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1.
Otol Neurotol ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38956761

ABSTRACT

OBJECTIVES: This study aimed to establish the minimal clinically important difference (MCID) and assess the responsiveness of the Chinese version of Zurich Chronic Middle Ear Inventory (ZCMEI-21-Chn). STUDY DESIGN: Prospective multicenter study. SETTING: Four Chinese tertiary referral centers admitting patients nationwide. PATIENTS: 230 adult patients with chronic otitis media (COM) undergoing tympanoplasty. INTERVENTION: Patients were required to complete the ZCMEI-21-Chn to measure health-related quality of life both preoperatively and postoperatively. An anchor-based method was used to determine the MCID of the derivative cohort by including the Global Rating of Change Questionnaire as an anchor. The generalizability and consistency with functional outcomes of the MCID estimates were externally examined in a validation cohort using a receiver operating characteristic curve analysis. RESULTS: A total of 161 and 69 patients were included in the derivative and validation cohort. The mean preoperative and postoperative ZCMEI-21-Chn total scores were 28.4 (standard deviation [SD] 14.5) and 17.5 (SD 12.6). The mean change in ZCMEI-21-Chn score was 10.9 (SD 14.3, p < 0.001). The MCIDs of the ZCMEI-21-Chn for improvement and deterioration were estimated at 13 (SD 13.0) and -7 (SD 12.9), accordingly. For patients who have reported an improved health-related quality of life, a cutoff value of 15.6 dB HL for elevation of the air-conducted hearing threshold was noticed. However, change of clinical importance judged according to MCID and Japan Otological Society criteria disagreed with each other, notably with a Cohen's kappa (κ) of 0.14 (p = 0.21) in the validation cohort. CONCLUSION: This study is the first to establish the MCID of a COM-specific questionnaire in Chinese. For the COM population undergoing surgical intervention, MCID values of 13 for improvement and -7 for deterioration are recommended. The results were externally validated to be generalizable to nationwide usage, yet distinguishable from the audiological criteria. The availability of the MCID greatly adds to the clinical utility of the ZCMEI-21-Chn by enabling a clinically meaningful interpretation of its score changes.

2.
Transl Oncol ; 47: 102054, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38970916

ABSTRACT

BACKGROUND: Gastric cancer stem cells (GCSCs) play crucial role in the development, recurrence, and resistance of gastric cancer (GC). Cinobufacini, a traditional Chinese medicine, offers significant advantages in improving tumor therapy. However, pre-clinical investigation into the antitumor effect and mechanism of Cinobufacini on GC is still lacking. Additionally, it has not been reported whether Cinobufacini is related to cancer stem cells (CSCs). METHODS: The CCK-8, clone formation, EdU staining, transwell and wound healing experiments were performed to assess the cell toxicity of Cinobufacini and demonstrate the preventive effects of Cinobufacini on proliferation, invasion, and migration of GC cells. Elucidating the underlying mechanism of Cinobufacini in GC based on the transcriptome sequencing. Flow cytometry assays, sphere formation assays, subcutaneous xenograft model in nude mice, and immunofluorescent staining have been used to investigate whether the anti-GC effect of Cinobufacini is associated with GCSCs and enhancing therapeutic response to 5-Fluorouracil (5-FU). RESULTS: Cinobufacini exerts minimal impact on normal human gastric epithelium cell GES-1, while significantly suppressing the proliferation, invasion, and migration of GC cell lines. Additionally, Cinobufacini attenuates the stemness of GCSCs by disrupting the AKT/GSK-3ß/ß-catenin signaling cascade. Moreover, Cinobufacin enhances the anti-tumor effects of 5-FU against GCSCs by reducing in vitro sphere formation and inhibiting subcutaneous graft tumor growth in vivo. CONCLUSIONS: Cinobufacini enhances the therapeutic response of 5-FU against GC by targeting CSCs via AKT/GSK-3ß/ß-catenin signaling axis. Our findings offer a crucial insight into the molecular mechanism of Cinobufacini's anticancer activity in GC.

3.
Chemosphere ; 361: 142516, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38850691

ABSTRACT

Activated siderite, endowed with excellent properties, was simply prepared by co-grinding with Fe sulfate to enhance its high reducing ability for Cr(VI). Batch experiments were conducted to investigate the main affecting parameters, such as material ratio, pH, temperature, etc. The removal of Cr(VI) by activated siderite was completed within 4 h of the reaction. The activated siderite maintained a high removal effect of Cr(VI) within a wide pH range (3-9). Various analytical methods, including XRD, SEM/EDS, XPS, etc., were employed to characterize the samples and discover variations before and after the reaction. The Fe (Ⅱ) in activated siderite becomes highly active, and it can even be released from the solid phase in the mildly acidic liquid phase to efficiently reduce Cr(VI) and mitigate its toxicity. These findings introduce an innovative approach for activating various minerals widely distributed in nature to promote the recovery of the ecological system.


