EGFR-mutant non-small cell lung cancer (NSCLC) is a common type of lung cancer, with EGFR tyrosine kinase inhibitors (EGFR-TKIs) being the standard first-line treatment. However, most patients with NSCLC eventually develop resistance to EGFR-TKIs. Studies on the mechanism underlying EGFR-TKI resistance have driven the development of personalized and precision medicine. Current strategies to address resistance include targeted therapy, immunotherapy, and novel drug treatments. Selecting the appropriate personalized treatment plan is crucial for improving the survival rate and quality of life of patients with EGFR-mutant NSCLC. Thus, this study provides a brief review of the current status and future perspectives in the treatment of EGFR-mutant NSCLC after progression on EGFR-TKI therapy.

ObjectiveTo investigate the possible mechanism of Quyu Jiedu Formula （祛瘀解毒方） in the treatment of endometriosis in terms of iron autophagy mediated by nuclear receptor coactivator 4/nuclear factor κB （NCOA4/NF-κB） signalling pathway. MethodsFifty female SD rats were randomly divided into sham surgery group， model group， mifepristone group， low- and high-dose Quyu Jiedu Formula group， with 10 rats in each group. In the sham surgery group， only operation of opening and closing abdomen was performed， and in the remaining groups， the rat with endometriosis was modelled by autotransplantation. On the next day after successful modelling， saline 2 ml/d was given by gavage to the sham surgery group and the model group； mifepristone 1.05 mg/（kg·d） was given by gavage to the mifepristone group； Quyu Jiedu Formula 12.23 g/（kg·d） and 48.92 g/（kg·d） were given to the low- and high-dosage Quyu Jiedu Formula groups， respectively administered for 4 weeks consecutively. In the remaining 4 groups， all ectopic endometrial tissues were removed from the rats. The volume of ectopic lesions was measured in the model group， the mifepristone group， and the low- and high-dose Quyu Jiedu Formula groups， and the pathological changes of endometrial/ectopic tissues were observed by HE staining， and the protein expression and expression of NCOA4， Ferritin Heavy Chain 1 （FTH1）， Panax quinquefolium （P62）， Microtubule-associated Protein 1 Light Chain 3β （LC3B）， and P-NF-κB protein expression and NCOA4， FTH1， LC3B， P62 mRNA expression were detected in the endometrium and ectopic tissues； the co-localisation of NCOA4 and LC3B， free iron content， and levels of interleukin 6 （IL-6） and tumour necrosis factor α （TNF-α） in endometrial/eutopic endometrial tissues were also detected. ResultsNo ectopic lesions were seen in the sham surgery group. The ectopic tissues of rats in the model group showed obvious pathological damage， while the pathological damage of the ectopic tissues of rats in each admi-nistration group was reduced to different degrees. Compared with the model group， the volume of ectopic lesions was reduced in the mifepristone group and the high- and low-dose Quyu Jiedu Formula groups， and the volume of ectopic lesions in the high-dose Quyu Jiedu Formula group and the mifepristone group was significantly smaller than that in the low-dose Quyu Jiedu Formula group （P＜0.01）. Compared with the sham surgery group， the ectopic tissues of the model group showed up-regulation of LC3BⅡ/LC3B I values， NCOA4， and P-NF-κB protein expression， down-regulation of P62 and FTH1 protein expression， increase in free iron content and IL-6 and TNF-α levels， and increase in the co-localisation positivity rate and co-localised cell density of NCOA4 and LC3B （P＜0.05 or P＜0.01）. Compared with the model group， the ectopic endothelial tissue LC3BⅡ/LC3BⅠ values and the expression of NCOA4 and P-NF-κB proteins were down-regulated in the low- and high-dose Quyu Jiedu Formula group and mifepristone group， the colocalisation positivity rate of NCOA4 and LC3B significantly reduced， and the content of free iron and the level of IL-6 decreased （P＜0.05 or P＜0.01）. Compared with the mifepristone group， P62 more obvious up-regulated and TNF-α level reduced in the high-dose Quyu Jiedu Formula group （P＜0.05）. Compared with the low-dose Quyu Jiedu Formula group， the free iron content of ectopic tissues and the levels of IL-6 and TNF-α reduced in the high-dose Quyu Jiedu Formula group （P＜0.01）. ConclusionThe mechanism of endometriosis treatment by Quyu Jiedu Formula may be related to the inhibition of iron autophagy mediated by the NCOA4/NF-κB signalling pathway in endometriotic tissues， which improves endometrial inflammation.

