OBJECTIVE: Despite the combination of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang (SB-SD) being a recognized Chinese medicinal herbal pair that is commonly used in the treatment of ovarian cancer, there is a poor understanding of their pharmacological mechanisms. This study examines the antitumor properties and potential mechanisms of SB-SD on human ovarian cancer A2780 cells through a multi-omics approach, establishing a pharmacological basis for clinical utilization. METHODS: A range of mass ratios and reagents were used in the hot reflux extraction of SB-SD. The inhibitory effect of the SB-SD extracts on A2780 cell proliferation was assessed using the cell-counting kit 8 assay. A zebrafish tumor implantation model was used to evaluate the effects of SB-SD extracts on tumor growth and metastasis in vivo. Transcriptomics and proteomics were used to investigate alterations in biological pathways in A2780 cells after treatment with different concentrations of SB-SD extract. Cell cycle, cell apoptosis, intracellular free iron concentration, intracellular reactive oxygen species (ROS) concentration, malondialdehyde (MDA), and mitochondrial membrane potential were measured. Real-time quantitative reverse transcription polymerase chain reaction and Western blotting were utilized to investigate the effects of heme catabolism and ferritinophagy on ferroptosis induced by SB-SD extract in A2780 cells. RESULTS: The 70% ethanol extract of SB-SD (a mass ratio of 4:1) inhibited A2780 cell proliferation significantly with a half maximal inhibitory concentration of 660 μg/mL in a concentration- and time-dependent manner. Moreover, it effectively suppressed tumor growth and metastasis in a zebrafish tumor implantation model. SB-SD extract induced the accumulation of free iron, ROS, MDA, and mitochondrial damage in A2780 cells. The mechanisms might involve the upregulated expression of ferritinophagy-related genes microtubule-associated protein 1 light chain 3, autophagy-related gene 5, and nuclear receptor coactivator 4. CONCLUSION SB-SD extract effectively inhibited the development of ovarian cancer both in vitro and in vivo. Its mechanism of action involved inducing ferroptosis by facilitating heme catabolism and ferritinophagy. This herbal pair holds promise as a potential therapeutic option for ovarian cancer treatment and may be utilized in combination with routine treatment to improve the treatment outcomes of ovarian cancer patients. Please cite this article as: Wang Z, Liu M, Li GX, Zhang L, Ding KY, Li SQ, Gao BQ, Chen P, Choe HC, Xia LY, Yang YT, Liu Y, Sui X, Ma JN, Zhang L. A herbal pair of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang induced ferroptosis in ovarian cancer A2780 cells via inducing heme catabolism and ferritinophagy. J Integr Med. 2024; 22(6): 666-683.
Ferroptosis/drug effects* ; Female ; Humans ; Animals ; Scutellaria/chemistry* ; Ovarian Neoplasms/genetics* ; Zebrafish ; Cell Line, Tumor ; Ferritins/genetics* ; Plant Extracts/pharmacology* ; Heme/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Cell Proliferation/drug effects* ; Reactive Oxygen Species/metabolism* ; Antineoplastic Agents, Phytogenic/pharmacology* ; Autophagy/drug effects* ; Apoptosis/drug effects*

