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1.
Article En | MEDLINE | ID: mdl-38763304

OBJECTIVE: Accurately predicting response during neoadjuvant chemoimmunotherapy for resectable non-small cell lung cancer (NSCLC) remains clinically challenging. In this study, we investigate the effectiveness of blood-based tumor mutational burden (bTMB) and a deep learning (DL) model in predicting major pathologic response (MPR) and survival from a phase II trial. METHODS: Blood samples were prospectively collected from 45 stage IIIA (N2) NSCLC patients undergoing neoadjuvant chemoimmunotherapy. An integrated model, combining the CT-based DL score, bTMB, and clinical factors, was developed to predict tumor response to neoadjuvant chemoimmunotherapy. RESULTS: At baseline, bTMB were detected in 77.8% (35 of 45) of patients. Baseline bTMB ≥11 Muts/Mb was associated with significantly higher MPR rates (77.8% vs. 38.5%, p = 0.042), and longer disease-free survival (DFS, p = 0.043), but not overall survival (p = 0.131), compared to bTMB < 11 Muts/Mb in 35 patients with bTMB available. The developed DL model achieved an area under the curve (AUC) of 0.703 in all patients. Importantly, the predictive performance of the integrated model improved to an AUC of 0.820 when combining the DL score with bTMB and clinical factors. Baseline circulating tumor DNA (ctDNA) status was not associated with pathological response and survival. Compared to ctDNA residual, ctDNA clearance before surgery was associated with significantly higher MPR rates (88.2% vs. 11.1%, p < 0.001) and improved DFS (p = 0.010). CONCLUSIONS: The integrated model shows promise as a predictor of tumor response to neoadjuvant chemoimmunotherapy. Serial ctDNA dynamics provide a reliable tool for monitoring tumor response.

2.
World J Surg Oncol ; 22(1): 109, 2024 Apr 25.
Article En | MEDLINE | ID: mdl-38664816

OBJECTIVES: Invasive mucinous adenocarcinoma (IMA) has a rare incidence with better prognosis than nonmucinous adenocarcinoma. We aimed to investigate the prognosis between limited resection and lobectomy for patients with clinical stage IA IMA ≤ 2 cm. METHODS: Data were taken from two cohorts: In Shanghai Pulmonary Hospital (SPH) corhort, we identified 403 patients with clinical stage IA IMA who underwent surgery. In the SEER corhort, 480 patients with stage T1 IMA who after surgery were included. Recurrence-free survival (RFS) for SPH corhort, lung cancer-specific survival (LCSS) for the SEER corhort and overall survival (OS) for both corhort were compared between patients undergoing lobectomy and limited resection by Log-rank and Cox proportional hazard regression model. RESULTS: In SPH corhort, patients who underwent limited resection had equivalent prognosis than those underwent lobectomy (5-year RFS: 79.3% versus. 82.6%, p = 0.116; 5-year OS: 86.2% versus. 88.3%, p = 0.235). However, patients with IMA > 2 to 3 cm had worse prognosis than those with IMA ≤ 2 cm (5-year RFS: 73.7% versus. 86.1%, p = 0.007). In the analysis of IMA > 2 to 3 cm subgroup, multivariate analysis showed that limited resection was an independent risk factor of RFS (hazard ratio, 2.417; 95% confidence interval, 1.157-5.049; p = 0.019), while OS (p = 0.122) was not significantly different between two groups. For IMA ≤ 2 cm, limited resection was not a risk factor of RFS (p = 0. 953) and OS (p = 0.552). In the SEER corhort, IMA ≤ 2 cm subgroup, limited resection was equivalent prognosis in LCSS (p = 0.703) and OS (p = 0.830). CONCLUSIONS: Limited resection could be a potential surgical option which comparable to lobectomy in patients with clinical stage IA IMA ≤ 2 cm.


