OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Neuraxial opioids, widely used in obstetric and perioperative pain management, often lead to unwanted itch, reducing patient satisfaction. While the μ-opioid receptor has been implicated in opioid-induced itch, the genetic basis for variable itch incidence remains unknown. This study examined 3616 patients receiving epidural opioids, revealing an itch occurrence of 26.55%, with variations among opioid types and gender. Analysis of the OPRM1 gene identified six single-nucleotide polymorphisms, notably rs1799971 (A118G), that correlated with opioid-induced itch. Mouse models with an equivalent A112G mutation showed reduced neuraxial opioid-induced itch and light touch-evoked itch, mirroring human findings. The 118G allele demonstrated an anti-itch effect without impacting analgesia, addiction, or tolerance, offering insights for risk stratification and potential anti-itch pretreatment strategies.
Receptors, Opioid, mu/genetics* ; Pruritus/chemically induced* ; Humans ; Analgesics, Opioid/administration & dosage* ; Female ; Male ; Animals ; Polymorphism, Single Nucleotide/genetics* ; Adult ; Mice ; Middle Aged

Objective:To investigate the clinical efficacy and major complications (postoperative hemorrhage and cerebral edema) of 3 surgical methods in spontaneous supratentorial intracerebral hemorrhage (SSICH).Methods:A retrospective analysis was performed; 294 patients with SSICH admitted to Department of Neurosurgery, Renmin Hospital of Wuhan University from December 2018 to October 2021 were selected. According to different surgical methods, these patients were divided into neuroendoscopic hematoma removal group ( n=126), stereotactic drilling and drainage group ( n=98), and craniotomy hematoma removal group ( n=70). The surgical efficacy and complications in the 3 groups were analyzed, and the postoperative residual hematoma and edema volumes were quantitatively calculated based on 3D Slicer software. Results:The hematoma evacuation rate in the neuroendoscopic hematoma removal group, stereotactic drilling and drainage group, and craniotomy hematoma removal group was 86.25%±2.27%, 44.45%±3.61%, and 75.45%±2.89%, respectively; Glasgow coma Scale scores at discharge were 13.51±1.28, 11.24±2.17 and 10.25±2.56, respectively; postoperative hemorrhage incidence was 16.1%, 26.0% and 22.9%, respectively; postoperative residual hematoma volume was (18.90±12.33) mL, (25.75±11.43) mL and (22.91±7.93) mL, and postoperative peak edema volume was (37.43±11.07) mL, (39.54±9.43) mL, and (42.26±10.94) mL, respectively; percentage of patients with peak edema on 3-5 days after surgery was 31.0%, 65.3% and 68.6%; the diameter of edema zone was (20.04±2.98) mm, (24.12±5.85) mm and (23.59±3.81) mm, respectively, on 7 days after surgery; percentage of patients with edema resolution was 45.2%, 24.5%, 42.9% and 76.2%, 57.1%, 62.9%, respectively, on 9-11 days and 12-14 days after surgery; these indexes in the neuroendoscopic hematoma removal group were significantly different compared with those in the other two groups ( P<0.05). Conclusion:Compared with stereotactic drilling and drainage or craniotomy hematoma removal, neuroendoscopic surgery can effectively remove the hematoma and reduce the occurrences of postoperative hemorrhage and brain edema.

Objective To investigate the biological function and molecular mechanism of solute carrier family 4,member 3(SLC43)in glioblastoma(GBM).Methods The expression difference of SLC4A3 in 30 GBM and 10 normal brain tissues were analyzed by immu-nohistochemistry.Kaplan-Meier survival analysis was used to evaluate the effect of SLC4A3 on the prognosis of GBM patients.The ex-pression of SLC4A3 in U87 and U251 cells was reduced by shRNA,and the changes in the proliferation,migration and invasion ability of GBM cells were detected after the knockdown,and Western blot was used to investigate the expression of epithelial-mesenchymal transi-tion(EMT)and NF-κB signaling pathway related proteins after SLC4A3 knockdown.Results SLC4A3 was overexpressed in GBM,and high expression of SLC4A3 was associated with poor prognosis.Knocking down SLC4A3 inhibited the proliferation,migration and in-vasion of U87 and U251 cells,and the expression levels of N-cadherin and Vimentin were down-regulated,while the expression levels of E-cadherin were increased.In addition,knocking down SLC4A3 inhibited the NF-κB signaling pathway and further found that nu-clear translocation of NF-κB p65 was inhibited.Conclusion SLC4A3mediates the NF-κB signaling pathway by regulating the nuclear translocation of NF-κB p65 to influence the growth and EMT of GBM cells,which is a novel prognostic biomarker for GBM.

