Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

Aim To explore the effect of hydroxysafflor yellow A(HSYA)on lipocalin 2(LCN2)-induced fer-roptosis in HT22 cells and the related mechanism.Methods Thirty male Sprague-Dawley(SD)rats were used to establish the middle cerebral artery occlu-sion/reperfusion(MCAO/R)model by the suture method.The rats were randomly divided into the Sham group,the MCAO/R group,and the MCAO/R+HSYA group.The infarct area was measured by TTC staining,and the degree of neurological deficit was evaluated by the Z-Longa scoring method.The expressions of LCN2 and 24P3R in brain tissues were detected by Western blot.LCN2 protein was added to HT-22 cells,and the cells were divided into the normal group,the LCN2 group,and the LCN2+HSYA group.The optimal con-centration of LCN2-induced neuronal ferroptosis was screened by LDH assay and Western blot,and the ex-pression levels of ferritin,FPN1,GPX4,SLC7A11,COX2,and 24P3R were detected.LCN2 was knocked down by siRNA transfection,and the expressions of GPX4 and ferritin were detected.The contents of glu-tathione(GSH),malondialdehyde(MDA),GPX4,and Fe2+were determined by colorimetry,and the expres-sion of GPX4 was detected by immunofluorescence.The binding force between HSYA and LCN2 was ana-lyzed by molecular docking technology.Results Ani-mal experiments showed that HSYA could reduce the cerebral infarction area and decrease the neurological function score of MCAO/R rats.Compared with the sham group,the levels of LCN2 and 24P3R increased in the MCAO/R group,while HSYA inhibited their ex-pressions.Cell experiments showed that the optimal concentration of LCN2 to induce ferroptosis in HT22 cells was 2 μmol·L-1.After knocking down LCN2 by siRNA transfection,compared with the LCN2 group,the expression levels of GPX4 and ferritin in the siLCN2 group increased significantly.Compared with the nor-mal group,the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH in the LCN2 group decreased signifi-cantly,while the concentration of Fe2+,and the expres-sions of MDA,COX2,and 24P3R increased.HSYA could increase the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH,reduce the contents of Fe2+and MDA,and inhibit the expressions of COX2 and 24P3R.Molecular docking showed that the binding en-ergy between HSYA and LCN2 was-8.0 kJ·mol-1.Conclusion HSYA can inhibit LCN2-induced ferrop-tosis in HT22 cells through the SLC7A11/GPX4 signa-ling pathway.

Aim To investigate the mechanism by which Aiweixin oral liquid(AWX)alleviates myocar-dial ischemia-reperfusion injury in rats through the reg-ulation of mitochondrial fusion and fission.Methods Seventy-two healthy male Sprague-Dawley rats were randomly assigned to six groups(n=12)using a ran-dom number table:sham surgery group,model group,low-dose AWX(1 mL·kg-1)group,medium-dose AWX(2 mL·kg-1)group,high-dose AWX(4 mL·kg-1)group,and positive control drug trimetazidine(10 mg·kg-1)group.A myocardial ischemia-reper-fusion injury(MIRI)model was established by ligating the left anterior descending coronary artery of the rat heart,followed by 30 minutes of ischemia and 90 mi-nutes of reperfusion.In the sham surgery group,only a suture was placed without ligation.The rats in the treatment groups were pre-gavaged with AWX starting 10 days prior to the modeling procedure.Lead Ⅱ elec-trocardiograms were recorded before and after reperfu-sion in each group to observe the changes in electrocar-diographic parameters.The myocardial infarct size in each group was assessed using TTC staining.The his-topathological changes in myocardial tissue were exam-ined under a light microscope using hematoxylin and eosin(HE)staining.The serum levels of adenosine triphosphate(ATP)and cardiac troponin I(cTnI)were measured using enzyme-linked immunosorbent as-say(ELISA).Superoxide dismutase(SOD)activity and