Adenocarcinoma, Mucinous , Lung Neoplasms , Pneumonectomy , Humans , Adenocarcinoma, Mucinous/surgery , Adenocarcinoma, Mucinous/pathology , Adenocarcinoma, Mucinous/mortality , Male , Female , Pneumonectomy/methods , Pneumonectomy/mortality , Lung Neoplasms/surgery , Lung Neoplasms/pathology , Lung Neoplasms/mortality , Middle Aged , Prognosis , Survival Rate , Aged , Follow-Up Studies , Neoplasm Invasiveness , Neoplasm Staging , Retrospective Studies , SEER Program , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Neoplasm Recurrence, Local/epidemiology
3.
Cells ; 13(6)2024 Mar 21.
Article En | MEDLINE | ID: mdl-38534399

CD19-specific CAR-T immunotherapy has been extensively studied for the treatment of B-cell lymphoma. Recently, cholesterol metabolism has emerged as a modulator of T lymphocyte function and can be exploited in immunotherapy to increase the efficacy of CAR-based systems. Acetyl-CoA acetyltransferase 1 (ACAT1) is the major cholesterol esterification enzyme. ACAT1 inhibitors previously shown to modulate cardiovascular diseases are now being implicated in immunotherapy. In the present study, we achieved knockdown of ACAT1 in T cells via RNA interference technology by inserting ACAT1-shRNA into anti-CD19-CAR-T cells. Knockdown of ACAT1 led to an increased cytotoxic capacity of the anti-CD19-CAR-T cells. In addition, more CD69, IFN-γ, and GzmB were expressed in the anti-CD19-CAR-T cells. Cell proliferation was also enhanced in both antigen-independent and antigen-dependent manners. Degranulation was also improved as evidenced by an increased level of CD107a. Moreover, the knockdown of ACAT1 led to better anti-tumor efficacy of anti-CD19 CAR-T cells in the B-cell lymphoma mice model. Our study demonstrates novel CAR-T cells containing ACAT1 shRNA with improved efficacy compared to conventional anti-CD19-CAR-T cells in vitro and in vivo.


Lymphoma, B-Cell , Receptors, Antigen, T-Cell , T-Lymphocytes , Animals , Mice , Acetyltransferases , Immunotherapy, Adoptive , Lymphoma, B-Cell/pathology , Antibodies , Cell Proliferation , RNA, Small Interfering
4.
J Thorac Dis ; 16(1): 604-614, 2024 Jan 30.
Article En | MEDLINE | ID: mdl-38410570

Background: Pulmonary adenocarcinoma with neuroendocrine differentiation (ADE_ned) is a relatively uncommon pathological classification, and there exists considerable debate regarding its prognosis and treatment. The purpose of this study was to analyze the survival difference between patients with neuroendocrine carcinoma (NEC), adenocarcinoma (ADE), or ADE_ned and to investigate the prognostic factors influencing the outcomes of individuals diagnosed with pulmonary ADE_ned. Methods: We retrieved information on 316 cases of ADE_ned, 188,823 cases of ADE, and 71,154 cases of NEC diagnosed between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. To account for potential confounding variables, propensity score matching (PSM) was employed. Comparative analyses were conducted to estimate the overall survival (OS) and cancer-specific survival (CSS). Finally, the Cox regression models were used to identify prognostic factors associated with pulmonary ADE_ned. Results: Prior to PSM, patients with lung ADE_ned had a worse OS rate than did those with lung ADE or NEC (5-year OS rate: 13.3% vs. 26.6% vs. 15.6%; P<0.001 and P=0.009, respectively). In terms of CSS, the 5-year CSS rate of patients with ADE_ned was superior to that of NEC but inferior to that of ADE (28.7% vs. 26.8% vs. 43.8%; P=0.006 and P<0.001, respectively). Following PSM, the 5-year survival rate of patients with ADE_ned remained lower than that of individuals with ADE or NEC in terms of OS (13.3% vs. 24.4% vs. 23.0%; P<0.001 and P<0001, respectively) and CSS (28.8% vs. 58.6% vs. 43.1%; P<0.001 and P=0.006, respectively). Finally, the results of the competitive risk regression analysis demonstrated that several variables, including sex, T stage, N stage, M stage, and surgery, were found to be independent prognostic factors for patients diagnosed with pulmonary ADE_ned (all P values <0.05). Conclusions: Patients with lung ADE_ned had a significantly poorer survival outcome compared to those with lung ADE or NEC. Furthermore, sex, tumor-node-metastasis (TNM) stage, and surgery were found to be independent prognostic indicators for cases with lung ADE_ned.

