ObjectiveTo explore the effect and mechanism of Taishan Panshi powder （TSPSP） on inhibiting oxidative stress injury in human chorionic trophoblast cells （HTR-8/SVneo）， and to uelucidate the underlying mechanism of TSPSP in the treatment of spontaneous abortion （SA）. MethodsGene differential analysis of SA was performed using the Gene Expression Omnibus （GEO） database and correlated with oxidative stress. Network pharmacology was employed to screen the active components of TSPSP， and a "Chinese medicine-component-target-disease" network was constructed to predict the mechanism of action of TSPSP. For in vitro validation experiments， HTR-8/SVneo cells were divided into blank group， model group， TSPSP-containing serum 2.5%， 5%， 10% groups， and nuclear factor E₂-related factor 2 （Nrf2） inhibitor group （ML385， 30 μmol·L^-1）. Except for the blank group， other groups were stimulated with 150 μmol·L^-1 H₂O₂ for 3 h to establish a cell oxidative stress injury model. After successful modeling， the blank group and model group were given 10% blank serum， each TSPSP-containing serum group was treated with the corresponding concentration of drug-containing serum， and the Nrf2 inhibitor group was additionally given 30 μmol·L^-1 ML385 on the basis of 10% TSPSP-containing serum. All groups of cells were continuously cultured under the above conditions for 24 h， and then samples were collected for subsequent detection. Cell viability in each group was detected by CCK-8 assay. Cell migration rate was detected by scratch test. The contents of malondialdehyde （MDA）， Fe²⁺， and Glutathione （GSH） were detected by enzyme-linked immunosorbent assay （ELISA）. Intracellular reactive oxygen species （ROS） level was detected by a fluorescent probe （DCF-DA）. The protein and mRNA expression levels of Kelch-like ECH-associated protein 1 （KEAP1）， Nrf2， and forkhead box protein O3 （FoxO3） in cells were detected by immunofluorescence （IF） and real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of KEAP1， Nrf2， FoxO3， Glutathione peroxidase 4 （GPX4）， and superoxide dismutase （SOD） in cells were detected by Western blot. ResultsThe GSE76862 and GSE22490 datasets were obtained from the GEO database. Differential gene analyses showed that the KEAP1， Nrf2， and FoxO3 genes were all associated with the disease. After matching with the oxidative stress pathway， nine significantly differential pathways were identified （P<0.05）， among which three contained the target genes Nrf2 and FoxO3. A total of 246 active ingredient targets of TSPSP and 2 804 SA-related targets were obtained through network pharmacology， and 154 potential action targets were obtained after taking the intersection. Topological analysis showed that targets such as KEAP1 and Nrf2 exhibited high degree values. GO and KEGG enrichment analyses indicated that the intersection targets were mainly involved in oxidative stress response， FOXO and MAPK signaling pathways， etc. In in vitro experiments， compared with the blank group， the cell viability in the model group was significantly decreased （P<0.01）. Compared with the model group， the cell viability in each TSPSP-containing serum group was significantly increased （P<0.01）. Compared with the 10% TSPSP-containing serum group， the cell viability in the ML385 group decreased to approximately 70% （P<0.01）. Compared with the blank group， the model group showed significantly increased contents of MDA， Fe²⁺， and ROS， decreased GSH expression （P<0.01）， significantly reduced cell migration rate （P<0.01）， and increased protein and mRNA expression levels of KEAP1 and FoxO3 （P<0.01）， while decreased protein and mRNA expression levels of Nrf2， GPX4， and SOD （P<0.01）. Compared with the model group， each TSPSP-containing serum group showed significantly decreased contents of MDA， Fe²⁺， and ROS， increased GSH expression （P<0.01）， significantly increased migration rate （P<0.01）， significantly decreased protein and mRNA expression levels of KEAP1 and FoxO3 （P<0.05， P<0.01）， and significantly increased protein and mRNA expression levels of Nrf2， GPX4， and SOD （P<0.05， P<0.01）. Compared with the 10% TSPSP-containing serum group， the ML385 group showed reversed trends in all indicators （P<0.05， P<0.01）. ConclusionTSPSP can inhibit H₂O₂-induced oxidative stress injury of trophoblast cells， and its mechanism of action may be related to the drug activating the KEAP1/Nrf2/FoxO3 signaling pathway.

