The study aims to explore the effects and mechanisms of water extract of Potentilla anserina (PA) on myelosuppression mice induced by cyclophosphamide based on metabonomics. The myelosuppressive mouse model was established by injected with cyclophosphamide and treated with water extract of PA. Thymus and spleen indexes, peripheral hemogram and bone marrow nucleated cells of each group was detected. Bone marrow pathology analysis was performed by hematoxylin-eosin staining. The levels of interleukin 3 (IL-3), interleukin 6 (IL-6), erythropoietin (EPO), granulocyte colony stimulating factor (GM-CSF), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in serum were measured. The changes of biomarkers and related metabolic pathways were analyzed by UPLC-Q-TOF/MS-based metabonomics. Animal experiments were approved by the Animal Ethics Committee of Southwest Minzu University. The high doses of PA could significantly improve the decrease of white blood cell (WBC), red blood cell (RBC) counts and hemoglobin (HGB) levels of mice induced by cyclophosphamide (P < 0.05), and significantly increase the number of nucleated cells and the area of hematopoietic tissue in femoral bone marrow. The medium and high doses of PA could significantly improve the serum levels of SOD, CAT, MDA, IL-6 and GM-CSF (P < 0.05), and have no significant effect on the expression of IL-3 and EPO (P > 0.05). Serum metabolomics analysis showed that the aqueous extracts of PA could alleviate myrosuppression by regulating the aminoacyl-tRNA, valine, leucine and isoleucine biosynthesis mediated by 13 different metabolites such as valine, leucine, asparagine and hydroxyisohexic acid. PA improve the inhibition of hematopoietic function in myelosuppression mouse, and its mechanisms may be related to anti-oxidation and promoting the expression of hematopoietic-related cytokines and regulating the related metabolic pathways.

Electroacupuncture may play a role in treatment of learning and memory impairment after ischemic stroke by regulating phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA)/cAMP response element binding protein (CREB) signaling pathway, nerve growth factor (NGF)/tyrosine kinase-A (TrkA) signaling pathway, Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway, Notch signaling pathway, erythropoietin-producing hepatocyte (Eph)/ephrin signaling pathway. The interactions among these pathways should be further explored in treatment of learning and memory impairment after ischemic stroke.
Humans ; Electroacupuncture ; Ischemic Stroke ; Learning ; Signal Transduction/physiology*

Heart Valve Diseases ; Heart Valve Prosthesis ; Humans ; Hypereosinophilic Syndrome/complications* ; Mitral Valve ; Thrombosis/etiology*

Objective To investigate the protective effect of Echinococcus granulosus hydatid cyst fluid protein (HCFP) on ovalbumin (OVA)-induced allergic rhinitis (AR) in mice. Methods Twenty-four BALB/c mice at ages of 8 to 10 weeks, each weighing approximately 20 g, were randomly divided into four groups, including groups A (blank control group), B (blank intervention group), C (AR model group) and D (AR+HCFP intervention group), with 6 mice in each group. On days 0, 2, 4, 6, 8, 10 and 12, mice in groups A, B, C and D were injected with 200 μL sterile phosphate buffered saline (PBS), 200 μL sterile PBS containing 20 μg HCFP, 200 μL sterile PBS containing 50 μg OVA and 5 mg Al(OH)₃ gel, and 200 μL sterile PBS containing 50 μg OVA, 5 mg Al(OH)₃ gel and 20 μg HCFP, respectively. On days 14 to 20, mice in groups A, B, C and D were administered with 40 μL sterile PBS, 40 μL sterile PBS containing 20 μg HCFP, 40 μL sterile PBS containing 2 mg OVA and 40 μL sterile PBS containing 2 mg OVA and 20 μL HCFP by nasal drop, respectively. Mouse behavioral changes were observed and behavioral scores were estimated. The serum levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-5, IL-10, transforming growth factor-β (TGF-β) and OVA-specific IgE antibody (OVA-sIgE) were measured using enzyme-linked immunosorbent assay (ELISA), and the pathological changes of mouse nasal mucosa were observed by hematoxylin and eosin (HE) staining. Results The mean behavioral score was significantly greater in Group C (6.83 ± 0.50) than in groups A (1.17 ± 0.52) and B (1.33 ± 0.52) (P < 0.05), while a lower mean behavioral score was estimated in Group D (3.50 ± 0.50) than in Group C (P < 0.05). There were significant differences among the groups in terms of serum IFN-γ (F = 4.08, P < 0.05), IL-4 (F = 275.90, P < 0.05), IL-5 (F = 96.82, P < 0.05), IL-10 (F = 77.67, P < 0.05), TGF-β (F = 9.98, P < 0.05) and OVA-sIgE levels (F = 44.69, P < 0.05). The serum IFN-γ level was significantly lower in Group C than in groups A, B and C (P < 0.05), and the serum levels of IL-4, IL-5 and OVA-sIgE were significantly higher in Group C than in groups A, B and C (P < 0.05), while the serum IL-10 and TGF-β levels were significantly greater in Group D than in Group C (P < 0.05). Microscopy showed apparent loss of nasal mucosa cilia, increased number and enlargement of goblet cells, interstitial edema and submucous vascular dilation in Group C, while the pathological changes of nasal mucosa were alleviated in Group D relative to Group C. Conclusions E. granulosus HCFP has a protective activity against OVA-induced allergic rhinitis in mice.

Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

Objective To investigate the regulatory role of recombinant Trichinella spiralis cysteine protease inhibitors (rTs-Cys) in induction of polarization of bone marrow-derived macrophages (BMDMs) in vitro. Methods BMDMs were captured and cultured in conditioned medium for 7 days. Then, mature BMDMs were harvested and assigned into four groups. Cells in Group A (negative control) were given 10 ng/mL IFN-γ combined with 100 ng/mL LPS, cells in Group B (positive control) were treated with IL-4 and IL-10 (at 10 ng/mL both), and cells in Group C (recombinant protein alone) were stimulated with 1 μg/mL rTs-Cys, while cells in Group D (protein co-culture) were simultaneously treated with 1 μg/mL rTs-Cys, 10 ng/mL IFN-γ and 100 ng/mL LPS. Cells and culture supernatant were collected 24 hour post-treatment, and the proportions of F4/80⁺, CD11b⁺, CD206⁺ and CD11c⁺ cells were detected by flow cytometry. The levels of interleukin IL-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-10 and transforming growth factor-β (TGF-β) in the cell culture supernatant were measured by ELISA and the CD86⁺ and CD206⁺ phenotypes were identified by immunofluorescent staining. Results Flow cytometry detected no significant difference in the proportion of F4/80⁺ CD11b⁺ CD11c⁺ cells among the four groups (F = 46.184, P < 0.001), and a lower proportion of F4/80⁺ CD11b⁺ CD11c⁺ cells was seen in groups C and D than in group A (all P values < 0.001). There was a significant difference in the proportion of F4/80⁺ CD11b⁺ CD206⁺ cells among the four groups (F = 11.032, P < 0.001), and a greater proportion of F4/80⁺ CD11b⁺ CD206⁺ cells was seen in groups C and D than in group A (all P values < 0.01). Immunofluorescent staining showed higher CD206⁺ expression and lower CD86⁺ expression in groups C and D than in Group A. There were significant differences in the IL-6 and (F = 3.950, P < 0.001) and TNF-α (F = 205.827, P < 0.001) levels in the cell culture supernatants among the four groups, and significantly lower IL-6 and TNF-α levels were measured in groups C and D than in Group A (both P < 0.05). There were significant differences in the IL-10 and (F = 8.274, P < 0.001) and TGF-β (F = 13.559, P < 0.01) levels in the cell culture supernatants among the four groups, and greater IL-10 and TGF-β levels were measured in Group C than in Group A (both P values < 0.01). In addition, the TGF-β level was significantly higher in Group D than in Group A (P < 0.05); however, there was no significant difference in the IL-10 level between groups D and A (P > 0.05). Conclusion rTs-Cys may induce the polarization of BMDMs to antiinflammatory M2 macrophages in vitro and inhibit the activation of M1 macrophages.

