OBJECTIVES: The neurotoxicity of carbon monoxide (CO) to the central nervous system is a key pathogenesis of delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). Our previous study found that retinoic acid (RA) can suppress the neurotoxic effects of CO. This study further explores, in vivo and in vitro, the molecular mechanisms by which RA alleviates CO-induced central nervous system damage. METHODS: A cytotoxic model was established using the mouse hippocampal neuronal cell line HT22 and primary oligodendrocytes exposed to CO, and a DEACMP animal model was established in adult Kunming mice. Cell viability and apoptosis of hippocampal neurons and oligodendrocytes were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Annexin V/propidium iodide (PI) double staining. The transcriptional and protein expression of each gene was detected using real-time fluorescence quantitative PCR (RT-qPCR) and Western blotting. Long noncoding RNA (lncRNA) SNHG15 and LINGO-1 were knocked down or overexpressed to observe changes in neurons and oligodendrocytes. In DEACMP mice, SNHG15 or LINGO-1 were knocked down to assess changes in central nervous tissue and downstream protein expression. RESULTS: RA at 10 and 20 μmol/L significantly reversed CO-induced apoptosis of hippocampal neurons and oligodendrocytes, downregulation of SNHG15 and LINGO-1, and upregulation of brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB) (all P<0.05). Overexpression of SNHG15 or LINGO-1 weakened the protective effect of RA against CO-induced cytotoxicity (all P<0.05). Knockdown of SNHG15 or LINGO-1 alleviated CO-induced apoptosis of hippocampal neurons and oligodendrocytes and upregulated BDNF and TrkB expression levels (all P<0.05). Experiments in DEACMP model mice showed that knockdown of SNHG15 or LINGO-1 mitigated central nervous system injury in DEACMP (all P<0.05). CONCLUSIONS RA alleviates CO-induced apoptosis of hippocampal neurons and oligodendrocytes, thereby reducing central nervous system injury and exerting neuroprotective effects. LncRNA SNHG15 and LINGO-1 are key molecules mediating RA-induced inhibition of neuronal apoptosis and are associated with the BDNF/TrkB pathway. These findings provide a theoretical framework for optimizing the clinical treatment of DEACMP and lay an experimental foundation for elucidating its molecular mechanisms.
Animals ; RNA, Long Noncoding/physiology* ; Brain-Derived Neurotrophic Factor/genetics* ; Carbon Monoxide Poisoning/complications* ; Mice ; Tretinoin/pharmacology* ; Nerve Tissue Proteins/metabolism* ; Membrane Proteins/metabolism* ; Apoptosis/drug effects* ; Hippocampus/cytology* ; Receptor, trkB/metabolism* ; Neurons/drug effects* ; Male ; Brain Diseases/etiology* ; Oligodendroglia/drug effects* ; Signal Transduction ; Cell Line

