Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 195
Filter
1.
Mar Drugs ; 22(4)2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38667800

ABSTRACT

Two new meroterpenoids, hyrtamide A (1) and hyrfarnediol A (2), along with two known ones, 3-farnesyl-4-hydroxybenzoic acid methyl ester (3) and dictyoceratin C (4), were isolated from a South China Sea sponge Hyrtios sp. Their structures were elucidated by NMR and MS data. Compounds 2-4 exhibited weak cytotoxicity against human colorectal cancer cells (HCT-116), showing IC50 values of 41.6, 45.0, and 37.3 µM, respectively. Furthermore, compounds 3 and 4 significantly suppressed the invasion of HCT-116 cells while also downregulating the expression of vascular endothelial growth factor receptor 1 (VEGFR-1) and vimentin proteins, which are key markers associated with angiogenesis and epithelial-mesenchymal transition (EMT). Our findings suggest that compounds 3 and 4 may exert their anti-invasive effects on tumor cells by inhibiting the expression of VEGFR-1 and impeding the process of EMT.


Subject(s)
Antineoplastic Agents , Colorectal Neoplasms , Epithelial-Mesenchymal Transition , Porifera , Terpenes , Humans , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Porifera/chemistry , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Terpenes/pharmacology , Terpenes/isolation & purification , Terpenes/chemistry , Epithelial-Mesenchymal Transition/drug effects , HCT116 Cells , Vascular Endothelial Growth Factor Receptor-1/metabolism , Vimentin/metabolism , Cell Line, Tumor , China
2.
Org Lett ; 26(1): 12-17, 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38127552

ABSTRACT

A versatile Co(III)-catalyzed C6-selective C-H activation/pyridine migration of 2-pyridones with available propiolates as coupling partners was demonstrated. This method features high atom economy, excellent regioselectivity, and good functional group tolerance by employing an inexpensive Co(III) catalyst under mild reaction conditions. Moreover, gram-scale synthesis and late-stage modifications of pharmaceuticals were performed to prove the effectiveness of these synthetic approaches.

3.
Ther Adv Med Oncol ; 15: 17588359231187205, 2023.
Article in English | MEDLINE | ID: mdl-37484525

ABSTRACT

Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1, programmed cell death ligand 1, and cytotoxic T lymphocyte-associated antigen-4 have shown significantly durable clinical benefits and tolerable toxicities and have improved the survival of patients with various types of cancer. Since 2018, the National Medical Products Administration of China has approved 17 ICIs as the standard treatment for certain advanced or metastatic solid tumors. As ICIs represent a broad-spectrum antitumor strategy, the populations eligible for cancer immunotherapy are rapidly expanding. However, the clinical applications of ICIs in cancer patient populations with special issues, a term that refers to complex subgroups of patients with comorbidities, special clinical conditions, or concomitant medications who are routinely excluded from prospective clinical trials of ICIs or are underrepresented in these trials, represent a great real-world challenge. Although the Chinese Society of Clinical Oncology (CSCO) has provided recommendations for screening before the use of ICIs in special populations, the recommendations for full-course management remain insufficient. The CSCO Expert Committee on Immunotherapy organized leading medical oncology and multidisciplinary experts to develop a consensus that will serve as an important reference for clinicians to guide the proper application of ICIs in special patient populations. This article is a translation of a study first published in Chinese in The Chinese Clinical Oncology (ISSN 1009-0460, CN 32-1577/R) in May 2022 (27(5):442-454). The publisher of the original paper has provided written confirmation of permission to publish this translation in Therapeutic Advances in Medical Oncology.