The community teaching bases play an important role in training of general practice talents. To raise the training quality, the development of their own capacity is crucial, but community medical institutions also need close cooperation with the departments of general practice in medical schools and the higher-level general hospitals. This article discusses the integration model of management, teaching and research in general practice talent training based on the cooperation of community teaching bases with relevant governmental departments, professional societies/associations, general hospitals and medical schools.

Objective:To investigate the status quo of educational and teaching research in community bases for general practice standardized residency training in China.Methods:The studies related to education research in community bases for general practice standardized residency training were searched from Chinese Journal Full Text Database (CNKI), Wanfang Database and China Science and Technology Journal Database (VIP) from inception to November 30, 2023. The keywords of "standardized training of general practitioner residents" or "general practice standardized training" or "general practitioner standardized training" or "general practice training" and "community-based teaching " or "community training" "community base" or "community teaching" were used for search, and affiliations of authors should contain"community health service center". The literature was read and summarized using Endnote and Excel software.Results:A total of 171 articles were retrieved that met the criteria, and 130 articles were finally selected for analysis according to the quality review criteria of the literature. The authors of articles were distributed in 78 institutions of 17 provinces or regions, with 9 provinces or regions having a total of 123 articles (94.6%) with 2 published articles or more, of which the highest number was found in Beijing and Shanghai. Seventeen institutions published 2 or more articles with a total of 69 articles (53.1%), including 67 articles (51.5%) were co-authored by 2 units. The ranking top ten institutions in terms of the number of articles published were 5 community health service centers in Beijing, 4 in Shanghai (co-authored with Shanghai Zhongshan Hospital). There were 46 articles (35.4%) published in core journals and 55 articles (42.3%) with fund-supported projects. The studies presented teaching methods, teaching and training contents, teaching evaluation and effects, teacher training, teaching base construction and information technology application.Conclusion:The educational and teaching research in community bases for general practice standardized training in China has gradually received attention, the researches were mainly carried out by community medical institutions, but the overall quality of research needs to be further improved.

Objective:To evaluate the effect of virtual reality arthroscopic simulation system combined with case-based learning (CBL) in orthopedic clinical teaching.Methods:From January 2021 to June 2022, a total of 36 residents who took the standardized residency training at Department of Articular Orthopedics in The Third Affiliated Hospital of Soochow University were enrolled in this study. They were randomized into an experimental group and a control group, with 18 trainees in each group. The experimental group adopted the virtual reality arthroscopic simulation system combined with CBL teaching mode, while the control group adopted simple endoscopic simulation training box with traditional teaching mode. Theoretical and practical tests and questionnaire survey were carried out to evaluate the teaching effects in two groups. SPSS 22.0 was performed to conduct t-test on the measurement data between the two groups. Results:The theoretical and practical test scores of the experimental group [(89.39±3.09) and (82.72±4.28)] were better than those of the control group [(86.22±4.43) and (76.61±5.65)], with statistically significant differences ( t= 2.49, P=0.018; t=3.66, P=0.001). The questionnaire survey showed that the experimental group was better than the control group in creating novel forms of courses [(4.94±0.24) vs. (4.11±0.58), t=5.62, P<0.001], simulating more real scenes [(4.83±0.38) vs. (3.78±0.43), t=7.80, P<0.001], inspiring learning interests [(4.78±0.43) vs. (4.00±0.59), t=4.51, P<0.001], improving practical skills [(4.83±0.38) vs. (3.83±0.51), t=6.61, P<0.001], and building career confidence [(4.50±0.62) vs. (3.06±0.54), t=7.47, P<0.001], with statistically significant differences (all P<0.001). Conclusions:The virtual reality arthroscopic simulation system combined with CBL teaching mode can better simulate the real clinical scenes, help inspire the interest of learning and quickly improve practical skills, thereby improving the effect of orthopedic clinical teaching.

