OBJECTIVE To explore the relationship between severe cardiotoxicity caused by oxaliplatin combined with capecitabine and genetic polymorphism， thereby providing references for safe clinical medication use. METHODS Clinical pharmacists conducted a correlation analysis on a case of severe cardiotoxicity in a rectal cancer patient at Qilu Hospital of Shandong University following first-time treatment with standard doses of oxaliplatin combined with capecitabine. Case reports of cardiotoxicity caused by oxaliplatin and capecitabine were retrieved from the Chinese and English databases such as CNKI and PubMed.Basic patient information， drug treatment plan， and cardiotoxic manifestations were extracted and summarized. Combined with the patient’s genetic polymorphism test results related to the metabolism and excretion of platinum-based and fluorouracil drugs， potential mechanisms and prevention strategies for cardiotoxicity induced by oxaliplatin and capecitabine were discussed. RESULTS The patient exhibited homozygous mutations in ABCB1 C3435T and G2677T/A， a heterozygous mutation in MTHFR A1298C， and a heterozygous mutation in GSTP1 A105G， indicating impaired metabolism and excretion of oxaliplatin and capecitabine. The pharmacists recommended discontinuing oxaliplatin and reducing capecitabine to 50% of the original dose for subsequent treatment. The physicians adopted this advice， and the patient experienced no further severe adverse reactions with stable disease progression. CONCLUSIONS Oxaliplatin and capecitabine may cause severe cardiotoxicity. Medical institutions with adequate resources should perform genetic polymorphism test related to drug metabolism and excretion in patients prescribed these agents. For patients with multiple gene mutations， close monitoring and appropriate dose reductions are recommended to ensure medication safety and efficacy.

The deficiency in immunogenicity and the presence of immunosuppression within the tumor microenvironment significantly hindered the efficacy of immunotherapy. Consequently, a nanoformulation containing metal sulfide of FeS and GSDMD plasmid (NP_FeS/GD) had been developed to effectively augment antitumor immune responses through dual activation of immunogenic PANoptosis and ferroptosis, as well as reprogramming immunosuppressive effects via H₂S amplification. The bioactive NP_FeS/GD exhibited controlled release of GSDMD plasmid, H₂S, and Fe²⁺ in response to the tumor microenvironment. Fe²⁺, H₂S, and the expression of GSDMD protein could effectively elicit highly immunogenic PANoptosis and ferroptosis. Furthermore, releasing H₂S could mitigate the overexpression of indoleamine 2,3-dioxygenase1 (IDO1) induced by immunogenic PANoptotic and ferroptotic cell death and disrupt the activity of IDO1. Consequently, NP_FeS/GD effectively triggered the antitumor innate and adaptive immune responses through induction of PANoptotic and ferroptotic cell death and reshaped the tumor immunosuppressive microenvironment to enhance antitumor immunotherapy for metastasis inhibition. This study unveiled the significant potential of immunogenic PANoptosis and ferroptosis in H₂S gas therapy for enhancing tumor immunotherapy, offering novel insights and ideas for the rational design of nanomedicine to enhance tumor immunogenicity while reprogramming the tumor immunosuppressive microenvironment.

