Objective To explore the clinical characteristics and prognostic analysis of acute corpus callosum in-farction.Methods A total of 1 466 patients with acute cerebral infarction admitted to the Neurology Department of Jiangbin Hospital in Guangxi from January 2019 to October 2023 and Neurology Department of Fuwai Hospital,Chinese Academy of Medical Sciences from January 2022 to December 2022.Among them,21 patients with acute corpus callosum infarction confirmed by MRI(observation group)and 25 patients with isolated subcortical infarction at the same period(control group)were selected.By comparing clinical data and follow-up information between two groups,we summarized the clinical characteristics of acute corpus callosum infarction,and analyzed the relevant factors affecting the prognosis of the corpus callosum infarction group.Results Acute corpus callosum infarction accounted for 1.43％(21/1 466)of patients with acute cerebral infarction in the same period.The main clinical manifestations include limb paralysis,cognitive decline,and speech impairment.Compared with the control group,the group with corpus callosum infarction had a longer onset visit time(P<0.05),more cognitive impair-ment(P<0.05),a higher proportion of mild stroke(P<0.05),more worsening symptoms during the course of the disease(P<0.05),a higher proportion of cardioembolic type(P<0.05),a lower proportion of small artery occlu?sion type(P<0.05)and a higher proportion of good prognosis(mRS score≤2 points)(P<0.05).The poor prog?nosis of corpus callosum infarction was found to be related to factors such as large lesions,multiple high?risk factors(≥3),concomitant lobar infarction and worsening of symptoms during the course of the disease.Conclusions Acute corpus callosum infarction often leads to cognitive impairment and mild limb paralysis,which frequently de?lays treatment.The poor prognosis is mainly related to factors such as lobar infarction,major lesions,and worsening of symptoms during the process.

Objective This study examines serum lipid metabolism characteristics in colorectal cancer patients and its diagnostic potential.Methods Serum samples from 57 colorectal cancer patients and 54 healthy controls underwent lipidomic analysis using ultra-high performance liquid chromatography-time-of-flight mass spec-trometry,combined with principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA).Differential lipids were identified based on criteria of P<0.05,VIP>1,and fold change<0.67 or>1.5.These lipids were further evaluated using receiver operating characteristic(ROC)analysis to identify biomarkers with strong diagnostic value.Results Five classes and 66 differential lipids were identified,with phos-phatidylcholine(PC)and triglyceride(TG)comprising 59.09%.KEGG pathway enrichment indicated involvement in glycerophospholipid and glycerol ester metabolism pathways.ROC analysis identified Sphinganine,MG(19∶0),LysoPC(18∶2),PA(42∶6),PC(36∶5),PC(36∶4),PC(38∶6),and PC(40∶8)as having areas under the curve greater than 0.85.Conclusion The lipid metabolic profile of colorectal cancer(CRC)patients can be systematically analyzed through the efficient enrichment of lipid metabolites in serum using the UPLC-Q/TOF-MS technique,in conjunction with a modified Bligh-Dyer method.The identification of eight specific lipids including Sphinganine,MG(19∶0),LysoPC(18∶2),PA(42∶6),PC(36∶5),PC(36∶4),PC(38∶6),and PC(40∶8)offer novel insights and parameters for differentiating between healthy individuals and those diagnosed with colorec-tal cancer.

OBJECTIVE: To assess the effectiveness of bone acupuncture in improving pain and function in degenerative lumbar spinal stenosis (DLSS) and compare it with Jiaji acupuncture. METHODS: From January to December 2023, 80 DLSS patients were treated with acupuncture and divided into bone acupuncture and Jiaji acupuncture groups. Among them, 40 patients in the bone acupuncture group included 15 males and 25 females, with a mean age of (60.60±6.98) years old;anthor 40 patients in the Jiaji acupuncture group included 16 males and 24 females, with a mean age of (61.48±9.55) years old. The Roland Morris disability questionnaire(RMDQ), walking distance, visual analogue scale(VAS), and the MOS item short from health survey(SF-36) of two groups at baseline, 2 weeks, 4 weeks, and 12 weeks post-treatment were compared. RESULTS: Eighty patients were followed up for 3 to 5 months with an average of (3.62±0.59) months. There was no significant differences in general data and the scores before treatment between two groups(P>0.05). The RMDQ scores in both groups decreased significantly at 2, 4 and 12 weeks after treatment compared with before treatment(P<0.05), at each time point after treatment, the decrease was more significant in the bone acupuncture group than in the Jiaji acupuncture group(P<0.05). The VAS of waist and leg in both groups was significantly lower at 2, 4 and 12 weeks after treatment that before treatment(P<0.05). At all time points after treatment, the waist VAS in the bone acupuncture group was reduced more significant than in the Jiaji acupuncture group(P<0.05);there was no significant difference in leg VAS at 2 and 12 weeks after treatment between two groups(P>0.05), the improvement was more significant in the bone acupuncture group in the 4 weeks after treatment than in the Jiaji acupuncture group. The SF-36 scores in both groups were significantly higher at 2, 4, and 12 weeks after treatment than before treatment(P<0.05);the SF-36 score raised more significant in the bone acupuncture group than in the Jiaji acupunture group(P<0.05). No significant difference in the walking distance between two groups at 2 weeks after treatment(P>0.05);the walking distance in the bone acupuncture group was significantly higher than that in the Jiaji acupuncture group at 4 and 12 weeks after treatment(P<0.05). CONCLUSION Bone-penetrating acupuncture moderately improves functional impairment, pain, and quality of life in patients with DLSS, showing better efficacy than Jiaji acupuncture.
Humans ; Female ; Male ; Middle Aged ; Acupuncture Therapy/methods* ; Spinal Stenosis/physiopathology* ; Aged ; Lumbar Vertebrae/physiopathology* ; Pain Management