5.
Plant Physiol Biochem ; 206: 108216, 2024 Jan.
Article En | MEDLINE | ID: mdl-38016370

Trace metals have relatively high density and high toxicity at low concentrations. Willow (Salix genus) is an excellent phytoremediation species for soil contaminated by trace metal ions. This study identified a cell number regulator (CNR) gene family member in Salix linearistipularis exhibiting strong metal ion resistance: SlCNR8. SlCNR8 expression was affected by various metal ions, including cadmium (Cd), zinc (Zn), copper (Cu), iron (Fe), and manganese (Mn). SlCNR8 overexpression enhanced Cd, Zn, Cu, and Fe resistance in transgenic poplar seedlings (84K) compared with the wild-type (WT). Moreover, transgenic poplar seedlings showed lower root Cd uptake and less Cd accumulation than WT under Cd stress. SlCNR8 was primarily localized to the nucleus and the plasma membrane-like cell periphery. Furthermore, SlCNR8 had transcriptional activation activity in yeast. The transcript levels of multiple metal ion transporters were altered in the roots of transgenic poplar seedlings compared to WT roots under Cd stress. These results suggest that SlCNR8 may enhance Cd resistance in transgenic poplar by reducing Cd uptake and accumulation. This may be related to altered transcription levels of other transporters or to itself. Our study suggests that SlCNR8 can be used as a candidate gene for genetic improvement of phytostabilisation of trace metals by genetic engineering.


Salix , Soil Pollutants , Cadmium/metabolism , Salix/genetics , Salix/metabolism , Zinc/metabolism , Biodegradation, Environmental , Seedlings/metabolism , Cell Count , Ions/metabolism , Soil Pollutants/metabolism , Plant Roots/metabolism
6.
Updates Surg ; 2023 Dec 07.
Article En | MEDLINE | ID: mdl-38060172

BACKGROUND: The advent of robot-assisted thoracoscopic surgery (RATS) has completely revolutionized the modality of thymectomy, which could reportedly achieve equivalent efficacy compared with a minimally invasive approach. This study was conducted to further compare the perioperative outcomes between these two modalities. METHODS: A retrospective single-center study that included patients receiving either a robotic or video-assisted thoracoscopic (VAT) thymectomy between February 2021 and January 2023 was conducted. All the patients were pathologically confirmed with thymic epithelial tumors. Clinical and pathological characteristics and perioperative outcomes were collected and compared between these two cohorts. RESULTS: A total of 190 patients were included in this study, with 61 (32.1%) and 129 (67.9%) receiving robotic and video-assisted thymectomy, respectively. The clinicopathological characteristics were not significantly different between these 2 groups. The size of the resected specimens in the RATS cohort was larger than the VATS cohort [median (IQR), 13.0 (8.0-16.0) vs. 9.0 (6.7-12.0) cm, p < 0.001], while the procedural duration was longer for the RATS group than its counterpart [median (IQR), 105 (85-143) vs. 85 (69-115) min, p = 0.001]. Moreover, no other significant difference was observed between these two groups. Since more than half of the robotic thymectomy was performed using a subxiphoid approach, a subgroup analysis was further conducted. Similarly, the robotic group through a subxiphoid approach harbored a longer procedural duration, and the size of the specimens obtained was larger than the VATS group [median (IQR), 14.0 (11.0-16.5) vs. 12.5 (8.5-15.0) cm, p = 0.061]. CONCLUSIONS: The early clinical efficacy of robotic thymectomy was proven comparable to the established VATS approach, and such a modality might have strength when obtaining larger specimens, which could contribute to improving long-term efficacy. Despite the longer procedural duration recorded in the early stage of conducting robotic thymectomy, further accumulation would help decrease the time.

7.
Int J Surg ; 109(12): 4126-4134, 2023 Dec 01.
Article En | MEDLINE | ID: mdl-37755369

BACKGROUND: The eighth edition of nodal classification is defined only by the anatomical location of metastatic lymph nodes and has limited prognostic discrimination power. The authors aimed to evaluate the prognostic significance and discriminatory capability of the number of metastatic lymph nodes (nN) in resected nonsmall cell lung cancer. MATERIALS AND METHODS: Patients with stage IA to IIIB resected nonsmall cell lung cancer between 1 January 2009 and 31 December 2013 were analyzed as a Chinese cohort. The optimal thresholds for the nN classification were determined by the X-tile. The receiver operating characteristic curve, net reclassification improvement and standardized net benefit calculated by decision curve analysis was estimated to quantify the nN classification's performance in prognostic stratification. External validation in the surveillance, epidemiology, and end results database was performed to test the robustness of the nN classification. RESULTS: Both cohorts showed a stepwise prognosis deterioration with increasing nN. One to three, four to six, and more than six were selected as optimal thresholds of nN classification in the Chinese cohort, which included 4432 patients, then validated in the SEER cohort ( n =28 022 patients). Multivariate Cox analysis showed the nN classification was an independent predictive factor for overall survival in both cohorts (Chinese cohort and SEER cohort: N 0 vs. N 1-3 , P <0.001; N 0 vs. N 3-6 , P <0.001; N 0 vs. N >6 , P <0.001). And prognostic discriminatory capability was improved in the nN classification compared with location-based N classification [5-year NRI score, 0.106 (95% CI: 0.049-0.132) and 5-year time-independent AUC, 0.593 (95% CI: 0.560-0.625) vs. 0.554 (95% CI: 0.520-0.588), P <0.001]. CONCLUSIONS: The nN classification tended to be a superior prognostic indicator than the location-based N classification. The number of metastatic lymph nodes should be considered in the future revision of the TNM system.


Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Lung Neoplasms/surgery , Retrospective Studies , Neoplasm Staging , Lymphatic Metastasis/pathology , Prognosis , Lymph Nodes/surgery , Lymph Nodes/pathology
9.
Int J Mol Sci ; 24(14)2023 Jul 13.
Article En | MEDLINE | ID: mdl-37511172

FKBP10, a member of the FK506-binding protein (FKBP) family, has been implicated in cancer development, although its prognostic function remains controversial. In this study, we analyzed the expression of FKBP10 in tumor tissues using online databases (TCGA) as well as our CRC cohort, and investigated the relationship between its subcellular expression pattern and patient outcomes. Cox regression analysis was used to determine the associations between different subcellular expression patterns of FKBP10 and clinical features of patients. We also discussed the expression level of FKBP10 based on different subcellular expression patterns. Our results showed that FKBP10 was significantly elevated in CRC tissues and exhibited three different subcellular expression patterns which were defined as 'FKBP10-C' (concentrated), 'FKBP10-T' (transitional) and 'FKBP10-D' (dispersive). The FKBP10-D expression pattern was only found in tumor tissues and was associated with unfavorable disease-free survival in CRC patients. High expression levels of FKBP10-C predicted an unfavorable prognosis of recurrence of CRC, while FKBP10-D did not. Our findings suggest that the subcellular expression patterns and expression level of FKBP10 play crucial prognostic roles in CRC, which revealed that FKBP10 may be a viable prognostic and therapeutic target for the diagnosis and treatment of CRC.


Colorectal Neoplasms , Peptidylprolyl Isomerase , Tacrolimus Binding Proteins , Humans , Clinical Relevance , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Peptidylprolyl Isomerase/metabolism , Tacrolimus Binding Proteins/genetics , Tacrolimus Binding Proteins/metabolism
10.
J Cancer Res Clin Oncol ; 149(14): 13311-13321, 2023 Nov.
Article En | MEDLINE | ID: mdl-37488397

INTRODUCTION: The benefits of adjuvant chemoradiation therapy (CRT) for heterogeneous pathological N2 (pN2) diseases remain unclear in non-small cell lung cancer (NSCLC). This study aimed to investigate suitable pN2 patients for adjuvant CRT. MATERIAL AND METHODS: This study retrospectively reviewed the data of patients with pN2 NSCLC in Shanghai Pulmonary Hospital from January 2012 to December 2016. Included cases were subdivided as highest mediastinal lymph node (HM) (n = 732) metastasis and non-HM metastasis (n = 677) groups according to the International Association for the Study of Lung Cancer (IASLC). Furthermore, the Kaplan-Meier and Cox models were used to evaluate the prognostic benefits of adjuvant CRT in heterogeneous pN2 subgroups. RESULTS: A total of 1409 patients were enrolled in this study, with a median follow-up time of 63.8 months. Patients with HM involvement had worse prognoses (p < 0.001 for recurrence-free survival (RFS) and overall survival (OS)). Furthermore, the survival improvement of adjuvant CRT was significant for these patients (p < 0.001 for RFS and p = 0.032 for OS), regardless of whether it was single (p < 0.001 for RFS and p = 0.029 for OS) or multiple pN2 (p < 0.001 for RFS and p = 0.026 for OS) diseases. According to multivariable cox analysis, the long-term RFS and OS in the cancerous HM group were independently predicted by pathological N stage (p = 0.002 for RFS and p < 0.001 for OS) and adjuvant CRT (p < 0.001 for RFS and p = 0.011 for OS). CONCLUSION: Metastatic HM was associated with a worse prognosis in pN2 disease. Our analysis supported that adjuvant CRT significantly improved both RFS and OS for these patients.

