Clinical outcomes following direct anterior approach during total hip arthroplasty without hip extension: a retrospective comparative study.

BACKGROUND: Traditional total hip arthroplasty (THA) using the direct anterior approach (DAA) requires a hip extension. This study aimed to compare the clinical outcomes of patients undergoing THA with DAA using either the no hip extension (NHE) or the traditional hip extension (THE) strategy. METHODS: A retrospective analysis of demographics, clinical and radiological outcomes, and occurrence of complications was performed using data from 123 patients treated between January 2020 and November 2021. The patients were categorised into two groups: NHE (84 patients) and THE (39 patients). RESULTS: The NHE group exhibited shorter operative time and had more male participants with higher ages. Comparable outcomes were observed in the visual analogue scale, Harris Hip, and Oxford Hip scores at the final follow-up. Furthermore, complications were observed in the NHE and THE groups, including two and one greater trochanteric fractures and three and one transfusions, respectively. CONCLUSIONS: Compared to the THE, employing the NHE strategy during THA with DAA in elderly and young female patients resulted in comparable clinical outcomes with several advantages, such as favourable surgical time. The NHE method also exhibited good safety and effectiveness. Therefore, the NHE strategy may be a favourable option for elderly and young female patients.

Arthroscopic inferior leaf meniscectomy of the involved anterior horn in the lateral meniscus horizontal tear via an accessary extreme far anteromedial portal.

BACKGROUND: An accessory extreme far anteromedial portal can improve visualisation and ease inferior leaf meniscectomy in patients with lateral meniscal anterior horn horizontal tears. However, the therapeutic outcomes of adding an accessory extreme far anteromedial portal remain unclear. This study aimed to evaluate the clinical efficacy of adding an accessory extreme far anteromedial portal for treating lateral meniscal horizontal tears involving the anterior horns. METHODS: This retrospective study included 101 patients with anterior horn involvement in lateral meniscal horizontal tears who underwent arthroscopic unstable inferior leaf meniscectomy between January 2016 and December 2020. The pathologies were diagnosed using physical examinations and magnetic resonance imaging. The anterior horn involved in the lateral meniscal horizontal tears was treated using inferior leaf meniscectomy. The primary endpoints were changes in the visual analogue scale, Lysholm, International Knee Documentation Committee, and Tegner scores at the final follow-up. The secondary endpoint was meniscal cure rate at 3 months postoperatively. The preoperative and postoperative functional scores were compared. The occurrence of complications was recorded. RESULTS: All patients were followed up for an average of 4.9 ± 1.2 years (range 2.3-7.5 years). After 4 months, none of the patients experienced pain, weakness, instability, or tenderness in the lateral joint line, achieving an imaging cure rate of 98%. At the final follow-up, significant postoperative improvements were observed in the average values of the visual analogue scale score (3.5 ± 0.7 vs. 0.7 ± 0.6), Lysholm score (62.7 ± 4.4 vs. 91.8 ± 3.1), International Knee Documentation Committee score (61.9 ± 3.7 vs. 91.7 ± 9.5), and Tegner score (2.0 ± 0.7 vs. 6.1 ± 0.7). Excellent Lysholm scores were obtained in 81 patients, and good outcomes were obtained in 18 patients, with an excellent-to-good rate of 98.0%. CONCLUSIONS: Inferior leaf resection via the accessory far anteromedial portal is a safe treatment option for the involved anterior horn in lateral meniscal horizontal tears. This approach enhances visibility and facilitates surgical procedures, with minimal complications.

Which patients with coronary artery disease should include oral nitrates on their discharge medication list?

