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: To observe the clinical effect and safety of Lu'e Biyan Formula (LBF) combined with loratadine in the treatment of moderate to severe allergic rhinitis (AR) patients with Fei (Lung)-qi deficiency-coldness (FQDC) syndrome. METHODS: From September 2023 to December 2024, moderate to severe AR patients with FQDC syndrome were recruited from the Outpatient Department of Integrated Traditional Chinese and Western Medicine for Pulmonary Diseases Part 1, China-Japan Friendship Hospital. Participants were randomly assigned to a test group and a control group by using a random number table at a ratio of 1:1. Both groups received oral loratadine tablets (10 mg, once daily) for 2 weeks. In addition, the test group received oral LBF (30 mL, twice daily), and the control group received a placebo of LBF. Changes in the Total Nasal Symptom Score (TNSS), Total Non-nasal Symptom Score (TNNSS), Visual Analog Scale (VAS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Chinese medicine (CM) syndrome scores before and after treatment were compared between groups. Moreover, the total effective rates and disease recurrence rates were compared. Adverse events (AEs) during the study period were also recorded. RESULTS: Totally 109 participants were recruited, and the full analysis set included 105 cases, 54 in the test group and 51 in the control group. Compared with the pre-treatment values, the scores of sneezing, runny nose, nasal obstruction, nasal itching, TNSS, TNNSS, VAS, RQLQ, and CM syndrome were significantly reduced in both groups at 1 and 2 weeks post-treatment and 12 weeks post-drug withdrawal (P<0.01). After treatment, the aforementioned scores in the test group were all markedly lower than those in the control group (P<0.01). Moreover, the total effective rate in the test group was higher than that in the control group (98.15% vs. 70.59%, P<0.01). After 12 weeks of drug withdrawal, there was no significant difference in the recurrence rate between groups (13.21% vs. 22.22%, P>0.05). No obvious AEs were observed in either group following treatment. CONCLUSIONS The combination of LBF with loratadine can effectively alleviate the symptoms of moderate to severe AR patients with FQDC syndrome, thereby improving their quality of life. This therapy demonstrated both precise effect and high safety. (Trial registration No. ITMCTR2025000589).
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Rhinitis, Allergic/drug therapy* ; Female ; Adult ; Double-Blind Method ; Quality of Life ; Qi ; Middle Aged ; Loratadine/therapeutic use* ; Medicine, Chinese Traditional ; Syndrome ; Lung/drug effects* ; Young Adult ; Treatment Outcome

Aim To study the neuroprotective effects of Herba siegesbeckiae extract on cerebral ischemia/ reperfusion rats and its mechanism. Methods Sixty SD rats were randomly divided into model group, low, middle and high dose groups of Herba siegesbeckiae, and Sham operation group, and the drug was given continuously for seven days. The degree of neurologic impairment was evaluated by mNSS, and the infarct volume was measured by MRI. The number of Nissl-posi- tive cells was detected by Nissl staining, and the apop- tosis was accessed by Tunel staining. Furthermore, the expression of Bax, Bcl-2 and NeuN was observed by Western blot, and the expression of NeuN was detected by immunofluorescence staining. The expression of IL- 1β, TNF-α and IL-6 mRNA was performed by RT- qPCR. Results The mNSS score and the volume of ischemic cerebral infarction in the model group were significantly increased, and Herba siegesbeckiae extract treatment significantly decreased the mNSS score and infarct volume (P<0.05, P<0.01). Herba siegesbeckiae extract could increase the number of Nissl-pos- itive cells and the expression of NeuN (P<0.01), and reduce the number of Tunel-positive cells (P<0.01). Western blot showed that Herba siegesbeckiae extract inhibited the expression of Bax, increased Bcl-2 and NeuN in ischemic brain tissue (P<0.01). RT-qPCR showed that Herba siegesbeckiae extract inhibited the expression of IL-1 β, TNF-α and IL-6 mRNA in the is-chemic brain tissue (P<0.01). Conclusions Herba siegesbeckiae extract can reduce the cerebral infarction volume, improve the neurological function damage, inhibit the apoptosis of nerve cells and the expression of inflammatory factors and promote the expression of NeuN, there by exerting protective effects on MCAO rats.

