Objective:To investigate the predictive value of tumor morphology in hepatoce-llular carcinoma (HCC) immunotherapy.Methods:The propensity score matching and retrospective cohort study was conducted. The clinical data of 227 HCC patients who underwent immunotherapy in The First Affiliated Hospital of University of Science and Technology of China from January 2021 to December 2023 were collected. There were 203 males and 24 females, aged (57±11)years. Of the 227 patients, 93 patients with regular tumor morphology of HCC evaluated by computed tomography (CT) or magnetic resonance imaging (MRI) were divided into the regular morphology group, and 134 patients with irregular tumor morphology of HCC evaluated by CT or MRI were divided into the irregular morphology group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) analysis of factors affecting prognosis of patients; (3) prognosis of patients after propensity score matching. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve. The Log-rank test was used for survival analysis. The Cox proportional hazards regression model was used for univariate and multivariate analyses. Propensity score matching was done by the 1∶1 nearest neighbor matching method, with a caliper value of 0.02. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of 227 HCC patients undergoing immunotherapy, 164 cases were successfully matched, including 82 cases in the regular morphology group and 82 cases in the irregular morphology group. After propensity score matching, the elimination of patients who underwent radical surgical resection in the past, tumor number and alpha fetoprotein confounding bias ensured comparability between the two groups. (2) Analysis of factors affecting prognosis of patients. Results of multivariate analysis showed that body mass index ≥25 kg/m 2 and irregular tumor morphology were independent risk factors affecting overall survival time of patients ( hazard ratio=0.891, 1.870, 95% confidence interval as 0.825-0.963, 1.151-3.038, P<0.05). (3) Prognosis of patients after propensity score matching. After propensity score matching, the median progression-free survival time was 11.9(95% confidence interval as 9.2-16.1)months for patients in the regular tumor morphology group and 6.4(95% confidence interval as 4.4-8.1)months for patients in the irregular tumor morphology group, the 1-year progress-free survival rate was 48.48% for patients in the regular tumor morphology group and 22.25% for patients in the irregular tumor morphology group. There was a significant difference in progress-free survival between patients in the regular tumor morphology group and the irregular tumor morphology group ( χ2=16.000, P<0.05). The median overall survival time was 27.2(95% confidence interval as 23.7-not reached)months for patients in the regular tumor morphology group and 18.1 (95% confidence interval as 15.8-20.8)months for patients in the regular tumor morphology group, the 1-year overall survival rate was 83.27% for patients in the regular tumor morphology group and 66.98% for patients in the irregular tumor morphology group. There was a significant difference in overall survival between patients in the regular tumor morphology group and the irregular tumor morphology group ( χ2=13.400, P<0.05). Conclusions:Tumor morphology has a predictive value for the efficacy of immunotherapy for HCC. Compared with HCC patients of regular tumor morphology, immunotherapy is less effective in patients with irregular tumor morphology.

AIM To investigate the effects of Congrong San on neuronal apoptosis and the Bax/Bcl-2/Caspase3 signaling pathway in a rat model of Alzheimer's disease(AD).METHODS A total of 60 2-month-old SD male rats were randomly divided into the blank group,the model group,the memantine hydrochloride group(0.025 g/kg)and low-dose,medium-dose and high-dose Congrong San groups(4.62,9.24,18.48 g/kg).All groups except the control group received stereotactic intracerebral injection of Aβ1-42 to establish AD models.Following the successful modeling,each group received its corresponding intragastric administration once daily for 28 consecutive days.After the administration,the rats had their learning and memory ability detected by the morris water maze test;their hippocampal neuronal morphology observed with HE and Nissl staining;their hippocampal neuronal apoptosis observed with TUNEL staining;and their hippocampal expressions of amyloid precursor protein(APP),β-site APP-cleaving enzyme 1(BACE1),and apoptosis-related proteins Bax,Bcl-2 and Caspase3 detected with Western blot assay.RESULTS Compared with the model group,the groups intervened with medium-dose and high-dose Congrong San exhibited improved learning and memory performance,alleviated hippocampal neuronal damage,increased Nissl body count(P＜0.01),reduced hippocampal apoptosis rate(P＜0.05,P＜0.01),decreased protein expressions of APP,BACE1,Bax and cleaved-Caspase3/Caspase3 ratio(P＜0.05,P＜0.01),and elevated Bcl-2 expression(P＜0.01).CONCLUSION Congrong San mitigates cognitive impairment,hippocampal neuronal damage,and apoptosis in AD rats,probably through inhibition of the Bax/Bcl-2/Caspase3 signaling pathway activation.