ObjectiveTo explore the effect and mechanism of Taishan Panshi powder （TSPSP） on inhibiting oxidative stress injury in human chorionic trophoblast cells （HTR-8/SVneo）， and to uelucidate the underlying mechanism of TSPSP in the treatment of spontaneous abortion （SA）. MethodsGene differential analysis of SA was performed using the Gene Expression Omnibus （GEO） database and correlated with oxidative stress. Network pharmacology was employed to screen the active components of TSPSP， and a "Chinese medicine-component-target-disease" network was constructed to predict the mechanism of action of TSPSP. For in vitro validation experiments， HTR-8/SVneo cells were divided into blank group， model group， TSPSP-containing serum 2.5%， 5%， 10% groups， and nuclear factor E₂-related factor 2 （Nrf2） inhibitor group （ML385， 30 μmol·L^-1）. Except for the blank group， other groups were stimulated with 150 μmol·L^-1 H₂O₂ for 3 h to establish a cell oxidative stress injury model. After successful modeling， the blank group and model group were given 10% blank serum， each TSPSP-containing serum group was treated with the corresponding concentration of drug-containing serum， and the Nrf2 inhibitor group was additionally given 30 μmol·L^-1 ML385 on the basis of 10% TSPSP-containing serum. All groups of cells were continuously cultured under the above conditions for 24 h， and then samples were collected for subsequent detection. Cell viability in each group was detected by CCK-8 assay. Cell migration rate was detected by scratch test. The contents of malondialdehyde （MDA）， Fe²⁺， and Glutathione （GSH） were detected by enzyme-linked immunosorbent assay （ELISA）. Intracellular reactive oxygen species （ROS） level was detected by a fluorescent probe （DCF-DA）. The protein and mRNA expression levels of Kelch-like ECH-associated protein 1 （KEAP1）， Nrf2， and forkhead box protein O3 （FoxO3） in cells were detected by immunofluorescence （IF） and real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of KEAP1， Nrf2， FoxO3， Glutathione peroxidase 4 （GPX4）， and superoxide dismutase （SOD） in cells were detected by Western blot. ResultsThe GSE76862 and GSE22490 datasets were obtained from the GEO database. Differential gene analyses showed that the KEAP1， Nrf2， and FoxO3 genes were all associated with the disease. After matching with the oxidative stress pathway， nine significantly differential pathways were identified （P<0.05）， among which three contained the target genes Nrf2 and FoxO3. A total of 246 active ingredient targets of TSPSP and 2 804 SA-related targets were obtained through network pharmacology， and 154 potential action targets were obtained after taking the intersection. Topological analysis showed that targets such as KEAP1 and Nrf2 exhibited high degree values. GO and KEGG enrichment analyses indicated that the intersection targets were mainly involved in oxidative stress response， FOXO and MAPK signaling pathways， etc. In in vitro experiments， compared with the blank group， the cell viability in the model group was significantly decreased （P<0.01）. Compared with the model group， the cell viability in each TSPSP-containing serum group was significantly increased （P<0.01）. Compared with the 10% TSPSP-containing serum group， the cell viability in the ML385 group decreased to approximately 70% （P<0.01）. Compared with the blank group， the model group showed significantly increased contents of MDA， Fe²⁺， and ROS， decreased GSH expression （P<0.01）， significantly reduced cell migration rate （P<0.01）， and increased protein and mRNA expression levels of KEAP1 and FoxO3 （P<0.01）， while decreased protein and mRNA expression levels of Nrf2， GPX4， and SOD （P<0.01）. Compared with the model group， each TSPSP-containing serum group showed significantly decreased contents of MDA， Fe²⁺， and ROS， increased GSH expression （P<0.01）， significantly increased migration rate （P<0.01）， significantly decreased protein and mRNA expression levels of KEAP1 and FoxO3 （P<0.05， P<0.01）， and significantly increased protein and mRNA expression levels of Nrf2， GPX4， and SOD （P<0.05， P<0.01）. Compared with the 10% TSPSP-containing serum group， the ML385 group showed reversed trends in all indicators （P<0.05， P<0.01）. ConclusionTSPSP can inhibit H₂O₂-induced oxidative stress injury of trophoblast cells， and its mechanism of action may be related to the drug activating the KEAP1/Nrf2/FoxO3 signaling pathway.

