.00 (183.00, 460.00), P=0.024; 504.50 (369.5, 725.25) vs 317.00 (231.50, 458.00), P=0.014; 672.50 (454.50, 969.50) vs 399.00 (246.50, 772.50), P=0.030; 967.50 (482.00, 2 066.50) vs 399.00 (246.50, 772.50), P=0.033]. The relative levels of anti-cyclic citrullinate peptide (CCP), colony-stimulating factor 2 (CSF2), intercellular adhesion molecule 1 (ICAM1) and collagen Ⅳ antibody were higher in interstitial fibrosis group than those in non-interstitial fibrosis group with statistical significance [100.00 (79.88, 167.50) vs 64.50 (37.00, 89.00), P=0.016; 146.25 (93.38, 244.75) vs 87.00 (66.00, 105.00), P=0.041; 132.50 (106.38, 229.50) vs 95.00 (55.00, 125.00), P=0.037; 432.50 (280.75, 653.75) vs 208.00 (192.00, 301.00), P=0.028]. Conclusions:As compared with HLA-DSA, the characteristic pathological manifestations of non-HLA antibodies post-KT include a lower incidence of microvascular inflammation and a higher incidence of interstitial fibrosis. For non-HLA antibody response values of characteristic pathological manifestations, the expressions of different non-HLA antibodies vary statistically.

[Objective]To explore the academic thought of erectile dysfunction in Fengshi Jinnang Milu written by Zhejiang physician FENG Zhaozhang,and to provide reference for clinical practice of erectile dysfunction.[Methods]It takes the chapter of"Fangmai Yangwei"in Fengshi Jinnang Milu as the main research object,combines with other chapters in the book to systematically sort out the academic thought characteristics of the book in the treatment of erectile dysfunction.[Results]FENG praised the theory of"Mingmen",and paid special attention to the role of Yin and Yang,water and fire in the occurrence and development of diseases.He discussed the etiology and pathogenesis of erectile dysfunction in detail in the chapter of"Fangmai Yangwei".He believed that the damage of the five internal organs was the precursor of erectile dysfunction,and the imbalance of Yin and Yang,stagnation of fire caused by various reasons could lead to the occurrence of this disease.In the treatment,many prescriptions were listed,focusing on tonifying Yin and Yang,and most of them were pills.At the same time,the drug delivery was mainly based on wine,ginger soup,salt soup,etc.It also had the method of taking different decoctions at different times and the method of taking medicine by solar terms,which was quite distinctive.[Conclusion]FENG's discussion on the etiology,pathogenesis,diagnosis and treatment of erectile dysfunction is quite detailed,and his understanding is distinctive.The academic thought of impotence in his book also has practical significance for the treatment of erectile dysfunction today.