the levels of malondialdehyde(MDA)and lactate dehydrogenase(LDH)were determined using bio-chemical assay kits.The protein expression levels of dynamin-related protein 1(dynamin-relatedprotein 1,DRP1),mitochondrial fission factor(mitochondrial fis-sion factor,MFF),mitochondrial fission protein 1(mi-tochondrial fission protein 1,FIS1),mitofusin 1(mito-fusion-1,MFN1),and mitofusin 2(mitofusion-2,MFN2)were evaluated by Western blot analysis.Re-sults Compared with the sham group,the model group exhibited aggravated myocardial tissue pathological damage,an increased percentage of myocardial infarct size,decreased serum SOD activity and ATP levels,and significantly elevated levels of MDA,cTnI,and LDH activity.Additionally,the protein expression of mito-chondrial fission factors DRP1,MFF,and FIS1 was up-regulated,while the expression of fusion-related factors MFN1 and MFN2 was downregulated.Compared with the model group,Aiweixin oral liquid significantly alle-viated myocardial injury,reduced the percentage of my-ocardial infarct size,increased serum SOD activity and ATP levels,decreased MDA content and cTnI and LDH activity,downregulated the protein expression of mito-chondrial fission factors DRP1,MFF,and FIS1,and up-regulated the protein expression of fusion-related factors MFN1 and MFN2.Conclusion Aiweixin oral liquid alleviates myocardial ischemia-reperfusion injury in rats by regulating abnormal mitochondrial fusion and fis-sion.

Aim To explore the effect of hydroxysafflor yellow A(HSYA)on lipocalin 2(LCN2)-induced fer-roptosis in HT22 cells and the related mechanism.Methods Thirty male Sprague-Dawley(SD)rats were used to establish the middle cerebral artery occlu-sion/reperfusion(MCAO/R)model by the suture method.The rats were randomly divided into the Sham group,the MCAO/R group,and the MCAO/R+HSYA group.The infarct area was measured by TTC staining,and the degree of neurological deficit was evaluated by the Z-Longa scoring method.The expressions of LCN2 and 24P3R in brain tissues were detected by Western blot.LCN2 protein was added to HT-22 cells,and the cells were divided into the normal group,the LCN2 group,and the LCN2+HSYA group.The optimal con-centration of LCN2-induced neuronal ferroptosis was screened by LDH assay and Western blot,and the ex-pression levels of ferritin,FPN1,GPX4,SLC7A11,COX2,and 24P3R were detected.LCN2 was knocked down by siRNA transfection,and the expressions of GPX4 and ferritin were detected.The contents of glu-tathione(GSH),malondialdehyde(MDA),GPX4,and Fe2+were determined by colorimetry,and the expres-sion of GPX4 was detected by immunofluorescence.The binding force between HSYA and LCN2 was ana-lyzed by molecular docking technology.Results Ani-mal experiments showed that HSYA could reduce the cerebral infarction area and decrease the neurological function score of MCAO/R rats.Compared with the sham group,the levels of LCN2 and 24P3R increased in the MCAO/R group,while HSYA inhibited their ex-pressions.Cell experiments showed that the optimal concentration of LCN2 to induce ferroptosis in HT22 cells was 2 μmol·L-1.After knocking down LCN2 by siRNA transfection,compared with the LCN2 group,the expression levels of GPX4 and ferritin in the siLCN2 group increased significantly.Compared with the nor-mal group,the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH in the LCN2 group decreased signifi-cantly,while the concentration of Fe2+,and the expres-sions of MDA,COX2,and 24P3R increased.HSYA could increase the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH,reduce the contents of Fe2+and MDA,and inhibit the expressions of COX2 and 24P3R.Molecular docking showed that the binding en-ergy between HSYA and LCN2 was-8.0 kJ·mol-1.Conclusion HSYA can inhibit LCN2-induced ferrop-tosis in HT22 cells through the SLC7A11/GPX4 signa-ling pathway.

