OBJECTIVE To explore the effect and mechanism of Prunus mume against hepatic fibrosis （HF）. METHODS Male SD rats were randomly divided into normal control group （n＝10） and modeling group （n＝50）. The modeling group established HF model using carbon tetrachloride. The modeled rats were randomly divided into model group （normal saline）， positive control group [colchicine， 0.09 mg/（kg·d）]， and P. mume low-dose， medium-dose and high-dose groups [1.35， 2.70， 5.40 g/（kg·d）]， with 9 rats in each group. They were given the corresponding drug/normal saline intragastrically， once a day， for 8 consecutive weeks. After the last medication， the liver index was calculated， while liver function indexes， liver fiber indexes， oxidative stress indicators and inflammatory factors of rats were measured. HE staining was used to observe the pathological changes in liver tissue of rats； Masson staining was used to observe the degree of HF in liver tissue of rats； transmission electron microscopy was used to observe the ultrastructure of liver tissue in rats； TUNEL staining was used to detect liver cell apoptosis in each group of rats. Western blot method was used to detect the protein expressions of transforming growth factor-β1 （TGF-β1） and platelet-derived growth factor （PDGF） in liver tissue of rats. RESULTS Compared with normal control group， the levels of alanine transaminase， alkaline phosphatase， aspartate transaminase， total bilirubin， malondialdehyde， procollagen type Ⅲ protein， Ⅳ-type pre collagenase， laminin， hyaluronic acid， interleukin-6， tumor necrosis factor-α， as well as the protein expressions of TGF-β1 and PDGF in model group were increased significantly， while the levels of superoxide dismutase and glutathione peroxidase were significantly reduced （P＜0.01）； the HE， Masson staining and transmission electron microscopy observation results showed obvious HF characteristics in rats of model group. Compared with model group， varying degrees of improvement in above indexes were observed in P. mume groups， and the above 2021BSZR011） indicators of rats in P. mume medium-dose and high-dose groups were reversed significantly （P＜0.05 or P＜0.01）. CONCLUSIONS P. mume has an anti-HF effect， which may be achieved through mechanisms such as antioxidation， anti-inflammation， reduction of collagen production， inhibition of PDGF protein expression， and regulation of TGF- β1 signaling pathway.

OBJECTIVE To explore the effect and mechanism of Prunus mume against hepatic fibrosis （HF）. METHODS Male SD rats were randomly divided into normal control group （n＝10） and modeling group （n＝50）. The modeling group established HF model using carbon tetrachloride. The modeled rats were randomly divided into model group （normal saline）， positive control group [colchicine， 0.09 mg/（kg·d）]， and P. mume low-dose， medium-dose and high-dose groups [1.35， 2.70， 5.40 g/（kg·d）]， with 9 rats in each group. They were given the corresponding drug/normal saline intragastrically， once a day， for 8 consecutive weeks. After the last medication， the liver index was calculated， while liver function indexes， liver fiber indexes， oxidative stress indicators and inflammatory factors of rats were measured. HE staining was used to observe the pathological changes in liver tissue of rats； Masson staining was used to observe the degree of HF in liver tissue of rats； transmission electron microscopy was used to observe the ultrastructure of liver tissue in rats； TUNEL staining was used to detect liver cell apoptosis in each group of rats. Western blot method was used to detect the protein expressions of transforming growth factor-β1 （TGF-β1） and platelet-derived growth factor （PDGF） in liver tissue of rats. RESULTS Compared with normal control group， the levels of alanine transaminase， alkaline phosphatase， aspartate transaminase， total bilirubin， malondialdehyde， procollagen type Ⅲ protein， Ⅳ-type pre collagenase， laminin， hyaluronic acid， interleukin-6， tumor necrosis factor-α， as well as the protein expressions of TGF-β1 and PDGF in model group were increased significantly， while the levels of superoxide dismutase and glutathione peroxidase were significantly reduced （P＜0.01）； the HE， Masson staining and transmission electron microscopy observation results showed obvious HF characteristics in rats of model group. Compared with model group， varying degrees of improvement in above indexes were observed in P. mume groups， and the above 2021BSZR011） indicators of rats in P. mume medium-dose and high-dose groups were reversed significantly （P＜0.05 or P＜0.01）. CONCLUSIONS P. mume has an anti-HF effect， which may be achieved through mechanisms such as antioxidation， anti-inflammation， reduction of collagen production， inhibition of PDGF protein expression， and regulation of TGF- β1 signaling pathway.

