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 explore the effects of astragalin(AST)on autophagy and apoptosis of astrocytes in the L4-5 dorsal horn of the spinal cord in mice with inflammatory pain induced by complete Freund's adjuvant(CFA).[Methods]Twenty-four male C57BL/6 mice,aged six months,were randomly assigned to four groups:control group,saline group,CFA model group,and CFA+AST group,six mice in each group.The inflammatory pain model was established by injection of 10 μL CFA into the right lateral malleolus fossa.The saline group were injected with an equal amount of normal saline at the same site.The inflammatory pain mice in CFA+AST group were further treated with AST(60 mg/kg)intraperitoneally once a day for 21 consecutive days.Multiplex immunofluorescence staining was used to detect the coexpression of autophagy-related factors including ATG 12 and Beclin-1,apoptosis-related factors including Cleaved-Caspase3 and Caspase9,and the astrocyte marker such as GFAP in the L4-5 spinal dorsal horn of the mice in each group.Western blot was used to examine the protein expression levels of autophagy-related proteins(ATG12,Beclin-1)and apoptosis-related proteins(Caspase 3,Caspase 9)in the L4-5 spinal dorsal horn of mice.[Results]Immunofluorescent staining showed that in the L4-5 dorsal horn of the spinal cord,the fluorescence intensity of ATG12(P<0.000 1)and Beclin-1(P<0.000 1)was significantly increased,while that of Cleaved-Caspase 3(P<0.001)and Caspase 9(P<0.000 1)was decreased in the CFA+AST group when compared to the CFA model group.Furthermore,AST could inhibit the activation of astrocytes.Western blot further confirmed that AST significantly upregulated the expression of ATG12(P<0.000 1)and Beclin-1(P<0.000 1)in the L4-5 spinal cord of CFA mice,and downregulated the expression of Caspase 3(P<0.01)and Caspase 9(P<0.001).[Conclusions]AST promotes autophagy of astrocytes and inhibits their apoptosis in the L4-5 spinal dorsal horn of CFA mice.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe dose-limiting adverse event of chemotherapy. Presently, the mechanism underlying the induction of CIPN remains unclear, and no effective treatment is available. In this study, through metabolomics analyses, we found that nab-paclitaxel therapy markedly increased serum serotonin [5-hydroxtryptamine (5-HT)] levels in both cancer patients and mice compared to the respective controls. Furthermore, nab-paclitaxel-treated enterochromaffin (EC) cells showed increased 5-HT synthesis, and serotonin-treated Schwann cells showed damage, as indicated by the activation of CREB3L3/MMP3/FAS signaling. Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells. Remarkably, venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy. In summary, our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions, and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
Paclitaxel/toxicity* ; Animals ; Albumins/adverse effects* ; Serotonin/metabolism* ; Mice ; Humans ; Male ; Female ; Venlafaxine Hydrochloride/therapeutic use* ; Neurotoxicity Syndromes/metabolism* ; Middle Aged ; Schwann Cells/metabolism* ; Peripheral Nervous System Diseases/drug therapy* ; Antineoplastic Agents

Curcumae Rhizoma, derived from the rhizome of Curcuma phaeocaulis, Curcuma kwangsiensis and Curcuma wenyujin, was called Ezhu in China. In the past, Curcumae Rhizoma extracts were obtained through water decoction or alternative methods, which showed significant anti-cancer effects. However, the mixed extracts contain various compound components of Curcumae Rhizoma, leading to an ambiguous mechanism of action for Curcumae Rhizoma extracts anti-cancer. Contemporary researchers have extracted the chemical components of Curcumae Rhizoma separately for experimental verification of its active ingredients in the anti-cancer field. Numerous studies demonstrated that curcumol, germacrone, β-elemene, and curcumin in Curcumae Rhizoma extracts have significant governing effects in anti-cancer activities. Pharmacological studies have shown that Curcumae Rhizoma suppresses cancer cell proliferation, invasion, and migration, triggering apoptosis and regulating cellular autophagy to achieve anticancer effects. Here, we summarized the research progress of Curcumae Rhizoma on anti-cancer effects from 2013 to 2022, aiming to explore the deeper molecular mechanisms of Curcumae Rhizoma's active components in cancer treatment.

