ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

Based on LI Gao's Academic Thought， focusing on the process of qi transformation and taking the regulation and restoration of metabolism and immunity as the entry point， a "source-pivot-convergence" diagnostic and therapeutic model for malignant tumors is constructed. In this model， spleen and stomach internal injury is the source of malignant tumor occurrence， while the disorder of ascending and descending is the pivot of the disease development， and the generation of yin fire is the convergence of malignant tumor progression. Based on this， the three major therapeutic methods of clearing the source， harmonizing the pivot， and resolving the convergence are established. To fortify spleen and boost qi， consolidate the root and clear the source， modified Buzhong Yiqi Decoction（补中益气汤）can be used. To raise the clear and direct the turbid downward， regulate qi and harmonize the pivot， modified Shengyang Yiwei Decoction （升阳益胃汤） is suggested. To restore balance and promote circulation， disperse accumulation and resolve convergence， modified Shengyang Sanhuo Decoction （升阳散火汤） is selected. In clinical practice， these formulas can be used in combination according to the complexity of the pathogenesis， and further adapted with prescriptions for promoting dispersion and penetrating pathogenic factors， resolving phlegm and promoting circulation， activating blood and eliminating concretions， which can provide a reference for the prevention and treatment of tumor diseases.

Based on LI Gao's Academic Thought， focusing on the process of qi transformation and taking the regulation and restoration of metabolism and immunity as the entry point， a "source-pivot-convergence" diagnostic and therapeutic model for malignant tumors is constructed. In this model， spleen and stomach internal injury is the source of malignant tumor occurrence， while the disorder of ascending and descending is the pivot of the disease development， and the generation of yin fire is the convergence of malignant tumor progression. Based on this， the three major therapeutic methods of clearing the source， harmonizing the pivot， and resolving the convergence are established. To fortify spleen and boost qi， consolidate the root and clear the source， modified Buzhong Yiqi Decoction（补中益气汤）can be used. To raise the clear and direct the turbid downward， regulate qi and harmonize the pivot， modified Shengyang Yiwei Decoction （升阳益胃汤） is suggested. To restore balance and promote circulation， disperse accumulation and resolve convergence， modified Shengyang Sanhuo Decoction （升阳散火汤） is selected. In clinical practice， these formulas can be used in combination according to the complexity of the pathogenesis， and further adapted with prescriptions for promoting dispersion and penetrating pathogenic factors， resolving phlegm and promoting circulation， activating blood and eliminating concretions， which can provide a reference for the prevention and treatment of tumor diseases.

BACKGROUND: T-cell lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is an aggressive form of hematological malignancy associated with poor prognosis in adult patients. Histone deacetylases (HDACs) are aberrantly expressed in T-LBL/ALL and are considered potential therapeutic targets. Here, we investigated the antitumor effect of a novel HDAC inhibitor, chidamide, on T-LBL/ALL. METHODS: HDAC1, HDAC2 and HDAC3 levels in T-LBL/ALL cell lines and patient samples were compared with those in normal controls. Flow cytometry, transmission electron microscopy, and lactate dehydrogenase release assays were conducted in Jurkat and MOLT-4 cells to assess apoptosis and pyroptosis. A specific forkhead box O1 (FOXO1) inhibitor was used to rescue pyroptosis and upregulated gasdermin E (GSDME) expression caused by chidamide treatment. The role of the FOXO1 transcription factor was evaluated by dual-luciferase reporter and chromatin immunoprecipitation assays. The efficacy of chidamide in vivo was evaluated in a xenograft mouse. RESULTS: The expression of HDAC1, HDAC2 and HDAC3 was significantly upregulated in T-LBL/ALL. Cell viability was obviously inhibited after chidamide treatment. Pyroptosis, characterized by cell swelling, pore formation on the plasma membrane and lactate dehydrogenase leakage, was identified as a new mechanism of chidamide treatment. Chidamide triggered pyroptosis through caspase 3 activation and GSDME transcriptional upregulation. Chromatin immunoprecipitation assays confirmed that chidamide led to the increased transcription of GSDME through a more relaxed chromatin structure at the promoter and the upregulation of FOXO1 expression. Moreover, we identified the therapeutic effect of chidamide in vivo . CONCLUSIONS This study suggested that chidamide exerts an antitumor effect on T-LBL/ALL and promotes a more inflammatory form of cell death via the FOXO1/GSDME axis, which provides a novel choice of targeted therapy for patients with T-LBL/ALL.
Humans ; Pyroptosis/drug effects* ; Forkhead Box Protein O1/genetics* ; Aminopyridines/pharmacology* ; Animals ; Mice ; Benzamides/pharmacology* ; Cell Line, Tumor ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Phosphate-Binding Proteins/metabolism* ; Histone Deacetylase Inhibitors/pharmacology* ; Jurkat Cells ; Histone Deacetylases/metabolism* ; Apoptosis/drug effects* ; Gasdermins