Objective To develop a CT-based weighted radiomic model that predicts tumor response to programmed death-1(PD-1)/PD-ligand 1(PD-L1)immunotherapy in patients with non-small cell lung cancer.Methods The patients with non-small cell lung cancer treated by PD-1/PD-L1 immune checkpoint inhibitors in the Peking Union Medical College Hospital from June 2015 to February 2022 were retrospectively studied and classified as responders(partial or complete response)and non-responders(stable or progressive disease).Original radiomic features were extracted from multiple intrapulmonary lesions in the contrast-enhanced CT scans of the arterial phase,and then weighted and summed by an attention-based multiple instances learning algorithm.Logistic regression was employed to build a weighted radiomic scoring model and the radiomic score was then calculated.The area under the receiver operating characteristic curve(AUC)was used to compare the weighted radiomic scoring model,PD-L1 model,clinical model,weighted radiomic scoring + PD-L1 model,and comprehensive prediction model.Results A total of 237 patients were included in the study and randomized into a training set(n=165)and a test set(n=72),with the mean ages of(64±9)and(62±8)years,respectively.The AUC of the weighted radiomic scoring model reached 0.85 and 0.80 in the training set and test set,respectively,which was higher than that of the PD-L1-1 model(Z=37.30,P<0.001 and Z=5.69,P=0.017),PD-L1-50 model(Z=38.36,P<0.001 and Z=17.99,P<0.001),and clinical model(Z=11.40,P<0.001 and Z=5.76,P=0.016).The AUC of the weighted scoring model was not different from that of the weighted radiomic scoring + PD-L1 model and the comprehensive prediction model(both P>0.05).Conclusion The weighted radiomic scores based on pre-treatment enhanced CT images can predict tumor responses to immunotherapy in patients with non-small cell lung cancer.
Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/drug therapy* ; B7-H1 Antigen/therapeutic use* ; Retrospective Studies ; Programmed Cell Death 1 Receptor ; Tomography, X-Ray Computed ; Immunotherapy

Aim To investigate the mechanism of Pi- ezol in the phenotypic changes of rat coronary arterial smooth muscle cells ( CASMCs) induced by high hydrostatic pressure.Methods CASMCs were isolated from Wistar rats and stimulated for 24 h at 0, 120 and 180 mmHg, respectively.The expressions of Piezol , contractile phenotvpe-related proteins including Cavl.2 ,SM-MHC ,cx-SMA and synthetic phenotvpe-re- lated proteins including OPN , MMP-2, Coll al were detected by Western blot.The effect of calcium influx mediated by Piezol was detected by Laser confocal mi- j j croscopy.CASMCs were treated with Piezol agonist Yodal , inhibitor GsMTx4 and Piezol-siHNA , respectively and the expressions of contractile phenotvpe and synthetic phenotvpe-related proteins were detected by Western blot.Results Compared with control ( 0 mmHg) , the expressions of Piezol , OPN, MMP-2 and Collal increased, but the expressions of Cavl.2,SM- MHC and cx-SMA decreased in 120 mmHg as well as 180 mmHg group.After stimulated by 180 mmHg high pressure, Piezol-mediated calcium influx was stronger than that in 0 mmHg group, hut decreased after Piezol knockdown.Treated with Yodal at 0 mmHg, the expression of contractile phenotvpe-related protein decreased while the expression of synthetic phenotvpe-re- lated protein increased compared with DMSO group..\Jfter using GsMTx4 to inhibit or siRNA to knockdown Piezol at 180 mmHg,the expression of contractile phe- notvpe-related protein increased and the expression of synthetic phenotype-related protein decreased compared with the control group.Conclusion Piezol promotes the transition from contractile phenotvpe to syn-thetic phenotvpe of CASMCs induced by high hydrostatic pressure.

Aim To investigate the role of calcium-independent phospholipase A2(iPLA2)in calcium regu-lation of intrarenal artery smooth muscle contraction.Methods The method of measuring the tension of isolated arterioles was used to explore the effect of bromoenol lactone(BEL), a specific inhibitor of iPLA2, on the tension of the intrarenal arteries in mice induced by different calcium channels, and the laser confocal calcium measurement technology was used to investigate the effect of BEL on the intracellular calcium influx mediated by arachidonic acid-mediated calcium channels.Results The intrarenal artery concentration dependent contractile response induced by the vasoconstrictors phenylephrine and 5-hydroxy tryptamine was inhibited by BEL(P<0.01).The contraction curve induced by CaCl2 was also inhibited by BEL(P<0.05).In the calcium-free K-H solution incubated with nifedipine, the intrarenal artery vasoconstriction caused by the release of sarcoplasmic reticulum calcium and the calcium influx of the SOC channel induced by CaCl2 was inhibited by BEL(P<0.05).BEL significantly inhibited the external calcium influx mediated by the ARC channel of human aortic smooth muscle cell lines incubated with nifedipine(P<0.01).Conclusions iPLA2 mediates the contractile response of intrarenal arteries by regulating the functions of L-type calcium channels, sarcoplasmic reticulum calcium release, SOC channels and ARC channels.

Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.

Objective:To discussed the clinical efficacy of addition and subtraction therapy of Shenling Baizhu San to antibiotic-associated diarrhea (AAD) with spleen-stomach deficiency and cold syndrome, and to investigate its effects on immune function and intestinal flora. Method:One hundred and fifteen patients were randomly divided into control group (57 cases) and observation group (58 cases) by random number table. Patients in control group got Shuangqi Ganjun Sanlian Huojun San, 2 bags/time, 2 times/days. Mengtuoshi San, 1 bag/time, 3 times/days, and they also got measures to prevent disturbance of water, electrolyte, acid-base balance and nutritional support. Based on the treatment in control group, patients in observation group also got addition and subtraction therapy of Shenling Baizhu San, 1 dose/day. The course of treatment was 7 days in both groups. Before and after treatment, scores of symptoms, intestinal secretory immunoglobulin (SIgA) levels, peripheral blood immunoglobulin A (IgA), G (IgG), M (IgM) and T lymphocyte subsets (CD3⁺, CD4⁺, CD8⁺and CD4⁺/CD8⁺). Detection of bacillus faccalis in feces before and after treatment and the bacteria were cultured to identify and count bifidobacterium, lactobacillus and enterococcus. In addition, diamine oxidase (DAO) and D-lactic acid levels were detected before and after treatment. Result:In rank sum test, clinical efficacy in observation group was better than that in control group (Z=2.268, P<0.01). Scores of main symptoms, secondary symptoms, spleen-stomach deficiency and cold syndrome were lower than those in control group(P<0.01). Levels of SIgA, IgA and IgG were significantly higher than those in the control group (P<0.01). Levels of CD3⁺, CD4⁺and CD4⁺/CD8⁺were higher than those in control group (P<0.05), while level of CD8⁺was lower than that in control group (P<0.05). Bacillus in faeces was significantly lower than that in control group(P<0.01). Count of enterococcus was lower than that in control group (P<0.05), while counts of bifidobacterium and lactobacillus were higher than those in control group (P<0.05). In addition, levels of DAO and D-lactic acid were significantly lower than those in control group (P<0.01). Conclusion:Based on conventional treatment, addition and subtraction therapy of Shenling Baizhu San can alleviate symptoms, improve clinical efficacy, improve immune function, regulate intestinal flora and promote the repair of intestinal mucosal barrier in the treatment of antibiotic-associated diarrhea (AAD) with spleen-stomach deficiency and cold syndrome.

OBJECTIVE: Todevelop a rapid and sensitive UHPLC-Q-orbitrap method for the identification of chemical constituents in Nelumbinis Folium. METHODS: Thermo Scientific Hypersil GOLD aQ(2.1 mm×100 mm,1.9 μm) was used with 0.1% formic acid-acetonitrile solution and 0.1% formic acid-water solution as the mobile phase in gradient elution. The extract was detected by Q-orbitrapmass spectrometry equipped with an ESI ion source in both positiveand negative mode. RESULTS: Based on the accurate mass-to-charge measurements, retention time, mass fragmentation patterns, compound discoverer software which can link to local compound database of Traditional Chinese Medicine from Thermo Scientific and online compound database from mzCloud, using Mass Frontier software to explain the fragmentations, a total of 53 compounds were screened and characterized, including 21 flavonoids,5 terpenes,13 alkaloids, 3 coumarins, 3 amino acids, 2 lignans and 6 other compounds. CONCLUSION: These results are helpful for the comprehensive quality control, better comprehension of the metabolism, and further study of the pharmacodynamic substances from Nelumbinis Folium.

