ObjectiveTo investigate the mechanism of action of Jiedu Huayu granules in improving liver injury in mice with acute liver failure （ALF） by observing its effect on a mouse model of ALF after prophylactic administration， and to provide a basis for clinical medication. MethodsA total of 60 specific pathogen-free male C57BL/6J mice were divided into normal group， model group， Jiedu Huayu granules group （JDHY group）， and farnesoid X receptor （FXR） agonist （GW4064） group using a random number table， with 15 mice in each group. The model of ALF was induced by a single intraperitoneal injection of D-galactosamine combined with lipopolysaccharide. The mice in the JDHY group were given prophylactic administration of 0.3 g/mL drug solution of Jiedu Huayu granules by gavage for 3 days before modeling， those in the normal group and the model group were given 0.9% NaCl solution by gavage， and those in the GW4064 group were given intraperitoneal injection of GW4064 for 3 consecutive days before modeling. The mice were sacrificed after modeling， and serum and liver tissue samples were collected. A veterinary automatic biochemical analyzer was used to measure the serum levels of total bilirubin （TBil）， total bile acids （TBA）， gamma-glutamyl transferase （GGT）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in mice from each group； HE staining was used to observe liver pathological changes； RT-PCR was used to measure the mRNA expression levels of FXR， fibroblast growth factor 15 （FGF15）， fibroblast growth factor receptor 4 （FGFR4）， small heterodimer partner （SHP）， and bile salt export pump （BSEP） in mice， and Western blot was used to measure the protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP. A one-way analysis of variance was used for comparison between groups， and the Dunett method was used for further comparison between two groups. ResultsCompared with the normal group， the model group had significant increases in the serum levels of TBil， ALT， AST， TBA， and GGT （all P<0.01）， and compared with the model group， the JDHY group and the GW4064 group had significant reductions in the serum levels of TBil， ALT， AST， TBA， and GGT （all P <0.01）. HE staining showed that compared with the model group， the JDHY group and the GW4064 group had milder pathological injury， a reduction in the area of hepatocyte necrosis， and alleviation of cellular swelling and edema. Compared with the normal group， the model group had significant reductions in the mRNA and protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP in liver tissue （all P <0.01）， and compared with the model group， the JDHY group and the GW4064 group had significant increases in the mRNA and protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP in liver tissue （all P <0.05）. ConclusionJiedu Huayu granules may alleviate liver injury in mice with ALF through the FXR/SHP axis.

Objective To establish a quality evaluation method for Abri Mollis Herba based on its morphological characteristics, microscopic features, and the determination of principal component contents. Methods The morphological characteristics of Abri Mollis Herba were identified by morphological authentication methods. Microscopic techniques were employed to observe the microscopic features of both the powdered form and cross-sectional tissue of Abri Mollis Herba. Additionally, a high-performance liquid chromatography （HPLC） method was developed to establish the quantify the main components, abrine and soyasaponin Bb, in Abri Mollis Herba. Results The morphological characteristics of Abri Mollis Herba were defined by numerous long pubescence on both the upper and lower surfaces of the leaflets, with indistinct veins and vein islands. The microscopic features mainly included non-glandular hairs, prismatic crystals, and crystal-sheathed fibers in the powdered form. In the root cross-section, xylem bundles, rays, vessels, and stone cells were visible. The stem cross-section displayed rays, vessels, and a hollow pith, while the leaf cross-section revealed collateral vascular bundles, vessels, and prismatic crystals. Conclusion The quality of Abri Mollis Herba could be effectively evaluated by the combination of morphological identification, microscopic authentication, and the quantification of main components abrine and soyasaponin Bb .

BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION ClinicalTrials.gov (NCT02763566).
Humans ; Female ; Fulvestrant/therapeutic use* ; Breast Neoplasms/metabolism* ; Aminopyridines/therapeutic use* ; Benzimidazoles/therapeutic use* ; Middle Aged ; Aromatase Inhibitors/therapeutic use* ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Letrozole/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anastrozole/therapeutic use*