BACKGROUND: Which patients with coronary artery disease (CAD) should have oral nitrates on their discharge medication list after coronary angiography (CAG)? To assess the relationship between oral nitrates included in the discharge medication list and major adverse cardiovascular events (MACEs) among CAD patients, we designed this retrospective cohort study. METHODS: A total of 2979 CAD patients hospitalised in the Department of Cardiology, Affiliated Hospital of Jining Medical University from May 2013 to October 2015 were enrolled, grouped according to whether oral nitrates were included at discharge after CAG, and followed up for MACEs for a mean of 4.42 years after discharge. The primary endpoint was MACEs. Multivariate Cox proportional hazards models were used to analyses potential confounding factors. Stratified analysis was used to observe the relationship between oral nitrates and MACEs by different covariates. RESULTS: The median follow-up time was 4.61 years, and 296 (9.94%) patients experienced MACEs. Multivariate Cox proportional hazards model analysis showed no association between oral nitrates on the discharge medication list and the occurrence of MACEs among patients with CAD (p > 0.05) after adjusting for some covariates, such as SYNTAX score (hazard ratio (HR): 1.18, 95% confidence interval (CI): 0.90-1.55, p = 0.2420). Stratified analysis revealed a higher incidence of MACEs among hypertensive patients prescribed oral nitrates at discharge (HR: 1.67, 95% confidence CI: 1.13-2.46, p = 0.0046). However, prescribing nitrates at discharge for patients with low uric acid levels increased the incidence of MACEs, which showed a possible trend towards significance (HR: 1.44, 95% CI: 0.99-2.09, p = 0.0525). CONCLUSION: There was no association between oral nitrates included in the discharge medication list and the development of MACEs among patients with CAD after adjusting for some covariates, such as SYNTAX score. Oral nitrates after discharge for CAD patients combined with hypertension increased the occurrence of MACEs. Oral nitrates after discharge for CAD patients combined with low uric acid levels may increase theoccurrence of MACEs, and close monitoring for any adverse events is recommended.

Application of magnetic resonance imaging-proton density fat fraction in liver fat quantification / 临床肝胆病杂志

Hepatic steatosis can be observed in chronic liver diseases of different etiologies. The main predisposing factors for hepatic steatosis include chronic viral hepatitis， cholestatic liver disease， alcoholic liver disease， and nonalcoholic fatty liver disease. Simple fatty liver disease is the initial manifestation of hepatic steatosis， followed by steatohepatitis， liver fibrosis， liver cirrhosis， and even hepatocellular carcinoma. With the development of medical imaging technology， magnetic resonance imaging-proton density fat fraction （MRI-PDFF） has been widely used in the diagnosis of fatty liver disease （FLD） in clinical practice. MRI-PDFF is gradually becoming the gold standard for the noninvasive diagnosis of FLD due to its high accuracy and good repeatability. This article reviews the clinical application of MRI-PDFF in liver fat quantification and related research advances.

Relationship between cerebrovascular reserve capacity and white matter lesions in the elderly based on magnetic resonance imaging / 中国辐射卫生

Objective To investigate the relationship between cerebrovascular reserve (CVR) capacity and white matter lesions in elderly people. Methods We included 315 participants aged ≥ 60 years in Jinan area of Shandong Province from May 2018 to July 2019. They underwent transcranial Doppler ultrasonography for assessing CVR, breath holding index (BHI), and arterial pulsatility index (PI). According to CVR capacity, they were divided into normal CVR group (CVR ≥ 20%, n = 206) and impaired CVR group (CVR < 20%, n = 109). Magnetic resonance imaging was performed to evaluate periventricular, subcortical, and total white matter hyperintensity (WMH) volumes and Fazekas scores. Results Compared with the normal CVR group, the impaired CVR group showed significantly higher volumes of periventricular, subcortical, and total WMHs and significantly higher proportions of Fazekas scores ≥ 2 (P < 0.01). Periventricular, subcortical, and total WMH volumes were negatively correlated with CVR (r = −0.70, −0.66, −0.73, P < 0.01) and BHI (r = −0.64, −0.65, −0.68, P < 0.01) and positively correlated with PI (r = 0.60, 0.65, 0.65, P < 0.01). After adjusting for confounding factors, periventricular, subcortical, and total WMH volumes were still negatively correlated with CVR and BHI (P < 0.01) and positively correlated with PI (P < 0.01). The logistic regression analysis showed that the risks of periventricular, subcortical, and total Fazekas score ≥ 2 in the impaired CVR group were 1.96 times (95% confidence interval [CI]: 1.17−3.27, P < 0.01), 1.84 times (95% CI: 1.11−3.05, P < 0.05), and 2.33 times (95% CI: 1.30−4.18, P < 0.01) that of the normal CVR group, respectively. Conclusion Impaired CVR is an independent risk factor for white matter lesions in the elderly.