Objective: To investigate the efficacy and predictors of autologous hematopoietic stem cell transplantation (auto-HSCT) in the treatment of T lymphoblastic lymphoma (T-LBL) . Methods: 41 patients with T-LBL who underwent auto-HSCT from April 2006 to July 2017 in the Department of Hematology, the First Affiliated Hospital of Soochow University and the Department of Lymphoma, Peking University Cancer Hospital were analyzed retrospectively. Results: ①Among 41 patients, there were 30 males and 11 females with median age of 24 (11-53) years old. According to the Ann Arbor staging, 33 (80.5%) patients were in stage Ⅲ/Ⅳ. 12 (29.3%) patients have mediastinal involvement, and 20 (48.8%) patients have bone marrow (BM) involvement. Before transplantation, there were 26 (63.4%) patients who achieved first complete remission (CR(1)) , the other 15 (36.6%) patients were in the non-CR(1) group, and there were 29 (70.7%) patients in the low-intermediate risk group (IPI<3 scores) , the other 12 (34.1%) patients were in the middle-high risk group (IPI≥3 scores) . ②The median follow-up was 29 (3-98) months. The 3-year overall survival (OS) and progression-free survival (PFS) for 41 patients were (64.3±8.2) % and (66.0±7.8) %, respectively. 3-year cumulative recurrence rate (CIR) was (30.7±7.4) %, and 3-year non-recurring mortality (NRM) was (4.8±4.6) %. ③The 3-year OS of the CR(1) group and the non-CR(1) group were (83.4±7.6) % and (38.9±12.9) % (P=0.010) , and the 3-year PFS of two groups were (83.8±7.4) % and (40.0±12.6) % (P=0.006) , respectively. The 3-year CIR of these two groups were (16.2±7.4) % and (53.3±12.9) % (P=0.015) , and the 3-year NRM were 0 and (14.3±13.2) % (P=0.157) , respectively. ④The 3-year OS of the IPI low-intermediate risk group and the high-intermediate risk group were (76.9±8.4) % and (35.7±15.2) % (P=0.014) and the 3-year PFS were (77.4±8.2) % and (40.0±14.6) (P=0.011) , respectively. The 3-year CIR of these two groups were (18.1±7.3) % and (60.0±14.6) % (P=0.006) , and the 3-year NRM were (5.6±5.4) % and 0 (P=0.683) , respectively. The OS and PFS of patients with low-intermediate risk group were significantly higher than the other group. Conclusion: Auto-HSCT could improve the survival of T-LBL. Pre-transplant status and IPI score are important predictors for survival T-LBL patients with auto-HSCT.
Adolescent ; Adult ; Child ; Disease-Free Survival ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Prognosis ; Retrospective Studies ; T-Lymphocytes ; Transplantation, Autologous ; Treatment Outcome ; Young Adult

Objective:To observe the morphological changes of carotid artery, thoracic aorta and superior mesenteric artery in spontaneously hypertensive rats(SHR), in order to further study the effect of Mangiferin on the expressions of inflammatory factors and monocyte chemoattract protein-1 (MCP-1)/c-chemokine receptor type 2 (CCR-2) pathway in SHR. Method:Forty spontaneously hypertensive rats were randomly divided into model group, benazepril group (10 mg·kg^-1·d^-1) and low, medium and high-dose mangiferin groups (25, 50, 100 mg·kg^-1·d^-1). Eight male WKY rats of the same age were selected as normal control group. Systolic blood pressure was observed every two weeks after eight weeks of administration. Morphology of carotid artery, thoracic aorta and superior mesenteric artery was observed by hematoxylin-eosin (HE) staining. Immunohistochemical assay (IHC) and Western blot were used to detect MCP-1 and CCR-2 protein expressions in thoracic aorta. MCP-1 and CCR-2 mRNA expression levels in thoracic aorta were detected by Real-time quantitative fluorescence PCR (Real-time PCR). Result:Compared with the normal group, the inflammatory cells in the model group increased significantly, the systolic blood pressure was significantly higher than that in the WKY group (P<0.01), and MCP-1, CCR-2 protein and mRNA expressions in thoracic aorta were increased obviously (P<0.01). Compared with model group, in high-dose benazepril and mangiferin groups, inflammatory cells were decreased significantly, endothelial margin and fibrous tissue infiltration were improved significantly, and systolic blood pressure was decreased significantly (P<0.01). MCP-1, CCR-2 protein and mRNA expression in thoracic aorta of benazepril and mangiferin groups decreased significantly (P<0.01). Conclusion:There are inflammation damages in carotid artery, thoracic aorta and superior mesenteric artery of spontaneously hypertensive rats. Mangiferin has an anti-inflammatory effect by possibly inhibiting the expressions of MCP-1/CCR-2 pathway in SHR vessels.

