OBJECTIVES: To explore the therapeutic mechanism of compound Centella asiatica formula (CCA) for alleviating Schistosoma japonicum (Sj)-induced liver fibrosis in mice. METHODS: The active components and targets of CCA were identified using the TCMSP database with cross-analysis of Sj-related liver fibrosis targets. A "drug-component-target-pathway-disease" network was constructed using Cytoscape 3.9.1. Functional enrichment analysis (GO/KEGG) was performed using DAVID. Molecular docking study was carried out to validate interactions between the core targets and the key compounds. For experimental validation of the results, 36 mice were divided into control group, Sj-infected model group, and CCA-treated groups. In the latter two groups, liver fibrosis was induced via abdominal infection with Sj cercariae for 8 weeks, followed by 8 weeks of daily treatment with CCA decoction or saline. Hepatic pathology of the mice was assessedwith HE and Masson staining, and hepatic expressions of collagen-I and collagen-III were detected using immunohistochemistry; serum IL-6 and TNF-α levels were determined with ELISA. Hepatic expressions of TLR4 and MyD88 proteins were analyzed with Western blotting. RESULTS: We identified a total of 107 bioactive CCA components and 791 targets, including 37 intersection targets linked to Sj-induced fibrosis. The core targets included TNF, TP53, JUN, MMP9, and CXCL8, involving the IL-17 signaling, lipid metabolism, TLR4/MyD88 axis, and cancer pathways. Molecular docking study confirmed strong binding affinity between quercetin (a primary CCA component) and TNF/TP53/JUN/MMP9. In Sj-infected mouse models, CCA treatment significantly attenuated hepatic inflammatory cell infiltration, reduced collagen-I and collagen-III deposition, improved tissue architecture, reduced serum IL-6 and TNF-α levels, and downregulated TLR4 and MyD88 expressions in the liver. CONCLUSIONS CCA mitigates Sj-induced liver fibrosis by targeting TNF, TP53, JUN, and MMP9 to modulate the TLR4/MyD88 pathway, thereby suppressing pro-inflammatory cytokine release, inhibiting hepatic stellate cell activation, reducing collagen deposition, and preventing granuloma formation in the liver.
Animals ; Toll-Like Receptor 4/metabolism* ; Mice ; Myeloid Differentiation Factor 88/metabolism* ; Schistosoma japonicum ; Liver Cirrhosis/parasitology* ; Schistosomiasis japonica ; Signal Transduction ; Molecular Docking Simulation ; Inflammation ; Centella/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Tumor Necrosis Factor-alpha/metabolism*

Objective:To explore the clinicopathological and molecular genetic features of adult hepatic mesenchymal hamartoma (MHL).Methods:A total of five confirmed adult MHL cases diagnosed at the Pathology Department of the First Medical Center of the People's Liberation Army General Hospital between 2009 and 2022 were collected. Histomorphological observation and immunohistochemical staining were conducted. Gene detection was performed by next-generation sequencing.Results:Among the five cases, four were male and one was female, aged 46-67 years, with an average age of 56.2 years. The maximum diameter was 5.3-13.5cm, and the average diameter was 9.2cm. Tumors were generally cystic, solid, or mixed cystic-solid. Histopathologically, in four out of five cases of MHL, malignant transformation occurred, of which three cases were malignantly transformed into undifferentiated embryonal sarcoma and one case was malignantly transformed into a malignant solitary fibrous tumor. NAB2-STAT6 gene rearrangements were identified.Conclusion:Adult MHL is a rare kind of tumor with malignant potential, and it is difficult to diagnose with preoperative imaging examinations. A fine-needle biopsy is rarely used for diagnosis, but surgical resection of symptomatic or enlarged lesions is recommended to rule out the possibility of malignancy and further diagnosis. Genetic testing results revealed the complex genetic alterations in MHL, and it was found that adult MHL can malignantly transform into malignant solitary fibrous tumors. We believe that genome-wide analysis is necessary to determine the unique molecular characteristics of MHL and identify potential targets for therapeutic intervention.