Aim To investigate the mechanism by which Aiweixin oral liquid(AWX)alleviates myocar-dial ischemia-reperfusion injury in rats through the reg-ulation of mitochondrial fusion and fission.Methods Seventy-two healthy male Sprague-Dawley rats were randomly assigned to six groups(n=12)using a ran-dom number table:sham surgery group,model group,low-dose AWX(1 mL·kg-1)group,medium-dose AWX(2 mL·kg-1)group,high-dose AWX(4 mL·kg-1)group,and positive control drug trimetazidine(10 mg·kg-1)group.A myocardial ischemia-reper-fusion injury(MIRI)model was established by ligating the left anterior descending coronary artery of the rat heart,followed by 30 minutes of ischemia and 90 mi-nutes of reperfusion.In the sham surgery group,only a suture was placed without ligation.The rats in the treatment groups were pre-gavaged with AWX starting 10 days prior to the modeling procedure.Lead Ⅱ elec-trocardiograms were recorded before and after reperfu-sion in each group to observe the changes in electrocar-diographic parameters.The myocardial infarct size in each group was assessed using TTC staining.The his-topathological changes in myocardial tissue were exam-ined under a light microscope using hematoxylin and eosin(HE)staining.The serum levels of adenosine triphosphate(ATP)and cardiac troponin I(cTnI)were measured using enzyme-linked immunosorbent as-say(ELISA).Superoxide dismutase(SOD)activity and the levels of malondialdehyde(MDA)and lactate dehydrogenase(LDH)were determined using bio-chemical assay kits.The protein expression levels of dynamin-related protein 1(dynamin-relatedprotein 1,DRP1),mitochondrial fission factor(mitochondrial fis-sion factor,MFF),mitochondrial fission protein 1(mi-tochondrial fission protein 1,FIS1),mitofusin 1(mito-fusion-1,MFN1),and mitofusin 2(mitofusion-2,MFN2)were evaluated by Western blot analysis.Re-sults Compared with the sham group,the model group exhibited aggravated myocardial tissue pathological damage,an increased percentage of myocardial infarct size,decreased serum SOD activity and ATP levels,and significantly elevated levels of MDA,cTnI,and LDH activity.Additionally,the protein expression of mito-chondrial fission factors DRP1,MFF,and FIS1 was up-regulated,while the expression of fusion-related factors MFN1 and MFN2 was downregulated.Compared with the model group,Aiweixin oral liquid significantly alle-viated myocardial injury,reduced the percentage of my-ocardial infarct size,increased serum SOD activity and ATP levels,decreased MDA content and cTnI and LDH activity,downregulated the protein expression of mito-chondrial fission factors DRP1,MFF,and FIS1,and up-regulated the protein expression of fusion-related factors MFN1 and MFN2.Conclusion Aiweixin oral liquid alleviates myocardial ischemia-reperfusion injury in rats by regulating abnormal mitochondrial fusion and fis-sion.