Objective To study whether electroacupuncture(EA)attenuates traumatic brain injury(TBI)by down-regulating glutamate carboxypeptidase Ⅱ(GCPII)gene expression in rats.Methods Rats were divided into Sham group(n=10),TBI group(n=11),TBI+EA group(n=11),TBI+EA+GCPII-NC group(n=11)and TBI+EA+GCPII-OE group(n=11).Sham group rats underwent sham surgery,while other groups rats underwent TBI modeling using an electronic brain injury instrument.The rats in Sham group and TBI group were fed normally,and the rats in other groups were treated with electroacupuncture for 14 days.On the basis of electroacupuncture treatment,rats in TBI+EA+GCPII-NC group and TBI+EA+GCPII-OE group were injected with GCPII-NC and GCPII-OE,respectively.After treatment,the cognitive function of rats was evaluated by neurological function score and Morris water labyrinth task.HE and TUNEL staining were performed on brain tissue.The water content,glutamate(Glu)content,calcium(Ca2+)concentration,superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px)and malondialdehyde(MDA)in brain tissue of rats in each group were measured.The mRNA or protein expression of GCPII,Bax,Bcl2 and cleaved caspase-3 in brain tissue were detected by qRT-PCR or Western blot.Results Compared with Sham group,the expression of mRNA and protein of GCPII in TBI group increased,the neurological function score and escape latency increased,the number of crossing the platform decreased,the water content increased,the cortex showed obvious damage,the content of Glu increased,the concentration of calcium increased,the levels of SOD,CAT and GSH-Px decreased,the level of MDA increased,the positive rate of TUNEL increased,the expression of Bax and cleaved caspase-3 protein increased,and the expression of Bcl2 protein decreased significantly(P<0.05).Compared with TBI group,the expression level of mRNA and protein of GCPII in TBI+EA group decreased,the neurological function score and escape latency decreased,the number of crossing platform increased,the water content decreased,the morphology of cortex improved obviously,the content of Glu decreased,the concentration of calcium decreased,the level of SOD,CAT and GSH-Px increased,the level of MDA decreased,the positive rate of TUNEL decreased,the expression level of Bax and cleaved caspase-3 protein decreased,and the expression level of Bcl2 protein increased significantly(P<0.05).Compared with TBI+EA group and TBI+EA+GCPII-NC group,the expression level of mRNA and protein of GCPII in TBI+EA+GCPII-OE group increased,neurological function score and escape latency increased,the number of crossing platform decreased,water content increased,cortical injury aggravated,Glu content increased,calcium concentration increased,SOD,CAT and GSH-Px levels decreased,MDA level increased,TUNEL positive rate increased,Bax and cleaved caspase-3 protein expression increased,and the expression of Bcl2 protein decreased significantly(P<0.05).Conclusion By down-regulating the expression of GCPII gene,electroacupuncture reduced the content of glutamate in the brain tissue of TBI rats,thereby inhibiting calcium overload,oxidative stress and neuronal apoptosis in the brain tissue,and thereby improving cognitive function and alleviating brain injury.