Background and purpose:The treatment of recurrent,metastatic,and treatment-na?ve advanced cervical cancer remains challenging.Immunotherapy in combination with chemotherapy and targeted therapy has shown preliminary clinical benefits,however,current evidence remains limited.This study aimed to evaluate the impact of camrelizumab combined with chemotherapy and targeted therapy on the prognosis of patients with recurrent,metastatic,and treatment-na?ve advanced cervical cancer.Methods:In this study,we conducted a retrospective analysis of the clinical data from 130 patients with recurrent,metastatic,and treatment-na?ve advanced cervical cancer admitted to Minhang Branch of Fudan University Shanghai Cancer Center from 2019 to 2025.The patients were categorized into the observation group(n=70),which included those who received camrelizumab with or without chemotherapy and targeted therapy,and the control group(n=60),including those who received chemotherapy and targeted therapy.Survival analysis was performed using the log-rank test,and univariate and multivariate Cox regression analyses were conducted to explore prognostic factors.This study was approved by the Ethics Committee of the Minhang Branch of Fudan University Shanghai Cancer Center[Approval number:(2024)Review No.(015)]and all informed consents were exempted.Results:The objective response rate(ORR)in the observation group was 72.9%,and the disease control rate(DCR)was 80.0%,which were significantly higher than those in the control group with an ORR of 20.0%(χ2=36.1,P＜0.001)and a DCR of 40.0%(χ2=21.8,P＜0.001).The median progression-free survival(PFS)in the observation group was not reached,significantly longer than that in the control group of 7.0 months(P＜0.001).Multivariate Cox regression analysis identified camrelizumab treatment as an independent protective factor for PFS(P＜0.001).Age,site of recurrence/metastasis,initial treatment approach,and histopathological type were not significantly associated with PFS.In the observation group,adverse events of grade 3 or higher were reported in 29 patients(41.4%),which primarily included vasculitis,hypothyroidism,hypersensitivity reactions,and diarrhea.Conclusion:The use of camrelizumab significantly improved treatment outcomes and prognosis for patients with recurrent,metastatic,and treatment-na?ve advanced cervical cancer,with significantly improved progression-free survival.Although a certain proportion of patients experienced adverse events of grade 3 or higher,the overall safety profile was acceptable.In clinical practice,immunotherapy offers a more effective treatment option for patients.

Objective To determine the effect of baicalein on high glucose-induced cardiac fibro-blast pyroptosis based on the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)pathway.Methods Rat cardiac fibroblasts were grouped into control,high glucose group,low-,medium-and high-dose baicalein(H-,M-and L-baicalein)groups,and H-baicalein+NLRP3 agonist(BMS-986299)group.Except for the control group,all other groups were cultured in DMEM medium containing 40 mmol/L glucose,then 12.5,25 and 50 μmol/L baicalein was added into the medium correspondingly,and 1 μmol/L BMS-986299 was used to treat the H-baicalein+NLRP3 agonist group.Lactate dehydrogenase(LDH)cytotoxicity assay were employed to detect cell cytotoxicity.qRT-PCR and Western blotting were performed to determine the expression of NLRP3,Caspase-1,and GSDMD at mRNA and protein levels.Results High glucose treatment induced more EdU positive cells,higher pyroptotic rate,stronger cytotoxicity,higher Col-Ⅰ and Col-Ⅲ contents,and enhanced mRNA and protein levels of NLRP3,Caspase-1 and GSDMD in comparison to the control group(P＜0.05).The H-baicalein+NLRP3 agonist group had more EdU positive cells(26.85±2.95 cells vs 15.43±1.82 cells,P＜0.05),higher pyroptotic rate[(33.45±4.02)％vs(17.34±2.15)％,P＜0.05],stronger cytotoxicity[(27.94±2.93)％vs(14.13±1.87)％,P＜0.05],and increased contents of Col-Ⅰ(107.58±13.39 ng/ml vs 58.73±8.36 ng/ml,P＜0.05)and Col-Ⅲ(118.43±13.95 ng/ml vs 68.74±8.57 ng/ml,P＜0.05),and enhanced expression of NLRP3,Caspase-1 and GSDMD at both mRNA and protein levels(P＜0.05)when compared with the H-baicalein group.Conclusion Baicalein inhibits high glucose-induced cardiac fibroblast pyroptosis by suppressing NLRP3/Caspase-1/GSDMD pathway.