Subject(s)
Chromium , Ferric Compounds , Oxidation-Reduction , Chromium/chemistry , Ferric Compounds/chemistry , Hydrogen-Ion Concentration , Iron/chemistry , Ferrous Compounds/chemistry , Minerals/chemistry , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/chemistry , Carbonates
4.
J Inflamm Res ; 17: 4055-4064, 2024.
Article in English | MEDLINE | ID: mdl-38939122

ABSTRACT

Objective: Osteitis is more prevalent in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), making the disease refractory and prone to recurrence. However, the pathophysiologic mechanism of osteitis formation in CRS has not been fully elucidated, and this study aimed to further elucidate the association of eosinophils and type 2 inflammatory mediators with osteitis in patients with CRSwNP. Methods: This retrospective study collected clinical data on 125 cases of CRSwNP. The participants were categorized into two groups based on the presence or absence of osteitis in their sinus CT scan. The groups were classified as the osteitis group and the non-osteitis group. The clinical baseline data, type 2 inflammatory mediators, and eosinophils were compared between the two groups. The correlation between these factors and the Global Osteitis score scale (GOSS) was also evaluated. Results: There were 69 cases in the osteitis group and 56 cases in the non-osteitis group of CRSwNP patients. The prevalence of concomitant asthma (P=0.009), SNOT-22 score, LUND-MAKAY score, and LUND-KEDENY score were significantly higher in the osteitis group than in the non-osteitis group (All P values were < 0.001); the absolute values of IL-13 (P<0.001), periosteal proteins (P<0.001), and tissue eosinophils (P < 0.05) were significantly higher in the osteitis group as compared with the non-osteitis group. Logistic regression analysis showed that IL-13 and periosteal proteins were risk factors for CRSwNP osteitis (P<0.001). ROC curve analysis revealed that IL-13 had the highest predictive value (AUC=0.786) with a cut-off value of 5.8059 pg/mL, the sensitivity of 58.0%, and a specificity of 89.3% respectively. Conclusion: Osteitis could indicate the more severe symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP), and elevated IL-13, periosteal proteins, and tissue eosinophils are risk factors for osteitis formation in patients with CRSwNP.

5.
J Fungi (Basel) ; 10(5)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38786665

ABSTRACT

This study investigates the effects of forest aging on ectomycorrhizal (EcM) fungal community and foraging behavior and their interactions with plant-soil attributes. We explored EcM fungal communities and hyphal exploration types via rDNA sequencing and investigated their associations with plant-soil traits by comparing younger (~120 years) and older (~250 years) temperate forest stands in Northeast China. The results revealed increases in the EcM fungal richness and abundance with forest aging, paralleled by plant-soil feedback shifting from explorative to conservative nutrient use strategies. In the younger stands, Tomentella species were prevalent and showed positive correlations with nutrient availability in both the soil and leaves, alongside rapid increases in woody productivity. However, the older stands were marked by the dominance of the genera Inocybe, Hymenogaster, and Otidea which were significantly and positively correlated with soil nutrient contents and plant structural attributes such as the community-weighted mean height and standing biomass. Notably, the ratios of longer-to-shorter distance EcM fungal exploration types tended to decrease along with forest aging. Our findings underscore the integral role of EcM fungi in the aging processes of temperate forests, highlighting the EcM symbiont-mediated mechanisms adapting to nutrient scarcity and promoting sustainability in plant-soil consortia.

6.
Front Surg ; 11: 1391718, 2024.
Article in English | MEDLINE | ID: mdl-38803548

ABSTRACT

Objective: To explore the clinical efficacy of intramedullary reduction techniques for irreducible intertrochanteric femoral fractures with negative medial cortical support. Methods: A retrospective analysis was conducted on 69 patients with irreducible intertrochanteric femoral fractures with negative medial cortical support treated in the Department of Orthopedics at Jiangsu Province Hospital (The First Affiliated Hospital of Nanjing Medical University) from July 2019 to December 2021. Patients were divided into Group A and Group B. Group A (experimental group) consisted of 36 cases with an average age of 76.2 ± 5.9 years, while Group B (control group) comprised 33 cases with an average age of 76.6 ± 6.3 years. Group A received treatment using intramedullary reduction techniques, while Group B received treatment using traditional extramedullary reduction techniques. Both groups achieved anatomic reduction of the medial cortex or slight positive support. Surgical duration, intraoperative fracture reduction time, intraoperative bleeding, intraoperative fluoroscopy time, fracture reduction quality, fracture healing, postoperative neck-shaft angle loss, femoral neck shortening, and hip joint functional recovery score (FRS) were compared between the two groups. Results: All patients were followed up for an average of 13.8 months. Group A showed superior outcomes compared to Group B in surgical duration, intraoperative fracture reduction time, intraoperative bleeding, intraoperative fluoroscopy time, fracture reduction quality, fracture healing, postoperative neck-shaft angle loss, and femoral neck shortening (P < 0.05). Hip joint function assessed by functional recovery score was better in Group A than Group B at 1 and 3 months postoperatively (P < 0.05), with no significant statistical difference at other time points (P > 0.05). Conclusion: For irreducible intertrochanteric femoral fractures with negative medial cortical support, intramedullary reduction techniques used during surgery demonstrated simplicity, significant reduction in surgical duration, decreased intraoperative bleeding, fewer amounts of intraoperative fluoroscopy, improved fracture reduction quality, and reduced surgical complexity. Further clinical research and application are warranted.

