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

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*

Abstract: Objective　To analyze the distribution characteristics of the main pathogens of HIV/AIDS patients with wound infections and provide basis for clinical diagnosis and treatment. Methods　The clinical data of 294 patients with positive secretions or pus specimens from 2016 to 2020 were analyzed retrospectively. Results　A total of 357 strains of pathogenic bacteria were isolated from 294 cases, of which 123 strains of Gram-negative bacilli (G-b), accounting for 34.5%, were mainly Escherichia coli (15.4%), Klebsiella pneumoniae (3.9%), and Pseudomonas aeruginosa (3.6%); Gram-positive bacilli (G+b) 14 strains, accounting for 3.9%; 108 Gram-positive cocci (G+c), accounting for 30.3%, of which 44 strains were coagulase-positive Staphylococcus aureus (12.3%), Coagulase-negative staphylococci were mainly Staphylococcus epidermidis (4.2%) and Staphylococcus hemolyticus (2.8%); 37 strains of fungi, accounting for 10.4%, were mainly Candida albicans (5.9%); 75 strains of Mycobacterium, accounting for 21.0%, including 41 strains of Mycobacterium tuberculosis (11.5%) and 34 strains of non-tuberculosis mycobacteria (9.5%). 52 of the 294 HIV/AIDS patients had mixed infections, accounting for 17.7%. There was significant difference in the distribution of G+c, G-b, mycobacteria and mixed infection among different specimen sources (P<0.05), and there was significant difference in the distribution of mycobacteria among different CD4+T lymphocyte counts (P<0.05). There was significant difference in the level of CD4+T lymphocytes between patients of different ages (P<0.05), and there was significant difference in the level of CD4+T lymphocytes from postoperative incision and other parts (P<0.05). Conclusions　Patients with HIV/AIDS are prone to combined wound infections with various pathogenic bacteria. We should strengthen the research on wound infection in HIV/AIDS patients, and timely send patients with a low number of CD4+T lymphocytes for secretion or pus culture, so as to carry out targeted treatment and improve the prognosis of patients.

Objective:This paper mainly discusses the health policy of early life of pregnant women and infants in Beijing as an example,and to provide the basis for policy formulation and optimization.Methods:By using the content analysis method,149 policy texts are divided into two dimensions:policy objectives and policy instruments.The results are described by manual coding,cross analysis and trend analysis.Results:In regard to Policy Objectives,improvement of maternal and child health service levels accounts for the biggest proportion(61.7%),whereas improvement of research level accounts for the least(8.1%).In the four dimensions of policy instruments,mandatory,spontaneous,capacity-building,and incentive tools account for 90%,55%,48%and 42%respectively.According to the trend analysis,integrity of policy system has been continuously improved and the proportion of infant and child care has also increased.Both cross-analysis and trend analysis have showed the strong use of coercive and incentive tools by relevant policies;The use of spontaneous and capacity-building tools is low and decreases over time.Conclusion:Improving the level of maternal and child health services is the core concern of Beijing's early life health policy.However,relatively little attention is paid to the family,infant and child care,and scientific research construction.As for Policy Instruments,mandatory tools are widely used;Incentive Tools and Spontaneous Tools are mainly applied in well-being and soft guidance;insufficient use of Capacity-building Tools.Suggestions:In the future,the policy system should be further improved,which should be targeted and deficiency-mending.It is suggested that more resources should be increased for the family system,more attention should be paid to vulnerable groups early in life,and more financial support should be applied to scientific research on maternal and child health.

The aggregation of macrophage-derived foam cells on vascular wall is considered to be a main cause of atherosclerosis. In the present study, we evaluated the inhibitory effect of the compound ilexpernoside C (IC1) extracted from Ilex pernyi (Aquifoliaceae) on foam cell formation in THP-1 macrophages cells which were induced by low density lipoproteins aggregates (LDL aggregates). Results showed that IC1 could significantly inhibit the formation of foam cells. The analysis on related receptors of foam cells indicated that IC1 could significantly decrease the expression of low density lipoprotein-related receptor 1(LRP1). Therefore, these findings indicated that IC1 inhibited the formation of foam cells by inhibiting endocytosis of macrophages, thus it may act as a potential anti-atherosclerotic agent.

Objective To identify the source of infection and risk factors and to provide control measures regarding an outbreak of gastroenteritis involving 30 villagers.Who attended the same wedding party held on March 5th,2012,a survey was carried out.Methods Case was defined as having onset of vomiting,nausea,stomachache or diarrhea among the attendees of a wedding party.We randomly selected and interviewed 140 from 470 attendees on their symptoms and food exposures at the wedding.We compared food-specific attack rates (AR) for gastroenteritis in a retrospective cohort study.The leftover foods were tested for Salmonella,Shigella,and Staphylococcus aureus.The leftover Boletus mushrooms were examined and species determined by the Kunming Institute of Botany,Chinese Academy of Sciences.Results Of the 140 attendees 61％ (85) developed gastroenteritis.Case-attendees had vomiting (94％),nausea (89％),stomachache (53 ％),and diarrhea (51％).The AR among attendees who ate Boletus mushroom was 69％ (81/118),compared to 18％ (4/22) of those who did not (RR＝3.8,95％ CI:1.5-9.2).When comparing the ARs between the attendees on consumption of other foods,data did not show statistically significant differences.Among the 7 species of Boletus identified from the leftover mushrooms,3 (B.venenatus,B.sinicus and B.magnificus) were toxic.Store keepers bought dried or fresh mushrooms from local villagers who had picked up them from the mountains.Salmonella,Shigella,and Staphylococcus aureus tests on those leftover food showed negative results.Conclusion Poisonous Boletus mushroom contributed to this outbreak.We recommended that education should be targeted on mushroom-pickers regarding how to recognize the poisonous mushrooms.Regulations and laws should also be developed to facilitate the necessary process.