Objective:To explore the correlation between the lesion imaging characteristics and the parent artery plaques detected by high-resolution magnetic resonance imaging (HR-MRI) in patients with recent small subcortical infarction (RSSI) in the lenticulostriate artery territory with mild stenosis of the parent artery.Methods:Consecutive patients with RSSI in the lenticulostriate artery territory admitted to Department of Neurology, the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2022 were prospectively enrolled. Patients with stenosis of <50% in the ipsilateral middle cerebral artery (MCA) who had completed HR-MRI were included. The RSSI lesion characteristics, such as the lowest slice involved (LS), total number of slices involved (TNS) were evaluated based on serialized axial levels of diffusion weighted imaging. HR-MRI was utilized to assess the presence of dorsal superior plaques in the M1 segment of the responsible MCA. Patients were divided into plaque group and non-plaque group based on the presence or absence of plaque. Logistic regression analysis was carried out to identify the lesion characteristics associated with the presence of dorsal superior plaques in the MCA. A receiver operating characteristic (ROC) curve was employed to estimate the predictive efficacy of these parameters for MCA plaques using the area under the curve (AUC) and the optimal cut-off point.Results:A total of 112 patients were incorporated into the final analysis. The age of these patients was (57.08±11.90) years, and 78 patients (69.64%) were male. Plaques were detected on the dorsal superior wall of the MCA in 57 cases (50.89%) as the plaque group, and the other 55 cases (49.11%) were regarded as the non-plaque group. Multivariate Logistic regression revealed that LS was significantly associated with MCA plaques ( OR=0.674, 95% CI 0.485-0.937, P=0.019). The optimal cut-off point (LS≤1) was determined by ROC curve analysis (AUC=0.640, P=0.007). Conclusion:The findings suggest that in RSSI patients with mild stenosis of the parent artery, an LS≤1 is notably associated with the presence of dorsal superior plaques on MCA as detected by HR-MRI.

Background and purpose:The treatment of recurrent,metastatic,and treatment-na?ve advanced cervical cancer remains challenging.Immunotherapy in combination with chemotherapy and targeted therapy has shown preliminary clinical benefits,however,current evidence remains limited.This study aimed to evaluate the impact of camrelizumab combined with chemotherapy and targeted therapy on the prognosis of patients with recurrent,metastatic,and treatment-na?ve advanced cervical cancer.Methods:In this study,we conducted a retrospective analysis of the clinical data from 130 patients with recurrent,metastatic,and treatment-na?ve advanced cervical cancer admitted to Minhang Branch of Fudan University Shanghai Cancer Center from 2019 to 2025.The patients were categorized into the observation group(n=70),which included those who received camrelizumab with or without chemotherapy and targeted therapy,and the control group(n=60),including those who received chemotherapy and targeted therapy.Survival analysis was performed using the log-rank test,and univariate and multivariate Cox regression analyses were conducted to explore prognostic factors.This study was approved by the Ethics Committee of the Minhang Branch of Fudan University Shanghai Cancer Center[Approval number:(2024)Review No.(015)]and all informed consents were exempted.Results:The objective response rate(ORR)in the observation group was 72.9%,and the disease control rate(DCR)was 80.0%,which were significantly higher than those in the control group with an ORR of 20.0%(χ2=36.1,P＜0.001)and a DCR of 40.0%(χ2=21.8,P＜0.001).The median progression-free survival(PFS)in the observation group was not reached,significantly longer than that in the control group of 7.0 months(P＜0.001).Multivariate Cox regression analysis identified camrelizumab treatment as an independent protective factor for PFS(P＜0.001).Age,site of recurrence/metastasis,initial treatment approach,and histopathological type were not significantly associated with PFS.In the observation group,adverse events of grade 3 or higher were reported in 29 patients(41.4%),which primarily included vasculitis,hypothyroidism,hypersensitivity reactions,and diarrhea.Conclusion:The use of camrelizumab significantly improved treatment outcomes and prognosis for patients with recurrent,metastatic,and treatment-na?ve advanced cervical cancer,with significantly improved progression-free survival.Although a certain proportion of patients experienced adverse events of grade 3 or higher,the overall safety profile was acceptable.In clinical practice,immunotherapy offers a more effective treatment option for patients.