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Objective To establish an HPLC method to determine the concentration of inositol nicotinate（IN） in rat skin, and study the pharmacokinetic characteristics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats. Methods HPLC method was used to establish a simple and rapid analytical method for the determination of IN concentration in the skin of rats at different time points after administration. The established method was used to study the pharmacokinetics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats, and the pharmacokinetic parameters were fitted with DAS software. Results The linearity of the analytical method was good in the concentration range of 0.25-20 μg/ml, the quantitative limit was 0.25 μg/ml, and the average recovery rate was 96.18%. The pharmacokinetic parameters of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats were as follows: t_1/2 was （4.555±2.054） h, T_max was （6±0）h, C_max was （16.929±2.153）mg/L, AUC_0−t was （150.665±16.568） mg·h /L ,AUC_0−∞ was （161.074±23.917） mg·h /L, MRT_（0−t） was （9.044±0.618）h, MRT_{（0−∞）} was （10.444±1.91） h, CLz/F was （0.19±0.03） L/（h·kg）, and Vz/F was （1.19±0.437） L/（h·kg）. Conclusion IN could quickly penetrate the skin and accumulate in the skin for a long time, which was beneficial to the pharmacological action of drugs on the lesion site for a long time. The method is simple, rapid, specific and reproducible, which could be successfully applied to the pharmacokinetic study of IN after transdermal administration in rats.

Deep medullary veins(DMVs)are critical components of the cerebral medullary venous system,responsible for venous drainage of the deep cerebral white matter.Recent research indicates that DMVs are closely related to cerebral small vessel disease(CSVD)and associated cognitive disorders.The morphological structure of DMVs can be clearly visualized on susceptibility weighted imaging and quantitative susceptibility mapping,which could potentially serve as markers for assessing the severity of CSVD.This article reviewed the anatomical characteristics and physiological functions of DMVs,as well as the mechanistic correlations between DMVs and various CSVD imaging markers,aiming to provide novel theoretical insights for early diagnosis and clinical management of CSVD.

Objective To investigate the thalamus and thalamic subnucleus volume changes in patients with trigeminal neuralgia(TN)and to preliminarily investigate whether there is a pain processing lateralization advantage in the thalamus.Methods The three-dimensional T1WI images of 56 TN patients and 56 matched healthy controls(HC)were collected,and thalamus and thalamic subnucleus volumes were extracted by automated segmentation via a region of interest(ROI)-based morphological analysis method.Results There was no significant difference in the whole thalamus volume between TN and HC groups.Compared with HC,the bilateral ventral lateral(VL)of the thalamus were significantly smaller in patients with right-sided trigeminal neuralgia(RTN),and no significant thalamic subnucleus volume changes were found in patients with left-sided trigeminal neuralgia(LTN).After mirror-flipping the whole-brain images of the LTN,it was found that the volume of ipsilateral thalamic VL of TN group was significantly reduced than that of HC group.The volume of ipsilateral mediodorsal lateral parvocellular(MD1)of TN group was significantly smaller than that of HC group.There was no significant difference in the volume of ipsilateral and contralateral thalamic subnucleus.Conclusion The thalamic subnucleus are exclusively reduced in volume in patients with TN,and there is no significant change in whole thalamus volume,suggesting no lateralization advantage for pain processing.

Objective To explore the clinical efficacy and safety of intravenous thrombolysis and dual antiplatelet therapy in the treatment of acute mild non-disabling ischemic stroke.Methods A retrospective cohort study was conducted,including 138 patients with acute mild non-disabling ischemic stroke[National Institutes of Health Stroke Scale(NIHSS)score≤5]from January 2022 to March 2024,within 6 h of onset.Patients were divided into an intravenous thrombolysis group(66 cases)and a dual antiplatelet group(72 cases).Propensity score matching was used to match patients 1∶1,resulting in 44 patients in each group after matching.Demographic data,clinical data,clinical outcome indicators,and adverse events were collected.The primary outcome was defined as a good functional outcome[modified Rankin Scale(mRS)score 0-2]at 90 d post-onset.Secondary outcomes included NIHSS scores at 24 h,72 h,and 7 d post-onset;the proportion of early neurological deterioration;intracranial and systemic hemorrhagic events within 90 d post-onset;and death within 90 d.Results ①Before matching,the intravenous thrombolysis group had a lower age and admission mRS score than that of the dual antiplatelet group,with statistically significant differences(all P＜0.05).After matching,there were no statistically significant differences between the two groups in terms of age,gender,hypertension,diabetes,cardiac disease,atrial fibrillation,hyper low density lipoprotein-cholesterol(LDL-C),hyperhomocysteinemia,prior stroke,prior smoking,admission NIHSS score,admission mRS score,location of stroke and TOAST classification(all P＞0.05);②There was no statistically significant difference in the proportion of patients with a good functional outcome at 90 d post-onset and the mRS score at 90 d between the intravenous thrombolysis group and the dual antiplatelet group[88.6％(39/44)vs 93.2％(41/44),P=0.458,P=0.308];③ The intravenous thrombolysis group had significantly lower median NIHSS scores at 24 h and 72 h post-onset compared to the dual antiplatelet group,with statistically significant differences[1 vs 2.5,1 vs 2,P=0.018,0.043].There were no statistically significant differences in the other efficacy and safety outcomes.Conclusions Intravenous thrombolysis therapy can bring significant short-term benefits to patients with acute mild non-disabling ischemic stroke,helping to shorten the time to recovery to a good neurological functional outcome,and does not increase the risk of bleeding and mortality.However,in terms of good functional outcomes at 90 d post-onset,its effects are similar to those of dual antiplatelet therapy.Nevertheless,there is an urgent need for larger sample,higher quality clinical studies to further validate these findings.

