Doxorubicin (DOX)-induced cardiotoxicity and sepsis-induced myocardial injury (SIMI) represent significant clinical challenges in patients undergoing chemotherapy, sharing a common pathological basis of oxidative stress and mitochondrial dysfunction. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has recently been shown to play a critical role in DOX-induced cardiotoxicity and lipopolysaccharide (LPS)-induced SIMI. This article systematically reviews the mechanisms underlying myocardial injury caused by DOX and sepsis, identifying ferroptosis as a central common pathway. DOX triggers a burst of reactive oxygen species within mitochondria and inhibits glutathione peroxidase 4 (GPX4) activity through redox cycling of its quinone group and high-affinity accumulation in mitochondrial cardiolipin. LPS, by activating pattern recognition receptors and related inflammatory signaling pathways, provokes a cytokine storm and mitochondrial dysfunction. Both can disrupt the core regulatory axis of cysteine-glutathione (GSH)-GPX4, synergistically promoting ferroptosis in cardiomyocytes. Moreover, epigenetic regulation plays a key role in DOX- and LPS-induced cardiomyocyte ferroptosis and may serve as a promising therapeutic target. A deeper understanding of the ferroptosis mechanism and its epigenetic regulatory network in the synergistic injury induced by DOX and sepsis is of great importance for developing novel strategies to mitigate chemotherapy-related cardiotoxicity and improve outcomes in cancer patients with concurrent infections.

ObjectiveTo identify potential influencing factors of urate crystal deposition at ankle/foot in patients with hyperuricemia （HUA）， and to analyze the predictive value of inflammatory indicators for urate crystal deposition in patients with different traditional Chinese medicine （TCM） syndromes， so as to provide potential reference for clinical risk assessment and individualized TCM intervention. MethodsA retrospective study was carried out with the enrollment of 231 HUA patients from The Third Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine between January 2021 and December 2024. The enrolled patients were further divided into a crystal deposition-positive group （143 cases） and a crystal deposition-negative group （88 cases） according to the results of dual-energy computed tomography （CT）. Sociodemographic data， living habits， serum uric acid levels， and inflammatory indicators of the enrolled patients were collcted， and TCM syndrome differentiation was performed. Furthermore， univariate analysis was used to compare inter-group differences in clinical characteristics. MMultivariate Logistic regression was applied to identify the influencing factors of urate crystal deposition. In addition， the receiver operating characteristic （ROC） curves were plotted to evaluate the predictive efficacy of inflammatory indicators for crystal deposition across different TCM syndromes. ResultsThere were statistically significant inter-group differences in the proportion of males， age， body mass index， proportion of mental labor， rate of low water intake， and rate of high-sugar beverage consumption （P<0.05），whereas no significant difference in low exercise intensity was found between the two groups. Furthermore， compared with the negative group， the positive group had higher serum uric acid level， neutrophil-to-lymphocyte ratio （NLR）， and platelet-to-lymphocyte ratio （PLR）， but lower systemic immune-inflammation index （SIRI） （P<0.05）. Regarding the distribution of TCM syndromes， the positive group was dominated by the dampness-heat accumulation syndrome （55/143，38.46%）， while the negative group was mainly characterized by the phlegm-turbidity obstruction syndrome （44/88，50.00%）. Multivariate Logistic regression analysis revealed that high-sugar beverage consumption， elevated NLR， and elevated PLR were risk factors for urate crystal deposition ［odd ratio （OR） = 8.002， 5.377， 1.034， respectively； 95% CI 1.572-40.732， 2.179-13.270， 1.013-1.054，all P<0.05］， while SIRI was a protective factor （OR = 0.869， 95% CI 0.778-0.971， P<0.05）. In the positive group， patients with the dampness-heat accumulation syndrome exhibited the highest NLR， while the lowest PLR and SIRI， showing statistically significant differences with those of other syndromes （all P<0.05）. In addition， ROC curve analysis indicated that for the dampness-heat accumulation syndrome， the combined "NLR + PLR" model had an area under the curve （AUC） of 0.901 （95% CI 0.850-0.951， P<0.01）， with a sensitivity of 89.1% and a specificity of 79.5%； for the blood stasis-heat obstruction syndrome， the combined "NLR + PLR" model had an AUC of 0.880 （95% CI 0.825-0.934， P<0.01）， with a sensitivity of 100.0% and a specificity of 67.3%； for the liver-kidney Yin-deficiency syndrome， the single PLR model had an AUC of 0.842 （95% CI 0.731-0.952， P<0.01）， with a sensitivity of 83.3% and a specificity of 84.0%. ConclusionUrate crystal deposition in HUA patients exhibits intimate associations with high-sugar beverage consumption as well as elevated NLR and PLR levels. Meanwhile， TCM syndrome differentiation has potential correlation with inflammatory characteristics. The inflammatory indicator-based prediction model constructed based on TCM syndromes exhibits good predictive value.

