In March 2024, three male and two female specimens of the genus Lispe were intercepted on cargo ships inbound for Wan Zai Port under Gongbei Customs. Based on morphological characteristics and molecular analysis, the specimens were identified as Lispe pumila. In this study, we describe the morphological features, diagnostic characteristics, and geographical distribution of L. pumila, with the aim of providing a reference for the identification of this species when intercepted at ports.

OBJECTIVE: To explore the functional roles and underlying mechanisms of neferine in the context of angiotensin II (Ang II)-induced hypertension and vascular dysfunction. METHODS: Male mice were infused with Ang II to induce hypertension and randomly divided into treatment groups receiving neferine or a control vehicle based on baseline blood pressure using a random number table method. The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg per minute), and neferine (0.1, 1, or 10 mg/kg), valsartan (10 mg/kg), or double distilled water was administered intragastrically once daily for 6 weeks. A non-invasive blood pressure system, ultrasound, and hematoxylin and eosin staining were performed to assess blood pressure and vascular changes. RNA sequencing and network pharmacology were employed to identify differentially expressed transcripts (DETs) and pathways. Vascular ring tension assay was used to test vascular function. A7R5 cells were incubated with neferine for 24 h and then treated with Ang II to record the real-time Ca²⁺ concentration by confocal microscope. Immunohistochemistry (IHC) and Western blot were used to evaluate vasorelaxation, calcium, and the extracellular signal-regulated kinase (ERK)1/2 pathway. RESULTS: Neferine treatment effectively mitigated the elevation in blood pressure, pulse wave velocity, aortic thickening in the abdominal aorta of Ang II-infused mice (P<0.05). RNA sequencing and network pharmacology analysis identified 355 DETs that were significantly reversed by neferine treatment, along with 25 potential target genes, which were further enriched in multiple pathways and biological processes, such as ERK1 and ERK2 cascade regulation, calcium pathway, and vascular smooth muscle contraction. Further investigation revealed that neferine treatment enhanced vasorelaxation and reduced Ca²⁺-dependent contraction of abdominal aortic rings, independent of endothelium function (P<0.05). The underlying mechanisms were mediated, at least in part, via suppression of receptor-operated channels, store-operated channels, or voltage-operated calcium channels. Neferine pre-treatment demonstrated a reduction in intracellular Ca²⁺ release in Ang II stimulated A7R5 cells. IHC staining and Western blot confirmed that neferine treatment effectively attenuated the upregulation of p-ERK1/2 both in vivo and in vitro, which was similar with treatment of ERK1/2 inhibitor PD98059 (P<0.05). CONCLUSIONS Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways.
Animals ; Angiotensin II ; Male ; Benzylisoquinolines/therapeutic use* ; Network Pharmacology ; Blood Pressure/drug effects* ; Sequence Analysis, RNA ; Mice ; Hypertension/chemically induced* ; Mice, Inbred C57BL ; Calcium/metabolism*

Objective To analyze the incidence and severity grading of treatment-related adverse event(TRAE)associated with programmed death-l/programmed death-ligand 1(PD-1/PD-L1)in-hibitors combined with various anticancer regimens.Methods A total of 356 tumor patients treated with PD-1/PD-L1 inhibitors were retrospectively selected as the study objects.The occurrence of ad-verse reactions in patients treated with PD-1/PD-L1 inhibitors combined with different anticancer regi-mens was recorded and analyzed.Results Among the 356 patients treated with PD-1/PD-L1 inhibi-tors in combination with various anticancer regimens,332 times of TRAEs were observed.Fatigue and adverse gastrointestinal reactions were the most prevalent,accounting for 31.93％(106/332)and 20.78％(69/332)respectively.Skin-related adverse reactions(appearing within 3 to12 weeks)and gas-trointestinal adverse reactions(5 to 10 weeks)occurred first,while fever(10 to 30 weeks)and pneumonia(12 to 32 weeks)presented later,with the longest observation time span.The lowest overall incidence of TRAE was observed in the combination of PD-1/PD-L1 inhibitors with cytotoxic T-lymphocyte-as-sociated antigen 4(CTLA-4)inhibitors(85.71％,36/42),while the highest was in the combina-tion with platinum-based doublet chemotherapy(96.88％,155/160).The incidence of grade 3 to 5 TRAEwas lowest in the combination of PD-1/PD-L1 inhibitors with radiotherapy(10.53％,6/57)and highest in the combination with vascular endothelial growth factor/vascular endothelial growth factor receptor(VEGF/VEGFR)targeted therapy(44.64％,25/56).There was no signifi-cant difference in the incidence and severity of TRAE among different tumors(P＞0.05).Conclu-sion When different anti-cancer regiments combined with PD-1/PD-L1 inhibitors,the overall inci-dence of TRAE is higher,among which the incidence of TRAE combined with CTLA-4 is relatively lowest,and the symptoms of TRAE combined with radiotherapy are relatively mild.

