Chaihu and Longgu Muli Decoction has demonstrated significant efficacy in the treatment of tachyarrhythmia accompanied by anxiety and depression. However, there is a lack of standardized guidelines for its clinical application. In this study, the Chaihu and Longgu Muli Decoction was investigated through extensive research on ancient and modern literature, as well as a collection of clinical medical records. The basic information, medication details, and diagnostic information from medical records, personal experience literature, and clinical cases in the treatment of tachyarrhythmia accompanied by anxiety were extracted and analyzed to preliminarily identify the prescription characteristics and syndrome patterns. Subsequently, the Delphi method was employed to construct an item pool based on the data obtained in the first step. An expert questionnaire was prepared to collect scores and revision opinions from experts regarding these items. After statistical analysis and group discussions, a second round of questionnaires was formed by screening out certain items. This process was repeated until a final item set for the treatment of tachyarrhythmia accompanied by anxiety with Chaihu and Longgu Muli Decoction was determined. These findings provided guidance for clinical prescription practices. By extracting 71 syndromes and signs, as well as 33 tongue and pulse characteristics, the main syndrome features included palpitations, chest tightness, irritability, etc., which were basically consistent with the ancient syndromes. Through frequency analysis and group discussions, 71 items were screened out. After screening, modification, and primary and secondary division, 11 main diagnostic items and 10 secondary diagnostic items were determined. On this basis, the research team believes that Chaihu and Longgu Muli Decoction is mainly indicated for the following syndromes in the treatment of tachyarrhythmia accompanied by anxiety(palpitations, poor sleep, bitter taste, dry mouth, irritability/easily angered/anxiety/fearfulness/easily startled, red tongue with greasy yellow coating, rapid pulse, high work/life pressure, tachyarrhythmia on electrocardiogram/Holter monitor, and positive results on anxiety scale). Secondary syndromes include chest tightness, shortness of breath, feeling heavy and weak in the body, sweating, poor appetite, constipation, greasy white tongue coating, wiry pulse, slippery pulse, or knotted and intermittent pulse.
Drugs, Chinese Herbal/therapeutic use* ; Humans ; Delphi Technique ; Anxiety/complications* ; Tachycardia/psychology* ; Female ; Male ; Middle Aged ; Adult ; Aged

OBJECTIVE: The molecular biology of alleles of ABO blood group A_el and B_el subtype from two samples was analyzed to explore the effect of mutations on the structure of glycosyltransferase. METHODS: The ABO phenotypes were identified by serological techniques, then exons 6 and 7 of ABO gene were amplified and sequenced, combined with haplotype analysis to determine the genotypes. Finally, homology modeling of the mutated A/B glycosyltransferase were conducted by Modeller software and the effect of mutations on the spatial structure was analyzed by PyMol software. RESULTS: The serological phenotypes of the two samples were A_el and B_el, and their genotypes were ABO*AW.37/ABO*O.01.01 and ABO*BEL.03/ABO*O.01.01, respectively. The three-dimensional structure modeling of the protein showed that, compared to the wild-type glycosyltransferase, two hydrogen bonds between the side chain of p.Glu314 and surrounding amino acid disappeared in the p.Lys314Glu mutant GTA; the hydrogen bonds between the side chain of p.Trp168 and surrounding amino acid also disappeared, and the hydrogen bond between the main chain of p.Trp168 and p.Gly165 was shortened to 3.3 Å in the p.Arg168Trp mutant GTB. CONCLUSION Mutations in exon 7 of ABO gene c.940A>G and c.502C>T are keys to the formation of AW.37 and BEL.03 alleles, resulting in decreased expression of A and B antigens, respectively.
ABO Blood-Group System/classification* ; Humans ; Genotype ; Mutation ; Alleles ; Glycosyltransferases/genetics* ; Exons ; Haplotypes ; Phenotype ; Models, Molecular

