ObjectiveTo explore the molecular mechanism of Buzhong Yiqitang in attenuating cisplatin resistance in non-small cell lung cancer （NSCLC） by inducing ferroptosis via poly（rC）-binding protein 1 （PCBP1）. MethodsThe serum containing Buzhong Yiqitang was prepared and cisplatin-resistant human non-small cell lung cancer （NSCLC） cells （A549/DDP） were cultured and randomly grouped as follows： Blank （10% blank serum）， model （10% blank serum+20 mg·L^-1 cisplatin）， Buzhong Yiqitang （10% serum containing Buzhong Yiqitang+20 mg·L^-1 cisplatin）， Fe-1 （10% blank serum+20 mg·L^-1 cisplatin+5 μmol·L^-1 Fe-1）， and Buzhong Yiqitang+Fe-1 （10% serum containing Buzhong Yiqitang+20 mg·L^-1 cisplatin+5 μmol·L^-1 Fe-1）. Firstly， PCR Array was used to screen ferroptosis-related genes regulated by Buzhong Yiqitang， and PCBP1 was identified as the target for studying the attenuation of cisplatin resistance by Buzhong Yiqitang. Subsequently， the median inhibitory concentration （IC₅₀） of cisplatin in each group was determined by the cell counting kit-8 （CCK-8） method and the resistance index （RI） was calculated. The ultrastructure of A549/DDP cells in each group was observed by transmission electron microscopy. The protein levels of PCBP1 and glutathione peroxidase 4 （GPX4） were determined by Western blot. The lipid reactive oxygen species （ROS） content in each group was determined by the C11-BODIRY 581/591 fluorescence probe. The ferrous ion assay kit was used to measure the ferrous ion content in each group. The malondialdehyde （MDA） assay kit was used to determine the MDA content in each group. ResultsCompared with model group， the IC₅₀ of cisplatin and the RI of A549/DDP cells decreased in the Buzhong Yiqitang group （P<0.05） but increased in the Fe-1 group （P<0.05）. The IC₅₀ of cisplatin and the RI of A549/DDP cells in the Buzhong Yiqitang+Fe-1 group were lower than those in the Fe-1 group （P<0.05）. Compared with the model group， the Buzhong Yiqitang group showed obvious mitochondrial ferroptosis， while the mitochondrial damage became less obvious after Fe-1 treatment. Compared with that in the Fe-1 group， the mitochondrial ferroptosis was aggravated after the intervention with Buzhong Yiqitang. Compared with blank group， the model group showed down-regulated expression levels of PCBP1 and GPX4 （P<0.05） and increased content of lipid ROS， ferrous ions， and MDA （P<0.05） in A549/DDP cells. Compared with model group， the Buzhong Yiqitang group showed down-regulated expression levels of PCBP1 and GPX4 （P<0.05） and increased content of lipid ROS， ferrous ions， and MDA （P<0.05）， while the Fe-1 group showed up-regulated expression levels of PCBP1 and GPX4 （P<0.05） and reduced content of lipid ROS， ferrous ions， and MDA （P<0.05）. Compared with the Fe-1 group， the Buzhong Yiqitang+Fe-1 group showed down-regulated expression levels of PCBP1 and GPX4 and increased content of lipid ROS， ferrous ions， and MDA （P<0.05）. ConclusionBuzhong Yiqitang attenuated cisplatin resistance in NSCLC by regulating PCBP1 to induce ferroptosis.