Objective To investigate the biological function and molecular mechanism of solute carrier family 4,member 3(SLC43)in glioblastoma(GBM).Methods The expression difference of SLC4A3 in 30 GBM and 10 normal brain tissues were analyzed by immu-nohistochemistry.Kaplan-Meier survival analysis was used to evaluate the effect of SLC4A3 on the prognosis of GBM patients.The ex-pression of SLC4A3 in U87 and U251 cells was reduced by shRNA,and the changes in the proliferation,migration and invasion ability of GBM cells were detected after the knockdown,and Western blot was used to investigate the expression of epithelial-mesenchymal transi-tion(EMT)and NF-κB signaling pathway related proteins after SLC4A3 knockdown.Results SLC4A3 was overexpressed in GBM,and high expression of SLC4A3 was associated with poor prognosis.Knocking down SLC4A3 inhibited the proliferation,migration and in-vasion of U87 and U251 cells,and the expression levels of N-cadherin and Vimentin were down-regulated,while the expression levels of E-cadherin were increased.In addition,knocking down SLC4A3 inhibited the NF-κB signaling pathway and further found that nu-clear translocation of NF-κB p65 was inhibited.Conclusion SLC4A3mediates the NF-κB signaling pathway by regulating the nuclear translocation of NF-κB p65 to influence the growth and EMT of GBM cells,which is a novel prognostic biomarker for GBM.

Objective:To investigate the clinical efficacy and major complications (postoperative hemorrhage and cerebral edema) of 3 surgical methods in spontaneous supratentorial intracerebral hemorrhage (SSICH).Methods:A retrospective analysis was performed; 294 patients with SSICH admitted to Department of Neurosurgery, Renmin Hospital of Wuhan University from December 2018 to October 2021 were selected. According to different surgical methods, these patients were divided into neuroendoscopic hematoma removal group ( n=126), stereotactic drilling and drainage group ( n=98), and craniotomy hematoma removal group ( n=70). The surgical efficacy and complications in the 3 groups were analyzed, and the postoperative residual hematoma and edema volumes were quantitatively calculated based on 3D Slicer software. Results:The hematoma evacuation rate in the neuroendoscopic hematoma removal group, stereotactic drilling and drainage group, and craniotomy hematoma removal group was 86.25%±2.27%, 44.45%±3.61%, and 75.45%±2.89%, respectively; Glasgow coma Scale scores at discharge were 13.51±1.28, 11.24±2.17 and 10.25±2.56, respectively; postoperative hemorrhage incidence was 16.1%, 26.0% and 22.9%, respectively; postoperative residual hematoma volume was (18.90±12.33) mL, (25.75±11.43) mL and (22.91±7.93) mL, and postoperative peak edema volume was (37.43±11.07) mL, (39.54±9.43) mL, and (42.26±10.94) mL, respectively; percentage of patients with peak edema on 3-5 days after surgery was 31.0%, 65.3% and 68.6%; the diameter of edema zone was (20.04±2.98) mm, (24.12±5.85) mm and (23.59±3.81) mm, respectively, on 7 days after surgery; percentage of patients with edema resolution was 45.2%, 24.5%, 42.9% and 76.2%, 57.1%, 62.9%, respectively, on 9-11 days and 12-14 days after surgery; these indexes in the neuroendoscopic hematoma removal group were significantly different compared with those in the other two groups ( P<0.05). Conclusion:Compared with stereotactic drilling and drainage or craniotomy hematoma removal, neuroendoscopic surgery can effectively remove the hematoma and reduce the occurrences of postoperative hemorrhage and brain edema.