7.
J Orthop Surg Res ; 19(1): 23, 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38166985

ABSTRACT

BACKGROUND: Osteoarthritis (OA) is a common degenerative disease involving articular cartilage, in which ferroptosis of chondrocytes plays an important role. Baicalin (BAI) exerts regulatory effects in a wide range of orthopedic diseases including OA, but its effect on ferroptosis of chondrocytes (CHs) is still unclear. The purpose of this study was to determine the effect of BAI on ferroptosis in human OA chondrocytes (OACs), and to explore its possible mechanism. METHODS: CHs were treated with IL-1ß (10 ng/mL) to simulate inflammation in vitro. Immunofluorescence, quantitative RT-PCR, Western blotting and cell viability assay were performed to evaluate the impacts of BAI on Fe2+ level, mitochondrial dysfunction, ferroptosis-related proteins, oxidative stress and cytotoxicity in CHs. Additionally, siRNA was made use of to knock out nuclear factor E2-related factor 2 (Nrf2) to analyze the role played by Nrf2 in BAI-induced CH ferroptosis. RESULTS: BAI eliminated IL-1ß-induced Fe2+ accumulation, changes in mitochondrial membrane potential and ferroptosis-related protein GPX4, SLC7A11, P53 and ACSL4 levels, as well as reactive oxygen species (ROS), lipid peroxidation (LPO) and malondialdehyde (MDA) accumulation in CHs. Besides, BAI reversed IL-1ß-induced decrease of Collagen II and increase of MMP13 in CHs. Meanwhile, BAI attenuated IL-1ß-induced CH toxicity and promoted Nrf2 antioxidant system activation. When Nrf2 was knocked down by siRNA, the effects of BAI on IL-1ß-induced ferroptosis-related proteins and antioxidant stress in CHs were significantly weakened. CONCLUSIONS: This study demonstrates that IL-1ß can induce CH ferroptosis. BAI is able to inhibit IL-1ß-induced CH ferroptosis and ECM degradation, and the specific mechanism may be that it can inhibit IL-1ß-induced CH ferroptosis by activating Nrf2 antioxidant system to attenuate the accumulation of intracellular ROS and lipid ROS.


Subject(s)
Ferroptosis , NF-E2-Related Factor 2 , Osteoarthritis , Humans , Antioxidants/pharmacology , Chondrocytes/metabolism , Ferroptosis/drug effects , Interleukin-1beta/pharmacology , Interleukin-1beta/metabolism , NF-E2-Related Factor 2/drug effects , NF-E2-Related Factor 2/metabolism , Osteoarthritis/metabolism , Reactive Oxygen Species/metabolism , RNA, Small Interfering , Signal Transduction
8.
Exp Ther Med ; 26(4): 498, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37753292

ABSTRACT

The aim of the present study was to investigate the clinical efficacy of three cannulated screws with parallel distribution in comparison with the 'gold standard' of inverting three cannulated screws with triangular distribution, in the treatment of femoral neck fractures in the elderly. A total of 106 elderly patients with femoral neck fractures treated at the Department of Orthopedics of the First Affiliated Hospital of Nanjing Medical University (Jiangsu Provincial Hospital) from October 2018 to March 2020 were retrospectively analyzed and divided into groups A and B. Group A consisted of 51 patients with a mean age of 73.3±6.8 years; and group B consisted of 55 patients with a mean age of 74.5±7.3 years. Group A was treated with closed reduction + inverted triangular distribution of three cannulated screws, while group B was treated with closed reduction + parallel distribution of three cannulated screws, and the general surgical conditions, including fracture reduction quality, fracture healing, incidence of avascular necrosis of the femoral head, and functional recovery scale (FRS) score of hip joint function were assessed in both groups. All patients were followed up for an average of 14.8 months. Compared with group A, group B had significant advantages in operation time, number of times intraoperative fluoroscopy was performed, number of intraoperative guide wire adjustments, and proportion of postoperative referrals to the intensive care unit (P<0.05). There were no significant differences in fracture reduction quality, fracture healing, incidence of avascular necrosis of the femoral head, and FRS score of hip joint function between groups A and B (P>0.05). For elderly patients with femoral neck fractures, distributing three cannulated screws in parallel after closed reduction achieved similar clinical efficacy to 'gold standard' inverted triangular distribution, and had obvious advantages in operation time, with significantly reduced surgical difficulty. This procedure is therefore deemed worthy of promotion and clinical application in the primary hospitals of China.