Objective:To investigate the association of urinary cadmium level with body mass index (BMI) and body circumferences among the older adults over 65 years old in 9 longevity areas of China.Methods:Subjects were older adults over 65 years old from the Healthy Aging and Biomarkers Cohort Study (HABCS) between 2017 and 2018 conducted in 9 longevity areas in China. A total of 1 968 older adults were included in this study. Information including socio-demographic characteristics, lifestyles, diet intake, and health status was collected by using questionnaires and physical examinations. Urine samples were collected to detect urinary cadmium and creatinine levels. Body circumferences included waist circumference, hip circumference and calf circumference. Subjects were divided into three groups (low:<0.77 μg/g·creatinine, middle:0.77-1.69 μg/g·creatinine, high:≥1.69 μg/g·creatinine) by tertiles of creatinine-adjusted urinary cadmium concentration. Multiple linear regression models were used to analyze the association of creatinine-adjusted urinary cadmium level with BMI and body circumferences. The dose-response relationship of creatinine-adjusted urinary cadmium concentration with BMI and body circumferences was analyzed by using restrictive cubic splines fitting multiple linear regression model.Results:The mean age of subjects was (83.34±11.14) years old. The median (Q1, Q3) concentration of creatinine-adjusted urinary cadmium was 1.13 (0.63, 2.09) μg/g·creatinine, and the BMI was (22.70±3.82) kg/m 2. The mean values of waist circumference, hip circumference, and calf circumference were (85.42±10.68) cm, (92.67±8.90) cm, and (31.08±4.76) cm, respectively. After controlling confounding factors, the results of the multiple linear regression model showed that for each increment of 1 μg/g·creatinine in creatinine-adjusted urinary cadmium, the change of BMI, waist circumference, hip circumference, and calf circumference in the high-level group was -0.28 (-0.37, -0.19) kg/m 2, -0.74 (-0.96, -0.52) cm, -0.78 (-0.96, -0.61) cm, and -0.20 (-0.30, -0.11) cm, respectively. The restrictive cubic splines curve showed a negative nonlinear association of creatinine-adjusted urinary cadmium with BMI ( Pnonlinear<0.001) and negative linear associations of creatinine-adjusted urinary cadmium with waist circumference ( Plinear<0.001), hip circumference ( Plinear<0.001), and calf circumference ( Plinear<0.001). Conclusion:Urinary cadmium level is significantly associated with decreased BMI, waist circumference, hip circumference and calf circumference among older adults over 65 years old in 9 longevity areas of China.

Acute leukemias caused by mixed lineage leukemia(MLL)gene rearrangements(MLL-r)are characterized by high invasiveness and a poor prognosis,with few specific treatment options available.MLL protein is essential in embryonic development and hematopoiesis.It exhibits histone methyltransferase activity and can interact with various proteins through its functional domains,thus regulating downstream target gene expression through epigenetic modifications.MLL-r leads to the formation of MLL fusion proteins(MLL-FPs),in which the C-terminal is replaced by fusion partner proteins;over 100 such partner proteins have been identified to date.In numerous studies of the molecular mechanism,Menin serves as an important cofacter in the leukemogenesis of MLL-FPs and participates in forming the key complex when interacting with the N terminal of MLL protein,resulting in the disregulation of certain targeted genes,which makes the development of Menin-MLL inhibitors theoretically possible.To date,several small molecules have been identified that inhibit Menin-MLL interaction,including thienopyrimidine derivatives,piperidine derivatives,pyrimidine derivatives,and macrocyclic mimic peptides.Based on these prototypes,at least seven drugs are currently undergoing clinical evaluation,with some promising preliminary data regarding safety,tolerability,and efficacy.This review summarizes the structure and function of MLL,the mechanism of the occurrence of MLL-r leukemia,and current Menin-MLL inhibitors tested in MLL-r leukemia.