Boosting synergism of chemo- and immuno-therapies via switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis by bisphosphonate coordination lipid nanogranules

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

Improved surgical exposure and early clinical outcomes using a femoral-release-first technique in direct anterior approach during total hip arthroplasty.

BACKGROUND: Total hip arthroplasty (THA) performed using the direct anterior approach (DAA) has demonstrated favourable early-, mid-, and long-term outcomes. However, the traditional femoral release technique remains technically demanding and is associated with challenges and a heightened risk of complications. This study aimed to compare the clinical outcomes of patients who underwent THA with DAA performed using either the femoral-release-first (FRF) or the traditional approach (TA) strategy. METHODS: A retrospective analysis of demographics, clinical and radiological outcomes, and occurrence of complications was performed using data from 106 patients between 2018 and 2019. The patients were categorised into two groups: FRF (44 hips) and TA (69 hips). RESULTS: The FRF group showed a reduced operative time, haemoglobin (Hb) drop, postoperative hospital stay, and more optimal acetabular cup anteversion angles. Furthermore, during the first 2 months postoperatively, the FRF group demonstrated superior visual analogue scale, Harris Hip, and Oxford Hip scores. In the TA group, two hips experienced greater trochanter fractures, and one experienced delayed incision healing. CONCLUSIONS: Compared with the TA, employing the FRF strategy during THA with DAA resulted in improved outcomes within the first 2 months postoperatively and comparable functional recovery beyond this period. The FRF method exhibited advantages such as favourable acetabular exposure and alignment and a reduced risk of complications. Therefore, the FRF strategy may be a favourable option.

miR5298b regulated taxol biosynthesis by acting on TcNPR3, resulting in an alleviation of the strong inhibition of the TcNPR3-TcTGA6 complex in Taxus chinensis.

Taxol, a valuable but rare secondary metabolite of the genus Taxus, is an effective anticancer drug. Understanding the regulation of taxol biosynthesis may provide a means to increase taxol content. The microRNA miR5298b was found to promote the accumulation of taxol and upregulate several taxol biosynthesis genes, including DBAT, TASY, and T5H, as demonstrated by experiments using the overexpression and mimicry of transient leaves. Moreover, miR5298b cleaves the mRNA sequence of TcNPR3, a homolog of the salicylic acid receptor AtNPR3/4. Overexpression and knockdown by RNA interference of TcNPR3 confirmed that it repressed taxol biosynthesis. These results indicate that miR5298b enhances taxol biosynthesis via the cleavage of TcNPR3. Yeast two-hybrid bimolecular fluorescence complementation and pull-down assays revealed that TcTGA6, a TGA transcription factor, physically interacted with TcNPR3. Functional experiments showed that TcTGA6 negatively regulates taxol biosynthesis by directly combining with the TGACG motif in the promoters of TASY, T5H, and T10H. TcNPR3 enhances TcTGA6 inhibition Luciferase assays showed that miR5298b alleviated the repression of the TcNPR3-TcTGA6 complex. In summary, miR5298b can cleave TcNPR3, thereby alleviating the inhibition of the TcNPR3-TcTGA6 complex to upregulate taxol biosynthesis genes.

Hip effusion/synovitis influences results after multiple drilling core decompression for bone marrow edema syndrome of hip.