Chronic heart failure(CHF)is the end-stage of a variety of heart diseases with complex pathogenesis,which may involve myocardial fibrosis,inflammation reaction and oxidative stress.Chinese materia medica has the characteristics of multiple pathways,levels,and targets in the treatment of CHF,with significant therapeutic effects.Based on the TCM theories,this article described the research progress of TCM and its effective components,TCM compounds and Chinese patent medicines in regulating TGF-β signaling pathway in the treatment of CHF,and summarized the mechanism and target of TCM regulating TGF-β pathway in the treatment of CHF,including inhibiting myocardial fibrosis,reducing inflammatory reaction and apoptosis,so as to provide a reference for the related research of Chinese materia medica in the treatment of CHF.

Objective:To assess the efficacy and safety of azacitidine combined with lenalidomide in MDS patients and explore potential mechanisms of therapeutic response.Methods:Sixteen MDS patients with TP53 mutations received azacitidine plus lenalidomide at ZhongDa Hospital, Southeast University (January 2021–June 2025). Efficacy and safety were assessed, and TP53 mutation status was correlated with treatment response. Whole-transcriptome sequencing and bioinformatics were used to explore molecular biomarkers associated with therapeutic efficacy.Results:Sixteen patients (median age 69.5 years, range 52–82; 8 males, 8 females) were enrolled. According to the Molecular International Prognostic Scoring System (IPSS-M), 1, 2, and 13 patients were classified as median low, high, and very high risk, respectively. Among 16 TP53-mutated patients, 11 had biallelic mutations and 5 had monoallelic mutations. Overall response rate was 56.3% (9/16), composite complete remission rate (CRc) was 31.3% (5/16), and hematology improvement rate was 25% (4/16). Among TP53-mutated patients, the response rate was 56.3% (9/16), with variant allele frequency dropping from 65.6% to 16.5% in responders ( P=0.017). In patients with TP53 mutations and complex karyotype, response rate was 53.8% (7/13), with 57.1% (4/7) showing disappearance of CK post-treatment. The most common grade 3–4 nonhematologic adverse events were infections (9/16, 56.3% ), including pneumonia (4/16, 25.0% ), gastrointestinal infections (3/16, 18.8% ), perianal infections (1/16, 6.3% ) and sepsis (1/16, 6.3% ). High CBX8 expression may be linked to treatment response. Conclusion:Azacitidine plus lenalidomide is an effective and safe therapy for MDS, including patients with TP53 mutations and complex karyotypes. Treatment markedly reduces TP53 variant allele frequency in responders, and high CBX8 expression may predict therapeutic response.