Venous system diseases mainly include varicose veins and venous malformations of lower limbs and the genital system. Most of them are chronic diseases that cause serious clinical symptoms to patients and affect their health and quality of life. Sclerotherapy has become the first-line therapy for venous system diseases. However, there are problems such as incomplete fibrosis and vascular recanalization after sclerotherapy, and improper operation will cause serious adverse consequences. Therefore, exploring a safe and effective sclerotherapy strategy is essential for developing clinically successful sclerotherapy. To solve the above problems, we proposed a new sclerotherapy strategy with a dual mechanism of "vascular damage and plasmin (PLA) system inhibition." We intended to construct a novel cationic surfactant (AEO_x-TA) by reacting tranexamic acid (TA), a parent structure, with fatty alcohol polyoxyethylene ether (AEO_x) by ester bonds. AEO_x-TA could damage vascular endothelium and initiate a coagulation cascade effect to induce thrombus. Furthermore, AEO_x-TA could be degraded by esterase and release the parent drug, TA, which could inhibit the PLA system to inhibit the degradation of thrombus and extracellular matrix and promote the process of vascular fibrosis. In addition, such surfactant-based sclerosants have foam-forming properties, and they can be blended with polyvinyl alcohol (PVA) to prepare a highly stable foam formulation (AEO_x-TA/P), which can achieve a precise drug delivery and prolonged drug retention time, thereby improving drug efficacy and reducing the risk of ectopic embolism. Overall, the novel cationic surfactant AEO_x-TA provides a new avenue to resolve the bottleneck: surfactant sclerosants' efficiency is relatively low in the current sclerotherapy.

Objective To investigate the effects of β-caryophyllene(BCP)on the browning of white adipose tissue in obese mice and the related mechanisms.Methods An obese mouse model was established via intraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution[14.4 mg/(kg·d)]in male Kun-ming mice.Obesity model mice were randomly divided into a model group(Model group)and a BCP administra-tion group(BCP-50 group);normal diet mice were set up as a control group(Control group),with 8 mice in each group.BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group,while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks.The oral glucose tolerance test was performed at the end of 4-week administration,and mice were executed after overnight fasting at the end of the experiment,and blood samples and adipose tissues were rap-idly collected for subsequent experimental tests.The kit was used to detect serological-related indexes;hematoxy-lin-eosin staining was conducted to observe the morphology of adipose tissue;immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1)in adipose tissue;Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α),peroxisome prolifera-tor-activated receptor γ(PPARγ),UCP1 and cannabinoid receptor 2(CNR2)proteins in epididymal white adi-pose(eWAT).Results Compared with the model group,the body mass of obese mice in the BCP-50 group was significantly reduced(P＜0.05),food intake was decreased(P＜0.01),insulin resistance was improved(P＜0.000 1),and the serum content of low-density lipoprotein cholesterol(LDL-C)and nonesterified fatty acid(NE-FA)in the obese mice was significantly reduced(P＜0.000 1 and P＜0.01).Total cholesterol(TC),triglycer-ide(TG),and high-density lipoprotein cholesterol(HDL-C)contents did not change significantly.In addition,the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P＜0.05);the adipocytes in eWAT and BAT were reduced;and the expression of the UCP1 protein was signifi-cantly elevated(P＜0.01 and P＜0.05).In addition to UCP1,the expression levels of PGC1α,PPARγ,and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P＜0.01,P＜0.05,and P＜0.001).Conclusion β-caryophyllene promotes white adipose tissue browning through up-regula-ting PPARγ/PGC-1α/UCP1 pathway expression,thus improving obesity.

Objective To investigate the effects of β-caryophyllene(BCP)on the browning of white adipose tissue in obese mice and the related mechanisms.Methods An obese mouse model was established via intraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution[14.4 mg/(kg·d)]in male Kun-ming mice.Obesity model mice were randomly divided into a model group(Model group)and a BCP administra-tion group(BCP-50 group);normal diet mice were set up as a control group(Control group),with 8 mice in each group.BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group,while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks.The oral glucose tolerance test was performed at the end of 4-week administration,and mice were executed after overnight fasting at the end of the experiment,and blood samples and adipose tissues were rap-idly collected for subsequent experimental tests.The kit was used to detect serological-related indexes;hematoxy-lin-eosin staining was conducted to observe the morphology of adipose tissue;immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1)in adipose tissue;Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α),peroxisome prolifera-tor-activated receptor γ(PPARγ),UCP1 and cannabinoid receptor 2(CNR2)proteins in epididymal white adi-pose(eWAT).Results Compared with the model group,the body mass of obese mice in the BCP-50 group was significantly reduced(P＜0.05),food intake was decreased(P＜0.01),insulin resistance was improved(P＜0.000 1),and the serum content of low-density lipoprotein cholesterol(LDL-C)and nonesterified fatty acid(NE-FA)in the obese mice was significantly reduced(P＜0.000 1 and P＜0.01).Total cholesterol(TC),triglycer-ide(TG),and high-density lipoprotein cholesterol(HDL-C)contents did not change significantly.In addition,the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P＜0.05);the adipocytes in eWAT and BAT were reduced;and the expression of the UCP1 protein was signifi-cantly elevated(P＜0.01 and P＜0.05).In addition to UCP1,the expression levels of PGC1α,PPARγ,and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P＜0.01,P＜0.05,and P＜0.001).Conclusion β-caryophyllene promotes white adipose tissue browning through up-regula-ting PPARγ/PGC-1α/UCP1 pathway expression,thus improving obesity.