Background::Although the treatment of peripheral T-cell lymphoma (PTCL) has undergone advancements during the past several years, the response rate and long-term effects with respect to patients with PTCL remain unsatisfactory—particularly for relapsed or refractory (R/R) patients. This phase II trial was designed to explore the efficacy and safety of an all-oral regimen of chidamide plus prednisone, cyclophosphamide, and thalidomide (CPCT) for R/R PTCL patients who could not tolerate the standard chemotherapy for a variety of reasons.Methods::We conducted a multicenter phase II clinical trial in which we combined chidamide (30 mg twice weekly) with prednisone (20 mg daily after breakfast), cyclophosphamide (50 mg daily after lunch), and thalidomide (100 mg daily at bedtime) (the CPCT regimen) for a total of fewer than 12 cycles as an induction-combined treatment period, and then applied chidamide as single-drug maintenance. Forty-five patients were ultimately enrolled from August 2016 to April 2021 with respect to Chinese patients at nine centers. Our primary objective was to assess the overall response rate (ORR) after the treatment with CPCT.Results::Of the 45 enrolled patients, the optimal ORR and complete response (CR)/CR unconfirmed (CRu) were 71.1% (32/45) and 28.9% (13/45), respectively, and after a median follow-up period of 56 months, the median progression-free survival (PFS) and overall survival (OS) were 8.5 months and 17.2 months, respectively. The five-year PFS and OS rates were 21.2% (95% confidence interval [CI], 7.9-34.5%) and 43.8% (95% CI, 28.3-59.3%), respectively. The most common adverse event was neutropenia (20/45, 44.4%), but we observed no treatment-related death.Conclusion::The all-oral CPCT regimen was an effective and safe regimen for R/R PTCL patients who could not tolerate standard chemotherapy for various reasons.Trial Registration::ClinicalTrials.gov, NCT02879526.

Aim To investigate the role and mecha-nism of CXC chemokine receptor 3(CXCR3)in hepa-toblastoma(HB).Methods The expression of CX-CR3 was detected by immunohistochemical and West-ern blot in 16 cases of HB tissue and adjacent normal liver tissue.The HB cells(Huh-6 and HepT1)were transfected with Con-shRNA,CXCR3-shRNA1,and CXCR3-shRNA2,respectively,and then divided into the Con-shRNA group,CXCR3-shRNA1 group,and CXCR3-shRNA2 group.Cell proliferation was detected by CCK-8 assay and EdU staining.Cell migration and invasion were detected by scratch and Transwell as-says.The expressions of β-catenin,c-Myc,cyclin D1,MMP-7 and MMP-9 were detected by Western blot.The tumor formation and tumor volume in each group were assessed using nude mouse xenograft tumor model,while the expressions of MMP-9 and Ki67 in tumor tissue were examined by immunohistochemistry.Results The expression of CXCR3 was up-regulated in HB tissue(P＜0.01).Compared to the Con-shR-NA group,the viability,proliferation,migration and invasion of Huh-6 and HepT1 cells in the CXCR3-shR-NA1 and CXCR3-shRNA2 groups were reduced(P＜0.01),the expressions of the Wnt/β-catenin signaling pathway related proteins were attenuated(P＜0.01),the tumor grew slowly and the volume was significantly reduced(P＜0.01),and the expressions of MMP-9 and Ki67 in tumor tissue decreased(P＜0.01).Con-clusions Downregulation of CXCR3 hinders the pro-liferation and migration of HB cells,potentially as-cribed to the attenuation of Wnt/β-catenin signaling regulation.