9.
Sci Total Environ ; 901: 166434, 2023 Nov 25.
Article in English | MEDLINE | ID: mdl-37598965

ABSTRACT

The combined pollution of microplastics (MPs) and Cd can affect plant growth and development and Cd accumulation, with most studies focusing on dryland soil. However, the effects of polyurethane (PU) controlled-release fertiliser coated MPs (PU MPs), which widely exist in rice systems, coupled with Cd on plant growth and Cd accumulation under flooding conditions are still unknown. Therefore, in the present study, in situ techniques were used to systematically study the effects of PU MPs and Cd coupling on the physiological and biochemical performance, metabolomics characteristics, rhizosphere bacterial community, and Cd bioavailability of rice in different soil types (red soil/cinnamon soil). The results showed that the effects of PU MPs on rice growth and Cd accumulation were concentration-dependent, especially in red soil. High PU concentration (1 %) inhibited rice root growth significantly (44 %). The addition of PU MPs inhibited photosynthetically active radiation, net photosynthesis, and transpiration rate of rice, mainly with low concentration (0.1 %) in red soil and high concentration (1 %) in cinnamon soil. PU MPs can enhance the expression of Cd resistance genes (cadC and copA) in soil, enhance the mobility of Cd, and affect the metabolic pathways of metabolites in the rhizosphere soil (red soil: fatty acid metabolism; cinnamon soil: amino acid degradation, heterobiodegradation, and nucleotide metabolism) to promote Cd absorption in rice. Especially in red soil, Cd accumulation in the root and aboveground parts of rice after the addition of high concentration PU (1 %) was 1.7 times and 1.3 times, respectively, that of the control (p < 0.05). Simultaneously, microorganisms can affect rice growth and Cd bioavailability by affecting functional bacteria related to carbon, iron, sulfur, and manganese. The results of the present study provide novel insights into the potential effects of PU MPs coupled with Cd on plants, rhizosphere bacterial communities, and Cd bioavailability.

10.
Article in Chinese | MEDLINE | ID: mdl-37549947

ABSTRACT

Objective:To observe the efficacy and safety of the M receptor antagonist Bencycloquidium bromide nasal spray in treatment of seasonal allergic rhinitis with runny nose as the main symptom. Methods:From August 2021 to September 2021, 134 patients with seasonal allergic rhinitis were enrolled in the otolaryngology Outpatient Department of Peking University Third Hospital, First Affiliated Hospital of Harbin Medical University and China-Japanese Friendship Hospital of Jilin University, including 71 males and 63 females, with a median age of 38 years. TNSS score and visual analogue scale(VAS) of total nasal symptoms were observed during 2 weeks of treatment with Bencycloquidium bromide nasal spray. Results:TNSS score decreased from (8.89±3.31) on day 0 to (3.71±2.51) on day 14(P<0.001), VAS score of nasal symptoms decreased from (24.86±7.40) on day 0 to (6.84±5.94) on day 14(P<0.001), VAS score of rhinorrhoea decreased from (6.88±2.06) on day 0 to (1.91±1.81) on day 14(P<0.001). Rhinoconjunctivitis quality of life questionnaire(RQLQ) score decreased from (94.63±33.35) on day 0 to (44.95±32.28) on day 14(P<0.001). The incidence of adverse reaction was low and no serious adverse events occurred during the whole experiment. Conclusion:Bencycloquidium bromide nasal spray has significant efficacy and good safety in the treatment of seasonal allergic rhinitis.