Objective To investigate the effects of β-caryophyllene(BCP)on the browning of white adipose tissue in obese mice and the related mechanisms.Methods An obese mouse model was established via intraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution[14.4 mg/(kg·d)]in male Kun-ming mice.Obesity model mice were randomly divided into a model group(Model group)and a BCP administra-tion group(BCP-50 group);normal diet mice were set up as a control group(Control group),with 8 mice in each group.BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group,while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks.The oral glucose tolerance test was performed at the end of 4-week administration,and mice were executed after overnight fasting at the end of the experiment,and blood samples and adipose tissues were rap-idly collected for subsequent experimental tests.The kit was used to detect serological-related indexes;hematoxy-lin-eosin staining was conducted to observe the morphology of adipose tissue;immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1)in adipose tissue;Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α),peroxisome prolifera-tor-activated receptor γ(PPARγ),UCP1 and cannabinoid receptor 2(CNR2)proteins in epididymal white adi-pose(eWAT).Results Compared with the model group,the body mass of obese mice in the BCP-50 group was significantly reduced(P＜0.05),food intake was decreased(P＜0.01),insulin resistance was improved(P＜0.000 1),and the serum content of low-density lipoprotein cholesterol(LDL-C)and nonesterified fatty acid(NE-FA)in the obese mice was significantly reduced(P＜0.000 1 and P＜0.01).Total cholesterol(TC),triglycer-ide(TG),and high-density lipoprotein cholesterol(HDL-C)contents did not change significantly.In addition,the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P＜0.05);the adipocytes in eWAT and BAT were reduced;and the expression of the UCP1 protein was signifi-cantly elevated(P＜0.01 and P＜0.05).In addition to UCP1,the expression levels of PGC1α,PPARγ,and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P＜0.01,P＜0.05,and P＜0.001).Conclusion β-caryophyllene promotes white adipose tissue browning through up-regula-ting PPARγ/PGC-1α/UCP1 pathway expression,thus improving obesity.

Objective: To investigate the effects of β-caryophyllene(BCP) on the browning of white adipose tissue in obese mice and the related mechanisms. Methods: An obese mouse model was establishedviaintraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution [14.4 mg/(kg·d)] in male Kunming mice. Obesity model mice were randomly divided into a model group(Model group) and a BCP administration group(BCP-50 group); normal diet mice were set up as a control group(Control group), with 8 mice in each group. BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group, while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks. The oral glucose tolerance test was performed at the end of 4-week administration, and mice were executed after overnight fasting at the end of the experiment, and blood samples and adipose tissues were rapidly collected for subsequent experimental tests. The kit was used to detect serological-related indexes; hematoxylin-eosin staining was conducted to observe the morphology of adipose tissue; immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1) in adipose tissue; Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α), peroxisome proliferator-activated receptor γ(PPARγ), UCP1 and cannabinoid receptor 2(CNR2) proteins in epididymal white adipose(eWAT). Results: Compared with the model group, the body mass of obese mice in the BCP-50 group was significantly reduced(P<0.05), food intake was decreased(P<0.01), insulin resistance was improved(P<0.000 1), and the serum content of low-density lipoprotein cholesterol(LDL-C) and nonesterified fatty acid(NEFA) in the obese mice was significantly reduced(P<0.000 1 andP<0.01). Total cholesterol(TC), triglyceride(TG), and high-density lipoprotein cholesterol(HDL-C) contents did not change significantly. In addition, the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P<0.05); the adipocytes in eWAT and BAT were reduced; and the expression of the UCP1 protein was significantly elevated(P<0.01 andP<0.05). In addition to UCP1, the expression levels of PGC1α, PPARγ, and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P<0.01,P<0.05, andP<0.001). Conclusion β-caryophyllene promotes white adipose tissue browning through up-regulating PPARγ/PGC-1α/UCP1 pathway expression, thus improving obesity.