End stage heart failure(ESHF) is the terminal stage of heart failure in patients with heart failure, or refractory heart failure. heart transplantation(HT) and mechanical circulatory assistance represented by ventricular assist device(VAD) are the main treatments for circulatory support in patients with ESHF. However, the serious shortage of donors has restricted the extensive development of HT. VAD technology, represented by left ventricular assist device(LVAD), has developed rapidly, and the 2-year survival rate after surgery has approached of HT. Although LVAD support can directly alleviate symptoms of left heart failure, it only partially relieves symptoms of right heart failure, resulting in high readmission rates.Therefore, more precise monitoring and regulation of right heart function in LVAD recipients is key to improving long-term prognosis. This article aims to provide an overview of strategies for the regulation of right heart function in patients after LVAD implantation.

ObjectiveTo observe the effects of Sargassum and Glycyrrhizae Radix et Rhizoma incompatible pair with the Haizao Yuhutang （HYT） on oxidative stress in the liver of goiter rats under the condition of 2 times the dose limit of the Pharmacopoeia of the People's Republic of China 2020. MethodA total of 128 male Wistar rats were randomly divided into a blank group， a model group， a euthyrox group （20 μg·kg^-1）， a HYT group （12.06 g·kg^-1）， a HYT without Sargassum （HYT-H） group （9.90 g·kg^-1）， a HYT without Glycyrrhizae Radix et Rhizoma （HYT-G） group （10.26 g·kg^-1）， a HYT without Sargassum and Glycyrrhizae Radix et Rhizoma （HYT-HG） group （8.10 g·kg^-1）， and a Sargassum and Glycyrrhizae Radix et Rhizoma （HG） group （3.96 g·kg^-1）. The blank group was given deionized water by gavage， and the others were given propylthiouracil （PTU） to replicate the goiter pathological model. Euthyrox was taken as a positive control drug， and the rest of the Chinese medicine groups were given the corresponding decoction by gavage， the material was collected 12 hours after the last dose. The serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， and the contents of superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， malondialdehyde （MDA）， reactive oxygen species （ROS） in liver tissue were detected in each group. The pathological changes in the liver were observed via hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was utilized to detect the mRNA expressions of Kelch-like Ech-associated protein 1 （Keap1）， nuclear factor E₂-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， p53 and Caspase-3 in liver tissues. Western blot was adopted to detect the protein expressions of Nrf2 and HO-1 in liver tissues in oxidative stress-related signaling pathways. ResultCompared with control group， the model group showed significantly increased serum ALT level and contents of MDA and ROS in liver tissues （P<0.05， P<0.01）， significantly reduced activities of SOD and GSH-Px in the liver （P<0.01）， significantly increased mRNA expression of Keap1 （P<0.01）， and significantly decreased mRNA and protein expressions of Nrf2 and HO-1 （P<0.05， P<0.01）. Compared with the model group， the HYT group manifested significantly reduced serum levels of AST， ALT， and ALP （P<0.05， P<0.01）， significantly reduced contents of MDA and ROS in liver tissue （P<0.01）， significantly increased the activities of SOD and GSH-Px （P<0.01）， significantly decreased mRNA expressions of Keap1， p53， and Caspase-3 （P<0.01）， and significantly increased mRNA and protein expressions of Nrf2 and HO-1 （P<0.05， P<0.01）. ConclusionUnder the condition of 2 times the dose limit of the Pharmacopoeia of the People's Republic of China 2020， Sargassum and Glycyrrhizae Radix et Rhizoma incompatible pair with the HYT on oxidative stress in the liver of goiter rats had different effects. The HYT that contains Sargassum and Glycyrrhizae Radix et Rhizoma has a protective effect on the liver of goiter rats， and the effect is better than that of the HG group， the euthyrox group， and the incomplete groups. Its mechanism may be related to activating the Nrf2/HO-1 signaling pathway to alleviate liver oxidative stress and inhibiting the p53/Caspase-3 signaling pathway to reduce hepatocyte apoptosis.