BACKGROUND: At present, it is not known whether hip effusion/synovitis affects the therapeutic effect of multiple drilling core decompression (MDCD) in patients with bone marrow edema syndrome of hip (BMESH). The aims were to assess hip effusion/synovitis and its relationship with results of MDCD in patients with BMESH. METHODS: The data of undergoing arthroscopic-assisted MDCD for treatment of BMESH with hip effusion/synovitis by one surgeon were retrospectively reviewed from the associated medical records at the Affiliated Hospital of Zunyi Medical University (2016-2019). Seven patients (9 hips) participated in this study. Patients were followed up at 1, 2, 3, 6, 12 and 24 months. Data included demographics and clinical outcomes. The pre- and postoperative pain and functional outcomes were measured with the visual analogue scale (VAS), Harris Hip Score (HHS), Hip Outcome Score Activities of Daily Living subscale (HOS-ADL), International Hip Outcome Tool-12 (iHOT-12) and range of motion (ROM). RESULTS: Seven patients (9 hips) were followed up. Disappearance of hip pain immediately obtained at rest after surgery. All of 7 patients returned to their former activity level at postoperative 3 months, bone marrow edema had disappeared on Magnetic Resonance Imaging (MRI). The VAS, HHS, HOS-ADL, iHOT-12, and ROM at postoperative 1 month had a significant difference (P < 0.05) compared with preoperative. It was also statistically significant (P < 0.05) when compared with other time points. At the final follow-up, all patients had no limited ROM, which was symmetrical with the contralateral of hip joint. Hip effusion/synovitis were observed in 9 hips. Labral tears, cartilage fissure, and loose bodies were observed in 1 hip, respectively. Kirschner wire tracks bleeding occurred in 1 hip. No other complications occurred. CONCLUSIONS: Hip effusion/synovitis could affect the clinical outcomes after MDCD in patients with BMESH. Arthroscopic procedure of hip effusion/synovitis can shorten postoperative pain relief time, disappearance time of bone marrow edema on MRI. It can simultaneously diagnose and treat other concomitant intraarticular pathologies, and be a safe operation with fewer complications.

Atrophic gastritis rather than Helicobacter pylori infection can be an independent risk factor of colorectal polyps: a retrospective study in China.

BACKGROUND: Colonoscopy is considered the most effective screening method for colorectal polyps. However, the longevity and complexity of the procedure makes it less desirable to screen for colorectal polyps in the general population. Therefore, it is essential to identify other independent risk factors. In this study, we explored the link between Hp infection, atrophic gastritis, and colorectal polyps to identify a new potential risk factors of colorectal polyps. METHODS: In this study, atrophic gastritis and intestinal polyps were diagnosed by endoscopy and pathology. All the 792 patients in this retrospective study were divided into sub-groups based on the presence of colorectal polyps. The correlation between polyps and atrophic gastritis was analyzed using the chi-square test and Kruskal-Wallis test. The receiver operating characteristic (ROC) curve was used to compare the predictive value for colorectal polyps between Hp infection and atrophic gastritis. Binary logistic regression was utilized to identify independent risk factors for colorectal polyps. RESULTS: Patients with colorectal polyps were primarily male with advanced age, and the number of patients with colorectal polyps had a higher association with smoking, alcohol drinking, and Hp infection than the control group. A positive correlation between the number of colorectal polyps and the severity of atrophic gastritis was observed. ROC analysis showed that atrophic gastritis was a better risk factors for colorectal polyps. Multivariate analysis identified atrophic gastritis as an independent risk factor for colorectal polyps (OR 2.294; 95% CI 1.597-3.296). CONCLUSIONS: Atrophic gastritis confirmed could be an independent risk factors for colorectal polyps.

New clinical application of digital intraoral scanning technology in occlusal reconstruction: A case report.

BACKGROUND: Digital intraoral scanning, although developing rapidly, is rarely used in occlusal reconstruction. To compensate for the technical drawbacks of current occlusal reconstruction techniques, such as time consumption and high technical requirements, digital intraoral scanning can be used in clinics. This report aims to provide a way of selecting the most suitable maxillo-mandibular relationship (MMR) during recovery. CASE SUMMARY: A 68-year-old man with severely worn posterior teeth underwent occlusal reconstruction with fixed prosthesis using digital intraoral scanning. A series of digital models in different stages of treatment were obtained, subsequently compared, and selected using digital intraoral scanning together with traditional measurements, such as cone beam computed tomography, joint imaging, and clinical examination. Using digital intraoral scanning, the MMR in different stages of treatment was accurately recorded, which provided feasibility for deciding the best occlusal reconstruction treatment, made the treatment process easier, and improved patient satisfaction. CONCLUSION: This case report highlights the clarity, recordability, repeatability, and selectivity of digital intraoral scanning to replicate and transfer the MMR during occlusal reconstruction, expanding new perspectives for its design, fabrication, and postoperative evaluation.

The effect of posterior cruciate ligament tibial avulsion fracture on functional outcomes in knees with concomitant ipsilateral lower limb fractures: a matched-cohort analysis.