4.
J Appl Clin Med Phys ; 24(11): e14097, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37438966

ABSTRACT

PURPOSE: This study aimed to assess the effects of bladder filling during cervical cancer radiotherapy on target volume and organs at risk (OARs) dose based on daily computed tomography (daily-CT) images and provide bladder-volume-based dose prediction models. METHODS: Nineteen patients (475 daily-CTs) comprised the study group, and five patients comprised the validation set (25 daily-CTs). Target volumes and OARs were delineated on daily-CT images and the treatment plan was recalculated accordingly. The deviation from the planning bladder volume (DVB), the correlation between DVB and clinical (CTV)/planning (PTV) target volume in terms of prescribed dose coverage, and the relationship of small bowel volume and bladder dose with the ratio of bladder volume (RVB) were analyzed. RESULTS: In all cases, the prescribed dose coverage in the CTV was >95% when DVB was <200 cm3 , whereas that in the PTV was >95% when RVB was <160%. The ratio of bladder V45 Gy to the planning bladder V45 Gy (RBV45 ) exhibited a negative linear relationship with RVB (RBV45  = -0.18*RVB + 120.8; R2  = 0.80). Moreover, the ratio of small bowel volume to planning small bowel volume (RVS) exhibited a negative linear relationship with RVB (RVS = -1.06*RVB +217.59; R2  = 0.41). The validation set results showed that the linear model predicted well the effects of bladder volume changes on target volume coverage and bladder dose. CONCLUSIONS: This study assessed dosimetry and volume effects of bladder filling on target and OARs based on daily-CT images. We established a quantitative relationship between these parameters, providing dose prediction models for cervical cancer radiotherapy.


Subject(s)
Radiotherapy, Intensity-Modulated , Uterine Cervical Neoplasms , Female , Humans , Urinary Bladder/diagnostic imaging , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted/methods , Uterine Cervical Neoplasms/diagnostic imaging , Uterine Cervical Neoplasms/radiotherapy , Tomography, X-Ray Computed , Radiotherapy, Intensity-Modulated/methods , Organs at Risk
5.
Org Lett ; 25(24): 4416-4421, 2023 Jun 23.
Article in English | MEDLINE | ID: mdl-37306363

ABSTRACT

A palladium-catalyzed olefination of meta-C-H bonds in arenes containing oxyamides using a nitrile template as the directing group has been established. The methodology exhibited high meta-selectivity and tolerated different functional groups such as benzyloxyamides and olefin substrates. The desired products were obtained in good yields. This approach enabled the modification of natural products and drugs and was also applicable on the gram-scale. Furthermore, the directing template was readily removed by selective cleavage of the amide bond or the O-N bond to obtain meta-functionalized hydroxylamines and benzyl alcohols. The proposed method holds great potential for the design of novel drugs.


Subject(s)
Alkenes , Palladium , Palladium/chemistry , Catalysis , Alkenes/chemistry , Amides , Benzyl Alcohols
6.
J Biomed Opt ; 28(6): 065005, 2023 06.
Article in English | MEDLINE | ID: mdl-37334208

ABSTRACT

Significance: Near-infrared (NIR) diffuse reflectance spectroscopy has been widely used for non-invasive glucose measurement in humans, as glucose can induce a significant and detectable optical signal change in tissue. However, the scattering-dominated glucose spectrum in the range of 1000 to 1700 nm is easily confused with many other scattering factors, such as particle density, particle size, and tissue refractive index. Aim: Our aim is to identify the subtle distinctions between glucose and these factors through theoretical analysis and experimental verification, in order to employ suitable methods for eliminating these interferences, thus increasing the accuracy of non-invasive glucose measurement. Approach: We present a theoretical analysis of the spectra of 1000 to 1700 nm for glucose and some scattering factors, which is then verified by an experiment on a 3% Intralipid solution. Results: We found that both the theoretical and experimental results show that the effective attenuation coefficient of glucose has distinct spectral characteristics, which are distinct from the spectra caused by particle density and refractive index, particularly in the range of 1400 to 1700 nm. Conclusions: Our findings can offer a theoretical foundation for eliminating these interferences in non-invasive glucose measurement, aiding mathematical methods to model appropriately and enhance the accuracy of glucose prediction.