Subject(s)
Rhinitis, Allergic, Seasonal , Rhinitis, Allergic , Male , Female , Humans , Adult , Rhinitis, Allergic, Seasonal/drug therapy , Nasal Sprays , Quality of Life , Administration, Intranasal , Rhinorrhea , Double-Blind Method , Treatment Outcome , Rhinitis, Allergic/drug therapy
11.
Oncol Lett ; 25(6): 269, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37216167

ABSTRACT

The present study aimed to investigate the predictive value of pretreatment fibrinogen (FIB) levels in patients with cancer who received immunotherapy as a second-line treatment. A total of 61 patients with stage III-IV cancer were included. The cut-off value of FIB for predicting overall survival (OS) was determined by receiver operating characteristic curve analysis. The prognostic value of pretreatment FIB on progression-free survival (PFS) and OS was determined by univariate and multivariate analyses. Based on a cut-off point of 3.47 g/l, patients were divided into low pretreatment FIB (<3.47 g/l) and high pretreatment FIB (≥3.47 g/l) groups. A high pretreatment FIB level was more common in older patients (P=0.03). Kaplan-Meier analysis showed that patients with high pretreatment FIB levels had shorter PFS and OS times than patients with low FIB levels (P<0.05). In multivariate analysis, pretreatment FIB was an independent prognostic factor for OS [hazard ratio (HR), 6.06; 95% CI, 2.01-18.28; P<0.01] and OS from the initiation of second-line treatment (HR, 3.69; 95% CI, 1.28-10.63; P=0.02). Overall, FIB is associated with survival outcome in patients with cancer who are administered immunotherapy as a second-line treatment.

12.
Clin. transl. oncol. (Print) ; 25(3): 685-695, mar. 2023.
Article in English | IBECS | ID: ibc-216427

ABSTRACT

Background Recent studies have shown that the activation of PI3K/AKT signaling pathway is an essential molecular mechanism participating in trastuzumab resistance in HER2 + GC (gastric cancer). However, how can we effectively inhibit AKT activity associated with drug resistance during trastuzumab treatment? Screening inhibitors against the upstream receptors of PI3K/AKT signaling pathway or interacting proteins of members has become an important way. Methods In this study, western blot, qRT-PCR, CCK8, Co-IP and other techniques were used to explore possible mechanisms participating in trastuzumab resistance in vitro. Besides, the xenograft mouse model and GC tissue samples from patients were used to further validate the in-vitro results. Results The expression of XB130 adaptor protein was remarkably increased in GC cell lines resistant to trastuzumab, and knockdown of XB130 could reverse the resistance via downregulating p-AKT. In addition, p-SRC (Tyr416) was increased in resistant cells, which could facilitate the binding of XB130 to PI3K p85α. It was also discovered that XB130 could negatively regulate PTEN gene transcription, and thus a positive feedback loop was formed between SRC-XB130-PTEN. Conclusions In HER2 + GC, XB130 contributes to trastuzumab resistance by stimulating the PI3K/AKT signaling pathway through binding to PI3K p85α under the mediation of SRC kinase and regulating PTEN gene transcription, and in turn forming a positive feedback loop between SRC-XB130-PTEN (AU)


Subject(s)
Animals , Mice , Adaptor Proteins, Signal Transducing/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Stomach Neoplasms , Trastuzumab/therapeutic use , Cell Line, Tumor , Drug Resistance, Neoplasm , PTEN Phosphohydrolase , Signal Transduction , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism
13.
J Exp Clin Cancer Res ; 42(1): 10, 2023 Jan 07.
Article in English | MEDLINE | ID: mdl-36609396

ABSTRACT

BACKGROUND: Posttranscriptional modification of tumor-associated factors plays a pivotal role in breast cancer progression. However, the underlying mechanism remains unknown. M6A modifications in cancer cells are dynamic and reversible and have been found to impact tumor initiation and progression through various mechanisms. In this study, we explored the regulatory mechanism of breast cancer cell proliferation and metabolism through m6A methylation in the Hippo pathway.  METHODS: A combination of MeRIP-seq, RNA-seq and metabolomics-seq was utilized to reveal a map of m6A modifications in breast cancer tissues and cells. We conducted RNA pull-down assays, RIP-qPCR, MeRIP-qPCR, and RNA stability analysis to identify the relationship between m6A proteins and LATS1 in m6A regulation in breast cancer cells. The expression and biological functions of m6A proteins were confirmed in breast cancer cells in vitro and in vivo. Furthermore, we investigated the phosphorylation levels and localization of YAP/TAZ to reveal that the activity of the Hippo pathway was affected by m6A regulation of LATS1 in breast cancer cells.  RESULTS: We demonstrated that m6A regulation plays an important role in proliferation and glycolytic metabolism in breast cancer through the Hippo pathway factor, LATS1. METTL3 was identified as the m6A writer, with YTHDF2 as the reader protein of LATS1 mRNA, which plays a positive role in promoting both tumorigenesis and glycolysis in breast cancer. High levels of m6A modification were induced by METTL3 in LATS1 mRNA. YTHDF2 identified m6A sites in LATS1 mRNA and reduced its stability. Knockout of the protein expression of METTL3 or YTHDF2 increased the expression of LATS1 mRNA and suppressed breast cancer tumorigenesis by activating YAP/TAZ in the Hippo pathway. CONCLUSIONS: In summary, we discovered that the METTL3-LATS1-YTHDF2 pathway plays an important role in the progression of breast cancer by activating YAP/TAZ in the Hippo pathway.