Ferroptosis is a form of programmed cell death characterized by overwhelmed lipid oxidation, and it has emerged as a promising strategy for cancer therapy. Enhanced ferroptosis could overcome the limitations of conventional therapeutic modalities, particularly in difficult-to-treat tumors. In this study, we developed a dual-modality therapy in nanomedicine by combining paclitaxel (PTX) chemotherapy and pyropheophorbide-a (Ppa) phototherapy. Heparin (HP) was grafted with poly(N-(2'-hydroxy) propyl methacrylamide) (pHPMA) using reversible addition-fragmentation chain transfer polymerization to form HP-pHPMA (HH), which was utilized to deliver Ppa and PTX, yielding HP-pHPMA-Ppa (HH-Ppa) and HP-pHPMA-PTX (HH-PTX), respectively. The prodrug-based combinational nanomedicine (HH-PP) was formed by co-assembly of HH-PTX and HH-Ppa. It was found that HH-PP treatment significantly disrupted lipid metabolism in triple-negative breast cancer (TNBC) cells, induced extensive lipid oxidation, and promoted ferroptosis. In vivo, HH-PP intervention achieved a tumor growth inhibition rate of 86.63% and activated adaptive immunity with an elevated CD8⁺ cytotoxic T cell infiltration level. This combinational nanomedicine offers a promising platform for co-delivery of multiple therapeutic agents. It exerts a promising anti-tumor effect via enhanced ferroptosis and ferroptosis-induced immune activation by disrupting lipid metabolism in TNBC cancer cells.

Radiation-induced thrombocytopenia (RIT) faces a perplexing challenge in the clinical treatment of cancer patients, and current therapeutic approaches are inadequate in the clinical settings. In this research, oxymatrine, a new molecule capable of healing RIT was screened out, and the underlying regulatory mechanism associated with magakaryocyte (MK) differentiation and thrombopoiesis was demonstrated. The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro. The ability to induce thrombopoiesis was subsequently demonstrated in Tg (cd41:enhanced green fluorescent protein (eGFP)) zebrafish and RIT model mice. In addition, we carried out network pharmacological prediction, drug affinity responsive target stability assay (DARTS) and cellular thermal shift assay (CETSA) analyses to explore the potential targets of oxymatrine. Moreover, the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, Western blot (WB), and immunofluorescence. Oxymatrine markedly promoted MK differentiation and maturation in vitro. Moreover, oxymatrine induced thrombopoiesis in Tg (cd41:eGFP) zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice. Mechanistically, oxymatrine directly binds to toll-like receptor 2 (TLR2) and further regulates the downstream pathway stimulator of interferon genes (STING)/nuclear factor-kappaB (NF-κB), which can be blocked by C29 and C-176, which are specific inhibitors of TLR2 and STING, respectively. Taken together, we demonstrated that oxymatrine, a novel TLR2 agonist, plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis, suggesting that oxymatrine is a promising candidate for RIT therapy.

Stroke is the second leading cause of disability and mortality worldwide, imposing a substantial socioeconomic burden on individuals and healthcare systems. Annually, approximately 14 million people experience stroke, with ischemic stroke comprising nearly 85% of cases, of which 10% to 20% involve large vessel occlusions. Currently, recombinant tissue plasminogen activator (tPA) remains the only approved pharmacological intervention. However, its utility is limited due to a narrow therapeutic window and low recanalization rates, making it applicable to only a minority of patients. Therefore, there is an urgent need for novel therapeutic strategies, including pharmacological advancements and combinatory treatments. Small-molecule natural medicines, particularly those derived from traditional Chinese herbs, have demonstrated significant therapeutic potential in ischemic stroke management. These compounds exert multiple neuroprotective effects, such as antioxidation, anti-inflammatory action, and inhibition of apoptosis, all of which are critical in mitigating stroke-induced cerebral damage. This review comprehensively examines the pathophysiology of acute ischemic stroke (AIS) and highlights the recent progress in the development of small-molecule natural medicines as promising therapeutic agents for cerebral ischemic stroke.
Humans ; Ischemic Stroke/physiopathology* ; Animals ; Neuroprotective Agents/therapeutic use* ; Drugs, Chinese Herbal/chemistry* ; Biological Products/therapeutic use* ; Stroke/drug therapy*

Background: Twenty-four-hour urinary free cortisol (UFC) measurement is the initial diagnostic test for Cushing’s syndrome (CS). We compared UFC determination by both direct and extraction immunoassays using Abbott Architect, Siemens Atellica Solution, and Beckman DxI800 with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, we evaluated the value of 24-hr UFC measured by six methods for diagnosing CS. Methods: Residual 24-hr urine samples of 94 CS and 246 non-CS patients were collected.A laboratory-developed LC-MS/MS method was used as reference. UFC was measured by direct assays (D) using Abbott, Siemens, and Beckman platforms and by extraction assays (E) using Siemens and Beckman platforms. Method was compared using Passing–Bablok regression and Bland–Altman plot analyses. Cut-off values for the six assays and corresponding sensitivities and specificities were calculated by ROC analysis. Results: Abbott-D, Beckman-E, Siemens-E, and Siemens-D showed strong correlations with LC-MS/MS (Spearman coefficient r = 0.965, 0.922, 0.922, and 0.897, respectively), while Beckman-D showed weaker correlation (r = 0.755). All immunoassays showed proportionally positive bias. The areas under the curve were 0.975 for Abbott-D, 0.972 for LCMS/MS, 0.966 for Siemens-E, 0.948 for Siemens-D, 0.955 for Beckman-E, and 0.877 for Beckman-D. The cut-off values varied significantly (154.8–1,321.5 nmol/24 hrs). Assay sensitivity and specificity ranged from 76.1% to 93.2% and from 93.0% to 97.1%, respectively. Conclusions Commercially available immunoassays for measuring UFC show different levels of analytical consistency compared to LC-MS/MS. Abbott-D, Siemens-E, and Beckman-E have high diagnostic accuracy for CS.