Subject(s)
Glucose , Spectroscopy, Near-Infrared , Humans , Spectroscopy, Near-Infrared/methods , Hematologic Tests , Particle Size , Scattering, Radiation
7.
Heliyon ; 9(4): e15051, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37012905

ABSTRACT

Background: Although current studies have identified sleep disorders as an independent risk factor for suicide, the relationship between sleep disorders and suicide risk has not been well established. This study explored whether anxiety and depressive symptoms are used as mediators to participate in the impact of sleep quality on suicide risk. Methods: This is a cross-sectional study. We administered a psychological questionnaire to the participants, using a combination of self-assessment and psychiatrist assessment.Sleep quality, suicide risk, level of anxiety and depressive symptoms were assessed by PSQI, NGASR, SAS and SDS.The study subjects were 391 hospitalized COVID-19 patients from Wuhan hospitals. We used model 6 in the PROCESS (version 3.5) plug-in of SPSS software to conduct mediation test with sleep quality as the independent variable, suicide risk as the dependent variable, level of anxiety and depressive symptoms as intermediate variables. Results: The severity of anxiety and depressive symptoms and the risk of suicide in the sleep disorder group (63.15 ± 13.71, 59.85 ± 13.38, 6.52 ± 3.67) were higher than those in the non-sleep disorder group (49.83 ± 13.14, 44.87 ± 10.19, 2.87 ± 3.26) (P < 0.001). The mediation model works well, The total indirect effect was 0.22 (95%CI = [0.17, 0.28]), and the direct effect was 0.16 (95%CI = [0.08, 0.24]). Limitations: This study used a self-assessment scale. Conclusions: Anxiety and depressive symptoms played a chain mediating role between sleep quality and suicide risk.

8.
Acad Radiol ; 30 Suppl 2: S114-S126, 2023 09.
Article in English | MEDLINE | ID: mdl-37003874

ABSTRACT

RATIONALE AND OBJECTIVES: This study assessed the role of second-look automated breast ultrasound (ABUS) adjunct to mammography (MAM) versus MAM alone in asymptomatic women and compared it with supplementing handheld ultrasound (HHUS). MATERIALS AND METHODS: Women aged 45 to 64 underwent HHUS, ABUS, and MAM among six hospitals in China from 2018 to 2022. We compared the screening performance of three strategies (MAM alone, MAM plus HHUS, and MAM plus ABUS) stratified by age groups and breast density. McNemar's test was used to assess differences in the cancer detection rate (CDR), the false-positive biopsy rate, sensitivity, and specificity of different strategies. RESULTS: Of 19,171 women analyzed (mean [SD] age, 51.54 [4.61] years), 72 cases of breast cancer (3.76 per 1000) were detected. The detection rates for both HHUS and ABUS combined with MAM were statistically higher than those for MAM alone (all p < 0.001). There was no significant difference in cancer yields between the two integration strategies. The increase in CRD of the integrated strategies was higher in women aged 45-54 years with denser breasts compared with MAM alone (all p < 0.0167). In addition, the false-positive biopsy rate of MAM plus ABUS was lower than that of MAM plus HHUS (p = 0.025). Moreover, the retraction in ABUS was more frequent in cases detected among MAM-negative results. CONCLUSION: Integrated ABUS or HHUS into MAM provided similar CDRs that were significantly higher than those for MAM alone in younger women (45-54 years) with denser breasts. ABUS has the potential to avoid unnecessary biopsies and provides specific image features to distinguish malignant tumors from HHUS.


Subject(s)
Breast Neoplasms , Ultrasonography, Mammary , Female , Humans , Middle Aged , Ultrasonography, Mammary/methods , Sensitivity and Specificity , Mammography , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/epidemiology , China/epidemiology
9.
Methods Mol Biol ; 2640: 445-452, 2023.
Article in English | MEDLINE | ID: mdl-36995612

ABSTRACT

Uncovering the transcriptomic signatures of quiescent muscle stem cells elicits the regulatory networks on stem cell quiescence. However, the spatial clues of the transcripts are missing in the commonly used quantitative analysis such as qPCR and RNA-seq. Visualization of RNA transcripts using single-molecule in situ hybridization provides additional subcellular localization clues to understanding gene expression signatures. Here, we provide an optimized protocol of smFISH analysis on Fluorescence-Activated Cell Sorting isolated muscle stem cells to visualize low-abundance transcripts.