OBJECTIVE To explore the main factors influencing the blood concentration of duloxetine， and provide a scientific basis for the individualized use of duloxetine. METHODS Retrospective analysis was conducted on 434 inpatients with depressive disorders at the First Hospital of Hebei Medical University， who were treated with duloxetine and underwent blood concentration monitoring between January 2022 and April 2024. The study examined the impact of various factors， including gender， age， body mass index （BMI）， gene phenotypes， combined medication， drug type （original/generic）， and genotyping results of gene single nucleotide polymorphism loci， on blood concentration and the concentration-to-dose （C/D） after dose adjustment. RESULTS The blood concentration of duloxetine was 76.65 （45.57， 130.31） ng/mL， and C/D was 0.96 （0.63， 1.60） ng·d/（mL·mg）. The blood concentration of duloxetine was positively correlated with the daily dose of administration （R2＝0.253 7， P＜0.001）. Blood concentration of duloxetine in 38.94% of patients exceeded the recommended range specified in the guidelines. Gender， age， BMI， combined use of CYP2D6 enzyme inhibitors， and CYP2D6 and CYP1A2 phenotypes had significant effects on C/D of duloxetine （P＜0.05）. CONCLUSIONS The patient’s age， gender， BMI， combined medication， and genetic phenotypes are closely related to the blood concentration of duloxetine.

Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

Objective To investigate the fatigue and workload status among medical students,and to explore the latent profiles of fatigue and workload and their effects on sleep and emotion.Methods A cross-sectional study design with convenience sampling was employed to distribute a comprehensive survey via mixed online and offline modes,and medical college students were enrolled as the subjects for this investigation.The general demographic data,depression,anxiety and stress scale,Pittsburgh sleep quality index,Epworth sleepiness scale,insomnia severity index,National Aeronautics and Space Administration task load index(NASA-TLX)and fatigue scale-14(FS-14)were used to investigate the basic information of the medical students,their emotions(depression,anxiety and stress),sleep(sleep quality,sleepiness and insomnia),workload and fatigue status.Based on latent profile analysis,the types of workload-fatigue profiles and differences in sleep and emotion were analyzed.Results A total of 485 medical students were enrolled,with an average age of(22.07±2.42)years.The total score of the NASA-TLX was 64.44±12.50,and the total score of the FS-14 was 7.90±3.63.Latent profile analysis identified 3 distinct workload-fatigue profiles:low workload-medium fatigue group(12.8％),medium workload-low fatigue group(32.8％),and high workload-high fatigue group(54.4％).Among these,the medium workload-low fatigue group exhibited the highest performance level(all P＜0.05),while the low workload-medium fatigue group showed the lowest effort level and performance level(all P＜0.05).The high workload-high fatigue group showed the highest task-related demand and frustration level(all P＜0.05).Regarding sleep and emotional status,the medium workload-low fatigue group had significantly better outcomes compared to the high workload-high fatigue group and the low workload-medium fatigue group(all P＜0.05).Conclusion Medical students experience a heavy workload and subjective fatigue.It is essential to appropriately adjust their workload,prioritize sleep and emotional well-being,and alleviate fatigue levels,so as to sustain personal physical and mental health.

INTRODUCTION: Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity. METHOD: Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases. RESULTS: A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P<0.05) and chemotherapy (92.8%±18.1, P<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients, of which 18 were severe. No patient receiving a third dose within 90 days of the second dose experienced severe infection. CONCLUSION This study demonstrates the benefit of early administration of the third dose among cancer patients.
Humans ; SARS-CoV-2 ; COVID-19/prevention & control* ; Treatment Outcome ; Neoplasms/drug therapy* ; Hematologic Neoplasms ; Vaccination ; RNA, Messenger ; Antibodies, Viral ; Immunogenicity, Vaccine