Objective:To investigate the status of post-traumatic stress disorder (PTSD) and its influencing factors in postoperative breast cancer patients.Methods:A convenience sampling method was used to select 410 postoperative breast cancer patients from the Provincial Hospital of the First Medical University of Shandong between January 2023 and December 2024. The PTSD Checklist-Civilian Version (PCL-C), the Connor-Davidson Resilience Scale (CD-RISC), and the Simple Coping Style Questionnaire (SCSQ) were used for assessment. Binary Logistic regression analysis was performed to analyze influencing factors.Results:A total of 410 questionnaires were distributed, and 405 valid questionnaires were returned, with an effective recovery rate of 98.78% (405/410). Among them, 150 patients were PTSD-positive. Binary Logistic regression analysis showed that educational level, monthly family income, psychological resilience, and coping style were influencing factors for PTSD in postoperative breast cancer patients ( P<0.05) . Conclusions:Low education level, low income, and negative coping style are risk factors for PTSD in postoperative breast cancer patients; positive coping style and high psychological resilience are protective factors. Clinical practitioners should develop preventive or intervention measures based on these influencing factors to reduce the occurrence of PTSD in postoperative breast cancer patients.

Aim To explore the mechanism of Cong Rong San on AD model rats based on protein kinase R-like endoplasmic reticulum kinase(PERK)-eukaryotic initiation factor 2α(eIF2α)-nuclear factor kappa B(NF-κB)signaling pathway.Methods Sixty mice were randomly divided into normal group,model group,Cong Rong San groups(4.62,9.24,18.48 g·kg-1)and donepezil group,with 10 mice in each group.All groups of rats received bilateral hippocampal injections of Aβ1-42 to establish the AD model,except the normal group.After the intragastric administration,the Morris water maze behavior test was performed for rats to test-ed the learning and memory abilities.Nissl staining was detected the quantity and Nissl bodies of nerve cells.To detect the nuclear translocation of NF-κB by immu-nofluorescence.To observe the ultrastructure of endo-plasmic reticulum by Transmission electron microsco-py.ELISA for Aβ1-42 and inflammatory cytokines quantification.Western blot was used to detect the ex-pression level of protein in the hippocampus in PERK-eIF2α-NF-κB signaling pathway.Results The morris water maze results showed that Cong Rong San im-proved the escape latency time,increased the number of platform crossings,and prolonged the time spent in the target quadrant in AD rats.(P＜0.05 or P＜0.01).Nissl staining shows the neuronal cells are ar-ranged neatly,nucleus are present and the number of Nissl bodies was numerous and the number of neurons was increased in various doses of Cong Rong San.Im-munofluorescence showed that the expression of NF-κB in the nucleus of rats was decreased(P＜0.05 or P＜0.01).The shape of endoplasmic reticulum was neat,no significantly expanded,and the structure was normal in various doses of Cong Rong San.The levels of Aβ1-42,IL-1,TNF-α and the ratio of p-PERK/PERK,p-eIF2α/eIF2α,p-NF-κB p65/NF-κB p65 in hippo-campus of Cong Rong San group was significantly de-creased in ELISA and Western blot test(P＜0.05 or P＜0.01).Conclusion Cong Rong San can alleviates the immune inflammatory response of neuronal cells in the ERS state for improve the learning and memory a-bility of AD rats,the mechanism of action may through restraint the activation of PERK-eIF2α-NF-κB signa-ling pathway.