Subject(s)
Gene Expression Profiling , Stem Cells , In Situ Hybridization, Fluorescence/methods , RNA/genetics , Muscles
10.
Sci Rep ; 13(1): 2111, 2023 02 06.
Article in English | MEDLINE | ID: mdl-36747075

ABSTRACT

In this study, we aimed to evaluate the anti-inflammatory and anti-apoptotic effects of melatonin (MLT) on neuropathic pain (NP)-induced anxiety and depression in a rat model. Adult male rats were separated into four groups, i.e., Sham-VEH: healthy animals received a vehicle, Sham-MLT (10 mg/kg), and chronic constrictive injury (CCI)-VEH: nerve ligation received the vehicle, and CCI-MLT. Next, we used behavioral tests to evaluate pain severity, anxiety, and depression. Finally, rats were sacrificed for molecular and histopathological studies. Behavioral tests showed that NP could induce depressive- and anxiety-like behaviors. NP activated NF-κB/NLRP3 inflammasome pathways by upregulating NF-κB, NLRP3, ASC, active Caspase-1, also enhancing the concentrations of cytokines (IL-1ß and IL-18) in the prefrontal cortex (PFC) and hippocampus (HC). NP upregulated Bax, downregulated Bcl2, and increased cell apoptosis in the HC and PFC. The rats treated with MLT eliminated the effects of NP, as the reduced pain severity, improved anxiety- and depressive-like behaviors, ameliorated NF-κB/NLRP3 inflammasome pathways, and modulated levels of cytokines in the HC and PFC. MLT could promote cell survival from apoptosis by modulating Bax and Bcl2. Therefore, it might be inferred that its anti-inflammatory and anti-apoptotic properties mediate the beneficial effects of MLT in NP-induced affective disorders.


Subject(s)
Melatonin , Neuralgia , Rats , Male , Animals , NF-kappa B/metabolism , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Melatonin/pharmacology , Melatonin/therapeutic use , bcl-2-Associated X Protein , Apoptosis , Anti-Inflammatory Agents/pharmacology , Cytokines/metabolism , Neuralgia/drug therapy
11.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-997659

ABSTRACT

ObjectiveTo explore the anti-gout effect and mechanism of Derris eriocarpa extract by network pharmacological analysis combined with in vivo and in vitro experimental verification. MethodThe chemical components and candidate targets of D. eriocarpa were obtained from the database. The key targets and potential active components of D. eriocarpa in the treatment of gout were screened by the protein-protein interaction analysis, and then the Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed for the key targets. A mouse model of hyperuricemia was established by intraperitoneal injection of hypoxanthine to observe the effect of D. eriocarpa alcohol extract on hyperuricemia. A rat model of gouty inflammation induced by the injection of microcrystalline sodium urate crystals into the foot and plantar was used to observe the effect of D. eriocarpa alcohol extract on gouty inflammation. A xylene-induced acute inflammation model was established to observe the anti-inflammatory effect of D. eriocarpa alcohol extract. The hot plate test and twisting test were performed to observe the pain-relieving effect of D. eriocarpa. The lipopolysaccharide (LPS)-induced RAW264.7 cells were used to study the anti-gout effect and mechanism of D. eriocarpa alcohol extract. ResultA total of 12 key targets and 15 potential active components were obtained from the D. eriocarpa-component-gout target network. The emodin, betulinic acid, and medicarpin endowed D. eriocarpa with anti-hyperuricemia, anti-inflammatory, and pain-relieving effects by acting on Toll-like receptor 4 (TLR4), NOD-like reception protein 3 (NLRP3), and nuclear factor (NF)-κB. Compared with the control group, the model groups showed elevated serum uric acid level in mice (P<0.01), increased swelling degree of rats (P<0.05, P<0.01), alleviated the auricular swelling of mice (P<0.05), reduced the twisting times of mice (P<0.05, P<0.01), and increased the hot plate pain threshold (P<0.05). Moreover, the model group showed up-regulated mRNA level of TLR4 and protein levels of TLR4, NF-κB, and NLRP3 in cells (P<0.01), and elevated levels of TLR4 and NF-κB in the cell supernatant (P<0.05, P<0.01). Compared with the model group, the alcoholic extracts (20, 10, 5 g·kg-1) of D. eriocarpa lowered the serum uric acid level in hyperuricemic mice (P<0.01), inhibited foot and plantar swelling in rats (P<0.05, P<0.01), down-regulated the mRNA level of TLR4 and the protein levels of TLR4, NF-κB, NLRP3 in cells, and lowered the levels of TLR4, TNF-α, NF-κB, and IL-6 in cell supernatants (P<0.05, P<0.01). ConclusionD. eriocarpa alcohol extract may exert the anti-gout, anti-inflammatory, and pain-relieving effects by regulating the TLR4/NF-κB/NLRP3 signaling pathway.

