For patients with advanced non-small cell lung cancer (NSCLC) harboring sensitive epidermal growth factor receptor (EGFR) mutations, guidelines prioritize the use of third-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), which offer higher objective response rate (ORR), longer progression-free survival (PFS), and better quality of life. However, due to the low proportion of elderly patients enrolled in clinical trials, the existing evidence is insufficient to fully guide clinical practice. This review examines the efficacy and safety differences of third-generation EGFR-TKIs as monotherapy or in combination in the elderly NSCLC by integrating subgroup analyses or pre-specified research objectives from prospective and retrospective studies. The results show that third-generation EGFR-TKIs have comparable efficacy in elderly patients to younger populations and are well-tolerated. Although combination therapies may extend survival time, the associated increased toxicity necessitates careful risk-benefit assessment.
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Humans ; Carcinoma, Non-Small-Cell Lung/enzymology* ; Lung Neoplasms/enzymology* ; ErbB Receptors/metabolism* ; Protein Kinase Inhibitors/adverse effects* ; Aged ; Antineoplastic Agents/adverse effects*

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective:To understand the epidemiological characteristics and trends of injury in older adults in Jiangsu Province from 2006 to 2022 and provide a scientific basis for developing prevention and control measures.Methods:The data on injury cases aged 60 and older were collected from 12 sentinel hospitals in Jiangsu Province during 2006-2022. The study analyzed the proportion of injury cases among the elderly in the overall population and calculated the annual percent change and average annual percent change (AAPC). A pairwise comparison between groups was performed, and the differences were judged according to the adjusted standardized residuals.Results:From 2006 to 2022, there were 218 426 injury cases among individuals aged 60 and older in Jiangsu Province, which accounted for an increasing proportion of injury cases within the entire population (AAPC=3.17%, P<0.001). The first five causes of elderly injury were falls (42.06%), road traffic injuries (20.20%), animal injuries (11.45%), knife/sharp injuries (9.43%), and blunt injuries (8.13%). From 2006 to 2022, the proportion of falls, animal injuries, and knife/sharp injuries among the elderly aged ≥60 showed an increasing trend, while the proportion of road traffic injuries and blunt injuries decreased (all P<0.001). The incidence of injury was highest in October, with a daily incidence peak between 8:00 and 10:00. Leisure activities (40.34%) were the major activity leading to injury. The injury occurred mainly at home (53.74%), and the injury intention was mainly unintentional (97.41%), all of which showed an increasing trend ( P<0.001). The injuries were mainly bruises (36.00%), and the most common injured positions of the body were low limbs (27.55%), all of which showed a decreasing trend ( P<0.001). About 69.80% of cases were slight, and 79.38% were discharged after treatment, which showed an increasing trend ( P<0.001). Conclusions:The injury data for individuals aged 60 and older in Jiangsu Province exhibited varying trends from 2006 to 2022. There was a noticeable increase in the proportion of elderly injury cases within the overall injury population, as well as an upward trend in falls, animal injuries, and knife/sharp injuries as leading causes of injury. It is imperative to actively develop prevention measures based on the epidemiological characteristics and evolving trends of elderly injuries in Jiangsu Province.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Thioredoxin reductase (TrxR) is one class of the most important antioxidant selenoproteins and is involved in regulating tumor genesis and progression. It has been reported that naphthoquinones can target and inhibit TrxR1 activity therefore produce reactive oxygen species (ROS) mediated by TrxR1, resulting into cellular redox imbalance and making the naphthoquinone compounds to become potential antitumor chemotherapy drugs. The purpose of this work is to explore the interaction between TrxR1 and menadione using biochemical and mass-spectrometric (MS) analyses, to further reveal the detailed mechanisms of TrxR1-mediated naphthoquinone reduction and inhibition of TrxR1 by naphthoquinone compounds. Using the site-directed mutagenesis and recombinantly expressed TrxR1 variants, we measured the steady-state kinetic parameters of menadione reduction mediated by TrxR1 and its variants, performed the inhibition analysis of menadione on TrxR1 activity, and eventually identified the interaction between menadione and TrxR1 through MS analysis. We found that Sec-to-Cys mutation at residue of 498 significantly enhanced the efficiency of TrxR1-mediated menadione reduction, though the Sec⁴⁹⁸ is capable to catalyze the menadione reduction, indicating that TrxR1-mediated menadione reduction is dominantly in a Se-independent manner. Mutation experiments showed that Cys⁴⁹⁸ is mainly responsible for menadione catalysis in comparison to Cys⁴⁹⁷, while the N-terminal Cys⁶⁴ is slightly stronger than Cys⁵⁹ regarding the menadione reduction. LC-MS results detected that TrxR1 was arylated with one molecule of menadione, suggesting that menadione irreversibly modified the hyper-reactive Sec residue at the C-terminus of selenoprotein TrxR1. This study revealed that TrxR1 catalyzes the reduction of menadione in a Se-independent manner meanwhile its activity is irreversibly inhibited by menadione. Hereby it will be useful for the research and development of naphthoquinone anticancer drugs targeting TrxR1.
Catalysis ; Drug Development ; Oxidation-Reduction ; Thioredoxin Reductase 1/metabolism* ; Vitamin K 3/metabolism*