11.
Sci Rep ; 13(1): 11512, 2023 07 17.
Article En | MEDLINE | ID: mdl-37460544

This study aimed to develop a robust predictive model for tetracycline (TC) adsorption onto biochar (BC) by employing machine learning techniques to investigate the underlying driving factors. Four machine learning algorithms, namely Random Forest (RF), Gradient Boosting Decision Tree (GBDT), eXtreme Gradient Boosting (XGBoost) and Artificial Neural Networks (ANN), were used to model the adsorption of TC on BC using the data from 295 adsorption experiments. The analysis revealed that the RF model had the highest predictive accuracy (R2 = 0.9625) compared to ANN (R2 = 0.9410), GBDT (R2 = 0.9152), and XGBoost (R2 = 0.9592) models. This study revealed that BC with a specific surface area (S (BET)) exceeding 380 cm3·g-1 and particle sizes ranging between 2.5 and 14.0 nm displayed the greatest efficiency in TC adsorption. The TC-to-BC ratio was identified as the most influential factor affecting adsorption efficiency, with a weight of 0.595. The concentration gradient between the adsorbate and adsorbent was demonstrated to be the principal driving force behind TC adsorption by BC. A predictive model was successfully developed to estimate the sorption performance of various types of BC for TC based on their properties, thereby facilitating the selection of appropriate BC for TC wastewater treatment.


Water Pollutants, Chemical , Adsorption , Kinetics , Tetracycline , Anti-Bacterial Agents , Charcoal , Machine Learning
12.
J Food Biochem ; 46(12): e14508, 2022 12.
Article En | MEDLINE | ID: mdl-36332190

Partially hydrolyzed guar gum (PHGG), a water-soluble dietary fiber, has shown beneficial physiological effects in various disease models and is used as a prebiotic to regulate intestinal function. However, its role in healthy states remains unclear. The purpose of this study was to investigate the effects of PHGG on gut flora composition and predict metabolic function in healthy mice. Our study showed that PHGG supplementation had significant duration-dependent effects on the composition and function of the intestinal flora of healthy mice. In specific, although the long-term supplementation of PHGG may increase the abundance of some beneficial bacterial species and promote beneficial phenotypes, it may also cause increased body weight and decreased abundance and diversity of gut microorganisms. Therefore, the long-term use of PHGG as a nutritional product still requires further investigation. PRACTICAL APPLICATIONS: As the importance of the gut microbiota has become more widely recognized, interventions that modulate the microbiome and its interaction with the host have gained much attention. While the capability of some prebiotics has largely been shown to have many beneficial effects, the evidence leaves much desirable, and microbiota regulation is explored differently in healthy or diseased states. Currently, the scientific community and regulatory authorities are beginning to pay attention to these unregulated and over-the-counter products claiming to possess probiotic and prebiotic properties. Studies exploring the rationality of these prebiotics as nutraceuticals for use in health states are essential. This study focuses on the effects of PHGG, a prebiotic, on intestinal flora, metabolism, and function when used in a healthy state over a long period. It is helpful to have a clearer understanding of the effect of PHGG on intestinal flora and the possible mechanisms of action to exert effects, which are indicative for the future application of PHGG as a nutraceutical or therapeutic agent..


Gastrointestinal Microbiome , Mice , Animals , Prebiotics , Galactans , Defecation
13.
Med Oncol ; 40(1): 9, 2022 Nov 09.
Article En | MEDLINE | ID: mdl-36352160

BRD4, a member of the bromodomain and extraterminal (BET) family, is elevated in multiple cancer tissues, including gastric cancer (GC). Targeted therapy with BRD4 may help improve the overall survival of patients with GC. Meanwhile, the approved multi-target kinase inhibitor, dasatinib, was recently reported to show varied tumor-suppressive effects in GC cells. This study investigated BRD4 expression in vivo and in vitro using immunohistochemistry and western blotting, respectively. We discussed the relationship between BRD4 expression and patient prognosis. Next, the antitumor efficacy of dasatinib was measured in BRD4-knockdown GC cells to determine the role of BRD4 blockage in dasatinib treatment. Finally, molibresib, a BET inhibitor, was used to measure the cooperative function of BRD4 inhibition and dasatinib treatment in three GC cell lines. Epithelial BRD4 expression was higher in tumoral and metastatic tissues and was strongly associated with unfavorable tumor, node, and metastasis stages and survival. BRD4 expression was heterogeneous in the three GC cell lines tested in vitro. In SGC7901, a BRD4-high GC cell line, knockdown of BRD4 using specific siRNAs suppressed cell growth individually and cooperatively with dasatinib. Moreover, molibresib and dasatinib showed a cooperative effect in suppressing the proliferation of BRD4-high GC cells. In conclusion, we confirmed that increased epithelial BRD4 expression is associated with poor disease stage and prognosis in GC and BRD4 blockage might be a valuable strategy to improve the sensitivity of dasatinib and other drugs in the chemotherapy of advanced GC.