Objective:To construct and validate a predictive model for pathological complete response (pCR) in patients with locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy.Methods:This retrospective observational study included 595 patients with stage T2-4 and (or) N+M0 LARC diagnosed in the Cancer Hospital of Chinese Academy of Medical Sciences and the Fourth Hospital of Hebei Medical University who had no metastases, tolerated neoadjuvant therapy, completed neoadjuvant therapy, and had undergone radical surgery after neoadjuvant therapy. The training set comprised 299 patients admitted to the Cancer Hospital of Chinese Academy of Medical Sciences from 2013 to 2018, the internal validation set 155 patients admitted from 2019 to 2023, and the external validation set 141 patients admitted to the Fourth Hospital of Hebei Medical University from 2013 to 2021. They were divided into pCR group and non-pCR groups according to postoperative pathology. Among the 299 patients in the training set, 247 were in the non-PCR and 52 in the pCR group; among the 155 patients verified internally, 113 were in the non-PCR and 42 in the pCR group; and among the 141 patients validated externally, 132 were in the non-pCR and nine in the pCR group. Logistic regression was used for univariate and multifactorial analysis to explore the factors associated with pCR and construct a nomogram prediction model. Receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA) were used to validate the performance of the predictive model.Results:Univariate and multivariate logistic regression analysis showed that carbohydrate antigen 19-9 ( P=0.040, OR=0.97, 95%CI: 0.93-0.99), neutrophil count ( P<0.001, OR=0.66, 95%CI: 0.52-0.84), tumor T stage: Stage IV ( P=0.011, OR=0.22, 95%CI: 0.07-0.70), tumor N stage: Stage I ( P=0.003, OR=0.22,95%CI:0.08-0.60), Stage II ( P<0.001, OR=0.03, 95%CI: 0.01-0.09) and involvement of mesorectal fascia ( P=0.004, OR=0.09, 95%CI: 0.02-0.47) were independent predictors of pCR. In the training set, the area under the receiver operating characteristic curve of the model was 0.92 (95%CI: 0.87-0.96), whereas in the internal and external validation sets, the AUCs were 0.78 and 0.81, respectively. The calibration curve showed that the prediction model had good prediction efficiency in both the training and verification sets. Decision curve analysis showed that the net benefit of the model was largest when the threshold probability was in the range of 5.2% to 89.7% (in the internal and external validation sets, the threshold probabilities were in the range of 15.7% to 92.3% and 2.2% to 84.1%, respectively). Conclusion:The nomogram model constructed in this study showed efficacy in predicting whether patients with LARC will achieve pCR after receiving neoadjuvant chemoradiotherapy.

Background and purpose:Next generation sequencing-identified genetic alterations of diffuse large B cell lymphoma(DLBCL)and baseline SUVmax detected by 18F-FDG PET/CT were correlated with patients'prognosis.However,their relationship and the associations with R-CHOP response of DLBCL are still unclear.This study aimed to analyze the association bewteen genetic alterations and 18F-FDG PET/CT SUVmax and their correlations with clinicopathological characteristics and R-CHOP response of DLBCL.Methods:A total of 225 cases of primary DLBCL detected by next generation sequencing using 481 lymphoma gene panel and examined by 18F-FDG PET/CT before treatment between 2022 and 2023 were collected.This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center(Ethical No.:050432-4-2307E)and acquired the informed consent of the patients.The translocations of BCL2,BCL6 and MYC were identified by fluorescence in situ hybridization.The clinicopathological characteristics and the PET/CT scan after R-CHOP chemotherapy were collected.Results:Finally,191 patients were enrolled in this study.The frequency of MYD88 mutation,TP53 mutation,copy number variations of CDKN2A/2B,CD79B mutation in the 191 DLBCL patients were 24.6%,27.2%,32.5%and 16.8%,respectively.The range of baseline SUVmax was 5.10-63.10(24.44±10.70,median 22.80).The baseline SUVmax of MYD88L265P DLBCL was significantly higher than that of MYD88 wild type(P=0.039).There were no significant associations of SUVmax with other gene alterations including TP53 mutation,CDKN2A/B loss,CD79B mutation,KMT2D mutation,TNFAIP3 mutation,B2M mutation,EZH2 mutation,BTG1/2 mutation,CREBBP mutation,gene translocations of MYC,BCL2 and BCL6.The higher SUVmax before treatment was correlated with higher serum lactate dehydrogenase(LDH)level(P=0.012)and non-germinal center B-cell-like(non-GCB)DLBCL(P=0.040).However,there was no significant association of SUVmax with R-CHOP response(P=0.714).TP53 mutation was significantly associated with the poor response of R-CHOP(P=0.001)and was an independent predictor of non-complete metabolic response(non-CMR).TP53 mutation combined with Ann Arbor stage,International Prognostic Index(IPI)score and serum LDH level could better predict R-CHOP response than each factor alone.Conclusion:MYD88L265P DLBCL had higher baseline 18F-FDG PET/CT SUVmax.The baseline SUVmax was not associated with R-CHOP response.However,TP53 mutation was significantly correlated with poor response of R-CHOP in DLBCL patients.TP53 mutation combined with clinicopathological characteristics could better predict R-CHOP response.The associations of gene alterations and SUVmax with prognosis of DLBCL patients needed to be explored in the future.