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*

AIM: To explore the correlation between remnant cholesterol(RC)and anterior ischemic optic neuropathy(AION).METHODS: A total of 80 cases of AION patients hospitalized in the department of ophthalmology of Linyi People's Hospital from January 2020 to December 2023 were selected as the observation group, and 80 cases of those who had completed health checkups in Linyi People's Hospital during the same period(without ischemic optic neuropathy and other fundus vasculopathies)were selected as the control group. The general data and biochemical indexes of the two groups were compared to evaluate the correlation between RC and AION.RESULTS: Compared with the control group, the levels of RC, fasting blood glucose(FBG), triglyceride(TG), total cholesterol(TC), and low-density lipoprotein cholesterol(LDL-C)in patients with AION were significantly higher than those in the control group(all P<0.01). Spearman correlation analysis showed that RC was positively correlated with TG, TC, and LDL-C(all P<0.01). Logistic regression analysis showed that RC and FBG were risk factors for the development of AION. The analysis of receiver operating characteristic(ROC)curves showed that the level of RC had a better predictive value for the development of AION compared with FBG.CONCLUSION: RC is associated with the development of AION and is a risk factor for the development of AION. Clinical standardization of the management of people with high RC values can reduce the risk of the development of AION, which is of clinical significance.

ObjectiveA rapid method for identification of chemical constituents in Baoyuantang reference sample was established in order to clarify the material basis of this formula. MethodBased on ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） and self-established database information， the chemical components in Baoyuantang were systematically characterized and identified. The chromatography was performed on a Waters ACQUITY UPLC HSS T3 column（2.1 mm×100 mm， 1.8 μm） with mobile phase of 0.1% formic acid aqueous solution（A）-0.1% formic acid acetonitrile solution（B） for gradient elution（0-3 min， 2%-19%B； 3-8 min， 19%B； 8-8.1 min， 19%-22%B； 8.1-14 min， 22%-29%B； 14-16 min， 29%B； 16-32 min， 29%-45%B； 32-32.1 min， 45%-90%B； 32.1-35 min， 90%-95%B； 35-36 min， 95%-98%B； 36-37 min， 98%-2%B； 37-40 min， 2%B）. Based on electrospray ionization（ESI）， continuum data format was collected in both positive and negative ion modes with a scanning range of m/z 50-1 500. Chemical constituents in the decoction of Baoyuantang were systematically analyzed by UNIFI 1.9.4 software matching， control comparison， The Encyclopedia of Traditional Chinese Medicine（ETCM） database search and literature reports. ResultA total of 229 components were identified under negative ion mode and 181 under positive ion mode， with a total of 322 components after removing duplicates， including 116 triterpene saponins， 66 flavonoids， 19 organic acids， 6 gingerphenols， 6 gingerols， 5 gingerones， 10 amino acids， 7 saccharides， 5 coumarins and 82 other components. Among them， 83， 141， 39， 35 and 38 components were attributed to Ginseng Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Astragali Radix， Cinnamomi Cortex and Zingiberis Rhizoma Recens， respectively. ConclusionIn this study， the rapid characterization and identification of multi-class components in Baoyuantang was realized， and it was confirmed that the material basis of this formula was mainly triterpenoid saponins， flavonoids， gingerols and organic acids， and the chemical composition was attributed and analyzed， which provided a reference for the subsequent quality control research.

Objective To evaluate the effectiveness and safety of moxibustion for knee osteoarthritis and the methodological quality of systematic reviews(SRs).Methods SRs of moxibustion for knee osteoarthritis were retrieved from CNKI,VIP,Wanfang Data,SinoMed,PubMed,Cochrane Library,Embase and Web of Science was conducted from the establishment of the databases to February 10,2022.AMSTAR 2 was used to assess the methodological quality of SRs.The randomized controlled trials(RCTs)included in these SRs were screened and summarized according to inclusion standard.RevMan 5.4 software was used for Meta-analysis,and GRADE approach was used to assess the certainty of evidence.Results A total of 15 SRs were included.The evaluation results of the AMSTAR 2 showed that the methodological quality was very low for 14 SRs,and low for other 1 SR.A total of 36 RCTs were included.Meta-analysis results showed that compared with the non-steroidal anti-inflammatory drugs(NSAIDs),the moxibustion group had better effects on improvement of WOMAC scores[mean difference(MD)=-5.95;95%confidence interval(CI):-9.25 to-2.65;low quality],relieving pain[MD=-1.26;95%CI:-2.19 to-0.32;very low quality],and improving effective rate[risk ratio(RR)=1.16;95%CI:1.11 to 1.22;low quality].In the moxibustion group,some patients experienced blisters,and most healed in 3 days.Conclusion Moxibustion has advantages in pain reduction and improving effective rate compared with routine Western therapy for knee osteoarthritis.However,well-designed high-quality RCTs are needed for further verification.