OBJECTIVE: To investigate the susceptibility of venetoclax-resistant acute myeloid leukemia (AML) cell lines to ferroptosis and to uncover the underlying molecular mechanisms using transcriptomic and metabolomic analysis methods. METHODS: Venetoclax-resistant AML cell lines were constructed using a low-dose concentration escalation method. The sensitivity of cells to chemotherapeutic drugs was detected by CCK-8 assay. The susceptibility of drug-resistant cell lines to ferroptosis was assessed using transcriptomic and metabolomic analysis methods. The expression of cellular GPX4 and SLC7A11 protein was detected by Western blot, and cell death and lipid peroxidation levels were measured by flow cytometry. Depmap database and TCGA cohort were applied to explore the effect of ferroptosis-related genes expression on prognosis. RESULTS: Venetoclax-resistant cell lines exhibited sensitivity to ferroptosis inducers RSL3, APR246, and sorafenib. The ferroptosis inhibitor Fer-1 partially inhibited cell death induced by these inducers. Compared with the parental cells, significant changes in metabolites and gene expression levels related to ferroptosis were observed in the resistant cell lines. In particular, deregulated expression of SLC7A11 and GPX4 may play critical role in ferroptosis susceptibility. Besides, GPX4 was identified as more important for AML cell survival and higher GPX4 expression may predict shortened overall survival, NPM1 mutant and IDH1 R132 mutation positive patients may prone to possess higher GPX4 expression. CONCLUSION Venetoclax-resistant AML cell lines remain susceptible to ferroptosis, higher GPX4 expression maybe a critical marker for poor prognosis. Regulating the expression of ferroptosis-related genes and metabolites may enhance the efficacy of venetoclax and provide new treatment options for AML patients.
Humans ; Ferroptosis ; Leukemia, Myeloid, Acute/metabolism* ; Sulfonamides/pharmacology* ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology* ; Drug Resistance, Neoplasm ; Metabolomics ; Cell Line, Tumor ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Amino Acid Transport System y+/metabolism* ; Transcriptome

OBJECTIVE: To investigate the effect and mechanism of Shuangshi Tonglin Capsules (SSTL) in the treatment of prostate fibrosis (PF). METHODS: Human prostate stromal cells (WPMY-1) were used for in vitro experiments to establish PF cell models induced with estradiol (E₂). The cell proliferation, migration and clonogenic capacity were determined by cell counting kit-8, scratch assay, and crystal violet staining, respectively. Sprague-Dawley rats were used for in vivo experiments. The changes in histomorphology and organ index of rat prostate by SSTL were determined. Pathologic changes and collagen deposition changes in rat prostate were observed by haematoxylin and eosin (HE) and Masson staining. Enzyme-linked immunosorbent assay kits were used to determine changes in rat PF markers fibroblast growth factor-23 (FGF-23), E₂ and prostate specific antigen (PSA). Mechanistically, changes in oxidative stress indicators by SSTL were determined in WPMY-1 cells and PF rats. Then the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) and transforming growth factor-β1 (TGF-β1)/Smad pathway-related proteins as well as Nrf2 and TGF-β1 mRNA were further detected by Western blot or quantitative real-time polymerase chain reaction both in vivo and in vitro. RESULTS: In the efficacy study, SSTL significantly reduced the proliferation, migration, and clonogenic ability of cells, improved the morphology of the glandular tissue, significantly reduced the prostate index, reduced glandular fibrous tissue and collagen deposition, and resulted in a significant decrease in the levels of FGF-23, E₂ and PSA (P<0.01 or P<0.05). In the mechanistic study, SSTL ameliorated oxidative stress by significantly increasing superoxide dismutase and glutathione peroxidase levels and decreasing malondialdehyde level in WPMY-1 cells and rats (P<0.01 or P<0.05). SSTL significantly elevated the expressions of Nrf2, HO-1, NAD(P)H quinone oxidoreductase 1 (NQO-1), and Smad7 proteins in both cells and rats, and significantly decreased the expressions of TGF-β1, collagen I, α-smooth muscle actin and Smad4 proteins (P<0.01 or P<0.05). SSTL also elevated the content of Nrf2 mRNA and decreased the content of TGF-β1 mRNA in cells and rats (P<0.01 or P<0.05). The Nrf2 inhibitor ML385 was added in in vitro experiments to further validate the pathway relevance. CONCLUSION SSTL was effective in improving PF in vivo and in vitro, and its mechanism of action may function through the Nrf2/TGF-β1 signaling pathway.
Male ; NF-E2-Related Factor 2/metabolism* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Signal Transduction/drug effects* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Humans ; Fibrosis ; Prostate/drug effects* ; Cell Proliferation/drug effects* ; Capsules ; Cell Movement/drug effects* ; Oxidative Stress/drug effects* ; Rats