Objective:To construct and validate a predictive model for pathological complete response (pCR) in patients with locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy.Methods:This retrospective observational study included 595 patients with stage T2-4 and (or) N+M0 LARC diagnosed in the Cancer Hospital of Chinese Academy of Medical Sciences and the Fourth Hospital of Hebei Medical University who had no metastases, tolerated neoadjuvant therapy, completed neoadjuvant therapy, and had undergone radical surgery after neoadjuvant therapy. The training set comprised 299 patients admitted to the Cancer Hospital of Chinese Academy of Medical Sciences from 2013 to 2018, the internal validation set 155 patients admitted from 2019 to 2023, and the external validation set 141 patients admitted to the Fourth Hospital of Hebei Medical University from 2013 to 2021. They were divided into pCR group and non-pCR groups according to postoperative pathology. Among the 299 patients in the training set, 247 were in the non-PCR and 52 in the pCR group; among the 155 patients verified internally, 113 were in the non-PCR and 42 in the pCR group; and among the 141 patients validated externally, 132 were in the non-pCR and nine in the pCR group. Logistic regression was used for univariate and multifactorial analysis to explore the factors associated with pCR and construct a nomogram prediction model. Receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA) were used to validate the performance of the predictive model.Results:Univariate and multivariate logistic regression analysis showed that carbohydrate antigen 19-9 ( P=0.040, OR=0.97, 95%CI: 0.93-0.99), neutrophil count ( P<0.001, OR=0.66, 95%CI: 0.52-0.84), tumor T stage: Stage IV ( P=0.011, OR=0.22, 95%CI: 0.07-0.70), tumor N stage: Stage I ( P=0.003, OR=0.22,95%CI:0.08-0.60), Stage II ( P<0.001, OR=0.03, 95%CI: 0.01-0.09) and involvement of mesorectal fascia ( P=0.004, OR=0.09, 95%CI: 0.02-0.47) were independent predictors of pCR. In the training set, the area under the receiver operating characteristic curve of the model was 0.92 (95%CI: 0.87-0.96), whereas in the internal and external validation sets, the AUCs were 0.78 and 0.81, respectively. The calibration curve showed that the prediction model had good prediction efficiency in both the training and verification sets. Decision curve analysis showed that the net benefit of the model was largest when the threshold probability was in the range of 5.2% to 89.7% (in the internal and external validation sets, the threshold probabilities were in the range of 15.7% to 92.3% and 2.2% to 84.1%, respectively). Conclusion:The nomogram model constructed in this study showed efficacy in predicting whether patients with LARC will achieve pCR after receiving neoadjuvant chemoradiotherapy.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

Neuropathic pain, a debilitating condition caused by dysfunction of the somatosensory nervous system, remains difficult to treat due to limited understanding of its molecular mechanisms. Bioinformatics analysis identified cerebellin 2 (CBLN2) as highly enriched in human and murine proprioceptive and nociceptive neurons. We found that CBLN2 expression is persistently upregulated in dorsal root ganglia (DRG) following spinal nerve ligation (SNL) in mice. In addition, transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription. SNL also induced SOX11 upregulation, with SOX11 and CBLN2 co-localized in nociceptive neurons. The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes, including upregulation of numerous NF-κB downstream targets. Consistently, CBLN2 activated NF-κB signaling, and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity, proinflammatory cytokines and chemokines production, and neuronal hyperexcitability. Together, these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
Animals ; Neuralgia/metabolism* ; Ganglia, Spinal/metabolism* ; Up-Regulation ; Mice ; NF-kappa B/metabolism* ; SOXC Transcription Factors/genetics* ; Male ; Neuroinflammatory Diseases/metabolism* ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics* ; Hyperalgesia/metabolism* ; Signal Transduction ; Spinal Nerves