Objective To explore the existence of natural loci on Marmota himalayana plague in Sichuan province and to provide basis for prevention and control of the disease. Methods Both epidemiological investigation and laboratory tests were used to provide the host animal and fleas of the vectors with Yersinia pestis carriers. Results 30 species of animals were found to belong to 10 orders. Ochotona curzoniae and M.himalayana were the most common ones while 7 species of the fleas belonged to 7 genera and 3 families. M.himalayana was the main reservoirs while Callopsylla dolabris and Oropsylla silantiewi served as vectors. The 13 Y.pestis were identified from 43 Marmota samples. 8 samples were identified under IHA, with the highest titer of herding-dogs serum as 1 : 10 240. 19 samples were F1 antigen positive using RIHA and the highest titer of M.himalayana serum was 1:409 600. The major foci was 4545 km2, distributed at Dege county in Sichuan province. Conclusion We have confirmed the existence of natural foci on M. Himalayana plague in Sichuan province.

OBJECTIVEThis study examined the relationship between the ultrastructural alterations of alveolar epithelial cells type II (AEC-II) and pulmonary surfactant protein A (SP-A) levels in the lung tissue of young rats with acute lung injury (ALI) in order to explore the possible mechanism of ALI.

METHODSForty-eight young Sprague-Dawley rats were randomly divided into control and ALI groups. The rats in the ALI group were intraperitoneally injected with 4 mg/kg of lipopolysaccharide (LPS) in order to induce ALI. The control subjects were injected with the same volume of normal saline. Rats were sacrificed at 24, 48 and 72 hrs after LPS or NS injection. Lung samples were obtained from the lower parts of the left lung and fixed with 2.5% glutaraldehyde for transmission electron microscope examination and for Western blot test of SP-A.

RESULTSThe microvilli of AEC-II disappeared 24 hrs after LPS injection. After 24 and 48 hrs of LPS injection, lamellar body (Lb) increased in number, enlarged in size and reduced in density, and the ring-like arrangement of Lb was present. By 48 hrs after LPS injection, giant Lb with vacuole-like deformity appeared. The contents of lung SP-A in the ALI group 24 hrs (6.52+/-0.62 vs 5.02+/-0.35; P<0.01) and 48 hrs (6.65+/-0.62 vs 5.01+/-0.36; P<0.01) after LPS injection were significantly higher than those in the control group. By 72 hrs after LPS injection, Lbs ruptured and were reduced in number. The shape of the nuclei was irregular and the border was blurred. The content of lung SP-A was greatly reduced in the ALI group 72 hrs after LPS injection compared with that in the control group (3.87+/-0.50 vs 5.22+/-0.36; P<0.01).

CONCLUSIONSThe alterations of AEC-II and lung SP-A were time-dependent in young rats with ALI induced by LPS. In the early stage of ALI, the lung SP-A content showed a compensatory increase. With the increasing injury of AEC-II cells, the secretion of SP-A presented with a decompensation and the lung SP-A content decreased. This may be one possible mechanism for the development of ARD.

Animals ; Female ; Lipopolysaccharides ; toxicity ; Male ; Microscopy, Electron ; Pulmonary Alveoli ; pathology ; ultrastructure ; Pulmonary Surfactant-Associated Protein A ; analysis ; Rats ; Rats, Sprague-Dawley ; Respiratory Distress Syndrome, Adult ; metabolism ; pathology

Objective To detect TB specific T cell responses by using the recombinant ESAT-6 protein as stimulus in Chinese HIV infected patients. Methods ELISPOT-IFN-γ assay by using the recombinant ESAT-6protein as stimulus to detect specific T cell responses in HIV( + ) patients with or without clinical manifestation of TB diseases. Results Recombinant ESAT-6 protein specific T cell responses show significant high frequencies in both of TB patients with or without HIV infection than that in the healthy control and HIV ( + ) group without clinical TB diseases. Conclusions The ELISPOT-IFN-γ assay by using recombinant ESAT-6 protein as stimulus could be used in diagnoses of TB infection in Chinese HIV infected patients.

Objective To compare and analyze the sensitivity,specificity of 4 domestic ELISA kits for detection of hepatitis B virus (HBV) markers (HBsAg,anti-HBs,HBeAg,anti-HBe,and anti-HBc).Methods Five hundred and ninety four serum samples collected from patients with chronic hepatitis B and abnormal blood donors were detected for HBV markers and by 4 domestic ELISA kits.Samples with conflicting results by different diagnostic kits were retested.Samples with the HBsAg values close to the cut-off point were detected by Abbott HBsAg confirmation kit (Architect HBsAg confirm).Sensitivity of the kits was determined,using the national sensitivity reference panels for HBsAg,anti-HBs,HBeAg,anti-HBe and anti-HBc.Results The rates of sensitivity on 4 domestic kits for detection of HBsAg were 4 to 10 times lower,and on the 4 domestic kits for detection of anti-HBs,HBeAg,anti-HBc and anti-HBc were 4 to 16 times lower,as compared to Abbott Architect kits.In addition,the domestic HBV ELISA kits had some false positive results.The total coincidence rates of HBsAg,anti-HBs,HBeAg,anti-HBe,anti-HBc were 96.46%-98.15%,94.28%-98.15%,98.15%-99.49%,90.07%-96.30%,92.09%-96.80%,respectively.Conclusion Both sensitivity and specificity of the domestically produced HBV ELISA kits should be improved.