Objective To explore the mechanism of Angelica Sinensis polysaccharide(ASP)promoting donor bone marrow transplantation(BMT)to reconstruct hematopoietic function of receptor mice by regulating bone marrow stromalcells(BMSCs).Methods Bone marrow mononuclear cells(BMMNCs)of male C57BL/6J mice aged 8-10 weeks were separated,purified and transplanted into female receptor mice of the same age.On the ninth day,receptor mice BMMNCs were separated,purified and transplanted again into female receptor mice.The transplanted receptor mice were divided into control group:sham irradiation;Irradiation(IR)group:a whole-body irradiation with a total dose of 8.0 Gy X-ray;BMT group:the receptor mice treated in the same way as the IR group and transplanted BMMNCs(5×106 cells)from male donor via the tail vein;BMT+ASP group:the receptor mice treated in the same way as the BMT group,and injected ASP[100 mg/(kg·d)×9]by intraperitoneal route from the first day of transplantation.Changes in body weight and survival rate of mice were recorded during modeling,receptor mice BMMNCs were collected to detect sex-determining region of Y(SRY)gene after building model,peripheral blood indexes,the number of BMMNCs in femur and histopathology of bone marrow were detected;BMSCs in receptor mice was separated and purified,BMSCs adhesion ability was observed,proliferation ability was detected by 5-ethynyl-2-deoxyuridine(EdU);The level of reactive oxygen species(ROS),the activity of superoxide dismutase(SOD)and the content of malondialdehyde(MDA)in BMSCs were detected;The levels of granulocyte-macrophage colony-stimulating factor(GM-CSF),stem cell factor(SCF),insulin-like growth factor 1(IGF-1)in culture supernatant of BMSCs were determined,CFU-Mix was counted after BMMNCs co-cultured with receptor BMSCs in each group for 48 hours;The expression of Notch signaling pathway related genes(Notch1,Jagged1,Hes1)in BMMNCs were measured by Real-time PCR.Results All mice in IR group were died,the body weight loss in BMT+ASP group was not obvious.The SRY gene was detected in the receptor female mice BMMNCs.Peripheral blood indexes and the number of BMMNCs were not significantly decreased in BMT+ASP group receptor mice,and bone marrow histopathological injury was reduced.ASP promoted the proliferation of BMSCs,decreased the contents of ROS and MDA,and increased the activity of SOD in BMSCs.ASP promoted the secretion of SCF,GM-CSF and IGF-1 in BMSCs,and increased CFU-Mix yield of BMMNCs co-cultured with receptor BMSCs.ASP increased the expression of Notch1,Jagged1 and Hes1 mRNA in BMMNCs.Conclusion The mechanism of ASP promoting receptor hematopoietic function reconstruction is related to reducing the oxidative stress damage of hematopoietic microenvironment,improving the secretion of hematopoietic growth factors in BMSCs,and regulating Notch signaling pathway.