BACKGROUND: At present, the optimal treatment for posterior cruciate ligament tibial avulsion fracture (PCLTAF) combined with concomitant ipsilateral lower limb fractures remains unclear. The present study aimed to assess the preliminary outcomes of treatment for PCLTAF with concomitant ipsilateral lower limb fractures by open reduction and internal fixation (ORIF). MATERIALS AND METHODS: The medical records of patients who sustained PCLTAF with concomitant ipsilateral lower limb fractures between March 2015 and February 2019 and underwent treatment at a single institution were retrospectively reviewed. Imaging examinations performed at the time of injury were applied to identify concomitant ipsilateral lower limb fractures. We used 1:2 matching between patients with PCLTAF combined with concomitant ipsilateral lower limb fractures (combined group; n = 11) and those with isolated PCLTAF (isolated group; n = 22). Outcome data were collected, including the range of motion (ROM) and visual analogue scale (VAS), Tegner, Lysholm, and International Knee Documentation Committee (IKDC) scores. At the final follow-up, the clinical outcomes were compared between the combined and isolated groups and between patients who underwent early-stage surgery and those who underwent delayed treatment for PCLTAF. RESULTS: Thirty-three patients (26 males, 7 females) were included in this study, with eleven patients having PCLTAF and concomitant ipsilateral lower limb fractures and a follow-up of 3.1 to 7.4 years (average, 4.8 years). Compared to patients in the isolated group, patients in the combined group demonstrated significantly worse Lysholm scores (85.7 ± 5.8 vs. 91.5 ± 3.9, p = 0.040), Tegner scores (4.4 ± 0.9 vs. 5.4 ± 0.8, p = 0.006), and IKDC scores (83.6 ± 9.3 vs. 90.5 ± 3.0, p = 0.008). Inferior outcomes were found in patients with delayed treatment. CONCLUSIONS: Inferior results were found in patients with concomitant ipsilateral lower limb fractures, while better outcomes were obtained in patients with PCLTAF through early-stage ORIF using the posteromedial approach. The present findings may help determine the prognoses of patients with PCLTAF combined with concomitant ipsilateral lower limb fractures treated through early-stage ORIF.

Environmental and economic assessment of the construction, operation, and demolition of a decentralized composting facility.

Decentralized waste treatment facilities are recently highlighted for the treatment of solid waste in rural areas for being cheap, flexible, and reliable. Among them, decentralized composting is most commonly used. Many forms of decentralized composting facilities also develop and apply in developing countries, but the environmental and economical performances remain unknown. Therefore, this study analyzed the environmental impacts and cost of a decentralized composting facility through life cycle assessment and life cycle cost. The functional unit was the construction, operation, and demolition the composting facility. Contribution and sensitivity analysis were also performed to find out the most influential processes and parameters. The facility had a 10-year designed life span and could treat about 5840 t organic waste in its life cycle. The life cycle environmental impacts were 646,700 kg CO2-eq, 8980 kg SO2-eq, -28 kg P-eq, 7.09 × 10-3 CTUh, 0.13 CTUh, and 16,754 kg oil-eq for climate change, terrestrial acidification, freshwater eutrophication, human toxicity cancer effects, human toxicity non-cancer effects, and fossil resources scarce, respectively. The life cycle cost was 1080.925 k CNY. When scaling to treating 1 t organic waste, the environmental impacts were close to those of similar decentralized and centralized composting facilities and the cost was lower than those of centralized biological treatment plants when excluding revenues from compost. According to the contribution and sensitivity analysis, the operation stage had the largest environmental impacts. The composting and compost substitution processes in the operation stage were the most sensitive processes. This study proved quantitatively that the decentralized facility was feasible both environmentally and economically and enriched the study cases for decentralized composting facilities.

Effect of DFIG control parameters on small signal stability in power systems.