12.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-995304

ABSTRACT

Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis. At present, the situation of tuberculosis control in China and even the world is severe. Bacillus Calmette-Guerin (BCG) vaccine is the only approved vaccine for tuberculosis, but its protective effect is limited. Hence, it is imperative to develop more effective tuberculosis vaccines. Currently, many new tuberculosis vaccine candidates are in clinical or preclinical trials. In this paper, to provide reference for the development of tuberculosis vaccines in China, the status of the research on vaccine candidates were reviewed and the progress in new tuberculosis vaccine strategies were summarized.

13.
Chinese Journal of Orthopaedics ; (12): 155-163, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-993423

ABSTRACT

Objective:To investigate the combination of internal fixation for periprosthetic fractures of the proximal femur (PFFF) after hip arthroplasty.Methods:The data of 58 patients with periprosthetic fractures after hip arthroplasty from May 2008 to March 2022 were retrospectively analyzed, including 31 males and 27 females. The average age was 75.5±18.2 years (range, 35-95 years). There were 39 total hip arthroplasty and 19 hemiarthroplasty; 37 biological prosthesis and 21 cemented prosthesis. Intraoperative periprosthetic fractures occurred in 6 cases and 52 cases postoperatively. Unified classification system (UCS): UCS IV.3A1 type 2 cases, 3A2 type 1 case, 3B1.1 type 19 cases, 3B2.1 type 25 cases, 3B3 type 2 cases, 3C type 9 cases. Fracture site: 3 cases in zone A (greater trochanter), 46 cases in zone B (around the femoral stem), and 9 cases in zone C (distal to the tip of the femoral stem. Internal fixation is composed of primary and secondary fixation, the main fixation method was the cerclage of steel wire or titanium cable, locking compression plate, and locking attachment plate fixation. The secondary fixation method was the cerclage of titanium cable, which was required to cover three zones A, B and C to form an overall balanced fixation. The modified Harris hip scores (mHHS), plate length, working length and screw number of different internal fixation combinations were compared.Results:The follow-up time was 54.2±21.6 months (range, 11-86 months). All patients showed signs of fracture healing at 10.2±1.5 weeks (range, 7-13 weeks) after operation, and bony union was observed at 19.6±1.3 weeks (range, 17-22 weeks) after operation. No delayed union or nonunion was observed. After operation, one case had a stress fracture and was revised with double-plate internal fixation; one case had a failed internal fixation and was revised with double-plate internal fixation and a large allograft bone graft. The mHHS score of UCSIV.3B2.1 group (80.3±4.6) was the lowest at 6 months after operation, and the difference between the groups of different types was statistically significant ( F=256.72, P<0.001). The score of simple internal fixation group (91.6±4.2) was higher than that of revision combined with internal fixation group (81.9±4.1), and the difference was statistically significant ( t=8.32, P<0.001). The plate length and working length were 24.9±2.5 cm and 12.6±1.7 cm for UCS IV.3B1.1, 25.4±2.6 cm and 13.6±1.8 cm for 3B2.1 and 28.1±2.5 cm and 4.9±1.9 cm for 3C, respectively ( F=5.33, P=0.005; F=6.78, P<0.001). The number of screws in zone A was significant difference among different UCS types ( F=52.67, P<0.001); UCS IV.3B1.1 (6.5±2.3) and 3B2.1 (6.7±2.2) were more than 3B3 (3.5±1.5) and 3C (3.7±1.6). The number of screws in zone B was significant difference among different UCS types ( F=42.15, P<0.001); The number of UCS IV.3B1.1 (2.3±1.6) and 3B2.1 (2.8±1.9) were significantly more than that of 3B3 (1.0±0.5) and 3C (1.2±0.6). The number of screws in zone C was significant differences among different UCS types ( F=39.62, P<0.001); The number of UCS IV.3B1.1 (3.8±1.9) and 3B2.1 (3.9±1.7) were more than that of 3B3 (2.0±0.5), the difference was statistically significant ( P<0.05). Conclusion:The function of hip after simple internal fixation of proximal femoral periprosthetic fractures was better than that of those who underwent revision at the same time; the number of screws of UCSIV.B1 and B2 is more than that of B3.