Objective To investigate the effects of Quyu Jiedu Prescription on iron autophagy in eutopic endometrial tissue of rats with endometriosis(EMS);To explore its mechanism in treating EMS.Methods A total of 50 female SD rats were randomly divided into blank group,model group,Western medicine group,Quyu Jiedu Prescription high-and low-dosage groups,with 10 rats in each group.Except for the blank group,all other groups were modeled using autologous transplantation method,and corresponding solutions were given by gavage for 4 weeks.HE staining was used to observe the morphology of eutopic endometrial tissue,the reagent kit was used to detect the content of ferrous ions(Fe2+)in eutopic endometrial tissue,Western blot was used to detect the protein expressions of nuclear receptor coactivator factor 4(NCOA4),ferritin heavy chain 1(FTH1),LC3BⅡ/Ⅰ and p62 in eutopic endometrial tissue,the mRNA expressions of NCOA 4,FTH1,LC3B and p62 were detected by qPCR,immunofluorescence colocalization was used to detect the co-localization of NCOA4 and LC3B in eutopic endometrial tissue.Results Compared with the blank group,the content of Fe2+in eutopic endometrial tissue of the model group decreased(P<0.01),the expression of NCOA4 protein and LC3B Ⅱ/Ⅰ ratio decreased(P<0.01),the expressions of FTH1 and p62 protein increased(P<0.05,P<0.01),the expression of NCOA4 mRNA decreased(P<0.01),the expression of p62 mRNA increased(P<0.01),and the co-localization of NCOA4-LC3B decreased(P<0.01).Compared with the model group,the content of Fe2+in eutopic endometrial tissue of each administration group increased(P<0.05,P<0.01),the expressions of FTH1 and p62 protein in Western medicine group decreased(P<0.05,P<0.01),the ratio of LC3B Ⅱ/Ⅰ in Quyu Jiedu Prescription high-dosage group increased(P<0.01),the expression of FTH1 and p62 protein decreased(P<0.05,P<0.01),the expression of NCOA4 protein and LC3B Ⅱ/Ⅰ ratio increased in Quyu Jiedu Prescription low-dosage group(P<0.05),while the expression of p62 protein decreased(P<0.05),the expression of NCOA4 mRNA increased in each administration group(P<0.01),and the co-localization of NCOA4-LC3B increased(P<0.05,P<0.01).There was no significant change in the morphology of eutopic endometrial tissue in each group.Conclusion Quyu Jiedu Prescription may activate the iron autophagy pathway mediated by NCOA4 to restore the activity of ferritin protein,increase the iron content,correct the imbalance of iron homeostasis in eutopic intima of EMS rats,and thus inhibit the development of EMS.

Objective To systematically retrieve relevant research on the application of exercise intervention dur-ing hematopoietic stem cell transplantation for hospitalized children at home and abroad,to generalize and summa-rize the content of exercise intervention,the effect of intervention,and safety monitoring,with the purpose of provid-ing reference bases for the clinical application of exercise intervention in the future.Methods In accordance with the scoping review framework,we systematically retrieved databases including Web of Science,PubMed,Scopus,Cochrane Library,Embase,CINAHL,CNKI,VIP Database,Wanfang Data and China Biomedical Literature Database,with a retrieval timeframe from database establishment to May 19,2023.Based on the criteria for inclusion and ex-clusion of literature,we screened,summarized,extracted,and analyzed the literature.Results A total of 17 pieces of literature were included,including 5 randomized controlled trials,9 quasi-experimental studies,and 3 mixed-method studies.There were 4 categories of exercise including aerobic,anti-gravity,resistance,and stretching;most of the ex-ercises were of low to moderate intensity;the exercise interventions had a positive impact on muscle strength,quali-ty of life,cardiorespiratory function,body composition,and hematological indices;the safety monitoring consisted of red blood cell,hemoglobin,and platelet counts,temperature,joint and muscle pains,as well as falls,and syringe shedding.Conclusion The application of exercise intervention is safe and feasible,with a positive effect on chil-dren with hematopoietic stem cell transplantation in muscle strength,quality of life.Medical staff should combine with the clinical situation to formulate a reasonable and unified exercise program and to carry out scientific and standardized exercise management.