Objective:To study the safety and feasibility of transcatheter arterial chemoembolization (TACE) combined with apatinib in the treatment of advanced hilar cholangiocarcinoma.Methods:Clinical data of 41 patients with hilar cholangiocarcinoma admitted to the First Affiliated Hospital of Zhengzhou University from November 2019 to October 2020 were prospectively collected, including 21 males and 20 females, aged (65.1±12.5) years. The drugs used for TACE were albumin paclitaxel and gemcitabine, which were performed once every four to six weeks for no more than six times. Apatinib were adminstered two days after each TACE. The primary endpoint was objective response rate (ORR) and the secondary endpoints were progression-free survival (PFS), overall survival (OS) and adverse events. Patients were followed-up by outpatient, inpatient or telephone review. Survival analysis was performed using the Kaplan-Meier method.Results:Hilar cholangiocarcinoma were confirmed in all 41 patients by pathology. All patients were treated with TACE for at least twice. Twenty-three patients achieved complete remission, 14 stable disease, and four partial remission, with an ORR of 56.1% and a disease control rate of 90.2%. The follow-up duration was (13.3±5.4) months without lost to follow-up. The median PFS was 9.0 months, the median OS was 14.0 months, the 1-year cumulative recurrence-free survival rate was 31.7%, and the 1-year cumulative survival rate was 65.9%. Treatment-related adverse events in this study were predominantly Clavien-Dindo grade 1 or 2, without grade 4 to 5.Conclusion:TACE combined with apatinib treatment could be safe and feasible for advanced hilar cholangiocarcinoma.

OBJECTIVE To assess the cost-effectiveness of durvalumab combined with chemotherapy as a first-line treatment for advanced biliary tract cancer from the perspective of the Chinese healthcare system. METHODS Using data from the TOPAZ-1 clinical trial， a three-state Markov model comprising progression-free survival （PFS）， progressive disease （PD） and death was developed， with a cycle length of 21 days and a 10-year time horizon. Patients in the observation group received durvalumab in combination with gemcitabine and cisplatin， whereas those in the control group received placebo plus the same chemotherapy regimen. The evaluation indexes were quality-adjusted life year （QALY） and the incremental cost-effectiveness ratio （ICER）. The willingness-to-pay （WTP） threshold was set at three times the 2024 Chinese per capita gross domestic product （GDP） （287 247 yuan/QALY）. The sensitivity analyses， along with scenario analyses， were performed. RESULTS In the base-case analysis， the ICER of observation group compared to control group was 1 166 344.46 yuan/QALY， far exceeding the WTP threshold， indicating that the regimen was not cost-effective. One-way sensitivity analysis identified the PD state utility， discount rate， cost of durvalumab， and PFS state utility as the main drivers of ICER variation. Probabilistic sensitivity analysis showed that， at the above WTP threshold， the probability of the acceeptance of this regimen was 0， further supporting the robustness of the base-case findings. In the scenario analysis， inclusion of a patient assistance program reduced the ICER to 235 885.16 yuan/ QALY， below the above WTP threshold， suggesting cost-effectiveness under this assistance program. However， when applying a regional WTP threshold set at three times the per capita GDP （158 475 yuan/QALY） of Gansu Province （the province with the lowest GDP in China in 2024）， the ICER remained above the threshold， indicating that the regimen was not cost-effective at the regional level. CONCLUSIONS At current pricing， durvalumab plus chemotherapy as a first-line treatment for advanced biliary tract cancer is not cost-effective in China. Although the introduction of a patient assistance program can substantially reduce the ICER and achieve cost-effectiveness at a WTP threshold set at three times the 2024 per capita GDP of China， due to limited affordability in low-income areas， the program remains not cost-effective.