Objective:To evaluate the effect of cathepsin B(CTSB)/NOD-like receptor pyrin domain containing 3(NLRP3)pathway on the polarization of macrophages induced by LPS.Methods:The well-growing RAW264.7 mouse mononuclear macrophage lines were cultured in vitro and divided into 3 groups(n=6)according to the random number table method:control group(C group),LPS group(L group)and LPS+CA074-me(CTSB inhibitors)group(B group).C group was cultured normally for 24 h,L group was cultured with LPS concentration of 1 μg/ml medium for 24 h.B group was pretreated with CTSB inhibitor CA074-me 30 μmol/L for 1 h before LPS induction,and co-cultured with LPS concentration of 1 μg/ml medium for 24 h.After 24 hours,the morphological changes of the cells were observed by microscope,the concentrations of IL-1β and IL-18 in the supernatant were determined by ELISA.The ex-pressions of cathepsin B precursor(pro-CTSB),mature cathepsin B(mature-CTSB),NLRP3,apoptosis-related speck protein(ASC)and apoptosis-related speck protein-1(caspase-1)were detected by Western blot.The mRNA expression levels of CD32,inducible ni-tric oxide synthase(iNOS),arginase 1(Arg-1)and CD206 were detected by qRT-PCR.The positive expression rates of M1 macro-phage surface marker CD86 and M2 macrophage surface marker CD206 were detected by flow cytometry.Results:Compared with group C,the morphology of cells in groups L and B became larger and pseudopodia appeared.The concentrations of IL-1β and IL-18 in cell supernatant were increased,the expressions of pro-CTSB,mature-CTSB,NLRP3,ASC and caspase-1 were increased,and the expressions of CD32,iNOS mRNA were up-regulated and the positive rates of CD86 and CD206 were increased(P<0.01).Arg-1 and CD206 mRNA in group B were up-regulated(P<0.01).Compared with group L,the pseudopodia of group B were reduced,and the morphology was closer to group C.The concentration of IL-1β and IL-18 in the supernatant,the expression of mature-CTSB,NLRP3,ASC and caspase-1,CD32 and iNOS mRNA and the positive rate of CD86 were down-regulated in group B.The expression of pro-CTSB,Arg-1 and CD206 mRNA and the positive rate of CD206 were increased(P<0.01).Conclusion:Inhibition of CTSB/NLRP3 pathway can reduce the inflammatory response,reduce the LPS-induced polarization of RAW264.7 cells to M1 macrophages,and pro-mote their polarization to M2 macrophages.

Objective:To investigate the status of post-traumatic stress disorder (PTSD) and its influencing factors in postoperative breast cancer patients.Methods:A convenience sampling method was used to select 410 postoperative breast cancer patients from the Provincial Hospital of the First Medical University of Shandong between January 2023 and December 2024. The PTSD Checklist-Civilian Version (PCL-C), the Connor-Davidson Resilience Scale (CD-RISC), and the Simple Coping Style Questionnaire (SCSQ) were used for assessment. Binary Logistic regression analysis was performed to analyze influencing factors.Results:A total of 410 questionnaires were distributed, and 405 valid questionnaires were returned, with an effective recovery rate of 98.78% (405/410). Among them, 150 patients were PTSD-positive. Binary Logistic regression analysis showed that educational level, monthly family income, psychological resilience, and coping style were influencing factors for PTSD in postoperative breast cancer patients ( P<0.05) . Conclusions:Low education level, low income, and negative coping style are risk factors for PTSD in postoperative breast cancer patients; positive coping style and high psychological resilience are protective factors. Clinical practitioners should develop preventive or intervention measures based on these influencing factors to reduce the occurrence of PTSD in postoperative breast cancer patients.