As a standard method for early stage prostate cancer, 125Ⅰ seed implantations are used widely in America. Although there are guidelines from American Brachytherapy Society and American Association of Physicists in Medicine, some hospitals still cannot implant the seeds properly according to the guidelines. Complications were observed inevitably. The medical events about seeds implantation in America from 2002 were investigated and the reasons were analyzed in this paper. Additionally, some solutions were given to avoid the medical events, so that the practitioners in China can learn from it and make sure the 125Ⅰ seeds implantation can be developed healthily and smoothly.

The clinical value of transvaginal ultrasound in clinical surgical treatment of cesarean scar pregnancy (CSP) was evaluated.The clinical data of 104 patients with CSP admitted at Tongji Hospital from 2013 to 2016 were collected and analyzed retrospectively,including the patients' age,gestational age,the size of gestational sac or uneven mass,the uterine scar thickness,β human chorionic gonadotropin (hCG) levels and so on.Of these 104 cases,30 cases were subjected to laparotomy,29 cases to laparoscopy,27 cases to hysteroscopy,16 cases to ultrasound-guided uterine curettage,and 2 cases to conservative treatment.The transvaginal ultrasound showed that uterine scar thickness and gestational sac or uneven mass size had significant difference (P＜0.05) among different surgical methods by comparatively analyzing the patients' data.It was suggested that transvaginal ultrasound may provide the valuable reference for choosing clinical surgical procedures for CSP.

Objective To investigate the dose distribution of esophageal stents carrying different diameters of radioactive 125I seeds in tumor target area. Methods A laser scanner was used to scan a piece of blank paper on which circles of 12 mm, 14 mm and 16 mm diameter and a 5 cm scale were drawn. The data were stored in JPEF format on the computer desktop. According to the circular diameter, simulations of the corresponding esophageal stents were established, which were divided into group A, group B and group C. By using image conversion program, 17 images with 5 mm slice-distance were created for each group; the images were transmitted to the computer treatment planning system (TPS) to simulate the 8 cm long esophageal stents of different diameters. TPS was used to sketch the gross tumor volume (GTV) in order to simulate the esophageal stent border that was used as the inner boundary of GTV, which was expanded 0.5 cm outward to be used as the external boundary of GTV. Beginning from the fifth level, the 4 cm-long GTV was drawn with circles. Setting the same prescription dose, from the fifth level to the thirteenth level the 125I seeds with 0.3, 0.4, 0.5, 0.6, 0.7, 0.8 and 0.9 mCi were successively loaded on the simulation of the esophageal stents. The distance between 125I seed layers was 1 cm; the average number of seeds distributed on each layer was 4 particles. The dose volume histogram (DVH) was obtained. The D90 (the dose received by 90% of the target) and V90 (the percentage of the GTV volume receiving 90% the prescription dose) were recorded.Result s The arithmetic mean D90 of group A, B and C was (77.24 ±19.92) Gy, (69.56 ±25.27) Gy and (56.38±20.08) Gy respectively, and no statistically significant differences existed between each other among the three groups (F=0.84,P=0.44). The V90 of group A, B and C was (77.76±30.73)%,(76.79±25.92)%and (64.10 ±32.49)% respectively, and no statistically significant differences existed between each other among the three groups (F=0.46,P=0.64). Conclusion When the diameter of radioactive esophageal stent is 12 mm, the activity of 125I seed of 0.6 mCi is recommended. When the diameter of radioactive esophageal stent is 14 mm or 16 mm, the activity of 125I seed of 0.7 mCi is recommended. Nevertheless, when the diameter of radioactive esophageal stent is 16 mm, distribution of every five 125I seeds on each layer is strongly recommended. These three kinds of esophageal stent diameter have no significant effect on the dosimetric parameters.