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

This study selected 6 529 plant-based Chinese materia medica(PCMM) from Chinese Materia Medica as research subjects and applied a random permutation test to explore the overall correlation characteristics between nature and flavor, as well as the correlation characteristics after distinguishing different medicinal parts and harvest seasons. The results showed that the overall correlation characteristics between nature and flavor in PCMM were significantly associated in the following pairs: cold and bitter, cool and bitter, cool and astringent, cool and light, neutral and sweet, neutral and astringent, neutral and light, neutral and sour, hot and pungent, and warm and pungent. When analyzing the data by distinguishing medicinal parts and/or harvest seasons, new correlation patterns emerged, characterized by the disappearance of some significant correlations and the emergence of new ones. When analyzing by medicinal parts alone, significant correlations were found in the following cases: cold and light in leaves, cold and salty in barks, cool and sweet in fruits and seeds, neutral and pungent in whole herbs, neutral and salty in stems, and warm and salty in flowers. However, no significant correlations were found between cool and bitter in stems and other types of herbs, cool and astringent in fruits, seeds, flowers, and other types of herbs, cool and light in leaves, fruits, seeds, barks, flowers and other types of herbs, neutral and sweet in barks, neutral and astringent in whole herbs and stems, neutral and light in leaves, fruits, seeds, and flowers, neutral and sour in whole herbs, stems, barks, flowers, and other types of herbs, and hot and pungent in whole herbs, stems, flowers, and other types of herbs. When analyzing by harvest season alone, significant correlations were found in the following cases: cold and salty, and cool and sour in herbs harvested in winter, and neutral and salty in herbs harvested year-round. However, no significant correlation was found between cool and light in herbs harvested in winter. When considering both medicinal parts and harvest seasons, compared to the independent influence of medicinal parts, 14 new significant correlations emerged(e.g., the correlation between cool and bitter in stems harvested in spring), while 53 previously significant correlations disappeared(e.g., the correlation between cool and bitter in barks harvested in summer). Compared to the independent influence of harvest seasons, 11 new significant correlations appeared(e.g., the correlation between cold and light in barks harvested in autumn), while 50 previously significant correlations disappeared(e.g., the correlation between hot and pungent in leaves harvested in winter). This study is the first to reveal the influence of medicinal parts and harvest seasons on the correlation between nature and flavor in PCMM, which highlights that these two factors can interact and jointly affect nature-flavor correlations. Further research is needed to explore the underlying mechanisms. This study provides a deeper understanding of the inherent scientific connotations of herbal properties and offers a theoretical foundation for the cultivation and harvesting of PCMM.
Seasons ; Plants, Medicinal/growth & development* ; Drugs, Chinese Herbal/chemistry* ; Taste

OBJECTIVE: To explore the optimal vertical traction weight, clinical efficacy, and safety of bidirectional cervical traction in the treatment of cervical kyphosis. METHODS: A total of 130 patients with neck pain and cervical kyphosis confirmed by cervical DR who visited the hospital from April 2023 to April 2024 were enrolled. They were divided into 4 groups according to the vertical traction weight accounting for 5%, 10%, 15%, and 20% of their body weight, respectively. The 5% body weight traction group included 33 cases (13 males and 20 females) with an average age of (34.00±10.58) years old;the 10% body weight traction group included 35 cases (17 males and 18 females) with an average age of (32.23±8.39) years old;the 15% body weight traction group included 32 cases (14 males and 18 females) with an average age of (33.88±10.09) years old;the 20% body weight traction group included 30 cases (11 males and 19 females) with an average age of (36.20±9.13) years old. Each group received treatment for 2 weeks. The visual analogue scale (VAS) score, neck disability index (NDI), and C₂-C₇ Cobb angle on cervical lateral X-ray films before and after treatment were recorded to evaluate the clinical efficacy of the 4 groups. RESULTS: When the traction weight was 10% and 15% of body weight, the pain VAS and NDI were significantly improved, and the C₂-C₇ Cobb angle increased, with statistically significant differences (P<0.05), and no adverse reactions occurred. However, in the 5% body weight group, the above indicators showed no significant changes, with no statistically significant differences (P>0.05). In the 20% body weight group, some patients could not tolerate the treatment, and adverse reactions such as dizziness, nausea, and aggravated neck pain occurred. CONCLUSION The optimal vertical traction weight of bidirectional cervical traction for cervical kyphosis is 10%-15% of body weight, which can effectively improve neck pain and cervical function, increase the C₂-C₇ Cobb angle of the cervical spine, with high safety, and is worthy of promotion and application.
Humans ; Male ; Female ; Traction/methods* ; Kyphosis/physiopathology* ; Adult ; Cervical Vertebrae/physiopathology* ; Middle Aged ; Neck Pain ; Young Adult