Objective:To learn about the clinical manifestations, laboratory test results, and prognosis of patients with acute and chronic brucellosis, and to provide a scientific basis for clinical diagnosis and treatment.Methods:A retrospective study was conducted to collect the clinical data of 776 patients with brucellosis admitted to the First Affiliated Hospital of Xinjiang Medical University from January 2013 to December 2023. The patients were divided into acute phase group and chronic phase group according to the course of disease. Their clinical manifestations, laboratory test results, and prognosis were compared and analyzed between the two groups.Results:Out of 776 patients with brucellosis, 649 were in the acute phase group and 127 were in the chronic phase group. Male accounted for 71.6% (556/776). The age was (44.91 ± 0.60) years old, mainly concentrated in the age range of 46 - 60 years old (38.0%, 295/776). Farmers were the main occupation, accounting for 58.4% (453/776). The disease occurred in all months of the year, with autumn being the peak period (33.9%, 263/776). The primary clinical manifestations were fever (64.7%, 502/776) and fatigue (40.5%, 314/776). The incidence rates of fever and fatigue in the acute phase group were higher than those in the chronic phase group [70.4% (457/649) vs. 35.4% (45/127), 42.5% (276/649) vs. 29.9% (38/127)], with statistically significant differences ( χ2 = 56.91, 7.01, P < 0.05). Complications of the osteoarticular system were the most common, accounting for 47.8% (371/776). Abnormal results of blood routine examinations were mainly characterized by decreased hemoglobin, decreased lymphocytes, and decreased white blood cells, accounting for 53.7% (417/776), 32.6% (253/776), and 22.6% (175/776), respectively. The incidence rate of decreased hemoglobin in the acute phase group was higher than that in the chronic phase group [63.5% (412/649) vs. 3.9% (5/127)], with a statistically significant difference ( χ2 = 151.49, P < 0.001). The remaining abnormal laboratory test results were mainly characterized by elevated erythrocyte sedimentation rate, elevated C-reactive protein, and elevated aspartate aminotransferase, accounting for 75.1% (583/776), 50.6% (393/776), and 39.8% (309/776), respectively. The incidence rates of elevated erythrocyte sedimentation rate and elevated aspartate aminotransferase in the acute phase group were higher than those in the chronic phase group [77.8% (505/649) vs. 61.4% (78/127), 43.3% (281/649) vs. 22.0% (28/127)], with statistically significant differences ( χ2 = 15.28, 20.02, P < 0.001). The overall positive rate of Brucella blood culture was 57.5% (446/776), and there was a statistically significant difference in blood culture between the two groups ( χ2 = 17.08, P = 0.002). The positive rate of blood culture in the acute phase group was higher than that in the chronic phase group [60.1% (390/649) vs. 44.1% (56/127)]. Ninety-four point three percent (732/776) of patients were treated with antibiotics, with rifampicin + doxycycline as the main treatment regimen (45.2%, 331/732). The median of antibiotic types used in the acute and chronic phase groups were 3 and 4, respectively. The overall incidence rate of adverse drug reactions was 3.8% (28/732). Eighty-seven point five percent (625/714) of patients improved or recovered after treatment, while 12.5% (89/714) did not recover or experienced relapse. Conclusions:The main clinical manifestations of brucellosis patients are fever and fatigue, with a higher incidence of complications in the osteoarticular system, and a better prognosis. The incidence of fever, fatigue, decreased hemoglobin, elevated erythrocyte sedimentation rate, elevated aspartate aminotransferase, and positive Brucella blood culture in patients in the acute phase are higher, and the types of antibiotics used are fewer than those in patients in the chronic phase.