ObjectiveTo evaluate the effectiveness of Lutongning granules in the treatment of trigeminal neuralgia in animal models and study its mechanism of action， so as to provide laboratory data support for the clinical application of Lutongning granules and precise treatment. MethodMale SD rats were randomly divided into normal group， model group， carbamazepine group （0.06 g·kg^-1·d^-1）， high-dose Lutongning group （2.70 g·kg^-1·d^-1）， and low-dose Lutongning group （1.35 g·kg^-1·d^-1） according to the stratified basic mechanical pain thresholds， with 10 rats in each group. A trigeminal neuralgia model of rats was prepared by injecting 30% talc suspension into the infraorbital foramen area of the rat. The drug groups were administered 10 mL·kg^-1 of drugs by gavage after 2 h of modeling. The normal group and the model group were administered distilled water by gavage under the same conditions once a day for 10 consecutive days. Von Frey brushes were used to determine the mechanical pain threshold of rats. A fully automated blood and body fluid analyzer was employed to detect the blood routine of rats. Hematoxylin and eosin （HE） staining was utilized to detect the pathological changes in the trigeminal ganglion and medulla oblongata tissue. Transmission electron microscopy was used to scan the ultrastructure of the medulla oblongata tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of inflammatory factors interleukin （IL）-1， IL-6， IL-8， tumor necrosis factor （TNF）-α， neuropeptide substance P， and β-endorphins （β-EP） in the serum of rats， and Western blot was used to detect the protein expression levels of IL-1β， purinergic receptor P2X7 （P2X7R）， and phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）. ResultCompared with that in the normal group， the pain threshold of rats in the model group was significantly lower （P<0.01）. The absolute value of neutrophils （NEUT#） and the percentage of neutrophils （NEUT） were significantly improved， and the percentage of lymphocytes （LYMPH） was significantly reduced （P<0.01）. The serum levels of IL-1， IL-6， IL-8， and TNF-α were significantly increased （P<0.01）. SP content in brain tissue was significantly increased， and β-EP content was significantly decreased （P<0.01）. The relative protein expression of IL-1β， P2X7R， and p-p38 MAPK was significantly increased （P<0.05）. HE staining and transmission electron microscopy results of medulla oblongata tissue revealed neuronal degeneration， mild proliferation of microglial cells， reduction in the number of myelinated nerves， and obvious demyelination. The trigeminal nerve fibers of rats were disarranged， and some nerve fibers showed vacuolization. Axons were swollen， and Schwann cells proliferated. Demyelination was observed. Compared with the model group， each administration group significantly increased the pain threshold of rats （P<0.05， P<0.01）， reduced NEUT# and NEUT， and elevated LYMPH （P<0.05， P<0.01）. The administration group significantly decreased the levels of IL-1， IL-6， IL-8， and TNF-α in serum and SP in brain tissue （P<0.01） and increased the level of β-EP （P<0.01）. They significantly down-regulated the protein expression of IL-1β， P2X7R， and p-p38 MAPK（P<0.05， P<0.01） and significantly ameliorated the pathological changes in medulla oblongata tissue and trigeminal nerves of rats. ConclusionLutongning Granules had significant therapeutic effects on trigeminal neuralgia induced by injection of talc into the infraorbital foramen of model rats， and the mechanism may be related to amelioration of P2X7R-mediated neuroinflammation and inhibition of demyelination of myelinated nerves.

OBJECTIVE To optimize the steaming and processing technology of wine-steamed Taxillus chinensis， and to characterize its quality. METHODS Using the content of avicularin， quercitrin， quercetin and appearance traits as evaluation indicators， the analytic hierarchy process （AHP）-entropy weight method was used to determine the weights of each indicator， and the comprehensive scores of those indicators were used as response values. Box-Behnken response surface method was used to investigate the effects of solid-liquid ratio （g/mL）， soaking time， and steaming time on the processing technology of wine-steamed T. chinensis， optimize the best processing technology， and verify it. Fifteen batches of T. chinensis decoction pieces from different origins were used to prepare wine-steamed T. chinensis using the best processing technology， and their qualities were characterized. RESULTS The optimal processing technology for wine-steamed T. chinensis was to take 100 g of T. chinensis decoction pieces， add 20 mL of yellow wine， seal and moisten for 2 h， steam at normal pressure for 1 h， take out and dry at 50 ℃. The surface of wine-steamed T. chinensis prepared by the optimal processing technology was reddish brown or brownish， and its powder was dark brown， with a hard or brittle texture that was easy to break， and had a slight aroma of alcohol， and an astringent taste. Results of microscopic and thin-layer identification for the stem cross-section of wine-steamed T. chinensis were the same as those of raw T. chinensis. The contents of moisture， total ash and acid-insoluble ash were 3.92%-8.75%， 2.27%-5.08%， and 0.19%-0.82%， respectively； the contents of water-soluble extract were 11.28%-18.56%， and the contents of alcohol-soluble extract were 3.36%-8.58%； the contents of avicularin， quercitrin， and quercetin were 0.22-1.64， 0.26-2.45， and 0.01-0.38 mg/g， respectively. CONCLUSIONS This study successfully optimized the processing technology of wine-steamed T. chinensis and preliminarily characterized its quality， which can provide reference for the standardized processing and establishment of quality standards for wine-steamed T. chinensis decoction mail：wyl@sxtcm.edu.cn pieces.