OBJECTIVE: To screen anti-tumor drugs that improve antigen processing and presentation in acute myeloid leukemia (AML) cells. METHODS: A TCR-like or TCR mimic antibody that can specifically recognize HLA-A*0201:WT1_126-134 ( RMFPNAPYL) complex (hereafter referred to as HLA-A2:WT1) was synthesized to evaluate the function of antigen processing and presentation machinery (APM) in AML cells. AML cell line THP1 was incubated with increasing concentrations of IFN-γ, hypomethylating agents (HMA), immunomodulatory drugs (IMiD), proteasome inhibitors (PI) and γ-secretase inhibitors (GSI), followed by measuring of HLA-ABC, HLA-A2 and HLA-A2:WT1 levels by flow cytometry at consecutive time points. RESULTS: The TCR-like antibody we generated only binds to HLA-A*0201⁺WT1⁺ cells, indicating the specificity of the antibody. HLA-A2:WT1 level of THP-1 cells detected with the TCR-like antibody was increased significantly after co-incubation with IFN-γ, showing that the HLA-A2:WT1 TCR like antibody could evaluate the function of APM. Among the anti-tumor agents screened in this study, GSI (LY-411575) and HMA (decitabine and azacitidine) could significantly increase the HLA-A2:WT1 level. The IMiD lenalidomide and pomalidomide could aslo upregulate the expression of HLA-A2:WT1 complex under certain concentrations of the drugs and incubation time. As proteasome inhibitors, carfilzomib could significantly decreased the expression of HLA-A2:WT1, while bortezomib had no significant effect on HLA-A2:WT1 expression. CONCLUSION HLA-A2:WT1 TCR-like antibody can effectively reflect the APM function. Some of the anti-tumor drugs can affect the APM function and immunogenicity of tumor cells.
Humans ; Leukemia, Myeloid, Acute/immunology* ; Antineoplastic Agents/pharmacology* ; Antigen Presentation/drug effects* ; HLA-A2 Antigen/immunology* ; Receptors, Antigen, T-Cell/immunology* ; Cell Line, Tumor ; Interferon-gamma

OBJECTIVE: To analyze the Epstein-Barr virus (EBV) load in different lymphocyte subsets, as well as clinical characteristics and outcomes in patients with hematologic malignancies experiencing EBV reactivation. METHODS: Peripheral blood samples from patients were collected. B, T, and NK cells were isolated sorting with magnetic beads by flow cytometry. The EBV load in each subset was quantitated by real-time quantitative polymerase chain reaction (RT-qPCR). Clinical data were colleted from electronic medical records. Survival status was followed up through outpatient visits and telephone calls. Statistical analyses were performed using SPSS 25.0. RESULTS: A total of 39 patients with hematologic malignancies were included, among whom 35 patients had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median time to EBV reactivation was 4.8 months (range: 1.7-57.1 months) after allo-HSCT. EBV was detected in B, T, and NK cells in 20 patients, in B and T cells in 11 patients, and only in B cells in 4 patients. In the 35 patients, the median EBV load in B cells was 2.19×10⁴ copies/ml, significantly higher than that in T cells (4.00×10³ copies/ml, P <0.01) and NK cells (2.85×10² copies/ml, P <0.01). Rituximab (RTX) was administered for 32 patients, resulting in EBV negativity in 32 patients with a median time of 8 days (range: 2-39 days). Post-treatment analysis of 13 patients showed EBV were all negative in B, T, and NK cells. In the four non-transplant patients, the median time to EBV reactivation was 35 days (range: 1-328 days) after diagnosis of the primary disease. EBV was detected in one or two subsets of B, T, or NK cells, but not simultaneously in all three subsets. These patients received a combination chemotherapy targeting at the primary disease, with 3 patients achieving EBV negativity, and the median time to be negative was 40 days (range: 13-75 days). CONCLUSION In hematologic malignancy patients after allo-HSCT, EBV reactivation commonly involves B, T, and NK cells, with a significantly higher viral load in B cells compared to T and NK cells. Rituximab is effective for EBV clearance. In non-transplant patients, EBV reactivation is restricted to one or two lymphocyte subsets, and clearance is slower, highlighting the need for prompt anti-tumor therapy.
Humans ; Hematologic Neoplasms/virology* ; Herpesvirus 4, Human/physiology* ; Epstein-Barr Virus Infections ; Hematopoietic Stem Cell Transplantation ; Virus Activation ; Lymphocyte Subsets/virology* ; Flow Cytometry ; Killer Cells, Natural/virology* ; Male ; Female ; B-Lymphocytes/virology* ; Viral Load ; Adult ; T-Lymphocytes/virology* ; Middle Aged