Stomach Neoplasms , Humans , Stomach Neoplasms/genetics , Nuclear Proteins/genetics , Dasatinib/pharmacology , Cell Cycle Proteins/metabolism , Transcription Factors/genetics , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic
14.
Ecotoxicol Environ Saf ; 245: 114116, 2022 Oct 15.
Article En | MEDLINE | ID: mdl-36174317

Phytoextraction in phytoremediation is one of the environmentally friendly methods used for restoring soils contaminated by heavy metals (HMs). The screening and identification of HM-resistant plants and their regulatory genes associated with HM ion transport are the key research aims in this field. In this study, a plant cadmium (Cd) resistance (PCR) gene family member, SlPCR6, was identified in roots of Salix linearistipularis, which exhibits strong HM resistance. The results revealed that SlPCR6 expression was induced in S. linearistipularis roots in response to Cd stress. Furthermore, SlPCR6 was mainly localized on the plasma membrane. Compared with the wild type, SlPCR6 overexpression reduced the Cd and copper (Cu) contents in the transgenic poplar (84 K) and increased its Cd and Cu resistance. The roots of transgenic poplar seedlings had lower net Cd and Cu uptake rates than wild type roots. Further investigation revealed that the transcript levels of multiple HM ion transporters were not significantly different between the roots of the wild type and those of the transgenic poplar. These results suggest that SlPCR6 is directly involved in Cd and Cu transport in S. linearistipularis roots. Therefore, SlPCR6 can serve as a candidate gene to improve the phytoextraction of the HMs Cd and Cu through genetic engineering.


Metals, Heavy , Populus , Salix , Soil Pollutants , Biodegradation, Environmental , Cadmium/metabolism , Copper/analysis , Metals, Heavy/analysis , Plant Roots/metabolism , Populus/genetics , Populus/metabolism , Salix/genetics , Salix/metabolism , Soil , Soil Pollutants/analysis
15.
Front Pharmacol ; 13: 929087, 2022.
Article En | MEDLINE | ID: mdl-36120370

This study aimed to explore novel targets for celastrol sensitization in colorectal cancer (CRC) based on differentially regulated signals in response to high- or low-dose celastrol. Targeting signals were investigated using Western blotting or phosphorylated receptor tyrosine kinase (RTK) arrays. Corresponding inhibitors for the signals were individually combined with low-dose celastrol for the assessment of combined anti-CRC effects, based on proliferation, apoptosis, colony assays, and xenograft models. The potential mechanism for the combination of celastrol and SHP2 inhibition was further examined. Low-dose celastrol (<1 µM) did not effectively suppress AKT and ERK signals in CRC cells compared to high-dose celastrol (>1 µM). However, when combined with an AKT or ERK inhibitor, low-dose celastrol could cooperatively suppress CRC proliferation. Furthermore, failed AKT or ERK inhibition by low-dose celastrol may be due to reactivated RTK-SHP2 signaling with negative feedback. The combination of celastrol and the SHP2 inhibitor resulted in greatly reduced AKT and ERK signals, as well as greater inhibition of CRC growth than celastrol alone. Moreover, the mechanism underlying combination suppression was also involved in the activation of immune cell infiltration (mainly for CD8+ cells) in CRC tissues. Failure to inhibit RTK-SHP2-AKT/ERK signaling contributed to the lack of CRC growth suppression by low-dose celastrol. However, the combination of celastrol and the SHP2 inhibitor resulted in synergistic inhibition of CRC growth and provided a promising therapeutic target.