Objective:To compare the diagnostic efficacy of 22 G fine needle aspiration (FNA) needles and 22 G end-cutting fine needle biopsy (FNB) needles for solid pancreatic lesion using both cytological and histological examination.Methods:Clinical data of 116 patients who underwent endoscopic ultrasound-guided fine needle aspiration/biopsy (EUS-FNA/FNB) at the Digestive Endoscopy Center of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from June 2022 to March 2023 were retrospectively analyzed. Sixty-three patients sampled with 22 G FNA needles were the FNA group, and 53 sampled with 22 G FNB needles were the FNB group. The diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and cytological and histological diagnostic yield of FNA needles and FNB needles for solid pancreatic lesions were compared.Results:There were no significant differences in age, gender, lesion location, lesion size, or the number of passes between the FNA group and the FNB group ( P>0.05). There were no significant differences in the diagnostic accuracy [93.7% (59/63) VS 90.6% (48/53), P=0.730], sensitivity [93.0% (53/57) VS 90.2% (46/51), P=0.732], specificity [100.0% (6/6) VS 100.0% (2/2), P=1.000], positive predictive value [100.0% (53/53) VS 100.0% (46/46), P=1.000] and negative predictive value [60.0% (6/10) VS 28.6% (2/7), P=0.335] of combined cytology and histology in distinguishing benign and malignant lesions between the two groups. In the FNA group, the diagnostic accuracy of combined cytology and histology was higher than cytology alone [93.7% (59/63) VS 81.0% (51/63), P=0.008], and was higher than histology alone without statistical significance [93.7% (59/63) VS 87.3% (55/63), P=0.125]. In the FNB group, the diagnostic accuracy of combined cytology and histology was higher than cytology alone [90.6% (48/53) VS 69.8% (37/53), P=0.001], but not than histology alone [90.6% (48/53) VS 90.6% (48/53)， P=1.000]. For solid masses located in pancreatic body/tail, the diagnostic accuracy for malignancy by histology using FNB needles tended to be higher than that of FNA needles [100.0% (17/17) VS 81.3% (26/32), P=0.080]. Conclusion:Both FNA needles and FNB needles exhibit adequate diagnostic yield for solid pancreatic masses when combining cytology and histology. FNB needles may offer a higher histological diagnostic yield.

To explore the mechanism by which vinegar-processed Euphorbiae Pekinensis Radix regulates gut microbiota and reduces intestinal toxicity, this study aimed to identify key microbial communities related to vinegar-induced detoxification and verify their functions. Using a derivatization method, the study measured the content of short-chain fatty acids(SCFAs) in feces before and after vinegar-processing of Euphorbiae Pekinensis Radix. Combined with the results of previous gut microbiota sequencing, correlation analysis was used to identify key microbial communities related to SCFAs content. Through single-bacterium transplantation experiments, the role of key microbial communities in regulating SCFAs metabolism and alleviating the intestinal toxicity of Euphorbiae Pekinensis Radix was clarified. Fecal extracts were then added to a co-culture system of Caco-2 and RAW264.7 cells, and toxicity differences were evaluated using intestinal tight junction proteins and inflammatory factors as indicators. Additionally, the application of a SCFAs receptor blocker helped confirm the role of SCFAs in reducing intestinal toxicity during vinegar-processing of Euphorbiae Pekinensis Radix. The results of this study indicated that vinegar-processing of Euphorbiae Pekinensis Radix improved the decline in SCFAs content caused by the raw material. Correlation analysis revealed that Bifidobacterium was positively correlated with the levels of acetic acid, propionic acid, isobutyric acid, n-butyric acid, isovaleric acid, and n-valeric acid. RESULTS:: from single-bacterium transplantation experiments demonstrated that Bifidobacterium could mitigate the reduction in SCFAs content induced by raw Euphorbiae Pekinensis Radix, enhance the expression of tight junction proteins, and reduce intestinal inflammation. Similarly, cell experiment results confirmed that fecal extracts from Bifidobacterium-transplanted mice alleviated inflammation and increased the expression of tight junction proteins in intestinal epithelial cells. The use of the free fatty acid receptor-2 inhibitor GLPG0974 verified that this improvement effect was related to the SCFAs pathway. This study demonstrates that Bifidobacterium is the key microbial community responsible for reducing intestinal toxicity in vinegar-processed Euphorbiae Pekinensis Radix. Vinegar-processing increases the abundance of Bifidobacterium, elevates the intestinal SCFAs content, inhibits intestinal inflammation, and enhances the expression of tight junction proteins, thereby improving the intestinal toxicity of Euphorbiae Pekinensis Radix.
Animals ; Mice ; Humans ; Acetic Acid/chemistry* ; Gastrointestinal Microbiome/drug effects* ; Fatty Acids, Volatile/metabolism* ; Bifidobacterium/genetics* ; Caco-2 Cells ; Intestines/microbiology* ; Drugs, Chinese Herbal/chemistry* ; Euphorbia/toxicity* ; RAW 264.7 Cells ; Male ; Feces/chemistry* ; Intestinal Mucosa/drug effects*

Aim To investigate the effect of overexpression of silent information regulator 1 (Sirtl) on cardiac function in mice with myocardial ischemia. Methods Myocardial specific Sirtl overexpression transgenic mice (Sirtl-Tg) and littermate control mice (C57BL/6J), half male and half female, were randomly divided into control sham operation group (Con), control model group (Con +ISO), Sirtl overexpression sham operation group (Sirtl-Tg) and Sirtl overexpression model group (Sirtl-Tg + ISO). Isoproterenol (ISO) was injected subcutaneously into the back of the neck at 100 mg • kg