Objective To investigate the effects of β-caryophyllene(BCP)on the browning of white adipose tissue in obese mice and the related mechanisms.Methods An obese mouse model was established via intraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution[14.4 mg/(kg·d)]in male Kun-ming mice.Obesity model mice were randomly divided into a model group(Model group)and a BCP administra-tion group(BCP-50 group);normal diet mice were set up as a control group(Control group),with 8 mice in each group.BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group,while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks.The oral glucose tolerance test was performed at the end of 4-week administration,and mice were executed after overnight fasting at the end of the experiment,and blood samples and adipose tissues were rap-idly collected for subsequent experimental tests.The kit was used to detect serological-related indexes;hematoxy-lin-eosin staining was conducted to observe the morphology of adipose tissue;immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1)in adipose tissue;Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α),peroxisome prolifera-tor-activated receptor γ(PPARγ),UCP1 and cannabinoid receptor 2(CNR2)proteins in epididymal white adi-pose(eWAT).Results Compared with the model group,the body mass of obese mice in the BCP-50 group was significantly reduced(P＜0.05),food intake was decreased(P＜0.01),insulin resistance was improved(P＜0.000 1),and the serum content of low-density lipoprotein cholesterol(LDL-C)and nonesterified fatty acid(NE-FA)in the obese mice was significantly reduced(P＜0.000 1 and P＜0.01).Total cholesterol(TC),triglycer-ide(TG),and high-density lipoprotein cholesterol(HDL-C)contents did not change significantly.In addition,the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P＜0.05);the adipocytes in eWAT and BAT were reduced;and the expression of the UCP1 protein was signifi-cantly elevated(P＜0.01 and P＜0.05).In addition to UCP1,the expression levels of PGC1α,PPARγ,and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P＜0.01,P＜0.05,and P＜0.001).Conclusion β-caryophyllene promotes white adipose tissue browning through up-regula-ting PPARγ/PGC-1α/UCP1 pathway expression,thus improving obesity.

Objective To investigate the effects of β-caryophyllene(BCP)on the browning of white adipose tissue in obese mice and the related mechanisms.Methods An obese mouse model was established via intraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution[14.4 mg/(kg·d)]in male Kun-ming mice.Obesity model mice were randomly divided into a model group(Model group)and a BCP administra-tion group(BCP-50 group);normal diet mice were set up as a control group(Control group),with 8 mice in each group.BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group,while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks.The oral glucose tolerance test was performed at the end of 4-week administration,and mice were executed after overnight fasting at the end of the experiment,and blood samples and adipose tissues were rap-idly collected for subsequent experimental tests.The kit was used to detect serological-related indexes;hematoxy-lin-eosin staining was conducted to observe the morphology of adipose tissue;immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1)in adipose tissue;Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α),peroxisome prolifera-tor-activated receptor γ(PPARγ),UCP1 and cannabinoid receptor 2(CNR2)proteins in epididymal white adi-pose(eWAT).Results Compared with the model group,the body mass of obese mice in the BCP-50 group was significantly reduced(P＜0.05),food intake was decreased(P＜0.01),insulin resistance was improved(P＜0.000 1),and the serum content of low-density lipoprotein cholesterol(LDL-C)and nonesterified fatty acid(NE-FA)in the obese mice was significantly reduced(P＜0.000 1 and P＜0.01).Total cholesterol(TC),triglycer-ide(TG),and high-density lipoprotein cholesterol(HDL-C)contents did not change significantly.In addition,the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P＜0.05);the adipocytes in eWAT and BAT were reduced;and the expression of the UCP1 protein was signifi-cantly elevated(P＜0.01 and P＜0.05).In addition to UCP1,the expression levels of PGC1α,PPARγ,and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P＜0.01,P＜0.05,and P＜0.001).Conclusion β-caryophyllene promotes white adipose tissue browning through up-regula-ting PPARγ/PGC-1α/UCP1 pathway expression,thus improving obesity.