14.
Chinese Pharmacological Bulletin ; (12): 1774-1781, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1013711

ABSTRACT

Aim To investigate the impact and mechanism of Weichang'an Pill(WCA),its ethanol extract(EE),water extract(WE),and active ingredients on the contraction of isolated rat ileum smooth muscles induced by acetylcholine(ACh). Methods In vitro tissue bath experiment,WCA,EE,WE,or their active ingredients were added under the action of ACh,and then the contraction tension of isolated ileum smooth muscle from rats was recorded. The binding affinity ofthe active ingredients to the muscarinic acetylcholine M3 receptor was explored by molecular docking. Results WCA,EE,and WE were able to considerably inhibit the excitatory contraction of the ileal smooth muscles induced by ACh. Costunolide,dehydrocostus lactone,santalol,muscone,emodin,chrysophanol,physcion,crotonoside,magnolol,and honokiol were also significantly effective against ACh-induced ileal smooth muscle contraction. Conclusions WCA,EE,WE,and their active ingredients may help to promote intestinal smooth muscle relaxation by blocking the binding of the M3 receptor on the membrane of ileal smooth muscle with ACh.

16.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-969896

ABSTRACT

Oral allergy syndrome (OAS) is an IgE-mediated hypersensitivity. Patients with pollen allergy will experience oropharyngeal allergy after eating fresh fruits or vegetables containing homologous pathogenesis-related allergen, occasionally accompanied by systemic symptoms, it is a special type of food hypersensitivity in which respiratory allergens and food allergens are similar structurally and lead to the cross-reactivity. At present, there is little research and attention to it in China. To master the definition, epidemiological characteristics, pathological mechanism, diagnosis, prevention and treatment of OAS is very important to the prevention and control of OAS. This article reviews the research progress of OAS, providing reference and prevention basis for clinicians to improve the diagnosis and differential diagnosis of OAS.


Subject(s)
Humans , Pollen , Food Hypersensitivity/diagnosis , Rhinitis, Allergic, Seasonal/therapy , Allergens , Fruit , Cross Reactions
17.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-964956