Subject(s)
Breast Neoplasms , Humans , Female , Methylation , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Cell Transformation, Neoplastic/genetics , Carcinogenesis/genetics , Transcription Factors/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Methyltransferases/genetics , Methyltransferases/metabolism
14.
Clin Transl Oncol ; 25(3): 685-695, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36284062

ABSTRACT

BACKGROUND: Recent studies have shown that the activation of PI3K/AKT signaling pathway is an essential molecular mechanism participating in trastuzumab resistance in HER2 + GC (gastric cancer). However, how can we effectively inhibit AKT activity associated with drug resistance during trastuzumab treatment? Screening inhibitors against the upstream receptors of PI3K/AKT signaling pathway or interacting proteins of members has become an important way. METHODS: In this study, western blot, qRT-PCR, CCK8, Co-IP and other techniques were used to explore possible mechanisms participating in trastuzumab resistance in vitro. Besides, the xenograft mouse model and GC tissue samples from patients were used to further validate the in-vitro results. RESULTS: The expression of XB130 adaptor protein was remarkably increased in GC cell lines resistant to trastuzumab, and knockdown of XB130 could reverse the resistance via downregulating p-AKT. In addition, p-SRC (Tyr416) was increased in resistant cells, which could facilitate the binding of XB130 to PI3K p85α. It was also discovered that XB130 could negatively regulate PTEN gene transcription, and thus a positive feedback loop was formed between SRC-XB130-PTEN. CONCLUSIONS: In HER2 + GC, XB130 contributes to trastuzumab resistance by stimulating the PI3K/AKT signaling pathway through binding to PI3K p85α under the mediation of SRC kinase and regulating PTEN gene transcription, and in turn forming a positive feedback loop between SRC-XB130-PTEN.


Subject(s)
Proto-Oncogene Proteins c-akt , Stomach Neoplasms , Humans , Animals , Mice , Trastuzumab/pharmacology , Trastuzumab/therapeutic use , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Signal Transduction , Adaptor Proteins, Signal Transducing/genetics , Cell Line, Tumor , Drug Resistance, Neoplasm , PTEN Phosphohydrolase
15.
Ying Yong Sheng Tai Xue Bao ; 34(12): 3214-3222, 2023 Dec.
Article in Chinese | MEDLINE | ID: mdl-38511359

ABSTRACT

We investigated species composition and community structure of a typical Quercus variabilis natural secondary forest in the northern foothills of the Qinling Mountains, within the dynamic monitoring plot of deciduous broad-leaved forest at the Louguantai experimental forest farm in Zhouzhi County, Shaanxi Province. The results showed that there were 3162 individual woody plants with diameter at breast height ≥1 cm in the plot, which were belonged to 42 species, 36 genera, and 25 families. The community genus's areal type was dominated by the temperate component, which accounted for 44.4%, and followed by the tropical component. The community was dominated by several tree species. The top three species with respect to importance value were Q. variabilis, Pinus tabuliformis, and Quercus aliena, with the sum of their importance value being 64.7%. The average DBH of all woody plants was 7.58 cm. The distribution of all individuals and dominant species in the tree layer was approximately normal, with more medium-size individuals. The community structure was stable. The community was poorly renewed, with a trend of population decline. Biodiversity indices varied considerably among different plots, being lower than those of subtropical broad-leaved evergreen forests. There was a significant correlation between community species distribution and environmental factors. Soil and topography explained 42.4% of the variation in community distribution. Altitude and soil alkali hydrolysable nitrogen had a significant effect on community distribution. Altitude, soil total phosphorus, and organic matter content significantly affected the species diversity of Q. variabilis communities. The stronger adaptability of Q. variabilis populations allowed them to become dominant in low-nutrient environments, which limited species diversity in the community.


Subject(s)
Quercus , Humans , Animals , Forests , Trees , Plants , China , Soil
16.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 36(10): 1249-1254, 2022 Oct 15.
Article in Chinese | MEDLINE | ID: mdl-36310462