Rubi Fructus has a long history of medicinal and edible use in China. It contains chemical components such as terpenes, flavonoids, phenolic acids, fatty acids, and alkaloids, and possesses various pharmacological activities, including antioxidant, anti-inflammatory, hypoglycemic, anti-tumor, anti-osteoporosis, and liver-protective effects. Rubi Fructus is widely applied in medical, health, and food fields. The quality of Rubi Fructus can directly affect the safety and effectiveness of clinical medication. Therefore, this article reviews the research progress on the chemical constituents and pharmacological effects of Rubi Fructus. Based on the concept of traditional Chinese medicine(TCM) quality markers(Q-markers), the article explores the screening and determination of Q-markers for Rubi Fructus from various aspects, including plant kinship, traditional efficacy, medicinal properties, measurability of chemical composition, different processing methods, producing areas, harvesting periods, and planting conditions. The components ellagic acid, kaempferol, quercetin, kaempferol-3-O-rutinoside, rutin, astragalin, tiliroside, and hyperoside are preliminarily proposed as Q-markers for Rubi Fructus, providing a reference for the quality control of Rubi Fructus.
Drugs, Chinese Herbal/pharmacology* ; Humans ; Rubus/chemistry* ; Fruit/chemistry* ; Quality Control ; Animals

Aim To explore the key components and mechanisms of Lizhong decoction in treating rats with cold-damp diarrhea based on network pharmacology,molecular docking technology and animal experiments.Methods By literature review and database collec-tion,the components of Lizhong decoction,therapeutic targets,and the mapping with diarrhea disease targets were conducted to construct an intersection target pro-tein-protein interaction network for screening core tar-gets,and GO and KEGG pathway enrichment analysis was performed to build an"active component-target-pathway"network,followed by molecular docking vali-dation.Forty-eight rats were randomly divided into the normal control group(K),model group(DG),Lizhong decoction group(LZDG),and Pulsatilla decoction group(BTDG).Subsequently,a rat cold-damp diar-rhea model was established using Senna combined with low-temperature high-humidity environment,and the rats were intervened with Lizhong decoction and Pul-satilla decoction.HE staining was used to detect path-ological changes in intestinal tissue,ELISA was em-ployed to measure the levels of peripheral blood IL-6,IL-10,IL-1 β,and TNF-α,and western blot was used to determine the expression of colon tight junction pro-teins.Results Network pharmacology initially identi-fied 125 compounds in Lizhong decoction,5 186 drug target components,438 disease targets,and 60"drug-disease"shared targets.GO and KEGG enrichment a-nalysis showed that signaling pathways such as IL-17 and TNF were highly enriched.Molecular docking in-dicated that the core components of the drug had good binding activity with corresponding key targets.Liz-hong decoction could effectively improve the clinical symptoms of rats with cold-damp diarrhea,and com-pared with the DG group,the diarrhea rate,diarrhea in-dex,and other related indicators also gradually de-creased to normal levels.Compared with the DG group,the LZDG group showed reduced inflammation levels and a recovery in energy metabolism levels.Conclusion It can regulate targets such as MMP9 and IL-17 signaling pathways through multi-components like Calycosin and formononetin to exert its therapeutic effect on cold-damp diarrhea.