Objective:To investigate the effects of Quyu Jiedu Decoction on the levels of free iron and NF-κB, IL-6 and TNF-α in ectopic tissues of rats with endometriosis.Methods:Totally 18 rats were divided into blank group, model group and Quyu Jiedu Decoction group according to the random number table method, with 6 rats in each group. Except for the blank group, the endometriosis model was prepared by autologous transplantation in the rest of the groups. Quyu Jiedu Decoction was given 13.23 g/kg of Quyu Jiedu Decoction, and the rats in the blank group and model group were gavaged with the same volume of normal saline for 4 consecutive weeks for consecutive 4 weeks. The pathological changes of endometriosis tissues of the three groups were observed by HE staining; the free iron content of the ectopic tissues of the rats was detected by ferrous ion colorimetric test box; ELISA was used to detect the levels of IL-6 and TNF-α; the expressions of NF-κB, IL-6 and TNF-α mRNA of rat ectopic tissues were detected by q-PCR.Results:The results of HE staining showed that there was more inflammatory cell infiltration in ectopic lesions in the model group, and the inflammatory cell infiltration of ectopic lesions in the Quyu Jiedu Decoction group was significantly improved. Compared with the model group, the content of free iron in ectopic tissues decreased ( P<0.05), the levels of IL-6 and TNF-α decreased ( P<0.05), and the mRNA expressions of NF-κB and TNF-α were down-regulated ( P<0.05). Conclusion:Quyu Jiedu Decoction can improve the expressions of free iron, IL-6, TNF-α and NF-κB in ectopic tissues of rats with endometriosis, and has a certain effect on alleviating the inflammatory state of ectopic tissues in rats with endometriosis.

Objective To explore the neuroprotective effect of curcumin(Cur)on Parkinson's disease model and its mechanism.Methods Sprague-Dawley rats were randomly divided into the control(CON)group,the model(PD)group,and the low-,medium-,and highdose curcumin(Cur)groups,with ten rats in each group.Lipopolysaccharide was injected into the substantia nigra to establish a Parkinson's disease model.Rats in the Cur groups were administered Cur intraperitoneally at doses of 20 mg/kg,40 mg/kg,and 60 mg/kg daily for 21 days.α-synuclein(α-syn),nuclear transcription factor κB proteins(NF-κB,IKBα,p-NF-κB,p-IKBα)and the activation levels of astrocytes were detected in rat brain tissues by immunohistochemistry(IHC).mRNA levels of pro-inflammatory cytokines(TNF-α,IL-β,IFN-γ,IL-6),inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2),NADPH oxidase complex(gp47phox,gp91phox,gp67phox),and apoptosis-related factors(Bax,Bcl-2,Caspase-3,and Caspase-9)were measured by quantitative reverse transcription polymerase chain reaction(qRT-PCR).The rotarod and pole climbing tests were used to evaluate the motor coordination of the rats.Results Compared to the CON group,PD rats showed significantly increased levels of α-syn,p-NF-κB,p-IKBα proteins,activation of astrocytes,TNF-α,IL-β,IFN-γ,IL-6,iNOS,COX-2,Bax,Caspase-3,Caspase-9,gp47phox,gp91phox and gp67phox mRNA levels(P<0.05);while the Bcl-2 level was significantly decreased(P<0.05).Compared with the PD group,the medium-and high-dose Cur treatment groups inhibited the aggregation of α-syn protein,reduced the activation of the NF-κB pathway,and the expression of inflammatory and apoptosis-related factors(P<0.05).Moreover,medium and high doses of Cur significantly improved the motor coordination in rats,and compared with the PD group,the performance of rotarod and pole climbing tests was significantly improved(P<0.05).Conclusion cur may inhibit the aggregation of α-syn by suppressing neuroinflammation and oxidative stress responses,thereby improving motor coordination in Parkinson's disease rats and exerting neuroprotective effects.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).