ABSTRACT

Objective: To evaluate short-term effectiveness of staged management for complex tibial plateau fracture with severe soft tissue injury. Methods: A clinical data of 12 patients with complex tibial plateau fractures and severe soft tissue injuries between July 2017 and March 2021 and met the selection criteria was retrospectively analyzed. There were 7 males and 5 females with an average age of 43.1 years (range, 33-58 years). All patients were traffic accident injuries and admitted to hospital within 24 hours after injury. The tibial plateau fractures were closed fractures. According to the Schatzker classification standard, the fractures were rated as type Ⅳ in 3 cases, type Ⅴ in 4 cases, and type Ⅵ in 5 cases. According to the Tscherne classification standard, the soft tissue injuries were rated as grade Ⅱ in 4 cases and grade Ⅲ in 8 cases. The treatment of all patients was divided into 3 stages. In the first stage, emergency trans-articular fracture fixation with external fixator was performed; in the second stage, the fracture reduction and internal fixation were performed and bone cement was implanted to fill the bone defect; in the third stage, the bone cement was removed and the bone graft was performed to repair defect. All patients performed joint function exercise after operation as early as possible. Results: There was no neurological symptom after all staged managements, the incisions healed by first intention, and no complications such as incision infection or necrosis occurred. All patients were followed up 6-32 months (mean, 16.9 months). The fractures were all anatomical reduction confirmed by the X-ray films after operation. During follow-up, there was no obvious loss of reduction, loosening and rupture of internal fixator, or collapse of the articular surface. All fractures healed after 14-20 weeks (mean, 17.6 weeks). The posterior slope angle of the tibial plateau was (9.7±2.3)° and the varus angle was (3.9±1.9)° immediately after bone grafting, and were (8.5±2.9)° and (4.3±1.9)° respectively at 6 months after operation. There was no significant difference between the two time points ( t=0.658, P=0.514; t=-1.167, P=0.103). At last follow-up, the Hospital for Special Surgery (HSS) score was 85-96 (mean, 91.2), and the range of motion of knee was 110°-135° (mean, 120.9°). Conclusion: The staged management for complex tibial plateau fracture with severe soft tissue injury can obtain good short-term effectiveness, but the long-term effectiveness needs to be further followed up.


Subject(s)
Soft Tissue Injuries , Tibial Fractures , Adult , Female , Humans , Male , Bone Cements , Fracture Fixation, Internal , Retrospective Studies , Soft Tissue Injuries/surgery , Tibial Fractures/surgery , Treatment Outcome , Middle Aged
17.
Ying Yong Sheng Tai Xue Bao ; 33(9): 2405-2412, 2022 Sep.
Article in Chinese | MEDLINE | ID: mdl-36131656

ABSTRACT

Forest is the main component of terrestrial ecosystems that harbors about 40% of the existing species on the earth. As a vital component of biodiversity, phyllosphere microbes in the canopy play a critical and unique role in maintaining plant health, improving host resistance, and influencing global biogeochemical cycle. However, the studies on the community structure of phyllosphere fungi in natural forests are scarce as compared to that on rhizosphere microbes. Consequently, we know litter about how phyllosphere fungi associates with leaf traits. In this study, we analyzed fungal community composition of canopy leaves of six dominant tree species (i.e., Pinus koraiensis, Tilia amurensis, Quercus mongolica, Acer mono, Fraxinus mandshurica, and Ulmus japonica), in a broad-leaved Korean pine forest of Changbai Mountain Nature Reserve in Jilin Province, using high-throughput sequencing. We compared the differences of phyllosphere fungal community structure and functional groups of different dominant tree species. Moreover, 14 key leaf functional traits of their host trees were measured to investigate the relationships between fungal community composition and leaf functional traits. We found that the dominant phyla and class of phyllosphere fungi were Ascomycota and Basidiomycota, and Dothideomycetes and Taphrinomycetes, respectively. Results of LEfSe analysis indicated that all the tree species except Ulmus japonica had significant biomarkers, such as the Eurotiomycetes of Pinus koraiensis and the Ascomycetes of Quercus mongolica. The main functional groups of phyllosphere fungi were pathotroph. The results of redundancy and envfit analysis showed that functional traits related to plant nutrient acquisition as well as resistance to diseases and pests were the main factors influencing the community structure of phyllosphere fungi.


Subject(s)
Pinus , Quercus , China , Ecosystem , Forests , Fungi , Republic of Korea , Trees
18.
Front Oncol ; 12: 918088, 2022.
Article in English | MEDLINE | ID: mdl-35965512