ABSTRACT

Baizhusan, derived from Key to Medicines and Patterns of Children's Diseases (《小儿药证直诀》) by QIAN Yi in Song dynasty, is a classical prescription that has been highly praised by doctors and widely used in clinical practice. It was included in the Catalogue of Ancient Classical Prescriptions (the second batch of Pediatrics) released by the National Administration of Traditional Chinese Medicine (TCM) in 2022. In this paper, the ancient documents related to Baizhusan were collected by bibliographical research, and the source, composition, herb origin and processing, dosage, decocting method, administration method, functions and indications of the prescription were analyzed and verified. A total of 211 ancient documents on Baizhusan were obtained, involving 116 ancient TCM books. It was found that there were many prescriptions named Baizhusan in ancient times, but the prescription named Baizhusan and composed of Ginseng Radix et Rhizoma, Poria, Atractylodis Macrocephalae Rhizoma, Pogostemonis Herba, Aucklandiae Radix, Glycyrrhizae Radix et Rhizoma, and Puerariae Lobatae Radix was first seen in Key to Medicines and Patterns of Children's Diseases, and is now generally known as Qiweibaizhusan. The composition and functions of Baizhusan were unified in past dynasties, and its herb origin and processing were basically clear. However, there was a dispute on the processing of Atractylodis Macrocephalae Rhizoma and Glycyrrhizae Radix et Rhizoma, which was solved by recommended use of soil-fried Atractylodis Macrocephalae Rhizoma and raw Glycyrrhizae Radix et Rhizoma. Boasting the functions of tonifying spleen, replenishing Qi, harmonizing stomach and promoting fluid production, Baizhusan treated a variety of symptoms such as diarrhea, consumptive thirst and loss of appetite, which were consistent in ancient and modern literature, but attention should be attached to the basic pathogenesis of spleen deficiency and fluid inadequacy. In addition, considerable disagreements were also observed about the dosage and decocting method of Baizhusan in the documents, and the combination ratio of Baizhusan in another version of Key to Medicines and Patterns of Children's Diseases of Wuyingdian Zhenben was the dominant standard for drug use in past dynasties.

18.
Acta Pharmaceutica Sinica B ; (6): 1145-1163, 2023.
Article in English | WPRIM (Western Pacific) | ID: wpr-971757

ABSTRACT

MEK is a canonical effector of mutant KRAS; however, MEK inhibitors fail to yield satisfactory clinical outcomes in KRAS-mutant cancers. Here, we identified mitochondrial oxidative phosphorylation (OXPHOS) induction as a profound metabolic alteration to confer KRAS-mutant non-small cell lung cancer (NSCLC) resistance to the clinical MEK inhibitor trametinib. Metabolic flux analysis demonstrated that pyruvate metabolism and fatty acid oxidation were markedly enhanced and coordinately powered the OXPHOS system in resistant cells after trametinib treatment, satisfying their energy demand and protecting them from apoptosis. As molecular events in this process, the pyruvate dehydrogenase complex (PDHc) and carnitine palmitoyl transferase IA (CPTIA), two rate-limiting enzymes that control the metabolic flux of pyruvate and palmitic acid to mitochondrial respiration were activated through phosphorylation and transcriptional regulation. Importantly, the co-administration of trametinib and IACS-010759, a clinical mitochondrial complex I inhibitor that blocks OXPHOS, significantly impeded tumor growth and prolonged mouse survival. Overall, our findings reveal that MEK inhibitor therapy creates a metabolic vulnerability in the mitochondria and further develop an effective combinatorial strategy to circumvent MEK inhibitors resistance in KRAS-driven NSCLC.