Objective To determine the effect of baicalein on high glucose-induced cardiac fibro-blast pyroptosis based on the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)pathway.Methods Rat cardiac fibroblasts were grouped into control,high glucose group,low-,medium-and high-dose baicalein(H-,M-and L-baicalein)groups,and H-baicalein+NLRP3 agonist(BMS-986299)group.Except for the control group,all other groups were cultured in DMEM medium containing 40 mmol/L glucose,then 12.5,25 and 50 μmol/L baicalein was added into the medium correspondingly,and 1 μmol/L BMS-986299 was used to treat the H-baicalein+NLRP3 agonist group.Lactate dehydrogenase(LDH)cytotoxicity assay were employed to detect cell cytotoxicity.qRT-PCR and Western blotting were performed to determine the expression of NLRP3,Caspase-1,and GSDMD at mRNA and protein levels.Results High glucose treatment induced more EdU positive cells,higher pyroptotic rate,stronger cytotoxicity,higher Col-Ⅰ and Col-Ⅲ contents,and enhanced mRNA and protein levels of NLRP3,Caspase-1 and GSDMD in comparison to the control group(P＜0.05).The H-baicalein+NLRP3 agonist group had more EdU positive cells(26.85±2.95 cells vs 15.43±1.82 cells,P＜0.05),higher pyroptotic rate[(33.45±4.02)％vs(17.34±2.15)％,P＜0.05],stronger cytotoxicity[(27.94±2.93)％vs(14.13±1.87)％,P＜0.05],and increased contents of Col-Ⅰ(107.58±13.39 ng/ml vs 58.73±8.36 ng/ml,P＜0.05)and Col-Ⅲ(118.43±13.95 ng/ml vs 68.74±8.57 ng/ml,P＜0.05),and enhanced expression of NLRP3,Caspase-1 and GSDMD at both mRNA and protein levels(P＜0.05)when compared with the H-baicalein group.Conclusion Baicalein inhibits high glucose-induced cardiac fibroblast pyroptosis by suppressing NLRP3/Caspase-1/GSDMD pathway.

Objective:To explore the correlation between the lesion imaging characteristics and the parent artery plaques detected by high-resolution magnetic resonance imaging (HR-MRI) in patients with recent small subcortical infarction (RSSI) in the lenticulostriate artery territory with mild stenosis of the parent artery.Methods:Consecutive patients with RSSI in the lenticulostriate artery territory admitted to Department of Neurology, the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2022 were prospectively enrolled. Patients with stenosis of <50% in the ipsilateral middle cerebral artery (MCA) who had completed HR-MRI were included. The RSSI lesion characteristics, such as the lowest slice involved (LS), total number of slices involved (TNS) were evaluated based on serialized axial levels of diffusion weighted imaging. HR-MRI was utilized to assess the presence of dorsal superior plaques in the M1 segment of the responsible MCA. Patients were divided into plaque group and non-plaque group based on the presence or absence of plaque. Logistic regression analysis was carried out to identify the lesion characteristics associated with the presence of dorsal superior plaques in the MCA. A receiver operating characteristic (ROC) curve was employed to estimate the predictive efficacy of these parameters for MCA plaques using the area under the curve (AUC) and the optimal cut-off point.Results:A total of 112 patients were incorporated into the final analysis. The age of these patients was (57.08±11.90) years, and 78 patients (69.64%) were male. Plaques were detected on the dorsal superior wall of the MCA in 57 cases (50.89%) as the plaque group, and the other 55 cases (49.11%) were regarded as the non-plaque group. Multivariate Logistic regression revealed that LS was significantly associated with MCA plaques ( OR=0.674, 95% CI 0.485-0.937, P=0.019). The optimal cut-off point (LS≤1) was determined by ROC curve analysis (AUC=0.640, P=0.007). Conclusion:The findings suggest that in RSSI patients with mild stenosis of the parent artery, an LS≤1 is notably associated with the presence of dorsal superior plaques on MCA as detected by HR-MRI.