Objective:To improve the quality standard of Xiaoer Shenzhu Jianpi Pills.Methods:The microscopic identification method was used to qualitatively identify Hordei Fructus Germinatus.TLC was used to qualitatively i-dentify of Atractylodis Macrocephalae Rhizoma,Glycyrrhizae Radix Et Rhizoma,Citri Reticulatae Pericapium.HPLC was adopted to determine the contents of hesperidin and ammonium glycyrrhizinate.Results:The microscop-ic identification of Hordei Fructus Germinatus had strong specificity and high viewing rate.The TLC identification spots of Atractylodis Macrocephalae Rhizoma,Glycyrrhizae Radix Et Rhizoma,Citri Reticulatae Pericapium were clear,with good separation and durability.The linear ranges of hesperidin and ammonium glycyrrhizinate were 0.060 0-1.501 0 μg and 0.020 1-0.502 2 μg,respectively(r≥0.999 8).The average recoveries(n=9)were 99％,96％and RSDs were 2.8％and 1.8％.The RSDs of precision,stability and repeatability of the two components were less than 3.0％.Conclusion:The newly established quality standard increases the quality control research of microscopic identification,thin layer chromatography and content determination.The experimental method is accurate and reliable,simple and fast,and has good applicability.It can be used for the quality control and evaluation of Xiaoer Shenzhu Jianpi Pills.

Objective To study the effects and mechanism of norcantharidin(NCTD)on proliferation and apoptosis of NB4 and K562 human leukemic cells by regulating phosphoprotein phosphatase 5 catalytic(PPP5C).Methods PC3.1 and PPP5C-PC3.1 plasmids were electroporated into NB4 and K562 cells.Stable NB4 and K562 cell lines were selected with geneticin(G418).Protein and mRNA expression levels of PPP5C were measured by Western blot and RT-qPCR,respectively.Proliferation,migration,and apoptosis of NB4 and K562 cells were determined by a CCK-8 assay,transwell assay,and Live & Dead? animal cell viability/toxicity detection kit,respectively.NB4 and K562 cells were divided into 0 μg/mL NCTD group and various NCTD dose groups,and cultured in RPMI 1640 medium containing 0,8,16,or 32 μg/ml NCTD.The Live & Dead? animal cell viability/toxicity detection kit measured the numbers of dead and live cells,and cell morphology was observed under a microscope.Western blot was used to measure protein expression levels of caspase 3,Cleaved caspase 3,JNK,p-JNK,p38,p-p38,and α-Tubulin.Results Proliferation,migration,and apoptosis of NB4 and K562 cells were enhanced by overexpression of PPP5C.Compared with 0 μg/mL NCTD group,NCTD promoted apoptosis in a dose-dependent manner.PPP5C overexpression antagonized the killing effect of NCTD on leukemic cells.Mechanistic investigations showed that PPP5C reduced the protein level of p-JNK by dephosphorylating and regulating the expression of apoptosis-related protein Cleaved caspase 3.Conclusions NCTD promotes apoptosis of NB4 and K562 cells and inhibits their proliferation by inhibiting PPP5C.

Objective To investigate the expression levels of plasma circular RNA PTP4A2(circPTP4A2)and circTLK2 in elderly patients with acute ischemic stroke(AIS)and their predic-tive value for neurological functional outcomes.Methods A total of 122 elderly AIS patients admitted to our department from May 2021 to December 2022 were prospectively recruited,and according to their modified Rankin Scale(mRS)score at 3 months after stroke onset,they were divided into a good outcome group(mRS score≤2,81 cases)and a poor outcome group(mRS score:3-6,41 cases).Their baseline data,and plasma circPTP4A2 and circTLK2 levels were compared between the two groups.Multivariate logistic regression analysis was employed to iden-tify prognostic factors for poor outcomes in the elderly AIS patients.ROC curve analysis was ap-plied to evaluate the prognostic value of circPTP4A2 and circTLK2 for adverse outcomes in the patients.Pearson correlation analysis was performed to assess the relationship of plasma levels of circPTP4A2 and circTLK2 with NIHSS score,as well as mRS score.Results The plasma expres-sion levels of circPTP4A2 and circTLK2 were significantly higher in the poor outcome group than the good outcome group[2.08(0.87,2.77)vs 0.93(0.63,1.20),1.71(0.92,2.80)vs 0.75(0.49,1.09),P＜0.01].Multifactor logistic regression analysis showed that plasma circPTP4A2 and circTLK2 were independent predictive factors for poor functional outcomes in elderly AIS patients(P＜0.01,P＜0.05).ROC curve analysis demonstrated that the AUC value of combined circPTP4A2 and circTLK2 in predicting poor outcome in elderly AIS patients was 0.787(95％CI:0.691-0.883).Pearson correlation analysis revealed that the expression levels of circPTP4A2 and cir-cTLK2 in elderly AIS patients were mildly positively correlated with baseline NIHSS scores(r=0.463,r=0.456;P＜0.01)and moderately positively correlated with mRS scores at 3 months after stroke onset(r=0.682,r=0.604;P＜0.01).Conclusion Plasma circPTP4A2 and circTLK2 may be potential biomarkers for predicting neurological functional outcomes in elderly AIS patients.