OBJECTIVES: To investigate the targets and mechanisms of 7-hydroxyethyl chrysin (7-HEC) in prevention and treatment of high-altitude cerebral edema (HACE) in rats. METHODS: Fifty-four male Wistar rats were randomly divided into normal control group, HACE model group, and 7-HEC-treated group (18 rats in each group). Except for the normal control group, rats in the two other groups were exposed to a hypobaric hypoxic chamber simulating a 7000 m altitude for 72 h to establish the HACE model. The 7-HEC-treated group was intraperitoneally injected with 7-HEC (150 mg·kg^－¹·d^－¹) for 3 consecutive days before modeling, while the model group received equivalent isotonic sodium chloride solution. Tandem Mass Tag (TMT) proteomics technology was used to detect differentially expressed proteins (DEPs) with screening criteria set at a fold change >1.2 and P<0.05. Western blotting was used to verify the expression levels of target proteins. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed. RESULTS: Compared with the normal control group, 256 DEPs were identified in the HACE model group. Compared with the HACE model group, 87 DEPs were identified in the 7-HEC-treated group. Among them, 19 DEPs that were dysregulated in the HACE model group were restored after 7-HEC intervention, of which seven (HSPA4, Arhgap20, SERT, HACL1, CCDC43, POLR3A, and PCBD1) were confirmed by Western blotting. GO enrichment analysis of the DEPs between the HACE model and 7-HEC-treated groups revealed their involvement in 13 biological processes, five cellular components, and two molecular functions. KEGG pathway analysis indicated associations with the mRNA surveillance pathway, Th17 cell differentiation, serotonergic synapse, RNA polymerase, protein processing in the endoplasmic reticulum, peroxisome, neuroactive ligand-receptor interaction, folate biosynthesis. PPI network analysis demonstrated that HSPA4, POLR3A, and HACL1, which were validated by Western blotting, interacted with multiple signaling pathways and ranked among the top 20 hub proteins by degree value, suggesting their potential role as core regulatory factors. Arhgap20, SERT and PCBD1 also exhibited interactions with several proteins, suggesting their potential as key regulatory proteins, whereas no interactions for CCDC43 were identified. CONCLUSIONS This study applied TMT proteomics to identify seven potential therapeutic targets of 7-HEC for the prevention and treatment of HACE. These targets may be involved in the pathogenesis of HACE through multiple pathways, including maintaining cellular homeostasis, ameliorating oxidative stress, regulating energy metabolism, and reducing vascular permeability.
Animals ; Male ; Proteomics/methods* ; Rats, Wistar ; Flavonoids/therapeutic use* ; Rats ; Brain Edema/etiology* ; Altitude Sickness/metabolism* ; Protein Interaction Maps

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

Objective To investigate the mechanisms of 6-hydroxygenistein(6-OHG)in the treatment of high-altitude hypoxia-induced lung injury.Methods The intersection targets of 6-OHG and high-altitude hypoxia-induced lung injury were identified using databases,including Swiss Target Prediction,SuperPred,GeneCards,and OMIM.The STRING database and Cytoscape software were used to construct a protein interaction network for the intersection targets of drugs and diseases,and targets with degree values greater than the median were identified as key targets.GO and KEGG enrichment analyses of key targets were performed using the DAVID database to identify relevant signaling pathways.The Maestro 13.7 software was used for molecular docking validation.A large hypobaric hypoxic chamber was used to establish a high-altitude lung injury model in mice.A total of 42 male BALB/c mice were randomly assigned to 3 groups(n=14 in each group),including a normal control group,which was exposed to the environmental conditions at the altitude of 1400 m and received a single intraperitoneal injection of normal saline,a model group,which received a single intraperitoneal injection of normal saline,and a 6-OHG group,which received a single intraperitoneal injection of 6-OHG at 100 mg/kg.Then,1 h after drug administration,mice in the model and 6-OHG groups were placed in a large hypobaric hypoxic simulation chamber for animal experiments.Then,they ascended to an altitude of 8 000 m at a speed of 10 m/s,remained in that environment for 24 h,and then descended to an altitude of 3500 m.Mice in the three groups were sacrificed,and their lung tissues were extracted to measure the water content in the lungs.Pathological changes were observed using HE staining,and the levels of malondialdehyde(MDA),H2O2,total superoxide dismutase(T-SOD),and glutathione(GSH)were measured.Western blot was performed to determine the expression levles of p-PI3K/PI3K,p-AKT/AKT,hypoxia-inducible factor 1α(HIF-1α),and vascular endothelial growth factor(VEGF)proteins.Results Key targets such as serine/threonine protein kinase 1(AKT1),HIF-1α,epidermal growth factor receptor(EGFR),matrix metalloproteinase 9(MMP9),and peroxisome proliferator-activated receptor A(PPARA)were identified.GO and KEGG enrichment analyses showed that the targets of 6-OHG in the treatment of high altitude hypoxia-induced lung injury were mainly involved in PI3K/AKT,HIF-1α/VEGF,tumor necrosis factor(TNF),and other signaling pathways.The results of animal experiments demonstrated that compared with the model group,the 6-OHG group showed significant improvement in the pathological damage of lung tissues induced by high altitude hypoxia,presenting statistically significant differences in the levels of MDA,H2O2,GSH,and T-SOD(P＜0.01).The results of Western blot assay revealed statistically significant differences in the p-PI3K/PI3K,p-AKT/AKT,HIF-1α,and VEGF levels in the lung tissues of the 6-OHG group compared with those of the model group(P＜0.01).The molecular docking results showed that 6-OHG could form stable binding with PI3K,AKT,HIF-1α,and VEGF.Conclusion 6-OHG may alleviate lung injury induced by high altitude hypoxia in mice by activating the PI3K/AKT signaling pathway and inhibiting the HIF/VEGF signaling pathway.