Objective To explore the effect of circFAT1 on myocardial injury in rats with diabetic cardiomyopathy(DCM)and the regu-latory mechanism of circFAT1 on the miR-211-5p/CCND2 axis.Methods A DCM rat model was established by injecting rats with high glucose and high fat feed combined with STZ.The rats were randomly separated into DCM,circ-NC,circFAT1,circFAT1+agomir-NC,and circFAT1+miR-211-5p agomir groups,with 20 rats in each group;rats fed regular feed were used as control.Real-time PCR was used to detect the levels of circFAT1,miR-211-5p,and CCND2in myocardial tissue and Western blotting was used to detect CCND2 expression in myocardial tissue.The levels of fasting blood glucose(FBG),total cholesterol(TC),and triglycerides(TG)of rats were recorded.Car-diac ultrasound was used to detect the cardiac function of rats.Furthermore,HE and Masson staining were used to observe the pathological morphology of myocardial tissue and TUNEL staining was used to detect myocardial apoptosis.Additionally,ELISA was used to detect the levels of interleukin-1β(IL-1β),IL-6,and tumor necrosis factor-α(TNF-α).Double luciferase reporter gene assay was used to verify the targeting relationship among circFAT1,miR-211-5p,and CCND2.Results Compared with the control group,the expression of circFAT1 and CCND2mRNA and protein and the levels of LVEF and LVFS decreased in the DCM group(P<0.05)whereas,the levels of FBG,TC,TG,LVEDd,LVEDs,CVF,cell apoptosis rate,IL-1β,IL-6,and TNF-αincreased(P<0.05).Compared with the DCM group,the levels of circFAT1,CCND2mRNA and protein,LVEF,and LVFS increased in the circFAT1 group(P<0.05),whereas the levels of FBG,TC,TG,LVEDd,LVEDs,CVF,cell apoptosis rate,IL-1β,IL-6,and TNF-α decreased(P<0.05).Furthermore,miR-211-5p agomir reversed the protective effect of circFAT1 on DCM myocardial injury,and the expression of CCND2mRNA and protein decreased(P<0.05).Conclu-sion circFAT1 alleviates myocardial tissue damage in rats with DCM by regulating the miR-211-5p/CCND2 axis.

Objective:To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications.Methods:This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression.Results:The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion:Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.

Objective To analyze the effect of circLRP6 on high glucose-induced renal tubular epithelial cell injury via miR-31-5p/high mobility group protein A1(HMGA1)axis regulation.Methods Human renal tubular epithelial HK-2 cells were cultured in vitro and divided into eight groups:control,high glucose,high glucose+si-NC,high glucose+si-circLRP6,high glucose+si-circLRP6+miR-NC,high glucose+si-circLRP6+miR-31-5p inhibitor,high glucose+si-circLRP6+miR-31-5p inhibitor+si-NC,and high glucose+si-circ-LRP6+ miR-31-5p inhibitor+si-HMGA1.The circLRP6,miR-31-5p,and HMGA1 mRNA levels were determined using real-time quantitative PCR.Cell supernatant IL-6 and tumor necrosis factor-α(TNF-α)levels,lactate dehydrogenase(LDH)activity,and malondialdehyde(MDA)content were also determined.Furthermore,flow cytometry was used to observe cell apoptosis.HMGA1,Bax,and Bcl-2 protein expression was detected by Western blotting.Finally,dual luciferase assay was used to report the targeting relationship of miR-31-5p with circLRP6 and HMGA1.Results Compared with the high glucose group,the HK-2 cell proliferation inhibition rate;cell superserum IL-6,TNF-α,LDH,and MDA levels;apoptosis rate;and Bax protein expression in the high glucose+si-circLRP6 group decreased significantly,whereas Bcl-2 protein expression increased significantly(all P＜0.05).Consequently,miR-31-5p downregulation possibly weakened the protective effect of si-circLRP6 on high glucose-induced renal tubular epithelial cell injury.HMGA1 expression inhibition reversed the effect of the si-circLRP6+miR-31-5p inhibitor on high glucose-induced renal tubular epithelial cell injury.Finally,miR-31-5p exhibited a targeting relationship with circLRP6 and HMGA1.Conclusion Si-circLRP6 protects high glucose-induced renal tubular epithelial cell injury via miR-31-5p upregulation and HMGA1 expression inhibition.