Syringa pinnatifolia, belonging to the family Oleaceae, is a species endemic to China. It is predominantly distributed in the Helan Mountains region of Inner Mongolia and Ningxia of China. The peeled roots, stems, and thick branches have been used as a distinctive Mongolian medicinal material known as "Shan-chen-xiang", which has effects such as suppressing "khii", clearing heat, and relieving pain and is employed for the treatment of cardiovascular and pulmonary diseases and joint pain. Over the past five years, significant increase was achieved in research on chemical constituents and pharmacological effects. There were a total of 130 new constituents reported, covering sesquiterpenoids, lignans, and alkaloids. Its effects of anti-myocardial ischemia, anti-cerebral ischemia/reperfusion, sedation, and analgesia were revealed, and the mechanisms of agarwood formation were also investigated. To better understand its medical value and potential of clinical application, this review updates the research progress in recent five years focusing on the chemical constituents and pharmacological effects of S. pinnatifolia, providing reference for subsequent research on active ingredient and support for its innovative application in modern medicine system.
Medicine, Mongolian Traditional ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Syringa/chemistry*

OBJECTIVE: To explore the efficacy and apoptosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of acute myeloid leukemia (AML) with ASXL1 mutation. METHODS: The clinical data of 80 AML patients with ASXL1 mutation treated in our hospital from January 2019 to December 2021 were retrospectively analyzed. The clinical characteristics of the patients were summarized, and the therapeutic effect and prognostic factors of allo-HSCT for the patients were analyzed. RESULTS: Among the 80 patients, 38 were males and 42 were females, and the median age was 39(14-65) years. There were 17 patients in low-risk group, 25 patients in medium-risk group and 38 patients in high-risk group. ASXL1 mutation co-occurred with many other gene mutations, and the frequent mutated genes were TET2 (71.25%), NRAS (18.75%), DNMT3A (16.25%), NPM1 (15.00%), CEBPA (13.75%). Among medium and high-risk patients, 29 underwent allo-HSCT, while 34 received chemotherapy. The 2-year overall survival (OS) rate and disease-free survival (DFS) rate of the allo-HSCT group were 72.4% and 70.2%, while those of the chemotherapy group were 44.1% and 34.0%, respectively. The statistical analysis showed significant differences between the two groups (both P < 0.01). Multivariate analysis showed that age at transplantation >50- years and occurrence of acute graft-versus-host disease after transplantation were poor prognostic factors for OS and DFS in transplantation patients. CONCLUSION Allo-HSCT can improve the prognosis of AML patients with ASXL1 mutation.
Humans ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Middle Aged ; Mutation ; Adult ; Repressor Proteins/genetics* ; Adolescent ; Retrospective Studies ; Aged ; Nucleophosmin ; Young Adult ; Transplantation, Homologous ; Prognosis ; Survival Rate

OBJECTIVE: To establish venetoclax-resistant acute myeloid leukemia (AML) cell lines, assess the sensitivity of venetoclax-resistant cell lines to the BCL-2 protein family, and investigate their resistance mechanisms. METHODS: CCK-8 method was used to screen AML cell lines (MV4-11, MOLM13, OCI-AML2) that were relatively sensitive to venetoclax. Low concentrations of venetoclax continuously induced drug-resistance development in the cell lines. Changes in cell viability and apoptosis rate before and after resistance development were measured using the CCK-8 method and flow cytometry. BH3 profiling assay was performed to anayze the transform of mitochondrion-dependent apoptosis pathway as well as the sensitivity of resistant cell lines to BCL-2 family proteins and small molecule inhibitors. Real-time fluorescence quantitative PCR (RT-qPCR) was utilized to examine changes in the expression levels of BCL-2 protein family members in both venetoclax-resistant cell lines and multidrug-resistant patients. RESULTS: Venetoclax-resistant cell lines of MV4-11, MOLM13, and OCI-AML2 were successfully established, with IC₅₀ values exceeding 10-fold. Under the same concentration of venetoclax, the apoptosis rate of resistant cells decreased significantly (P < 0.05). BH3 profiling assay revealed that the drug-resistant cell lines showed increased sensitivity to many pro-apoptotic proteins (such as BIM,BID and NOXA). RT-qPCR showed significantly upregulated MCL1 and downregulated NOXA1 were detected in drug-resistant cell lines. Expression changes in MCL1 and NOXA1 in venetoclax-resistant patients were consistent with our established drug-resistant cell line results. CONCLUSION The venetoclax-resistant AML cell lines were successfully established through continuous induction with low concentrations of venetoclax. The venetoclax resistance resulted in alterations in the mitochondrial apoptosis pathway of the cells and an increased sensitivity of cells to pro-apoptotic proteins BIM, BID, and NOXA, which may be associated with the upregulation of MCL1 expression and downregulation of NOXA1 expression in the drug-resistant cells.
Humans ; Sulfonamides/pharmacology* ; Drug Resistance, Neoplasm ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology* ; Leukemia, Myeloid, Acute/pathology* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis ; Antineoplastic Agents/pharmacology*

Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

Objective To construct a three-dimensional statistical shape model of the pelvis and analyze the individual variation and gender differences of the three-dimensional shape of the pelvis.Methods We collected CT data from 201 Chinese individuals and used deep learning to automatically reconstruct three-dimensional models of the pelvis.Through three-dimensional model registration,dense correspondence mesh mapping,and the use of statistical shape modelling(SSM)and principal component(PC)analysis method,we extracted models of variations(MoV)of pelvic shape changes and statistically compared the shape MoV between males and females.Results We analysed the top 10 principal components of shape variations,which accounted for 86.1％of the total variability.Among them,PC01,PC02,and PC04 showed significant differences between genders(P＜0.001),accounting for a total variability of 60.1％.PC08 and PC 10 demonstrated pelvic asymmetry,accounting for a total variability of 3.8％.Conclusion We constructed a three-dimensional statistical shape model of the pelvis in Chinese individuals,revealing the morphological variation and sex differences of Chinese pelvis.

Mesenchymal stem cells have emerged as a promising cell therapy for anti-tumor research due to their homing properties,low immunogenicity,anti-angiogenic activity,anti-inflammatory properties,and paracrine effects.Paclitaxel has been clinically used for over thirty years in the treatment of various tumors such as ovarian cancer,lung cancer,and breast cancer.However,the broad-spectrum anti-tumor properties of paclitaxel are not possessed by the aforementioned cell therapies.Moreover,its adverse reactions,including peripheral neuropathy,bone marrow suppression,and gastrointestinal reactions,have long plagued cancer patients.In recent years,many studies have focused on combining cell therapy with chemotherapy to achieve better treatment outcomes,giving rise to a new drug delivery system that utilizes mesenchymal stem cells as carriers for delivering chemotherapeutic drugs.This review summarizes the research progress in MSC-based drug delivery systems for paclitaxel.

A purified polysaccharide with a galactose backbone(SPR-1,Mw 3,622 Da)was isolated from processed Polygonati Rhizoma with black beans(PRWB)and characterized its chemical properties.The backbone of SPR-1 consisted of[(4)-β-D-Galp-(1]9→ 4,6)-β-D-Galp-(1 → 4)-α-D-GalpA-(1 → 4)-α-D-GalpA-(1 →4)-α-D-Glcp-(1 → 4,6)-α-D-Glcp-(1 → 4)-α/β-D-Glcp,with a branch chain of R1:β-D-Galp-(1 → 3)-β-D-Galp-(1 → connected to the →4,6)-β-D-Galp-(1 → via O-6,and a branch chain of R2:α-D-Glcp-(1 →6)-α-D-Glcp-(1 → connected to the →4,6)-α-D-Glcp-(1 → via O-6.Immunomodulatory assays showed that the SPR-1 significantly activated macrophages,and increased secretion of NO and cytokines(i.e.,IL-1β and TNF-α),as well as promoted the phagocytic activities of cells.Furthermore,isothermal titration calorimetry(ITC)analysis and molecular docking results indicated high-affinity binding between SPR-1 and MD2 with the equilibrium dissociation constant(KD)of 18.8 μM.It was suggested that SPR-1 activated the immune response through Toll-like receptor 4(TLR4)signaling and downstream responses.Our research demon-strated that the SPR-1 has a promising candidate from PRWB for the TLR4 agonist to induce immune response,and also provided an easily accessible way that can be used for PR deep processing.