Objective To explore the relationship between serum Interleukin-27(IL-27),Cystatin C(CysC),and Glyceraldehyde-3-phosphate dehydrogenase(GAPDH)antibodies and the severity of disease in children with Neuromyelitis optica spectrum disorder(NMOSD),as well as their impact on prognosis.Methods A total of 102 children with NMOSD admitted to Kunming Children's Hospital from July 2019 to July 2023 were selected,along with 102 healthy during the same period.Serum levels of IL-27,CysC,and GAPDH antibodies were compared between children with NMOSD and healthy children.The levels of serum IL-27,CysC,and GAPDH antibodies were compared among children with varying disease severity.The correlations between serum IL-27,CysC,GAPDH antibodies and disease condition,cerebrospinal fluid markers were analyzed.And 102 children with NMOSD received individualized treatment and were followed up for 1 year.The prognosis was evaluated based on disease relapse,and patients were divided into recurrence group and non-recurrence group.The clinical data,serum IL-27,CysC,and GAPDH antibody levels were compared between the two groups.the impact of serum IL-27,CysC,and GAPDH antibodies on disease recurrence was analyzed,and the predictive value of serum IL-27,CysC,and GAPDH antibodies for disease recurrence was evaluated.Results Children with NMOSD had lower levels of serum IL-27 and CysC and higher levels of GAPDH antibodies than healthy children(P<0.05).Serum IL-27 and CysC levels were negatively correlated with Aquaporin 4(AQP4)-IgG antibody positivity,the number of spinal cord-involved segments,Expanded disability status scale(EDSS)scores,cerebrospinal fluid protein content,and white blood cell count.In contrast GAPDH antibodies were positively correlated with these parameters(P<0.05).After 1-year follow-up,2 cases were lost to follow-up,21 cases relapsed,and 79 cases did not,which were included in the relapse group and non-relapse group,respectively.There were significant differences in the number of spinal cord-involved segments,EDSS scores,and cerebrospinal fluid protein content between the relapse group and non-relapse group(P<0.05).The levels of serum IL-27 and CysC were lower and the levels of GAPDH antibodies were higher in the relapse group than the non-relapse group(P<0.05).Serum IL-27,CysC,and GAPDH antibodies were significantly associated with disease relapse(P<0.05).The Area under the curve(AUC)values for predicting disease recurrence in children with NMOSD based on serum IL-27,CysC,and GAPDH antibodies were 0.748,0.791,and 0.747,respectively,with optimal cutoff values of 38.77 pg/mL,0.79 mg/L,and 55.81 pg/mL,respectively.The combined prediction of disease relapse using these three markers had an AUC of 0.900,which was superior to individual prediction values(Z=2.215,2.137,2.220,P=0.024,0.033,0.023).Conclusion The levels of serum IL-27,CysC,and GAPDH antibodies are significantly correlated with the disease severity and prognosis in children with NMOSD,and can effectively predict the risk of disease recurrence.Combined detection provides more reliable predictive value.

Objective To investigate the clinical characteristics and prognosis of acute myeloid leukemia(AML)patients with PTPN11 gene mutation.Methods Total 115 adult AML patients who underwent initial diagnosis,treatment,and second-generation sequencing(NGS)detecting at hospital were recruited in this study.Clinical da-ta included disease characteristics,treatment efficacy,long-term prognosis,immune cell subpopulations,and leu-kemia stem cells were collected to analyze the clinical characteristics and prognosis of AML patients with PTPN11 gene mutation.Results PTPN11 gene mutation rate in newly diagnosed adult AML was 9.57％,and the mutation site mainly occurred in exon 3 region with all mutation type being point mutation.Compared with PTPN11 wild-type group,PTPN11 gene mutation group had a higher early mortality rate(18.18％vs 4.00％,P=0.048),a lower complete response rate(33.33％vs 67.71％,P=0.039),a higher recurrence rate(83.33％vs 42.31％,P=0.043),a shorter median overall survival time(9 months vs 20 months,P=0.026),a lower proportion of ef-fector T cells[(1.39±0.12)％vs(3.56±0.46)％,P=0.038],and a higher proportion of leukemia stem cells[(13.82±3.66)％vs(3.87±1.40)％,P=0.021].Conclusion PTPN11 gene mutation is a poor prognostic marker for AML.Those patients have a high early mortality rate,low complete remission rate,high recurrence rate,short median overall survival time,a low proportion of effector T cells,and a high proportion of leukemia stem cells.

Objective:This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients.Methods:Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy.Results:A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P＜0.001). Conclusions:Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.