Urachal carcinoma (UrC)is a rare urological malignancy. UrC is not obvious in its early symptoms, and is mostly in the advanced stage at diagnosis, with a poor prognosis. Surgical treatment was preferred by partial cystectomy + resection of complete umbilical and umbilical urinary catheter ± pelvic lymph node dissection, and more than 90% of UrC were confirmed as adenocarcinoma through postoperative pathology. Systemic treatment is often based on treatment protocols for bladder adenocarcinoma or colorectal adenocarcinoma.This article reviews recent domestic and international research on UrC, summarizing its incidence, clinical characteristics, diagnosis, and treatment.

Objective:To investigate the effect of astragaloside A (AS-A) on the photoreceptor degeneration induced by sodium iodate (NaIO 3) and its related mechanism. Methods:Sixty healthy male C57BL/6J mice, aged 6-8 weeks, were randomly divided into normal control (NC) group, NaIO 3 group, and ASA group, with twenty mice in each group. 30 min before modeling, AS-A group mice were intraperitoneally injected with 100 μl AS-A at a dose of 100 mg/kg body weight. 30 min later, mice in NaIO 3 group and AS-A group were intraperitoneally injected with 100 μl NaIO 3 at a dose of 30 mg/kg body weight. Subsequently, AS-A group mice were administered AS-A twice daily at 12 h intervals until the end of the experiment. On day 1 post-modeling, zonula occludens-1 (ZO-1) immunohistochemistry was performed to observe the structure of retinal pigment epithelium (RPE) cells; real-time quantitative polymerase chain reaction (qPCR) was conducted to detect the mRNA expression of various retinal chemokine ligand-2 ( Ccl2), interleukin-1 beta ( Il-1β), mixed lineage kinase domain-like protein ( Mlkl), receptor-interacting protein kinase 3 ( Ripk3), and tumor necrosis factor ( Tnf). On day 3 post-modeling, immunohistochemistry was performed to observe the expression of ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acid protein (GFAP) in the retina; TdT-mediated dUTP nick-end labeling (TUNEL) assay was used to detect photoreceptor cell death in each group. On day 4 post-modeling, fundus morphology of mice in each group was observed by fundus color photography and optical coherence tomography (OCT). Hematoxylin-eosin staining (HE) was used to observe the morphological structure of the retina in each group. Inter-group comparisons between two groups were conducted using independent samples t-test, while comparisons among three groups were performed using one-way ANOVA. Results:Fundus color photography and OCT examination showed that a large number of scattered yellow-white subretinal nodular structures in the fundus of NaIO 3 group mice, and a large number of strong reflection areas in the RPE layer. The number of strong reflection areas in the RPE layer was reduced in the AS-A group. Immunohistochemical analysis of ZO-1 showed that ZO-1 was largely lost on the RPE cell membrane in that NaIO 3 group; whereas in the AS-A group, ZO-1 was evenly distributed on the RPE cell membrane. HE staining results showed circular black deposits were visible in the RPE layer of the NaIO 3 group, and the inner and outer segments of photoreceptors were severely damaged, with a significant decrease in the number of outer nuclear layer (ONL) cell nuclei; whereas in the AS-A group, the RPE layer pigments were orderly, the inner and outer segments of photoreceptors were intact, and the number of ONL cell nuclei significantly increased. The results of TUNEL staining show that numerous TUNEL-positive cell nuclei were observed in the ONL of the retina in the NaIO 3 group, while the number of TUNEL-positive cell nuclei in the ONL of the retina was significantly reduced in the AS-A group, with statistically significant differences ( t=2.66, P<0.05). The analysis of qPCR data showed that compared with the AS-A group, the relative expression levels of Mlkl, Ripk3, Ccl2, Il-1β and Tnf mRNA in the retina were significantly increased in the NaIO 3 group, with statistically significant differences ( F=39.18, 10.66, 53.51, 41.40, 24.13; P<0.001). Immunohistochemical staining results showed that compared with NC group and AS-A group, the positive expression of GFAP in retina of NaIO 3 group was significantly increased, and the difference was statistically significant ( F=9.62, P<0.05). Conclusion:AS-A antagonizes NaIO 3-induced photoreceptor degeneration in part by inhibiting photoreceptor cell death and neuroinflammation. Meanwhile, AS-A treatment protects against NaIO 3-triggered perturbation of retinal homeostasis.