16.
Comput Math Methods Med ; 2022: 8490473, 2022.
Article En | MEDLINE | ID: mdl-36017152

In this study, 897 surgical instruments used for comprehensive management of hand supply from January to December 2019 were selected as the control group. Similarly, 1086 surgical instruments administered with 6Sigma from January to December 2020 were selected as the observation group. By observing and comparing the differences between the two groups of patients in the operating room equipment cleaning pass rate and general indicators, other related pass rate, operating room equipment defects, and doctors' satisfaction with equipment, to explore the application value and influence of comprehensive nursing in operating room and disinfection supply center combined with 6Sigma management in operating room equipment management. The results show that the application of hand-supply integration combined with 6Sigma management has a good effect on operating room equipment management, which significantly improves the qualified rate of operating room equipment cleaning and the satisfaction of doctors to the equipment, and reduces the defects of operating room equipment, which has a certain reference value for operating room equipment management.


Disinfection , Operating Rooms , Disinfection/methods , Humans , Surgical Instruments
17.
Front Pharmacol ; 13: 919553, 2022.
Article En | MEDLINE | ID: mdl-35873560

The therapeutic effects of electroacupuncture (EA) on the comorbidity of visceral pain and anxiety in patients with inflammatory bowel disease (IBD) is well known. It has been known that the ventral hippocampus (vHPC) and the cannabinoid type 1 receptors (CB1R) are involved in regulating anxiety and pain. Therefore, in this study, we determined whether EA reduces visceral pain and IBD-induced anxiety via CB1R in the vHPC. We found that EA alleviated visceral hyperalgesia and anxiety in TNBS-treated IBD mice. EA reversed over-expression of CB1R in IBD mice and decreased the percentage of CB1R-expressed GABAergic neurons in the vHPC. Ablating CB1R of GABAergic neurons in the vHPC alleviated anxiety in TNBS-treated mice and mimicked the anxiolytic effect of EA. While ablating CB1R in glutamatergic neurons in the vHPC induced severe anxiety in wild type mice and inhibited the anxiolytic effect of EA. However, ablating CB1R in either GABAergic or glutamatergic neurons in the vHPC did not alter visceral pain. In conclusion, we found CB1R in both GABAergic neurons and glutamatergic neurons are involved in the inhibitory effect of EA on anxiety but not visceral pain in IBD mice. EA may exert anxiolytic effect via downregulating CB1R in GABAergic neurons and activating CB1R in glutamatergic neurons in the vHPC, thus reducing the release of glutamate and inhibiting the anxiety circuit related to vHPC. Thus, our study provides new information about the cellular and molecular mechanisms of the therapeutic effect of EA on anxiety induced by IBD.

18.
Comput Math Methods Med ; 2022: 8610517, 2022.
Article En | MEDLINE | ID: mdl-35633927

Background: Occupational exposure seriously threatens the physical and mental health of professionals and has become an important public health problem. In clinical medical and nursing work, medical staff, especially nursing staff, are faced with the status quo of occupational exposure with high risk, serious harm, and severe situation. Therefore, a sound management system must be established to control the occupational exposure of nurses. Aims: According to the PRECEDE management model, evaluate the operating room nurses' knowledge, belief, and behavior scores on the protection of surgical smoke, understand their awareness of surgical smoke and the current status of protection, improve the mastery rate and protection compliance of surgical smoke-related knowledge in the operating room, reduce the harm of surgical smoke to the human body, and provide a basis for smoke protection.Materials and methods. 125 doctors working in the operating room of our hospital were selected as the control group of this study, and 112 nonsmoke-exposed nurses working in the operating room of our hospital were selected as the observation group. The nurses' knowledge-belief behavior scores and self-evaluation scores of smoke influence were counted before and after the intervention in the operating room. SPSS25.0 was used to process the data. Tests and repeated measures analysis of variance were used to compare the effects before and after intervention. Results: After one month of intervention, the knowledge scores of nurses in the operating room on the protection of surgical smoke increased significantly, and the difference was significant (P < 0.05); the scores of related concepts, physical properties, chemical properties, and authoritative protection standards increased significantly (P < 0.05). There was no significant increase in the scores of smoke hazards (P > 0.05); the attitude of smoke protection increased significantly, which was statistically significant (P < 0.05); and the behavior compliance of smoke protection was significantly increased, which was statistically significant (P < 0.05). After one month of intervention, the self-evaluation score of smoke effect of operating room nurses decreased significantly, and the difference was statistically significant (P < 0.05). The data was analyzed by repeated measure analysis of variance. The knowledge of surgical smoke (F = 65.570, P < 0.001), attitude (F = 78.307, P < 0.001), and behavior (F = 403.015, P < 0.001) scores gradually increased. The observation group's total cholesterol, low-density lipoprotein cholesterol, and the proportion of low-density lipoprotein cholesterol were higher than that of the control group, and the proportion of high-density lipoprotein cholesterol was lower than that of the control group. The difference was statistically significant P < 0.05. Conclusion: After the intervention of operating room nurses under the guidance of PRECEDE management mode, the theoretical knowledge of operating room nurses is effectively improved, the operations are standardized, the self-evaluation scores of smoke influence are reduced, and the safety level of operating room is improved. More importantly, the health of nursing staff is fully guaranteed.