BACKGROUND:Percutaneous kyphoplasty assisted by C-arm under local anesthesia requires continuous adjustment of the puncture direction under multiple C-arm fluoroscopy.The establishment time of the working channel is longer,and the intraoperative pain stimulation of patients is larger.With the help of the robot,the puncture can be successfully performed at one time,which can significantly improve the experience of patients and reduce the risk of bone cement leakage.OBJECTIVE:To compare the patient experience and other outcomes of percutaneous kyphoplasty using robot-assisted and conventional C-arm fluoroscopy under local anesthesia.METHODS:A total of 241 patients with single-stage osteoporotic vertebral compression fracture were selected from Sichuan Academy of Medical Sciences·Sichuan Provincial People's Hospital(Affiliated Hospital,University of Electronic Science and Technology of China).132 patients underwent robot-assisted percutaneous kyphoplasty under local anesthesia(robot-assisted group).109 cases of conventional C-arm assisted percutaneous kyphoplasty under local anesthesia(conventional fluoroscopy group).Patients'intraoperative experience evaluation,bone cement injection amount,operation time,working channel establishment time,hospitalization cost and complications were recorded.Puncture deviation and bone cement leakage were evaluated by imaging on the first day after surgery.RESULTS AND CONCLUSION:(1)The intraoperative experience of 59 patients in the robot-assisted group was rated as"very good",43 as"good",16 as"average",10 as"poor",and 4 as"very poor,"while that of 30 patients in the conventional fluoroscopy group was rated as"very good",44 cases were"good",21"average",9"poor",and 5"very poor."There was a significant difference between the two groups in intraoperative experience evaluation(Z=-2.546,P=0.011).Intraoperative pain visual analog scale score was lower in the robot-assisted group than that in the conventional fluoroscopy group(t=-9.513,P=0.000).Totally 84 patients in the robot-assisted group and 47 patients in the conventional fluoroscopy group were willing to undergo percutaneous kyphoplasty again when necessary,and there was a significant difference between the two groups(Z=-2.730,P=0.006).(2)The operation time and hospitalization cost of the robot-assisted group were more than those of the conventional fluoroscopy group(t=2.860,P=0.003;t=36.522,P=0.000).The working channel establishment time of robot-assisted group was shorter than that of conventional fluoroscopy group(t=-27.066,P=0.000).The puncture deviation of robot-assisted group was better than that of conventional fluoroscopy group(Z=-3.656,P=0.000).The cement leakage of robot-assisted group was lower than that of conventional fluoroscopy group(χ2=7.284,P=0.007).(3)It is concluded that under local anesthesia,patients with robot-assisted percutaneous kyphoplasty have good surgical experience,with advantages of accurate puncture,short time to establish working channel,and low leakage rate of bone cement.