Objective:To explore the optimal storage condition and time of umbilical cord blood from collection to preparation.Methods:Collect cord blood samples from 30 healthy newborns,with each new born's umbilical cord blood was divided into two parts on average.One part was stored in cold storage(4 ℃)and the other was stored at room temperature(20-24 ℃).Samples were taken at 24,36,48,60 and 72 h,respectively,total nucleated cells(TNC)count and TNC viability was analyzed.Flow cytometry was used to detect the ratio of viable CD34+cells to viable CD45+cells and viability of CD34+cells,and colony-forming unit-granulocyte-macrophage(CFU-GM)count was performed by hematopoietic progenitor cell colony culture.The change trend of each index over time was observed,and the differences in each index was compared between cold storage and room temperature storage under the same storage time.Results:The TNC count(r4℃=-0.9588,r20-24℃=-0.9790),TNC viability(r4℃=-0.9941,r20 24 ℃=-0.9970),CD34+cells viability(r4℃=-0.9932,r20-24℃=-0.9828)of cord blood stored in cold storage(4 ℃)and room temperature storage(20-24 ℃)showed a consistent downward trend with the prolongation of storage time.The percentage of viable CD34+cells(r4℃=0.9169,r20-24 ℃=0.7470)and CFU-GM count(r4℃=-0.2537,r20-24℃=-0.8098)did not show consistent trends.When the storage time was the same,the TNC count,TNC viability,CD34+cells viability and CFU-GM count of cord blood stored in cold storage were higher than those stored at room temperature.Under the same storage time(24,36,48,60 or 72 h),TNC viability in room temperature storage was significantly lower than that in cold storage(P＜0.001),but TNC count,percentage of viable CD34+cells and CFU-GM count were not significantly different between room temperature storage and cold storage.When stored at room temperature for 24 h and 36 h,the viability of CD34+cells was significantly lower than that in cold storage(P＜0.001,P＜0.01),when the storage time for 48,60 and 72 h,there was no significant difference in the CD34+cells viability between room temperature storage and cold storage.Conclusion:It is recommended that cord blood be stored in cold storage(4 ℃)from collection to preparation,and processed as soon as possible.

Corydalis Rhizoma is a commonly used traditional Chinese medicine(TCM) for regulating Qi and relieving pain in clinical practice, with remarkable efficacy. However, its pharmacodynamic substances are not yet fully understood and require further research. In this study, 24 compounds were isolated and identified from the aqueous extracts of vinegar-processed Corydalis Rhizoma using techniques such as macroporous adsorption resin column chromatography, Sephadex LH-20 column chromatography, and semi-preparative high-performance liquid chromatography. Their structures were determined based on their physicochemical properties and spectroscopic methods, including UV, IR, HR-MS, 1D NMR, and 2D NMR. Among these, compounds 1 and 2 are two rare natural α-carbonamide alkaloids, named yanhuoxamide A(compound 1) and yanhuoxamide B(compound 2), respectively. Compounds 3-24 are known compounds, identified as xanthoplanine(3), stigmast-4-ene-3,6-dione(4), norchelerythrine(5), ethyl ferulate(6), 6-hydroxymethyl-3-pyridinol(7), 6-(\[1,3\]dioxolo\[4,5-g\]isoquinoline-5-carbonyl)-2,3-dimethoxy-benzoic acid methyl ester(8), 1H-indole-3-carbaldehyde(9), 4-hydroxy-3-methoxy ethyl cinnamate(10), berberal(11), oblongine trifluoroacetate(12), thalbaicalidine(13), cyclopiamide(14), nicotinamide(15), dehydrocorypalline trifluoroacetate(16), 6-acetonyldihydrochelerythrine(17), 6-acetonyldihydrosanguinarine(18), norsanguinarine(19), oxysanguinarine(20), bulbocapnine(21), corydine(22),(-)-(13aS)-stylopine(23), and(-)-(9S,13S)-pallidine(24). Among these, compounds 3-15 were isolated from the genus Corydalis for the first time, and compounds 16-24 were isolated from Corydalis Rhizoma for the first time. Additionally, the inhibitory activity of compounds 1 and 2 on acetylcholinesterase(AChE) was evaluated.