Objective To explore the scientificity and feasibility of using weighted rank-sum ratio (RSR) method based on diagnosis-related groups ( DRGs) indicators in nursing performance evaluation. Methods Homepage data of medical records were extracted from inpatients discharged in 2017, and " CN-DRGs" burster was used to obtain the DRGs data. Data of medical safety were obtained from the nursing adverse event management system, while data of nursing grading information and medical expenses were obtained from the hospital information system, and the patient satisfaction was obtained in a questionnaire survey. Based on the indicators available, the weighted RSR was applied to evaluate the nursing performance from the 11 dimensions, namely workload, nursing competence, nursing quality, nursing personnel allocation, patient satisfaction, etc. Results The results of the weighted RSR showed that 43, 39, and 6 wards of total 88 wards of the hospital were rated as excellent, medium and poor grades respectively. The results of ANOVA showed that the difference of the 3 grades was significant (F=170. 391, P<0.001). The nursing performance evaluation results were consistent with the actual situation. Conclusions The evaluation of nursing performance with weighted RSR method based on DRGs indicators prove its practical application value, as this method can not only provide data support for nursing personnel allocation, but also provide reference for nursing quality evaluation and supervision.

OBJECTIVETo describe and analyze the complications of subcutaneous venous access port for patients with gastrointestinal malignancy.

METHODSData of 1 912 patients with gastrointestinal malignancy who accepted chemotherapy in our department via subcutaneous venous access ports, including 127 cases in upper arm, 865 cases in subclavicular vein and 920 cases in internal jugular vein, from June 2007 to April 2016 were analyzed retrospectively. Associated complications and risk factors were emphatically investigated.

RESULTSPostoperative complications were confirmed in 233 patients(12.2%), and complication morbidity was 37.0%(47/127), 15.5%(134/865), 6.7%(62/920) in upper arm group, subclavicular vein group, internal jugular vein group respectively, whose difference was statistically significant (χ=71.060, P=0.000). Sixty-one(3.2%) patients developed early complications (in the day of insertion, including catheter dislocation, pneumothorax, arterial damage). Early complication morbidity of upper arm group (14.2%, 18/127) was higher as compared to subclavicular vein group (3.4%, 29/865) and internal jugular vein group(1.5%, 14/920) with significant difference (χ=57.867, P=0.000). Postoperative long-term complications (catheter dislocation, thrombosis, pinch-off syndrome, infusion base exposure, catheter detachment) were found in 182(9.5%) patients. Morbidity of long-term complication was 5.2%(48/920) in internal jugular vein group, which was significantly lower than 22.8% (29/127) in upper arm group and 12.1% (105/865) in subclavicular vein group with statistically significant difference (χ=50.828, P=0.000). Multivariate analysis indicated that subclavicular vein intubation (OR=0.536, 95%CI: 0.341 to 0.843; P=0.007 OR=0.156, 95%CI: 0.096 to 0.253, P=0.000), internal jugular vein intubation (OR=0.156, 95%CI: 0.096 to 0.253, P=0.000), operation time <40 minutes (OR=0.458, 95%CI: 0.342 to 0.613, P=0.000) and standardized training (OR=0.233,95%CI: 0.171 to 0.318, P=0.000) were protective factors of postoperative complication; besides, subclavicular vein intubation (OR=0.458, 95%CI: 0.342 to 0.613, P=0.000), internal jugular vein intubation (OR=0.233, 95%CI: 0.171 to 0.318, P=0.000) and standardized training (OR=0.313, 95%CI: 0.173 to 0.568, P=0.000) were protective factors of thrombosis.