The maintenance of hematopoietic stem cells (HSCs) is a complex process involving numerous cell-extrinsic and -intrinsic regulators. The first member of the cyclin-dependent kinase family of inhibitors to be identified, p21, has been reported to perform a wide range of critical biological functions, including cell cycle regulation, transcription, differentiation, and so on. Given the previous inconsistent results regarding the functions of p21 in HSCs in a p21-knockout mouse model, we employed p21-tdTomato (tdT) mice to further elucidate its role in HSCs during homeostasis. The results showed that p21-tdT+ HSCs exhibited increased self-renewal capacity compared to p21-tdT- HSCs. Zbtb18, a transcriptional repressor, was upregulated in p21-tdT+ HSCs, and its knockdown significantly impaired the reconstitution capability of HSCs. Furthermore, p21 interacted with ZBTB18 to co-repress the expression of cKit in HSCs and thus regulated the self-renewal of HSCs. Our data provide novel insights into the physiological role and mechanisms of p21 in HSCs during homeostasis independent of its conventional role as a cell cycle inhibitor.
Animals ; Hematopoietic Stem Cells/cytology* ; Cyclin-Dependent Kinase Inhibitor p21/genetics* ; Mice ; Cell Self Renewal ; Repressor Proteins/genetics* ; Mice, Inbred C57BL ; Mice, Knockout ; Humans ; Gene Expression Regulation

Cancer immunotherapy has become a new generation of anti-tumor treatment, but its indications still focus on several types of tumors that are sensitive to the immune system. Therefore, effective strategies that can expand its indications and enhance its efficiency become the key element for the further development of cancer immunotherapy. Natural products are reported to have this effect on cancer immunotherapy, including cancer vaccines, immune-check points inhibitors, and adoptive immune-cells therapy. And the mechanism of that is mainly attributed to the remodeling of the tumor-immunosuppressive microenvironment, which is the key factor that assists tumor to avoid the recognition and attack from immune system and cancer immunotherapy. Therefore, this review summarizes and concludes the natural products that reportedly improve cancer immunotherapy and investigates the mechanism. And we found that saponins, polysaccharides, and flavonoids are mainly three categories of natural products, which reflected significant effects combined with cancer immunotherapy through reversing the tumor-immunosuppressive microenvironment. Besides, this review also collected the studies about nano-technology used to improve the disadvantages of natural products. All of these studies showed the great potential of natural products in cancer immunotherapy.

Objeetive To analyze the clinicopathologic features of proliferative sclerosing IgA nephropathy and the efficacy of prednisone therapy.Methods A retrospective analysis was conducted,enrolling 50 patients with biopsy-proven primary proliferative sclerosing IgA nephropathy who were admitted in the Hospital from January 2005 to June 2015-26 males and 24 females,mean age (36.8 ± 10.4) years.Clinicopathologic features and prednisone therapeutic effect were analyzed.Results The clinical manifestations of 50 cases were nephritis syndrome with varying degrees of renal insufficiency,including 32 cases (64.0％) with hypertension,15 cases (30.0％) with microscopic hematuria.Renal biopsy showed the incidence of glomerular global sclerosis was 17.0％-47.2％,tubular atrophy/ interstitial fibrosis outstanding (T0 50％,T1 32％,T2 18％).After prednisone treatment,compared with sustained remission group and relapse group,invalid patients had higher incidence of hypertension (P ＜ 0.05),relatively lower Hb (P ＜ 0.01) and serum albumin,more significant renal dysfunction (P ＜ 0.01),more severe glomerular global sclerosis,segmental sclerosis,tubular atrophy/ interstitial fibrosis,while the lower interstitial inflammatory cell infiltration.During the follow-up,which lasted from 6 to 132 months (median 27.3 months),the effective rate of treatment was 74.0％ after sufficient prednisone or half dose prednisone therapy.Repeated recurrence rate was 32.0％.At the end of the follow-up period,13(26.0％) patients entered the stage of uremia.Conclusions Application of glucocorticoids in the treatment of proliferative sclerosing IgA nephropathy can protect renal function and delay the progression of renal impairment.The efficacy of glucocorticoids therapy is significantly associated with the presence or absence of hypertension,the degree of renal function impairment,and the severity of the onset of renal pathology.