Objective To investigate the effects of β-caryophyllene(BCP)on the browning of white adipose tissue in obese mice and the related mechanisms.Methods An obese mouse model was established via intraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution[14.4 mg/(kg·d)]in male Kun-ming mice.Obesity model mice were randomly divided into a model group(Model group)and a BCP administra-tion group(BCP-50 group);normal diet mice were set up as a control group(Control group),with 8 mice in each group.BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group,while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks.The oral glucose tolerance test was performed at the end of 4-week administration,and mice were executed after overnight fasting at the end of the experiment,and blood samples and adipose tissues were rap-idly collected for subsequent experimental tests.The kit was used to detect serological-related indexes;hematoxy-lin-eosin staining was conducted to observe the morphology of adipose tissue;immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1)in adipose tissue;Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α),peroxisome prolifera-tor-activated receptor γ(PPARγ),UCP1 and cannabinoid receptor 2(CNR2)proteins in epididymal white adi-pose(eWAT).Results Compared with the model group,the body mass of obese mice in the BCP-50 group was significantly reduced(P＜0.05),food intake was decreased(P＜0.01),insulin resistance was improved(P＜0.000 1),and the serum content of low-density lipoprotein cholesterol(LDL-C)and nonesterified fatty acid(NE-FA)in the obese mice was significantly reduced(P＜0.000 1 and P＜0.01).Total cholesterol(TC),triglycer-ide(TG),and high-density lipoprotein cholesterol(HDL-C)contents did not change significantly.In addition,the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P＜0.05);the adipocytes in eWAT and BAT were reduced;and the expression of the UCP1 protein was signifi-cantly elevated(P＜0.01 and P＜0.05).In addition to UCP1,the expression levels of PGC1α,PPARγ,and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P＜0.01,P＜0.05,and P＜0.001).Conclusion β-caryophyllene promotes white adipose tissue browning through up-regula-ting PPARγ/PGC-1α/UCP1 pathway expression,thus improving obesity.

Objective To investigate the effects of β-caryophyllene(BCP)on the browning of white adipose tissue in obese mice and the related mechanisms.Methods An obese mouse model was established via intraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution[14.4 mg/(kg·d)]in male Kun-ming mice.Obesity model mice were randomly divided into a model group(Model group)and a BCP administra-tion group(BCP-50 group);normal diet mice were set up as a control group(Control group),with 8 mice in each group.BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group,while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks.The oral glucose tolerance test was performed at the end of 4-week administration,and mice were executed after overnight fasting at the end of the experiment,and blood samples and adipose tissues were rap-idly collected for subsequent experimental tests.The kit was used to detect serological-related indexes;hematoxy-lin-eosin staining was conducted to observe the morphology of adipose tissue;immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1)in adipose tissue;Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α),peroxisome prolifera-tor-activated receptor γ(PPARγ),UCP1 and cannabinoid receptor 2(CNR2)proteins in epididymal white adi-pose(eWAT).Results Compared with the model group,the body mass of obese mice in the BCP-50 group was significantly reduced(P＜0.05),food intake was decreased(P＜0.01),insulin resistance was improved(P＜0.000 1),and the serum content of low-density lipoprotein cholesterol(LDL-C)and nonesterified fatty acid(NE-FA)in the obese mice was significantly reduced(P＜0.000 1 and P＜0.01).Total cholesterol(TC),triglycer-ide(TG),and high-density lipoprotein cholesterol(HDL-C)contents did not change significantly.In addition,the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P＜0.05);the adipocytes in eWAT and BAT were reduced;and the expression of the UCP1 protein was signifi-cantly elevated(P＜0.01 and P＜0.05).In addition to UCP1,the expression levels of PGC1α,PPARγ,and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P＜0.01,P＜0.05,and P＜0.001).Conclusion β-caryophyllene promotes white adipose tissue browning through up-regula-ting PPARγ/PGC-1α/UCP1 pathway expression,thus improving obesity.