Objective:To investigate the predictive value of tumor morphology in hepatoce-llular carcinoma (HCC) immunotherapy.Methods:The propensity score matching and retrospective cohort study was conducted. The clinical data of 227 HCC patients who underwent immunotherapy in The First Affiliated Hospital of University of Science and Technology of China from January 2021 to December 2023 were collected. There were 203 males and 24 females, aged (57±11)years. Of the 227 patients, 93 patients with regular tumor morphology of HCC evaluated by computed tomography (CT) or magnetic resonance imaging (MRI) were divided into the regular morphology group, and 134 patients with irregular tumor morphology of HCC evaluated by CT or MRI were divided into the irregular morphology group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) analysis of factors affecting prognosis of patients; (3) prognosis of patients after propensity score matching. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve. The Log-rank test was used for survival analysis. The Cox proportional hazards regression model was used for univariate and multivariate analyses. Propensity score matching was done by the 1∶1 nearest neighbor matching method, with a caliper value of 0.02. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of 227 HCC patients undergoing immunotherapy, 164 cases were successfully matched, including 82 cases in the regular morphology group and 82 cases in the irregular morphology group. After propensity score matching, the elimination of patients who underwent radical surgical resection in the past, tumor number and alpha fetoprotein confounding bias ensured comparability between the two groups. (2) Analysis of factors affecting prognosis of patients. Results of multivariate analysis showed that body mass index ≥25 kg/m 2 and irregular tumor morphology were independent risk factors affecting overall survival time of patients ( hazard ratio=0.891, 1.870, 95% confidence interval as 0.825-0.963, 1.151-3.038, P<0.05). (3) Prognosis of patients after propensity score matching. After propensity score matching, the median progression-free survival time was 11.9(95% confidence interval as 9.2-16.1)months for patients in the regular tumor morphology group and 6.4(95% confidence interval as 4.4-8.1)months for patients in the irregular tumor morphology group, the 1-year progress-free survival rate was 48.48% for patients in the regular tumor morphology group and 22.25% for patients in the irregular tumor morphology group. There was a significant difference in progress-free survival between patients in the regular tumor morphology group and the irregular tumor morphology group ( χ2=16.000, P<0.05). The median overall survival time was 27.2(95% confidence interval as 23.7-not reached)months for patients in the regular tumor morphology group and 18.1 (95% confidence interval as 15.8-20.8)months for patients in the regular tumor morphology group, the 1-year overall survival rate was 83.27% for patients in the regular tumor morphology group and 66.98% for patients in the irregular tumor morphology group. There was a significant difference in overall survival between patients in the regular tumor morphology group and the irregular tumor morphology group ( χ2=13.400, P<0.05). Conclusions:Tumor morphology has a predictive value for the efficacy of immunotherapy for HCC. Compared with HCC patients of regular tumor morphology, immunotherapy is less effective in patients with irregular tumor morphology.

Aim To investigate the effects of Congrong San(CRS)on learning and memory ability,hippocam-pal neuronal injury,and ferroptosis in rats with Alzhei-mer's disease(AD)and to explore the related mecha-nisms.Methods AD rat models were established and divided into Sham,Model,CRS low-dose,CRS medium-dose,CRS high-dose,and memantine groups.After treatment,Morris water maze,HE and Nissl staining,transmission electron microscopy,immunofluorescence staining,Western blot,and kit assays were performed to assess learning and memory ability,hippocampal neuro-nal injury,ferroptosis-related indicatorsand glucose reg-ulated protein 78 ku(GRP78)-(proteinkinaseR-li-keERkinase)PERK-(activating transcription factor 4)ATF4 pathway protein expression.Results Com-pared with the model group,rats in the CRS medium-and high-dose groups and the memantine group showed significant improvement in learning and memory abili-ty,reduced hippocampal neuronal injury,increased number of Nissl bodies,and ameliorated endoplasmic reticulum swelling and mitochondrial damage.In addi-tion,the expressions of GRP78,p-PERK/PERK,and ATF4 were downregulated,while GPX4 expression was upregulated in the CRS medium-and high-dose groups and the memantine group.Moreover,MDA content de-creased,and SOD and GSH-PX levels increased in these groups.Conclusions CRS can improve the learning and memory ability in AD rats,reduce hipp-ocampal neuronal injury and ferroptosis,and its mecha-nism may be related to the inhibition of the GRP78-PERK-ATF4 pathway,enhancement of GPX4 expres-sion,and reduction of oxidative stress levels,providing a new approach for the clinical treatment of AD.