Objective To investigate potential causative associations between immunophenotype traits and cervical cancer by using two-sample Mendelian randomization(MR)analysis.Methods The genetic instrumental variables(IVs)of 731 immunophenotypes of peripheral blood were obtained from the GWAS Catalog database.The GWAS summary data of cervical cancer were obtained from FinnGen database.The inverse-variance weighted(IVW),weighted mode,weighted median,and MR Egger methods were used for evaluations.The sensitivity analysis and reverse Mendelian randomization analysis were conducted to eliminate bias and reverse causality.The MR Steiger directionality test was further used to ascertain the reverse causal relationship between immune cells and cervical cancer.Results A total of 71 immune cell subtypes associated with cervical cancer were identified,of which 31 had a strong association.The majority of the B cell panel was protective factors for cervical cancer.B-cell activating factor receptor(BAFF-R)was the most frequently expressed molecule in this analysis.It is expressed on several B cell subtypes.The CD20 on IgD+CD38+B cell(OR=1.887,95%CI:1.078-3.306,P=0.026)is the risk factor for cervical cancer.In cDC panels,the CD123 expression on plasmacytoid dendritic cell(OR=2.48,95%CI:1.229-5.003,P=0.011),CD123 expression on CD62L+plasmacytoid dendritic cell(OR=2.5,95%CI:1.231-5.077,P=0.011),CD80 expression on plasmacytoid dendritic cell(OR=2.62,95%CI:1.244-5.515,P=0.011),and CD80 expression on CD62L+plasmacytoid dendritic cell(OR=2.641,95%CI:1.246-5.596,P=0.011)were positively associated with the incidence of cervical cancer.All gynecological cancers in this study have no statistically significant effect on immune cells,according to reverse MR analysis.Conclusion This study emphasized the genetically predicted causality between immune cells and cervical cancer.In clinical practice,it is important to pay attention to the screening of peripheral blood immune cells for patients with cervical cancer.

Objective To study the cognitive protective effect and optimal dose of dexmedetomidine hydrochloride (DEX) in patients with severe depression treated with modified electroconvulsive therapy (MECT).Methods A total of 120 patients with severe depression in our hospital from June 2021 to Decem-ber 2022 were randomly divided into DEX group (D1,D2,D3 group) and control group,with 30 cases in each group.DEX 0.2,0.4,and 0.6 μg/kg were intravenously pumped 10 min before anesthesia in groups D1,D2, and D3,respectively,and the same volume of normal saline was pumped in the control group.The heart rate (HR),mean arterial pressure (MAP),spontaneous breathing recovery time,recovery time,mini-mental state examination (MMSE) score at T0,one d and three d after operation,and adverse reactions were compared a-mong the four groups before anesthesia (T0),10 min after infusion of DEX (T1),after anesthesia induction and loss of consciousness (T2),at the end of MECT (T3),and five min after MECT (T4).Results At T1 and T2,HR in group D1 and HR and MAP in groups D2 and D3 were lower than those at T0,and the differences were statistically significant (P<0.05).At T3,the HR and MAP of the four groups reached the peak,but at T4,the HR and MAP gradually decreased.At T4,the HR and MAP of the control group were higher than those at T0,and the HR and MAP of the D2 and D3 groups were lower than those at T0,the differences were statistically significant (P<0.05).The recovery time of spontaneous breathing in D1,D2 and D3 groups was shorter than that in the control group,and the dosage of propofol was lower than that in the control group,the differences were statistically significant (P<0.05).The recovery time from long to short was D3,D2 and D1 group,and the difference was statistically significant (P<0.05).At one d and three d after operation,the MMSE scores of D1,D2 and D3 groups were higher than those of the control group,and the MMSE score of D3 group was the highest,the difference was statistically significant (P<0.05).Conclusion DEX can reduce MECT stress response and postoperative adverse reactions in patients with severe depression in a dose-de-pendent manner,and protect cognitive function.

Objective: Healthcare workers (HCWs) suffered from a heavy mental health burden during the coronavirus disease-2019 (COVID-19) pandemic. We aimed to explore the differences in sleep disturbance in three waves of the COVID-19 pandemic in Taiwan among HCWs. Moreover, factors associated with sleep disturbances in the third wave were investigated. Methods: This study, with three waves of cross-sectional surveys, recruited first-line and second-line HCWs. The level of sleep disturbance and related demographic variables were collected through self-report questionnaires. Differences in sleep disturbance across the three waves were compared with analysis of variance. Factors associated with the level of sleep disturbance were identified using univariate linear regression and further used for multivariate stepwise and bootstrap linear regression to identify the independent predictors. Results: In total, 711, 560, and 747 HCWs were included in the first, second, and third waves, respectively. For first-line HCWs, sleep disturbance was significantly higher in the third wave than in the first wave. The level of sleep disturbance gradually increased across the three waves for all HCWs. In addition, sleep disturbance was associated with depression, posttraumatic stress disorder (PTSD) symptoms, anxiety about COVID-19, vaccine mistrust, and poorer physical and mental health among first-line HCWs. Among second-line HCWs, sleep disturbance was associated with younger age, depression, PTSD symptoms, lower preference for natural immunity, and poorer physical health. Conclusion The current study identified an increase in sleep disturbance and several predictors among HCWs. Further investigation is warranted to extend the application and generalizability of the current study.