CONCLUSIONSSubcutaneous venous access port implantation is a preferable access to central vein. Appropriate intubation approach and standardized training may reduce postoperative complications effectively. Internal jugular vein approach is safer and more reliable than upper arm vein and subclavian vein approach.

Nutrition support therapy can improve the general condition of the patient and is one of the main factors to ensure the success of the operation. Enhanced recovery after surgery (ERAS) improves the recovery following gastrointestinal surgery by reducing postoperative stress response. The application of nutrition support in ERAS includes nutrition risk assessment before surgery and preoperative nutrition treatment for malnutrition. The time to fasting and clear liquid was shortened to 6 h and 2 h before anesthesia induction. Early postoperative recovery of oral feeding can improve the patient's clinical outcome. The application of ERAS enables the development and improvement of clinical nutrition concepts, and deepens the role of nutrition support therapy, which is conducive to the recovery of patients.

BACKGROUND: Ankle fracture combined with deltoid ligament rupture and distal tibiofibular syndesmosis injury occurs occasionally. Its treatment with distal tibiofibular syndesmosis screw fixation or deltoid ligament repair remains controversial. The former appears with poor reduction, broken nails, secondary surgery and other problems.OBJECTIVE: To observe the clinical effectiveness of suture anchor repair for ankle fracture combined with deltoid ligament injury.METHODS: Twelve patients with ankle fracture combined with deltoid ligament injury were selected from the First Affiliated Hospital of Guangzhou University of Chinese Medicine between January 2013 and December 2015. All patients were treated with open reduction, internal fixation, and anchor repair, but without distal tibiofibular syndesmosis screw fixation. The curative efficacy and joint stability were observed.RESULTS AND CONCLUSION: (1) All patients were followed-up for more than 12 months. (2) The modified Baird-Jackson scoring system showed excellent in nine cases, good in two cases, average in one case, poor in none case, and the excellent and good rate was 92%. (3) At 1 year after internal fixation, the X-ray examination showed the malleolus gap and talus slope angle of the affect side were (3.47±0.12) mm and (0.45±0.18)°, and the malleolus gap and talus slope angle of the healthy side were (3.44±0.05) mm and (0.43±0.14)°, and there was no significant difference between two sides (P > 0.05). (4) These results indicate that the suture anchor can repair the anatomy and biomechanics of deltoid ligament with stable ankle joint, and secondary surgery is unnecessary.

At present,the AIDS epidemic situation in college students is becoming more and more serious.In view of the particularity of colleges students and the lack of professional team for AIDS prevention and control in colleges and universities,there exists ethical issues when carry out the prevention and control for AIDS in colleges and universities such as the ethical issue in publicity and education,the ethical issue in AIDS behavioral intervention,the ethical issue in the consultation and detection for AIDS.This paper suggests that it should confront the current situation of AIDS prevention and control,improve the professional level of carrying out AIDS prevention and control,adhere to the necessary principles of AIDS prevention and control,and explore a new mode to construct AIDS prevention and control in colleges and universities.