The doubly-fed induction generator (DFIG) with virtual inertia control and reactive damping control gives a renewable energy generation system inertia and damping characteristics similar to those of a thermal power plant, and the parameters of the control strategy have a direct impact on the small-signal stability of the system. This paper firstly introduces the operating characteristics and control strategies of DFIG-based damping control and virtual inertia control, establishes a small-signal model of the control-based DFIG integrated interconnected system, and investigates the effects of virtual inertia and reactive damping values on the small-signal stability of the system; then, the maximum damping ratio of the interval oscillation mode in small disturbance analysis is taken as the optimization objective, and the control parameters are the optimization variables. An optimization method of inertia and damping parameters is established for improving the small disturbance stability of the system. The results show that the optimization procedure could improve the damping ratio of the interval oscillation mode while ensuring the system frequency. The effects of virtual inertia and reactive damping values on the small signal stability of the system are investigated, and an optimal allocation model and method for virtual inertia used to improve the small disturbance stability of the system is proposed.

Risk Factors for Level-VII Lymph Node Metastases of Thyroid Neoplasms: A Meta-Analysis.

OBJECTIVE: The present study conducted a meta-analysis to forecast the risk factors associated with level-VII lymph node metastases in case of thyroid neoplasms, intending to assist in determining the requirement for level-VII lymph node lymphadenectomy during the surgery. METHODS: Electronic databases, PubMed, Embase, the Cochrane Library, CNKI, Wanfang Data, VIP, and CBM electronic databases were searched for studies focused on level-VII lymph node metastases in thyroid neoplasms, published up to April 2021. Stata 13.1 software was used for analyses. RESULTS: The literature search identified a total of 997 studies. Among these, 8 studies, involving 1813 patients, were included in the present case. All these studies were case-control studies. Results for meta-analysis showed that male (OR = 1.340, 95% CI: 1.018-1.764, P = .037), age < 45 years (OR = 4.178, 95% CI: 1.601-10.908, P = .003), tumor size ≥ 2.0 cm (OR = 1.960, 95% CI: 1.079-3.562, P = .027), extrathyroidal extension (OR = 2.037, 95% CI: 1.578-2.630, P < .001), distant metastasis (OR = 2.775, 95% CI: 2.005-3.840, P < .001), central lymph node metastasis (OR = 3.500, 95% CI: 1.127-10.874, P = .03), contralateral cervicolateral metastasis (OR = 2.119, 95% CI: 1.514-2.965, P < .001), and bilateral nodal metastasis (OR = 4.651, 95% CI: 2.697-8.020, P < .001) acted as risk factors for level-VII lymph node metastases. In addition to this, sensitivity analyses and bias test showed that the results of meta-analysis were reliable and stable and involved no publication bias. CONCLUSION: In the present study, male gender, age < 45 years, tumor size ≥ 2.0 cm, extrathyroidal extension, distant metastasis, central lymph node metastasis, contralateral cervicolateral metastasis, and bilateral nodal metastasis were identified as risk factors for level-VII lymph node metastases in case of thyroid neoplasms.

EGFR-TKI Combined with Pemetrexed versus EGFR-TKI Monotherapy in Advanced EGFR-mutated NSCLC: A Prospective, Randomized, Exploratory Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We aimed to evaluate whether the addition of pemetrexed is effective in improving progression-free survival (PFS) in epidermal growth factor receptor (EGFR)–mutated patients with or without concomitant alterations. @*Materials and Methods@#This multicenter clinical trial was conducted in China from June 15, 2018, to May 31, 2019. A total of 92 non–small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations were included and divided into concomitant and non-concomitant groups. Patients in each group were randomly treated with EGFR–tyrosine kinase inhibitor (TKI) monotherapy or EGFR-TKI combined with pemetrexed in a ratio of 1:1. PFS was recorded as the primary endpoint. @*Results@#The overall median PFS of this cohort was 10.1 months. There were no significant differences in PFS between patients with and without concomitant and between patients received TKI monotherapy and TKI combined with pemetrexed (p=0.210 and p=0.085, respectively). Stratification analysis indicated that patients received TKI monotherapy had a significantly longer PFS in non-concomitant group than that in concomitant group (p=0.002). In concomitant group, patients received TKI combined with pemetrexed had a significantly longer PFS than patients received TKI monotherapy (p=0.013). Molecular dynamic analysis showed rapidly emerging EGFR T790M in patients received TKI monotherapy. EGFR mutation abundance decreased in patients received TKI combined chemotherapy, which supports better efficacy for a TKI combined chemotherapy as compared to TKI monotherapy. A good correlation between therapeutic efficacy and a change in circulating tumor DNA (ctDNA) status was found in 66% of patients, supporting the guiding role of ctDNA minimal residual disease (MRD) in NSCLC treatment. @*Conclusion@#EGFR-TKI monotherapy is applicable to EGFR-sensitive patients without concomitant alterations, while a TKI combined chemotherapy is applicable to EGFR-sensitive patients with concomitant alterations. CtDNA MRD may be a potential biomarker for predicting therapeutic efficacy.