Objective To study whether electroacupuncture(EA)attenuates traumatic brain injury(TBI)by down-regulating glutamate carboxypeptidase Ⅱ(GCPII)gene expression in rats.Methods Rats were divided into Sham group(n=10),TBI group(n=11),TBI+EA group(n=11),TBI+EA+GCPII-NC group(n=11)and TBI+EA+GCPII-OE group(n=11).Sham group rats underwent sham surgery,while other groups rats underwent TBI modeling using an electronic brain injury instrument.The rats in Sham group and TBI group were fed normally,and the rats in other groups were treated with electroacupuncture for 14 days.On the basis of electroacupuncture treatment,rats in TBI+EA+GCPII-NC group and TBI+EA+GCPII-OE group were injected with GCPII-NC and GCPII-OE,respectively.After treatment,the cognitive function of rats was evaluated by neurological function score and Morris water labyrinth task.HE and TUNEL staining were performed on brain tissue.The water content,glutamate(Glu)content,calcium(Ca2+)concentration,superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px)and malondialdehyde(MDA)in brain tissue of rats in each group were measured.The mRNA or protein expression of GCPII,Bax,Bcl2 and cleaved caspase-3 in brain tissue were detected by qRT-PCR or Western blot.Results Compared with Sham group,the expression of mRNA and protein of GCPII in TBI group increased,the neurological function score and escape latency increased,the number of crossing the platform decreased,the water content increased,the cortex showed obvious damage,the content of Glu increased,the concentration of calcium increased,the levels of SOD,CAT and GSH-Px decreased,the level of MDA increased,the positive rate of TUNEL increased,the expression of Bax and cleaved caspase-3 protein increased,and the expression of Bcl2 protein decreased significantly(P<0.05).Compared with TBI group,the expression level of mRNA and protein of GCPII in TBI+EA group decreased,the neurological function score and escape latency decreased,the number of crossing platform increased,the water content decreased,the morphology of cortex improved obviously,the content of Glu decreased,the concentration of calcium decreased,the level of SOD,CAT and GSH-Px increased,the level of MDA decreased,the positive rate of TUNEL decreased,the expression level of Bax and cleaved caspase-3 protein decreased,and the expression level of Bcl2 protein increased significantly(P<0.05).Compared with TBI+EA group and TBI+EA+GCPII-NC group,the expression level of mRNA and protein of GCPII in TBI+EA+GCPII-OE group increased,neurological function score and escape latency increased,the number of crossing platform decreased,water content increased,cortical injury aggravated,Glu content increased,calcium concentration increased,SOD,CAT and GSH-Px levels decreased,MDA level increased,TUNEL positive rate increased,Bax and cleaved caspase-3 protein expression increased,and the expression of Bcl2 protein decreased significantly(P<0.05).Conclusion By down-regulating the expression of GCPII gene,electroacupuncture reduced the content of glutamate in the brain tissue of TBI rats,thereby inhibiting calcium overload,oxidative stress and neuronal apoptosis in the brain tissue,and thereby improving cognitive function and alleviating brain injury.

Objective:To study the safety and feasibility of transcatheter arterial chemoembolization (TACE) combined with apatinib in the treatment of advanced hilar cholangiocarcinoma.Methods:Clinical data of 41 patients with hilar cholangiocarcinoma admitted to the First Affiliated Hospital of Zhengzhou University from November 2019 to October 2020 were prospectively collected, including 21 males and 20 females, aged (65.1±12.5) years. The drugs used for TACE were albumin paclitaxel and gemcitabine, which were performed once every four to six weeks for no more than six times. Apatinib were adminstered two days after each TACE. The primary endpoint was objective response rate (ORR) and the secondary endpoints were progression-free survival (PFS), overall survival (OS) and adverse events. Patients were followed-up by outpatient, inpatient or telephone review. Survival analysis was performed using the Kaplan-Meier method.Results:Hilar cholangiocarcinoma were confirmed in all 41 patients by pathology. All patients were treated with TACE for at least twice. Twenty-three patients achieved complete remission, 14 stable disease, and four partial remission, with an ORR of 56.1% and a disease control rate of 90.2%. The follow-up duration was (13.3±5.4) months without lost to follow-up. The median PFS was 9.0 months, the median OS was 14.0 months, the 1-year cumulative recurrence-free survival rate was 31.7%, and the 1-year cumulative survival rate was 65.9%. Treatment-related adverse events in this study were predominantly Clavien-Dindo grade 1 or 2, without grade 4 to 5.Conclusion:TACE combined with apatinib treatment could be safe and feasible for advanced hilar cholangiocarcinoma.