Objective:To observe effect of Zeqi Tang in intervening mice with orthotopic lung cancer model, in order to observe its anti-tumor mechanism. Method:An in situ mouse model of non-small cell lung cancer was established through intrapulmonary injection with 1×10⁵ LLC-luc cells. The model mice were intragastrically administered with Zeqi Tang(0.171 g·mL^-1) or normal saline for 35 days. Appearance (spirit, hair, appetite, sleep), survival period and Zeqi Tang anti-tumor effect were observed, weekly vital imaging was performed to detect the fluorescence signal in the lungs of mice. Flow cytometry was used to detect the NK cell content in the spleen of the model mice. CD107α was used to detect the degranulation of NK cells in the spleen of mice after administration of Zeqi Tang. Kromasil 100 5 C₁₈ column was used and eluted with acetonitrile-0.025%phosphoric acid in a gradient mode, with flow rate at 1.0 mL·min^-1, column temperature at 35℃ and detection wavelength of 265 nm, as to establish the fingerprint of Zeqi Tang. The fingerprints of 10 batches of samples was evaluated by using the Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System Software (2012 Edition) recommended by the Chinese Pharmacopoeia Commission, in order to complete the quality control of Zeqi Tang. Result:Zeqi Tang could significantly inhibit the lung fluorescence signal of lung cancer in situ model mice and prolong the survival of mice(P<0.05, P<0.01). After the intervention with Zeqi Tang, the NK cells in the tumors increased significantly(P<0.01), and the degranulation of CD107α also increased significantly(P<0.01). Moreover, the HPLC-DAD fingerprint of Zeqi Tang showed a significant increase in the fingerprint similarity of 10 batches of lacquer soup aqueous extract. Moreover, the HPLC-DAD fingerprint of Zeqi Tang showed that the fingerprint similarity of 10 batches of lacquer soup aqueous extract was ≥ 0.9, indicating that small differences between the batches. Conclusion:Zeqi Tang may enhance the tumor growth and prolong the survival period of mice by up-regulating the number of NK cells in mice and enhancing their degranulation function. The evaluation of similarity of HPLC fingerprint of Zeqi Tang reflects the quality of lacquer soup to a certain extent, and can provide reference for further study.

Objective:To assess the influence of glimepiride on the plasma concentrations and antihypertensive effects of losartan and its active metabolite losartan carboxylic acid(E-3174) in the patients with type 2 diabetes mellitus and hypertension. Methods:Pragmatic randomized controlled trial was used in the clinical study. Forty-five patients were enrolled and randomized into glimepiride group and the control group. Losartan was used as the antihypertensive drug in the two groups. After two-week interference,the plasma concentrations of losartan and its active metabolite E-3174 were determined using an LC-MS/MS method and the reduction of hyperten-sion was measured. Results:The plasma trough concentrations of losartan in glimepiride group was not higher than those in the control group,and those of E-3174 in glimepiride group was not lower than those in the control group. Additionally,the reduction of hyperten-sion was similar in the two groups. Conclusion: Glimepiride does not influence the plasma concentrations and the antihypertensive effects of losartan and its active metabolite E-3174 in the patients with type 2 diabetes mellitus and hypertension, suggesting no drug-drug interactions between them. Owing to the small sample,large clinical trial should be performed to confirm the above conclusion.