Objective:To establish and validate the prediction model for bone marrow metastasis (BMM) in malignant tumors by screening out laboratory multiparameters.Methods:This case-control study collected 444 cases of malignant tumor patients who were hospitalized in the First Hospital of Jilin University from March 2018 to March 2024, including 243 cases for model establishment set and 201 cases for model validation set. The model establishment set was divided into BMM positive group (81 cases) and BMM negative group (162 cases), and the model validation set was divided into positive group (67 cases) and a negative group (134 cases). We collected patients′ clinical information such as gender, age, clinical diagnosis, and results of 47 laboratory tests including routine blood analysis, coagulation, liver function, tumor markers, potassium, sodium, chloride, and calcium ion tests, bone marrow morphology, and bone marrow biopsy. BMM was taken as the outcome event, differencial variables were analyzed using inter group comparisons, the correlation among parameters was analyzed using Pearson correlation analysis, the risk factors for BMM were analyzed using multivariate conditional logistic regression analysis, to establish logistic model, followed by efficiency evaluation on BMM predictive model using receiver operating characteristic (ROC) curves.Results:In the model establishment set, Pearson correlation analysis of 28 parameters that differed between the BMM positive and negative groups revealed that the correlation coefficients of 17 parameters, including mean platelet volume (MPV), hematocrit (HCT), hemoglobin (HGB), and prothrombin time (PT), were no more than 0.6 ( P<0.05). Further multivariate conditional logistic regression analysis demonstrated that MPV, HGB, HCT, PT, red cell distribution width (RDW), platelet count (PLT), alkaline phosphatase (ALP), chloride (Cl -), and mean erythrocyte hemoglobin concentration (MCHC) were the risk factors of BMM occurence in malignancy [MPV ( OR=9.929, 95% CI 2.688-71.335), HCT ( OR=8.232, 95% CI 6.223-9.841), HGB ( OR=4.300, 95% CI 1.947-16.577), PT ( OR=3.738, 95% CI 1.359-11.666), RDW ( OR=1.995, 95% CI 1.275-3.807), ALP ( OR=1.025, 95% CI 1.012-1.045), PLT ( OR=1.014, 95% CI 1.002-1.031), MCHC ( OR=0.724, 95% CI 0.523-0.880) and Cl -( OR=0.703, 95% CI 0.472-0.967)]. In the model establishment set, combiation of risk factors provided an AUC of 0.943 (95% CI 0.898-0.987, P<0.001), a sensitivity of 86.3%, and a specificity of 89.2% for BMM prediction. In the model validation set, the AUC was 0.924 (95% CI 0.854-0.960, P<0.001), with a sensitivity and specificity of 86.7% and 83.8%, respectively. Conclusion:This study built and validated a multiple-parameter model for BMM, which may facilitate the timely detection of BMM and provide reference for decision making of bone marrow aspiration.