Breast cancer （BC） ranks first in the incidence rate of female malignant tumor， the notable features of which include high invasive behavior， high malignant degree and poor prognosis. Resveratrol， a plant antioxidant， has been identified as a potential therapeutic agent for the occurrence and progress of BC. This article explores the mechanism of resveratrol intervention in BC by evaluating several in vitro and in vivo studies. It was found that resveratrol can weaken the proliferation and survival ability of BC cells， suppress their growth， metastasis， and invasion， and reverse their resistance to adriamycin by promoting cell apoptosis， regulating autophagy， inhibiting glycolysis and regulating the tumor microenvironment， expressions of matrix metalloproteinases， epithelial-mesenchymal transition and drug-resistant proteins， etc. The limited number of clinical trial studies on resveratrol， mainly focusing on prevention effect of it on breast cancer， may be one of the reasons that affect the comprehensive evaluation of the anti-cancer efficacy of resveratrol.

Breast cancer （BC） ranks first in the incidence rate of female malignant tumor， the notable features of which include high invasive behavior， high malignant degree and poor prognosis. Resveratrol， a plant antioxidant， has been identified as a potential therapeutic agent for the occurrence and progress of BC. This article explores the mechanism of resveratrol intervention in BC by evaluating several in vitro and in vivo studies. It was found that resveratrol can weaken the proliferation and survival ability of BC cells， suppress their growth， metastasis， and invasion， and reverse their resistance to adriamycin by promoting cell apoptosis， regulating autophagy， inhibiting glycolysis and regulating the tumor microenvironment， expressions of matrix metalloproteinases， epithelial-mesenchymal transition and drug-resistant proteins， etc. The limited number of clinical trial studies on resveratrol， mainly focusing on prevention effect of it on breast cancer， may be one of the reasons that affect the comprehensive evaluation of the anti-cancer efficacy of resveratrol.

Objective:To compare the effects of drug-loaded microsphere TACE (D-TACE) and iodinated oil emulsion TACE (cTACE) on liver fibrosis in the treatment of advanced hepatocellular carcinoma (HCC).Methods:Clinical data of 113 patients with HCC treated with D-TACE or cTACE at the First Affiliated Hospital of Zhengzhou University from October 2019 to September 2020 were retrospectively analyzed, including 96 males and 17 females, aged (56.8±9.8) years old. According to treatment protocol, patients were divided into two groups: the D-TACE group ( n=57) and the cTACE group ( n=56). Liver fibrosis panel, fibrosis index (FIB-4), aspartate aminotransferase to platelet ratio index (APRI), and liver stiffness measurement (LSM) were compared between the groups at four timepoints: pre-treatment, one month after the first TACE, one month after the second TACE, and 12 months after the first TACE. Follow-ups were conducted through outpatient visits or telephone reviews to assess patient survivals. Data including the progression-free survival (PFS) and number of TACE sessions were compared between the two groups. Results:The D-TACE group received 2.84±1.12 sessions of treatment during the observation period, compared to 4.05±1.44 sessions of cTACE group ( t=4.94, P<0.001). The median PFS in D-TACE and cTACE groups were 10.0 and 5.0 months, respectively ( P<0.001). At one month after the second TACE and at 12 months after the first TACE, patients in cTACE group had a higher serum levels of fibrosis markers including hyaluronic acid, type IV collagen, type III procollagen N peptide and laminin than those in D-TACE group (all P<0.05). At the same timepoints, patients in cTACE group also had higher APRI, FIB-4 and LSM than those in D-TACE group (all P<0.05). Conclusion:Compared to cTACE, patients in D-TACE group received fewer sessions of treatment during the first year after initial TACE, and the degree of liver fibrosis was also lower in D-TACE group.