Objective To develop and validate a fast Monte Carlo(MC)-based patient-specific quality assurance(PSQA)tool using the treatment log files that is suitable to be used in the online adaptive radiotherapy for pencil beam scanning proton therapy(PBSPT-ART).Methods The proposed tool first used the delivery log file of a PBSPT plan to reversely reconstruct the PBSPT(rPBSPT)plan,and then used an in-house developed graphic processing unit(GPU)-accelerated virtual particle MC(VPMC)dose engine to calculate the dose distribution of the rPBSPT plan.The rPBSPT dose calculated by VPMC was then compared to the rPBSPT dose calculated by another independent MC dose engine(MCsquare),using 3D gamma analysis to verify the accuracy of VPMC calculation.As a demonstration of the feasibility of developed log file-based PSQA,the VPMC calculated dose of the rPBSPT plan was compared to the pre-delivery second check dose of the corresponding PBSPT plan calculated by MCsquare,using 3D gamma analysis.3D gamma analysis employes a criterion of 2 mm/2%/10%.Twenty patients with different disease sites were representatively selected to validate the efficiency and accuracy of the tool.Results The average calculation time of a rPBSPT plan by VPMC was(5.88±4.00)s in the accuracy verification.Compared to MCsquare,the passing rate of the 3D gamma analysis was 99.47%±0.72%.In the proposed PSQA tool demonstration,the passing rate of comparing the VPMC calculated rPBSPT dose to MCsquare calculated second check dose of the corresponding PBSPT plan was 98.91%±0.92%.Conclusion The accuracy and efficiency of the tool can meet the requirements of PSQA in the online PBSPT-ART workflow.

Objective:To investigate lymph node metastasis(LNM)in the prostatic anterior fat pad(PAFP)of PCa patients after robot-assisted radical prostatectomy(RARP),and analyze the clinicopathological features and prognosis of LNM in the PAFP.Methods:We retrospectively analyzed the clinicopathological data on 1 003 cases of PCa treated by RARP in the Department of Urolo-gy of PLA General Hospital from January 2017 to December 2022.All the patients underwent routine removal of the PAFP during RARP and pathological examination,with the results of all the specimens examined and reported by pathologists.Based on the pres-ence and locations of LNM,we grouped the patients for statistical analysis,compared the clinicopathological features between different groups using the Student's t,Mann-Whitney U and Chi-square tests,and conducted survival analyses using the Kaplan-Meier and Log-rank methods and survival curves generated by Rstudio.Results:Lymph nodes were detected in 77(7.7％)of the 1 003 PAFP samples,and LNM in 11(14.3％)of the 77 cases,with a positive rate of 1.1％(11/1 003).Of the 11 positive cases,9 were found in the upgraded pathological N stage,and the other 2 complicated by pelvic LNM.The patients with postoperative pathological stage≥T3 constituted a significantly higher proportion in the PAFP LNM than in the non-PAFP LNM group(81.8％[9/11]vs 36.2％[359/992],P=0.005),and so did the cases with Gleason score ≥8(87.5％[7/8]vs 35.5％[279/786],P=0.009).No statisti-cally significant differences were observed in the clinicopathological features and biochemical recurrence-free survival between the pa-tients with PAFP LNM only and those with pelvic LNM only.Conclusion:The PAFP is a potential route to LNM,and patients with LNM in the PAFP are characterized by poor pathological features.There is no statistically significant difference in biochemical recur-rence-free survival between the patients with PAFP LNM only and those with pelvic LNM only.Routine removal of the PAFP and inde-pendent pathological examination of the specimen during RARP is of great clinical significance.

Objective To develop and validate a fast Monte Carlo(MC)-based patient-specific quality assurance(PSQA)tool using the treatment log files that is suitable to be used in the online adaptive radiotherapy for pencil beam scanning proton therapy(PBSPT-ART).Methods The proposed tool first used the delivery log file of a PBSPT plan to reversely reconstruct the PBSPT(rPBSPT)plan,and then used an in-house developed graphic processing unit(GPU)-accelerated virtual particle MC(VPMC)dose engine to calculate the dose distribution of the rPBSPT plan.The rPBSPT dose calculated by VPMC was then compared to the rPBSPT dose calculated by another independent MC dose engine(MCsquare),using 3D gamma analysis to verify the accuracy of VPMC calculation.As a demonstration of the feasibility of developed log file-based PSQA,the VPMC calculated dose of the rPBSPT plan was compared to the pre-delivery second check dose of the corresponding PBSPT plan calculated by MCsquare,using 3D gamma analysis.3D gamma analysis employes a criterion of 2 mm/2%/10%.Twenty patients with different disease sites were representatively selected to validate the efficiency and accuracy of the tool.Results The average calculation time of a rPBSPT plan by VPMC was(5.88±4.00)s in the accuracy verification.Compared to MCsquare,the passing rate of the 3D gamma analysis was 99.47%±0.72%.In the proposed PSQA tool demonstration,the passing rate of comparing the VPMC calculated rPBSPT dose to MCsquare calculated second check dose of the corresponding PBSPT plan was 98.91%±0.92%.Conclusion The accuracy and efficiency of the tool can meet the requirements of PSQA in the online PBSPT-ART workflow.