Clinical Competence , Occupational Exposure , Cholesterol , Humans , Lipoproteins, LDL , Occupational Exposure/adverse effects , Occupational Exposure/prevention & control , Operating Rooms
19.
Histopathology ; 81(1): 119-127, 2022 Jul.
Article En | MEDLINE | ID: mdl-35486499

AIMS: The presence of micropapillary (MIP) in early-stage lung adenocarcinoma is associated with a poorer prognosis, especially in patients undergoing sublobectomy. However, data on the sensitivity of frozen section (FS) evaluation of MIP is still limited. We included the concept of a filigree pattern on FS to assess its effect on the diagnostic sensitivity and specificity of MIP, and to verify its prognostic value in stage T1 lung adenocarcinoma. METHODS: A panel of five pathologists evaluated 125 patients with T1 lung adenocarcinoma from January to February 2014 as a study cohort, and 151 patients from January to February 2020 as a validation cohort. The diagnostic accuracy of the filigree and classical micropapillary (cMIP) pattern on FS was investigated. RESULTS: The diagnostic sensitivity of the MIP pattern on FS increased from 43.2% to 65.3% and 56.8% to 81.1% in the study cohort and validation cohort, respectively, and both with good specificity. Filigree not only increased the sensitivity of identifying MIP when there was an absence of cMIP, but also increased the sensitivity when the presence of a minor amount of cMIP. The almost perfect agreement among five pathologists was reached on cMIP and substantial agreement was reached on the filigree in the two cohorts. Moreover, the cMIP and filigree were both correlated with poorer recurrence-free survival (pcMIP = 0.003; pfiligree = 0.032) and overall survival (pcMIP = 0.004; pfiligree = 0.005). CONCLUSIONS: The identification of a filigree may improve the diagnostic sensitivity of the MIP pattern on FS. FS was feasible for the detection of filigree and cMIP patterns in stage T1 lung adenocarcinomas.


Adenocarcinoma of Lung , Lung Neoplasms , Adenocarcinoma of Lung/pathology , Frozen Sections , Humans , Lung Neoplasms/pathology , Neoplasm Staging , Prognosis , Retrospective Studies
20.
Article En | MEDLINE | ID: mdl-35416960

OBJECTIVES: This study intends to appraise the feasibility of double sleeve lobectomy after neoadjuvant chemotherapy in central non-small-cell lung cancer with bronchovascular aggression. METHODS: This retrospective study included non-small-cell lung cancer patients who received double sleeve lobectomy from January 2014 to June 2020. Patients were divided into 2 groups: the neoadjuvant chemotherapy group and the non-neoadjuvant chemotherapy group. Demographic data and perioperative outcomes were compared between these 2 groups. RESULTS: Of the 110 patients who received double sleeve lobectomy during this period, 35 patients (31.8%) received neoadjuvant chemotherapy. Compared with the non-neoadjuvant chemotherapy group, patients who received neoadjuvant chemotherapy were associated with younger age (P = 0.026), smaller pathologic tumour size (P = 0.005), higher forced expiratory volume in 1 s (P = 0.007), higher forced expiratory volume in 1 s of predicted value (P = 0.005) and higher clinical stage (P < 0.001). In the neoadjuvant chemotherapy group, 18 patients (51.4%) attained a partial response and 17 patients (48.6%) achieved stable disease. The postoperative hospital stays (P = 0.042) and chest tube drainage duration (P = 0.030) were longer in the neoadjuvant chemotherapy group and other perioperative performances were similar between these 2 groups. No statistically significant difference was reported in postoperative complications and mortality between these 2 groups. CONCLUSIONS: The intraoperative performance and postoperative outcomes of double sleeve lobectomy following neoadjuvant chemotherapy were similar to direct surgery, indicating that double sleeve lobectomy after neoadjuvant chemotherapy is feasible and safe in central lung cancer involving both the pulmonary artery and bronchus.


Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/surgery , Feasibility Studies , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Pneumonectomy/adverse effects , Retrospective Studies
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