AIM To investigate the effects of Yiqi Juanbi Formula on chondrocyte pyroptosis in rat models of collagen-induced arthritis(CIA).METHODS Fifty rats were subcutaneously injected at the tail base with an emulsion containing equal volumes of bovine type Ⅱ collagen and incomplete Freund's adjuvant(IFA)to establish the CIA models.These rats were then randomly assigned to the model group,the methotrexate group(0.35 mg/kg),and the low-dose,medium-dose,and high-dose Yiqi Juanbi Formula groups(9.4,18.7,37.4 g/kg),in contrast to the ten intact rats serving in the normal control group.Following four weeks of intragastric administration,the rats had their general conditions observed;their joint swelling and arthritis indices measured;their ankle joint pathology assessed by HE staining;their serum levels of IL-1β,IL-18 and TNF-ɑ detected by ELISA;their mRNA expressions of NLRP3,Caspase-1,GSDMD,IL-1β,IL-18 and TNF-ɑ in ankle cartilage quantified by RT-qPCR;their protein expressions of NF-κB,NLRP3 and Caspase-1 in ankle cartilage analyzed by Western blot;and their NLRP3 and GSDMD positive expressions in ankle cartilage examined by immunohistochemistry.RESULTS Compared to the control group,the model group showed significantly increased joint swelling and arthritis indices(P＜0.01);elevated serum levels of IL-1 β,IL-18 and TNF-ɑ(P＜0.01);pathological changes including cartilage surface defects,reduced cell count,altered cellular morphology,irregular cell arrangement,and significant inflammatory cell infiltration in synovial tissue;upregulated mRNA expressions of NF-κB,NLRP3,Caspase-1,GSDMD,IL-1β,IL-18 and TNF-ɑ(P＜0.01)and increased protein expressions of NF-κB,NLRP3 and Caspase-1(P＜0.01)in ankle cartilage;enhanced positive expressions of NLRP3 and GSDMD in ankle cartilage(P＜0.01).Compared to the model group,the groups intervened with methotrexate or medium-or high-dose Yiqi Juanbi Formula exhibited reduced joint swelling and arthritis indices(P＜0.01);alleviated pathological damage in ankle joints;decreased serum levels of IL-1β,IL-18 and TNF-ɑ(P＜0.01);downregulated mRNA expressions of NF-κB,NLRP3,Caspase-1,GSDMD,IL-1β,IL-18 and TNF-ɑ(P＜0.05,P＜0.01),and reduced protein expressions of NF-κB,NLRP3 and Caspase-1(P＜0.05,P＜0.01)in ankle cartilage;and diminished positive expressions of NLRP3 and GSDMD in ankle cartilage(P＜0.01).CONCLUSION Yiqi Juanbi Formula alleviates inflammation in CIA rats,potentially by inhibiting the activation of the NF-κB/NLRP3/Caspase-1 signaling pathway,thereby suppressing chondrocyte pyroptosis.

Aim To explore the mechanism of Cong Rong San on AD model rats based on protein kinase R-like endoplasmic reticulum kinase(PERK)-eukaryotic initiation factor 2α(eIF2α)-nuclear factor kappa B(NF-κB)signaling pathway.Methods Sixty mice were randomly divided into normal group,model group,Cong Rong San groups(4.62,9.24,18.48 g·kg-1)and donepezil group,with 10 mice in each group.All groups of rats received bilateral hippocampal injections of Aβ1-42 to establish the AD model,except the normal group.After the intragastric administration,the Morris water maze behavior test was performed for rats to test-ed the learning and memory abilities.Nissl staining was detected the quantity and Nissl bodies of nerve cells.To detect the nuclear translocation of NF-κB by immu-nofluorescence.To observe the ultrastructure of endo-plasmic reticulum by Transmission electron microsco-py.ELISA for Aβ1-42 and inflammatory cytokines quantification.Western blot was used to detect the ex-pression level of protein in the hippocampus in PERK-eIF2α-NF-κB signaling pathway.Results The morris water maze results showed that Cong Rong San im-proved the escape latency time,increased the number of platform crossings,and prolonged the time spent in the target quadrant in AD rats.(P＜0.05 or P＜0.01).Nissl staining shows the neuronal cells are ar-ranged neatly,nucleus are present and the number of Nissl bodies was numerous and the number of neurons was increased in various doses of Cong Rong San.Im-munofluorescence showed that the expression of NF-κB in the nucleus of rats was decreased(P＜0.05 or P＜0.01).The shape of endoplasmic reticulum was neat,no significantly expanded,and the structure was normal in various doses of Cong Rong San.The levels of Aβ1-42,IL-1,TNF-α and the ratio of p-PERK/PERK,p-eIF2α/eIF2α,p-NF-κB p65/NF-κB p65 in hippo-campus of Cong Rong San group was significantly de-creased in ELISA and Western blot test(P＜0.05 or P＜0.01).Conclusion Cong Rong San can alleviates the immune inflammatory response of neuronal cells in the ERS state for improve the learning and memory a-bility of AD rats,the mechanism of action may through restraint the activation of PERK-eIF2α-NF-κB signa-ling pathway.