OBJECTIVE To optimize the steaming and processing technology of wine-steamed Taxillus chinensis， and to characterize its quality. METHODS Using the content of avicularin， quercitrin， quercetin and appearance traits as evaluation indicators， the analytic hierarchy process （AHP）-entropy weight method was used to determine the weights of each indicator， and the comprehensive scores of those indicators were used as response values. Box-Behnken response surface method was used to investigate the effects of solid-liquid ratio （g/mL）， soaking time， and steaming time on the processing technology of wine-steamed T. chinensis， optimize the best processing technology， and verify it. Fifteen batches of T. chinensis decoction pieces from different origins were used to prepare wine-steamed T. chinensis using the best processing technology， and their qualities were characterized. RESULTS The optimal processing technology for wine-steamed T. chinensis was to take 100 g of T. chinensis decoction pieces， add 20 mL of yellow wine， seal and moisten for 2 h， steam at normal pressure for 1 h， take out and dry at 50 ℃. The surface of wine-steamed T. chinensis prepared by the optimal processing technology was reddish brown or brownish， and its powder was dark brown， with a hard or brittle texture that was easy to break， and had a slight aroma of alcohol， and an astringent taste. Results of microscopic and thin-layer identification for the stem cross-section of wine-steamed T. chinensis were the same as those of raw T. chinensis. The contents of moisture， total ash and acid-insoluble ash were 3.92%-8.75%， 2.27%-5.08%， and 0.19%-0.82%， respectively； the contents of water-soluble extract were 11.28%-18.56%， and the contents of alcohol-soluble extract were 3.36%-8.58%； the contents of avicularin， quercitrin， and quercetin were 0.22-1.64， 0.26-2.45， and 0.01-0.38 mg/g， respectively. CONCLUSIONS This study successfully optimized the processing technology of wine-steamed T. chinensis and preliminarily characterized its quality， which can provide reference for the standardized processing and establishment of quality standards for wine-steamed T. chinensis decoction mail：wyl@sxtcm.edu.cn pieces.

Postoperative pain seriously affects the recovery process of patients, resulting in prolonged hospital stay and increased care costs. Appropriate application of patient-controlled analgesia devices can effectively relieve perioperative acute pain. In 1994 patient-controlled analgesia began to be used in Peking Union Medical College Hospital, and the Acute Pain Service Working Group was established in 2004. With the cooperation of anesthesiologists and specialist nurses, the group jointly has implemented the whole process and standardized management based on patient-controlled analgesia, and constantly improved and innovated working methods, laying a solid foundation for the development of postoperative pain management. This paper systematically reviews and summarizes the work from the aspects of clinical focus, nursing management experience, promotion and dissemination of pain treatment concepts, and development of acute pain service model under the new situation, with the hope of providing valuable reference for comprehensively strengthening pain management in the process of diagnosis and treatment, and enhancing patients' satisfaction with perioperative analgesia services.

Objective To analyze the current status,research hotspots and development trends in the field of immune responses in the microenvironment after spinal cord injury(SCI). Methods Literatrues about immune responses in the microenvironment after SCI were searched from CNKI and the Web of Science Core Collection,from inception to March,2024.VOSviewer and CiteSpace were used to conduct a vi-sual analysis of authors,countries,institutions,journals,co-cited references and keywords. Results A total of 152 Chinese and 455 English studies were included.The number of publications increased annually,and China and the United States were leading research efforts in this field.In the Chinese literature,Zhu Yue was the most prolific author,and China Medical University was the leading institution.In the English literature,Phil-lip Popovich was the most prolific and highly cited author,and Ohio State University was the leading institution.Journal of Neuroscience and Experimental Neurology were identified as key journals.The research hotspots in both languages focused on immune activation,inflammatory response and functional recovery.Researches on stem cell transplantation,macrophage and traditional Chinese medicine were particularly prominent in the regu-lation of immune responses after SCI. Conclusion Immune responses in the microenvironment have emerged as a central focus in SCI research.The emphasis of current researches is shifting from mechanistic exploration to the investigation of immunomodulatory strate-gies,with several cutting-edge technologies showing significant potential in this regard.Moving forward,increas-ing collaboration across regions and institutions are essential to promote information sharing,accelerate scientific progress,and facilitate clinical translation,ultimately enhance patient rehabilitation outcomes.