ObjectiveTo observe the pharmacodynamic effects of Cinnamomi Cortex on the incretin effect in the rat model of diabetes mellites （DM） induced by streptozotocin （STZ） and explore the underlying mechanism from glucagon-like peptide-1 （GLP-1） and dipeptidyl peptidase-4 （DPP-4）. MethodForty SD rats were randomly assigned into blank， model， sitagliptin （0.1 g·kg^-1）， and low- and high-dose Cinnamomi Cortex （0.45 and 0.9 g·kg^-1， respectively） groups. The DM rat model was established by a high-fat diet combined with intraperitoneal injection of 40 mg·kg^-1 STZ in other groups except the blank group. The intervention lasted for 8 weeks. The status， body weight， water intake， food intake， and fasting blood glucose （FBG） of the rats were observed and determined. Hematoxylin-eosin staining was employed to reveal the pathological changes of the pancreas， and immunohistochemistry to detect the expression of glucagon in the pancreas. Biochemical assay was employed to measure the serum levels of lipid metabolism indexes such as total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein （LDL）， and high-density lipoprotein （HDL）. Enzyme-linked immunosorbent assay was employed to determine the levels of glycosylated hemoglobin， insulin， glucagon， GLP-1， and glucose-dependent insulinotropic polypeptide （GIP） in rat serum， and Western blot to determine the protein levels of GLP-1 and DPP-4 in the pancreas. ResultAfter 8 weeks of intervention， the model group showed higher body weight， FBG， TC， TG， LDL， glycosylated hemoglobin， glucagon， insulin， and insulin resistance index and lower HDL， GLP-1， and GIP than the blank group （P<0.05， P<0.01）. The Cinnamomi Cortex groups showed lower body weight， FBG， TC， TG， LDL， glycosylated hemoglobin， glucagon， insulin， and insulin resistance index and higher HDL， GLP-1， and GIP than the model group （P<0.05， P<0.01）. The Cinnamomi Cortex groups showed recovered morphology of islet cells and no nucleus aggregation. Compared with the model group， the Cinnamomi Cortex groups showed declined levels of glucagon in the center of islet cells. Compared with the blank group， the model group showed up-regulated protein level of DPP-4 and down-regulated protein level of GLP-1 （P<0.01）. Compared with the model group， the high-dose Cinnamomi Cortex groups showed down-regulated protein level of DPP-4 and up-regulated protein level of GLP-1 （P<0.05）. ConclusionCinnamomi Cortex may reduce blood glucose and improve incretin effect to lower the blood glucose level by regulating DPP-4 and GLP-1 in DM rats.

Objective:To observe the effects of acupuncture at Houxi(SI3)and Huantiao(GB30)on the expression levels of nuclear factor kappa B(NF-κB),inducible nitric oxide synthase(iNOS),and nitric oxide(NO)of NF-κB inflammatory signaling pathway in L5 spinal nerve root of lumbar disc herniation(LDH)model rats and explore the mechanism of acupuncture in LDH treatment.Methods:Forty specific-pathogen-free healthy male Sprague-Dawley rats were randomly divided into a sham operation group,a model group,acupuncture group 1,and acupuncture group 2,with 10 rats in each group.The non-compression nucleus protrusion model was made by puncturing L4-L5 spinous process space and injecting autologous nucleus suspension.Acupuncture at bilateral Shenshu(BL23),Dachangshu(BL25),and Weizhong(BL40)was carried out in acupuncture group 1,and acupuncture at bilateral Houxi(SI3)and Huantiao(GB30)in acupuncture group 2.All rats were treated with balanced reinforcing and reducing needling manipulations,and the needles were retained for 30 min/time with one episode of needling manipulation every 10 min,once a day,14 times in total.The threshold value of paw withdrawal pain was measured by a thermal stimulation pain instrument;the serum NF-κB,iNOS,and NO levels were measured by enzyme-linked immunosorbent assay.The pathomorphological changes of spinal nerve roots were observed by hematoxylin-eosin(HE)staining;quantitative reverse transcription polymerase chain reaction was used to detect iNOS mRNA expression in spinal nerve roots;the NF-κB and iNOS protein expression in spinal nerve roots was detected by the immunofluorescence method.Results:Compared with the sham operation group,the threshold of paw withdrawal pain in the model group was decreased,and the expression levels of serum NF-κB,iNOS,and NO were increased;HE staining showed many degenerated and dissolved Schwann cells in spinal nerve roots with vacuolar changes;meanwhile,the expression levels of NF-κB and iNOS proteins,and the iNOS mRNA in spinal nerve roots were increased.Compared with the model group,the paw withdrawal pain thresholds in acupuncture group 1 and acupuncture group 2 were increased,and the increase in acupuncture group 2 was greater(P<0.05);the expression levels of serum NF-κB,iNOS,and NO in acupuncture group 1 and acupuncture group 2 were decreased,especially in acupuncture group 2(P<0.01);the vacuolar changes of spinal nerve roots,and the degeneration and lysis of Schwann cells in acupuncture group 1 and acupuncture group 2 were decreased,which were more obvious in acupuncture group 2;the NF-κB and iNOS protein expression and the iNOS mRNA expression levels in spinal nerve roots of acupuncture group 1 and acupuncture group 2 were decreased,especially in acupuncture group 2(P<0.01).Conclusion:Acupuncture at Houxi(SI3)and Huantiao(GB30)can improve the morphology of spinal nerve roots,inhibit the NF-κB and iNOS protein expression levels in spinal nerve roots and the serum NO level,and relieve the pain caused by inflammation of spinal nerve roots,which may be one of the mechanisms of acupuncture in LDH treatment.

Renal cell carcinoma (RCC) is the third most common malignant tumor of the genitourinary system. During disease progression, RCC can undergo local and/or distant metastasis, which seriously affects the prognosis of the patient. With the advancements in targeted therapy and immunotherapy for advanced RCC, treatment for locally advanced RCC has changed. Studies have focused on applying targeted therapy or immunotherapy in the perioperative period. This article aims to review progress on treatment of locally advanced RCC to offer references for novel treatment strategies.