BACKGROUND:Percutaneous kyphoplasty assisted by C-arm under local anesthesia requires continuous adjustment of the puncture direction under multiple C-arm fluoroscopy.The establishment time of the working channel is longer,and the intraoperative pain stimulation of patients is larger.With the help of the robot,the puncture can be successfully performed at one time,which can significantly improve the experience of patients and reduce the risk of bone cement leakage.OBJECTIVE:To compare the patient experience and other outcomes of percutaneous kyphoplasty using robot-assisted and conventional C-arm fluoroscopy under local anesthesia.METHODS:A total of 241 patients with single-stage osteoporotic vertebral compression fracture were selected from Sichuan Academy of Medical Sciences·Sichuan Provincial People's Hospital(Affiliated Hospital,University of Electronic Science and Technology of China).132 patients underwent robot-assisted percutaneous kyphoplasty under local anesthesia(robot-assisted group).109 cases of conventional C-arm assisted percutaneous kyphoplasty under local anesthesia(conventional fluoroscopy group).Patients'intraoperative experience evaluation,bone cement injection amount,operation time,working channel establishment time,hospitalization cost and complications were recorded.Puncture deviation and bone cement leakage were evaluated by imaging on the first day after surgery.RESULTS AND CONCLUSION:(1)The intraoperative experience of 59 patients in the robot-assisted group was rated as"very good",43 as"good",16 as"average",10 as"poor",and 4 as"very poor,"while that of 30 patients in the conventional fluoroscopy group was rated as"very good",44 cases were"good",21"average",9"poor",and 5"very poor."There was a significant difference between the two groups in intraoperative experience evaluation(Z=-2.546,P=0.011).Intraoperative pain visual analog scale score was lower in the robot-assisted group than that in the conventional fluoroscopy group(t=-9.513,P=0.000).Totally 84 patients in the robot-assisted group and 47 patients in the conventional fluoroscopy group were willing to undergo percutaneous kyphoplasty again when necessary,and there was a significant difference between the two groups(Z=-2.730,P=0.006).(2)The operation time and hospitalization cost of the robot-assisted group were more than those of the conventional fluoroscopy group(t=2.860,P=0.003;t=36.522,P=0.000).The working channel establishment time of robot-assisted group was shorter than that of conventional fluoroscopy group(t=-27.066,P=0.000).The puncture deviation of robot-assisted group was better than that of conventional fluoroscopy group(Z=-3.656,P=0.000).The cement leakage of robot-assisted group was lower than that of conventional fluoroscopy group(χ2=7.284,P=0.007).(3)It is concluded that under local anesthesia,patients with robot-assisted percutaneous kyphoplasty have good surgical experience,with advantages of accurate puncture,short time to establish working channel,and low leakage rate of bone cement.

The ultrasonic manifestations of benign and malignant breast imaging-reporting and data system(BI-RADS)4 lesions overlap in some degrees,is able to result in unnecessary biopsy or untimely therapy.Accurate classifying the nature of BI-RADS 4 breast lesions can provide reliable references for clinical decision-making.The progresses of application of new ultrasonic technologies,including automated breast volume scanner,superb micro-vascular imaging,elastography,contrast-enhanced ultrasound and artificial intelligence for assisting diagnosis of BI-RADS 4 lesions were reviewed in this article.

Surgery is the main treatment for patients with hepatocellular carcinoma to achieve long-term survival. However, only 20%-30% of patients can receive radical surgery. How to optimize the surgery oriented comprehensive treatment strategy and enable patients to successfully downstage to surgery are key issues to be solved in hepatocellular carcinoma treatment in China. Selective internal radiation therapy with yttrium-90 microspheres ( 90Y-SIRT) has strong ability of tumor killing, and it is reported that 90Y-SIRT is an ideal downstaging and bridging therapy for hepatocellular carcinoma, due to its superior downstaging efficacy compared with transarterial chemoembolization. Based on the introduction of characteristics of 90Y-SIRT, the authors review the clinical research progress of 90Y-SIRT in the preoperative downstaging and bridging treatment of hepatocellular carcinoma before liver transplantation, and discuss 90Y-SIRT-based conversion strategy. The 90Y-SIRT has shown syner-gistic effect with targeted therapy and immunotherapy, and will have a broad application prospect in downstaging and conversion therapy in the future.

Surgery is the main treatment for patients with hepatocellular carcinoma to achieve long-term survival. However, only 20%-30% of patients can receive radical surgery. How to optimize the surgery oriented comprehensive treatment strategy and enable patients to successfully downstage to surgery are key issues to be solved in hepatocellular carcinoma treatment in China. Selective internal radiation therapy with yttrium-90 microspheres ( 90Y-SIRT) has strong ability of tumor killing, and it is reported that 90Y-SIRT is an ideal downstaging and bridging therapy for hepatocellular carcinoma, due to its superior downstaging efficacy compared with transarterial chemoembolization. Based on the introduction of characteristics of 90Y-SIRT, the authors review the clinical research progress of 90Y-SIRT in the preoperative downstaging and bridging treatment of hepatocellular carcinoma before liver transplantation, and discuss 90Y-SIRT-based conversion strategy. The 90Y-SIRT has shown syner-gistic effect with targeted therapy and immunotherapy, and will have a broad application prospect in downstaging and conversion therapy in the future.