Corydalis/chemistry* ; Rhizome/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Molecular Structure ; Amides/chemistry* ; Magnetic Resonance Spectroscopy ; Chromatography, High Pressure Liquid ; Alkaloids/chemistry*

Divisions at the periphery and midzone of mitochondria are two fission signatures that determine the fate of mitochondria and cells.Pharmacological induction of excessively asymmetric mitofission-associated cell death(MFAD)by switching the scission position from the mitochondrial midzone to the periphery represents a promising strategy for anticancer therapy.By screening a series of pan-inhibitors,we identified pracinostat,a pan-histone deacetylase(HDAC)inhibitor,as a novel MFAD inducer,that exhibited a significant anticancer effect on colorectal cancer(CRC)in vivo and in vitro.Pracinostat increased the expression of cyclin-dependent kinase 5(CDK5)and induced its acetylation at residue lysine 33,accelerating the formation of complex CDK5/CDK5 regulatory subunit 1 and dynamin-related protein 1(Drp1)-mediated mitochondrial peripheral fission.CRC cells with high level of CDK5(CDK5-high)displayed midzone mitochondrial division that was associated with oncogenic phenotype,but treatment with pracinostat led to a lethal increase in the already-elevated level of CDK5 in the CRC cells.Mechanistically,pracinostat switched the scission position from the mitochondrial midzone to the periphery by improving the binding of Drp1 from mitochondrial fission factor(MFF)to mitochondrial fission 1 protein(FIS1).Thus,our results revealed the anticancer mechanism of HDACi pracinostat in CRC via activating CDK5-Drp1 signaling to cause selective MFAD of those CDK5-high tumor cells,which implicates a new paradigm to develop potential therapeutic strategies for CRC treatment.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective: To analyze the clinical features, efficacy and prognosis factors of core binding factor (CBF) acute myeloid leukemia (AML) children in South China. Methods: This was a retrospective cohort study. Clinical data of 584 AML patients from 9 hospitals between January 2015 to December 2020 was collected. According to fusion gene results, all patients were divided into two groups: CBF-AML group (189 cases) and non-CBF-AML group (395 cases). CBF-AML group were divided into AML1-ETO subgroup (154 cases) and CBFβ-MYH11 subgroup (35 cases). Patients in CBF-AML group chosen different induction scheme were divided into group A (fludarabine, cytarabine, granulocyte colony stimulating factor and idarubicin (FLAG-IDA) scheme, 134 cases) and group B (daunorubicin, cytarabine and etoposide (DAE) scheme, 55 cases). Age, gender, response rate, recurrence rate, mortality, molecular genetic characteristics and other clinical data were compared between groups. Kaplan-Meier method was used for survival analysis and survival curve was drawn. Cox regression model was used to analyze prognostic factors. Results: A total of 584 AML children were diagnosed, including 346 males and 238 females. And a total of 189 children with CBF-AML were included, including 117 males and 72 females. The age of diagnosis was 7.3 (4.5,10.0)years, and the white blood cell count at initial diagnosis was 21.4 (9.7, 47.7)×10⁹/L.The complete remission rate of the first course (CR1) of induction therapy, relapse rate, and mortality of children with CBF-AML were significantly different from those in the non-CBF-AML group (91.0% (172/189) vs. 78.0% (308/395); 10.1% (19/189) vs. 18.7% (74/395); 13.2% (25/189) vs. 25.6% (101/395), all P<0.05). In children with CBF-AML, the CBFβ-MYH11 subgroup had higher initial white blood cells and lower proportion of extramedullary invasion than the AML1-ETO subgroup, with statistical significance (65.7% (23/35) vs. 14.9% (23/154), 