ABSTRACT

Background: High serum uric acid (SUA) levels increase the risk of overall cancer morbidity and mortality, particularly for digestive malignancies. Nevertheless, the correlation between SUA level and clinical outcomes of the postoperative patients with colorectal cancer (CRC) treated by chemotherapy is unclear. This study aimed at exploring the relationship between baseline SUA level and progression-free survival (PFS), disease control rate (DCR), and safety in postoperative CRC patients receiving chemotherapy. Patients and Methods: We conducted a retrospective study to evaluate the relationship between baseline SUA level and PFS, DCR, and incidence of serious adverse events of 736 postoperative CRC patients treated with FOLFOX, FOLFIRI or XELOX at our center. Results: Data from our center suggested that high baseline SUA level is linked to poor PFS in non-metastatic CRC patients using FOLFOX (HR=2.59, 95%CI: 1.29-11.31, p=0.018) and in male patients using FOLFIRI (HR=3.77, 95%CI: 1.57-39.49, p=0.012). In patients treated by FOLFIRI, a high SUA is also linked to a low DCR (p=0.035). In patients using FOLFOX, high baseline SUA level is also linked to a high incidence of neutropenia (p=0.0037). For patients using XELOX, there is no significant correlation between SUA level and PFS, effectiveness, or safety. Conclusions: These findings imply that a high SUA level is a promising biomarker associated with poor PFS, DCR and safety of postoperative CRC patients when treated with FOLFOX or FOLFIRI.

19.
J Hazard Mater ; 438: 129507, 2022 09 15.
Article in English | MEDLINE | ID: mdl-35999736

ABSTRACT

Biodegradable mulch film (BDM) is considered as an environmentally sustainable alternative to low density polyethylene (LDPE) mulch film. However, the low degradation rate of BDM resulted in residues in soil after service period which were similar to LDPE mulch film. Distinguishing the differential responses of crop growth, soil bacteria and metabolism to residues of BDM and LDPE mulch films is favourable for comparing the environmental toxicities of the two materials. The results indicated that emergence rate and yield of Chinese cabbage (Brassica campestris L. ssp. chinensis Makino) were significantly inhibited by two types mulch residues. BDM residues significantly decreased bacterial diversity by 1.2-2.3% through the enrichment of dominant phyla and inhibition of inferior phyla, while LDPE mulch residues not. The effects of BDM residues on soil metabolite spectrum were stronger than LDPE mulch residues with significant increase (3.9% 5.8%) in the abundance of total metabolites. Besides the pathways of metabolism, organismal systems, environmental information processing influenced by LDPE mulch resides, differential pathways including human diseases and cellular processes were also determined in soil with BDM residues. According to all the results of the present study, prior to the promotion of BDM, its influences on soil safety must be carefully investigated through critical and systematic research.


Subject(s)
Polyethylene , Soil , Agriculture/methods , Bacteria , Humans , Plastics , Soil/chemistry , Soil Microbiology
20.
Photodiagnosis Photodyn Ther ; 39: 102964, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35705143

ABSTRACT

BACKGROUND AND AIMS: This study was designed to explore the effects of Yes-associated protein (YAP) knockdown on human osteosarcoma (HOS) cell sensitivity to Pyropheophorbide-α methyl ester-mediated photodynamic therapy (MPPa-PDT), and to assess how YAP silencing in combination with treatment with the ferroptosis inducer Erastin improves HOS cell sensitivity to MPPa-PDT in an effort to better clarify the molecular mechanisms underlying these phenotypes. METHODS: At 12 h post-MPPa-PDT, Hoechst staining and flow cytometry were conducted to evaluate the apoptotic death of HOS cells. The expression of YAP in these cells at 12 h post-MPPa-PDT treatment was assessed via Western blotting and immunofluorescent staining. BODIPY581/591-C11 was used to evaluate lipid peroxidation. Following shYAP lentiviral transduction, Western blotting was conducted to assess the expression of proteins associated with proliferation, apoptosis, and ferroptosis. EdU assays and clonogenic assays were performed to analyze cellular proliferation. Erastin-treated HOS cells were used to establish a ferroptosis model. Western blotting was used to measure ferroptosis-associated protein levels following shYAP and erastin treatment, while changes in proliferation and MDA levels in each group were examined using an MDA kit. RESULTS: At 12 h post-MPPa-PDT, HOS cells exhibited apoptotic characteristics including nuclear fragmentation and pyknosis, with concomitant increases in apoptosis-associated proteins as detected via Western blotting and apoptotic induction as measured via flow cytometry. Phosphorylated YAP levels fell and non-phosphorylated YAP levels rose following such treatment. Transfection with shYAP was successful as a means of generating stable HOS cell lines, and Western blotting analyses of these cells revealed reductions in proteins associated with cellular proliferation together with the upregulation of apoptosis-related proteins.  MDA assays indicated that erastin combined with YAP knockdown enhanced the sensitivity of HOS cells to MPPa-PDT treatment. CONCLUSIONS: These data indicate that ferroptosis and YAP knockdown can enhance osteosarcoma cell sensitivity to MPPa-PDT therapy.


Subject(s)
Bone Neoplasms , Ferroptosis , Osteosarcoma , Photochemotherapy , Porphyrins , Apoptosis , Bone Neoplasms/drug therapy , Cell Line, Tumor , Esters , Humans , Osteosarcoma/drug therapy , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Porphyrins/pharmacology
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