Mechanism of HES1 regulating herceptin resistance in gastric cancer cells by ferroptosis / 药学学报

Drug resistance of cancer cells is the main causes of chemotherapy failure, and gene mutation or function loss is key factor to induce drug resistance. Previous studies have shown that hairy and enhancer of split 1 (HES1) is up-regulated in herceptin-resistant gastric cancer cells, and inhibition of its activity can reverse its resistance while the potential mechanism has not yet been elucidated. In this study, we employed CRISPR/Cas9 to establish HES1 knock-out cell line (△HES1/NCI N87R) to investigate the functions of HES1 in herceptin resistance of NCI N87R cells and its potential mechanisms. We investigated proteomics profiling of △HES1/NCI N87R cells based on quantitative proteomics. Gene ontology analysis was conducted by GeneSet Enrichment Analysis (GSEA) and Metascape database, and pathway enrichment analysis was done using GeneAnalytics database. The selected molecules were quantified by Western blot and some pathways were verified by using inhibitors. The results showed that the resistance to herceptin of △HES1/NCI N87R cells decreased compared to NCI N87R cells. Proteomic data demonstrated that the expression of 1 263 genes changed significantly in △HES1/NCI N87R cells, among which 761 genes were up-regulated while 502 ones down-regulated comparing with NCI N87R cells. Pathway analysis showed that ferroptosis, fatty acid β-oxidation, autophagy and glutathione metabolism, etc. exhibited notable changes in △HES1/NCI N87R cells. The functional studies showed that the levels of iron ion and malondialdehyde increased, and glutathione decreased in △HES1/NCI N87R cells. It was further found that Fer-1, a ferroptosis inhibitor, could reverse the expression of pTP53, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in △HES1/NCI N87R cell, and reduce the sensitivity of △HES1/NCI N87R cells to herceptin. It is suggested that HES1 regulated the resistance of NCI N87R cells to herceptin through TP53/SLC7A11/GPX4 signaling pathway, and targeting TP53/SLC7A11/GPX4 signal axis mediated by HES1 is a potential strategy to reverse herceptin resistance in gastric cancer.

Identification and analysis of AP2/ERF gene family of Panax notoginseng and function of PnDREB84 gene / 药学学报

The AP2/ERF gene family is one of the largest transcription factor families in the plant kingdom, and plays an important role in response to biological and abiotic stresses, plant hormone responses, and plant growth and development. In this study, the AP2/ERF family of Panax notoginseng was identified by bioinformatics methods, and the physicochemical properties, structure, phylogenetic relationship, expression pattern and function of PnDREB4 gene of the family were analyzed. The results showed that 140 AP2/ERF family members were identified in P. notoginseng, which were divided into DREB, ERF, AP2, RAV and Sololit subgroups. The physicochemical properties and motifs of proteins were similar among the subgroups. There were 34 differentially expressed genes in the AP2/ERF family of Fusarium oxysporum infected P. notoginseng plants, and 19 genes were up-regulated. The expression level of PnDREB84 was up-regulated with the extension of Fusarium oxysporum infection time in the range of 0-96 h. The content of ABA and SA in P. notoginseng plants overexpressing PnDREB84 gene increased after 4 ℃ stress. The results showed that PnDREB84 gene plays a dual regulatory role in the process of biological stress and abiotic stress. PnDREB84 gene can be used as a potential molecular marker for the breeding of new varieties of P. notoginseng. The identification of AP2/ERF transcription factor and function analysis of PnDREB84 gene of P. notoginseng provided data support for the analysis of stress resistance mechanism of P. notoginseng and the breeding of new varieties.