Acute Disease ; Adult ; Humans ; Iliac Artery ; Lower Extremity ; blood supply ; Male ; Nephrotic Syndrome ; complications ; Thrombosis ; etiology

Objective:To investigate the expression of anti-endothelial cell antibodies(AECA) in patients serum with anti-neutrophil cytoplasmic antibody( ANCA) negative pauci-immune deposition type crescentic glomerulonephritis and its relationship with clinical signatures. Methods:We selected 94 pauci-immune deposition type crescentic glomerulonephritis patients from 2010 to 2015 treated in our hospital,45 of which with ANCA-negative( observation group) and 49 cases of ANCA-positive patients ( control group) , AECA levels of each groups serum were detected by Western blot test. Results: The average age of the observation group and Bermingham vasculitis activity score(BVAS) respectively (41. 08 +9. 43) years old and (15. 03 +3. 82),significantly lower than the control group (P<0. 05);the observation group had fever,joint pain accounted for 26. 67% and 13. 33%,significantly lower than the control group ( P<0. 05 );the observation group of nephrotic syndrome accounted for 48. 89%, higher than the control group ( P<0. 05);observation group positive rate of serum AECA was 46. 67%,significantly lower than the control group 81. 63% (P<0. 05);the observation group IgG-AECA identified 7 proteins,while the control group had identified 11 proteins,of which the observation group the positive rate of anti 90 kD antibody was 13. 33%( 6/45 ) , significantly lower than the control group 51. 02%( 25/49 ) ( P<0. 05 );observation group of anti 76 kD antibody positive patients had rash ratio of 100%, significantly higher than negative patients ( P<0. 05),anti 200 kD antibody positive the BVAS score of the patients was (18. 02 + 2. 51),which was significantly higher than that of the negative patients ( P < 0. 05 ) . Conclusion: The different level of AECA in ANCA negative pauci-immune crescentic glomerulonephritis patients may be associated with certain clinical manifestations;clinical manifestations differences between the ANCA negative and positive patients may be associated with different expression of the AECA related,the detail need a further study.

OBJECTIVETo evaluate the protective effect of quercetin against lipopolysaccharide (LPS)-induced cardiac injury in mice.

METHODSC57BL/6J mice were randomized into 4 groups to receive intraperitoneal injection of saline (negative control) or LPS (20 mg/kg), or fed with quercetin (100 mg/kg for 7 days) with or without subsequent LPS injection (quercetin+LPS group and quercetin control group, respectively). Six hour after LPS injection, the mice were tested for cardiac function with an echocardiograph, and the protein expressions of Bax, Bcl-2, iNOS, and eNOS in the myocardium were evaluated with Western blotting; serum NO concentration was also measured. The survival of the mice within 5 days after LPS injection was recorded to draw the survival curve.

RESULTSQuercetin pretreatment significantly improved the cardiac function of LPS-challenged mice (P<0.05), and attenuated LPS-induced increment in myocardial iNOS expression and decrement in eNOS level. LPS significantly increased the myocardial Bax expression and slightly decreased Bcl-2 expression; quercetin pretreatment decreased Bax expression to the control level and significantly lowered Bax/Bcl-2 ratio as compared with the LPS group. Serum NO level was significantly increased by nearly 2.5 folds in LPS-challenged mice, but was markedly decreased with quercetin pretreatment (P<0.05). The 5-day survival rate of LPS-treated mice was 10%, which was increased to 45% in quercetin- pretreated mice (P<0.05).

CONCLUSIONQuercetin can alleviate LPS-induced cardiac dysfunctions in mice to increase their survival rate following LPS challenge.

Animals ; Cardiotonic Agents ; pharmacology ; Heart ; drug effects ; Lipopolysaccharides ; adverse effects ; Mice ; Mice, Inbred C57BL ; Myocardium ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Nitric Oxide Synthase Type III ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Quercetin ; pharmacology