2.9% (1/35) vs. 16.9% (26/154), both P<0.05). AML1-ETO subgroup had more additional chromosome abnormalities (75/154), especially sex chromosome loss (53/154). Compared with group B, group A had more additional chromosome abnormalities and a higher proportion of tumor reduction regimen, with statistical significance (50.0% (67/134) vs. 29.1% (16/55), 34.3% (46/134) vs. 18.2% (10/55), both P<0.05). Significant differences were found in 5-years event free survival (EFS) rate and 5-year overall survival (OS) rate between CBF-AML group and non-CBF-AML group ((77.0±6.4)%vs. (61.9±6.7)%,(83.7±9.0)%vs. (67.3±7.2)%, both P<0.05).EFS and OS rates of AML1-ETO subgroup and CBFβ-MYH11 subgroup in children with CBF-AML were not significantly different (both P>0.05). Multivariate analysis showed in the AML1-ETO subgroup, CR1 rate and high white blood cell count (≥50×10⁹/L) were independent risk factors for EFS (HR=0.24, 95%CI 0.07-0.85,HR=1.01, 95%CI 1.00-1.02, both P<0.05) and OS (HR=0.24, 95%CI 0.06-0.87; HR=1.01, 95%CI 1.00-1.02; both P<0.05). Conclusions: In CBF-AML, AML1-ETO is more common which has a higher extramedullary involvement and additional chromosome abnormalities, especially sex chromosome loss. The prognosis of AML1-ETO was similar to that of CBFβ-MYH11. The selection of induction regimen group FLAG-IDA for high white blood cell count and additional chromosome abnormality can improve the prognosis.
Male ; Female ; Humans ; Child ; Retrospective Studies ; RUNX1 Translocation Partner 1 Protein/genetics* ; Core Binding Factor Alpha 2 Subunit/therapeutic use* ; Prognosis ; Leukemia, Myeloid, Acute/genetics* ; Cytarabine/therapeutic use* ; Oncogene Proteins, Fusion/genetics* ; Chromosome Aberrations

Aim To study the effect of salidroside (SAL) on cerebral vascular endothelial cells of rats with ischemic brain injury and its mechanism of action. Methods Twenty-four healthy adult SD male rats were prepared by bolt plugging method to prepare MCAO models,and randomly divided into sham surgery group ( Sham ) , model group ( MCAO ) , and SAL administration group (MCAO + SAL) ,and the concentration of SAL was 50 mg • kg ~ , with a continuous administration for six days. Western blot was used to detect the protein expression of ICAM-1, VCAM-1 , E-se-lectin,and P-selectin in injured brain tissue of rats. In vitro cell experiments using HUVECs were subjected to different concentrations of salidroside (0. 1,1,10 jjunol • L ) and LPS (100 ^g • L ) intervened for 24 hours,and CCK-8 was employed to detect the effects of SAL and LPS on the survival of HUVECs. In vitro an-giogenesis experiments, LPS group ( 100 (jLg • L~ ) and SAL administration group ( LPS + Sal) intervened in HUVECs for 24 hours,and the concentrations of SAL administration were 0. 1,1, and 10 jjunol • L , then the effects of LPS and SAL on their angiogenesis were observed. The protein expressions of ICAM-1, VCAM-1 ,E-selectin,and P-selectin in HUVECs were detected by Western blot. Results SAL could reduce the expression of ICAM-1, VCAM-1, E-selectin, and P-selectin in ischemic brain tissue of MCAO rats. In vitro experimental studies found that salidroside had no effect on the survival of HUVECs. LPS inhibited the angiogenesis of HUVECs, and after the action of SAL, SAL (1,10 jjimol • L ) reversed the effect of LPS and promoted its angiogenesis. Compared with the control group,the expressions of ICAM-1, VCAM-1, E-selectin and P-selectin of HUVECs after LPS stimulation increased, while the expressions of ICAM-1, VCAM-1 , E-selectin and P-selectin were significantly reduced after the addition of SAL, which promoted the angiogenesis ability of HUVECs. Conclusions SAL can improve the ability of cell regeneration in rats with ischemic brain injury and promote the ability of blood vessel formation.