19.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-989624

ABSTRACT

Objective:To explore the medication law and core TCM prescriptions of Jia Yuejin in the treatment of coronary heart disease (CHD) complicated with depressive disorder (DD) by analyzing target-based network and mining clinical data.Methods:The targets of CHD complicated with DD were obtained by GeneCards, OMIM, TTD and other databases, and then the protein-protein interaction network of the two disease targets was constructed and then screened out the core targets. The Metascape platform was used to perform GO and KEGG pathway enrichment analysis on the intersection targets respectively to analyze the mechanism of action of CHD complicated with DD. Then TCMSP was used to query the active components acting on the targets and the Chinese materia medica containing these active components, and the data were imported into Cytoscape 3.9.0 to construct the core target-active component-Chinese materia medica network for network topology analysis. The outpatient clinical data of Jia Yuejin from January 1, 2015 to January 1, 2021 were collected, and data mining was conducted by using the Ancient and Modern Medical Case Cloud Platform (V2.3.5) to obtain his commonly used prescriptions. The results were fitted with the core TCM prescriptions obtained by target network analysis, and the drugs in the core prescriptions were analyzed.Results:Totally 1 501 intersection targets were obtained by protein interaction network analysis of CHD complicated with DD, which could be divided into 4 core target clusters, including inflammation cause, subclass tumor cause, subclass lipid metabolism factor, and fibrosis factor; a total of 480 active components were obtained by TCMSP, which belonged to 181 types of Chinese materia medica, including 8 core components: quercetin, kaempferol, luteolin, carotene, beta-carotene, acacetin, formononetin and ellagic acid. GO enrichment analysis yielded 61 results, mainly including positive regulation of protein phosphorylation, signal receptor agonist activity, side of membrane , etc.; KEGG pathway enrichment analysis yielded a total of 20 results, mainly including cancer pathways, lipid and atherosclerosis, JAK-STAT signaling pathway, etc. Clinical data mining included 120 cases and 148 prescriptions, including 135 types of Chinese materia medica; the properties were mainly mild, warm, slightly cold and cold; the tastes were mainly sweet, bitter and light, and the medicine mainly belongs to the lung, spleen, liver, heart, stomach, kidney and other meridians; drug association analysis, cluster analysis and complex network analysis were used to synthesize common prescriptions. The core TCM prescriptions obtained from common prescription and target network analysis were fitted: Pinelliae Rhizoma, Glycyrrhizae Radixet Rhizoma, Bupleuri Radix, Cyperi Rhizoma, Salviea Miltiorrhizae Radix et Rhizoma, Corydalis Rhizoma, Codonopsis Radix, Astragali Radix, Acori Tatarinowii Rhizoma. Conclusion:The medication law of Jia Yuejin in the treatment of CHD complicated with DD is in accordance with core TCM prescriptions. This study can provide guidance for clinical treatment and further research of CHD complicated with DD.

20.
Eur J Radiol ; 157: 110567, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36283194

ABSTRACT

OBJECTIVES: Flow cytometry (FC) is a critical diagnostic approach for guiding targeted chemotherapy and cellular immunotherapy for relapsed and refractory lymphoma patients. The aim of the study was to investigate the value of ultrasound-guided fine needle aspiration (FNA) to improve the quality of FC specimens in relapsed and refractory diffuse large B-cell lymphoma (R/R DLBCL). METHODS: Twenty patients with R/R DLBCL after standard treatment were included. The primary lesions of all cases were confirmed by pathology. FNA and core needle biopsy (CNB) were both used for ultrasound-guided puncture, the specimens obtained by FNA are directly examined by FC, and the specimens by CNB were subjected to FC after grinding. The accuracy of FC with the two methods were evaluated using histopathology as the gold standard. RESULTS: Of the 20 R/R DLBCL cases, 19 were diagnosed as DLBCL pathologically and one was diagnosed as inflammatory granuloma. Among the specimens obtained by CNB, 14 cases examined by FC after grinding showed abnormal mature B cells, five cases were missed, all cases are not misdiagnosed. Among the specimens obtained by FNA, 18 cases showed FC-confirmed abnormal mature B cells, one case was missed, all cases are not misdiagnosed. The sensitivity, specificity, and accuracy of FC with CNB and FNA were 73.68 % (14/19) vs 94.73 % (18/19), 100 % (1/1) vs 100 % (1/1), and 75 % (15/20) vs 97.14 % (19/20), respectively. The sensitivity of the two puncture methods of FC of DLBCL was statistically different (p < 0.001). CONCLUSION: Sampling with ultrasound-guided FNA is of great value to improve the quality of FC specimens. FNA can significantly improve the sensitivity and accuracy of FC diagnosis in R/R DLBCL.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Lymphoma, Non-Hodgkin , Humans , Biopsy, Fine-Needle/methods , Sensitivity and Specificity , Image-Guided Biopsy , Biopsy, Large-Core Needle/methods , Ultrasonography, Interventional , Lymphoma, Large B-Cell, Diffuse/diagnostic imaging , Retrospective Studies
SELECTION OF CITATIONS
SEARCH DETAIL
...