Objective:To evaluate the efficacy and safety of combining third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) with brain radiotherapy in patients with newly diagnosed EGFR mutation-positive non-small cell lung cancer (NSCLC) with brain metastases. Methods:A retrospective analysis was performed on the clinical data of patients with newly diagnosed EGFR-mutant NSCLC with brain metastases who received first-line treatment with third-generation EGFR-TKI with or without brain radiotherapy at the Fourth Affiliated Hospital of Guangxi Medical University between January 2018 and December 2022. Patients treated with EGFR-TKI plus brain radiotherapy were assigned to the combination group, while those treated with EGFR-TKI alone were assigned to the monotherapy group. Intracranial progression-free survival (iPFS), progression-free survival (PFS), overall survival (OS), intracranial disease control rate (iDCR), intracranial objective response rate (iORR), and adverse events were compared between groups. Subgroup analyses were performed according to EGFR exon 19 deletion (19del) and exon 21L858R mutation status. Survival was estimated using the Kaplan-Meier method, with the log-rank test applied for group comparisons and univariate analysis, while multivariate analysis was conducted using Cox proportional hazards regression model. Results:A total of 107 patients were included: 57 (53%) in the monotherapy group and 50 (47%) in the combination group. The combination therapy significantly improved iORR (80% vs. 60%, P=0.023), prolonged median OS (37.7 vs. 31.6 months, P=0.004), and extended median iPFS (21.8 vs. 16.7 months, P=0.018). The iDCR was 100% in both groups, and the difference in median PFS was not statistically significant (18.6 vs. 15.2 months, P=0.086). In the 19del subgroup ( n=53), patients in the combination group had longer OS ( P=0.028) and iPFS ( P=0.028). In the 21L858R subgroup ( n=54), the median OS was also longer in the combination group ( P=0.050). Multivariate analysis identified TKI monotherapy and an Eastern Cooperative Oncology Group (ECOG) performance status score=2 as independent adverse prognostic factors for iPFS, while TKI monotherapy, age ≥65 years, ECOG score=2, and >3 brain metastases were the independent adverse prognostic factors for OS. The incidence of adverse events did not differ significantly between groups (all P>0.05). Conclusions:First-line combination therapy with third-generation EGFR-TKI and cranial radiotherapy provides superior efficacy and acceptable safety compared with EGFR-TKI monotherapy in patients with EGFR-mutant lung adenocarcinoma and brain metastases. Both EGFR 19del and 21L858R mutation subgroups benefit from the combined treatment approach.

Objective To study the immune regulatory effect of total flavonoids from houttuynia cordata on herpes simplex keratitis(HSK)mice and preliminarily explore its mechanism.Methods A surgical blade to mark the"#"character on the corneal epithelial layer of Balb/c mice and inoculate with I type herpes simplex virus(HSV-1)was used to construct an HSK model.The successfully identified HSK mice were randomly divided into model group,low(75 mg/kg)and high-dose(300 mg/kg)total flavonoids from houttuynia cordata groups,and high-dose total flavonoids from houttuynia cordata+toll like receptor(TLR)2 agonist Pam3CSK4(0.3 mg/kg)group.A control group was also established with 12 mice in each group.During the modeling and administration period,the corneal lesions in mice were observed daily using a slit-lamp microscope and scored.After administration,HE staining was used to observe the pathological changes of the mouse cornea.ELISA was used to detect the levels of interferon-γ(INF-γ),interleukin-2(IL-2),IL-4,and IL-6 in mouse serum.Western blot was used to detect the protein expression levels of TLR2,myeloid differentiation factor 88(MyD88),nuclear factor-kappaB p65(NF-κB p65)and p-NF-κB p65 in mouse corneal tissue.Results Compared with the control group,the model group mice showed corneal edema,ulcers,and neovascularization,with severe corneal damage and a large number of inflammatory cell infiltration.The serum levels of INF-γ and IL-2 significantly decreased,while the levels of IL-4 and IL-6 significantly increased(P<0.01).The protein expression levels of TLR2 and MyD88 and protein ratios of p-NF-κB p65/NF-κB p65 in corneal tissue significantly increased(P<0.01).Compared with the model group,the low and high dose of total flavonoids from houttuynia cordata groups showed improved corneal injury,the corneal lesion score significantly dereased(P<0.01).The serum levels of INF-γ and IL-2 significantly increased,while the levels of IL-4 and IL-6 significantly decreased(P<0.01).The protein expression levels of TLR2 and MyD88 and protein ratios of p-NF-κB p65/NF-κB p65 in corneal tissue significantly decreased(P<0.01).However,the TLR2 agonist Pam3CSK4 partially reversed the improvement effects of total flavonoids from houttuynia cordata on keratitis and immune imbalance in HSK mice.Conclusion The total flavonoids of houttuynia cordata can effectively improve corneal damage,regulate immune response,and suppress inflammation levels in HSK mice.Its mechanism of action may be related to the regulation of TLR2/NF-κB signaling pathway.

Aim To investigate the effects of the fangchinoline derivative LYY-32 on the biological prop-erties of the BLM642-1290 DNA helicase,in order to lay a foundation for further research on its antitumor activity.Methods Fluorescence polarization assay,malachite green-phosphate and ammonium molybdate colorime-try,and fluorescein-labeled DNA gel electrophoresis experiments were conducted to study the effects of fangchinoline derivative LYY-32 on the DNA binding activity,ATPase activity,and DNA unwinding activity of BLM642-1290 DNA helicase.The effects of LYY-32 on the DNA unwinding activity of DNA helicase in cells were studied using fluorescent techniques and time-lapse microscopy.Ultraviolet spectral scanning was used to investigate the effects of LYY-32 on the confor-mation of the BLM642-1290 DNA helicase.Results At a concentration of 10 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to dsDNA was 53.17％.At a concentration of 5 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to ssDNA was 88.49％.The inhibition rate of LYY-32 on the ATPase activity of BLM642-1290 DNA he-licase was 89.3％at a concentration of 50 μmol·L-1.When the concentration of LYY-32 exceeded 5μmol·L-1,its inhibition rate on the DNA unwinding activity of BLM642-1290 DNA helicase was 100％.LYY-32 also significantly inhibited the DNA unwinding ac-tivity of DNA helicase in cells.However,LYY-32 had no effect on the conformation of BLM642-1290 DNA heli-case.Conclusion The DNA binding activity,AT-Pase activity,and DNA unwinding activity of BLM642-1290 DNA helicase could be significantly inhibi-ted by the fangchinoline derivative LYY-32.

BACKGROUND:Studies have shown that the vulnerability and elasticity of carotid plaques are related to the presence and degree of neovascularization within the plaque. Ultrasound,as the preferred measure to screen and evaluate vulnerable carotid plaques,is non-invasive,easy to perform,highly reproducible and radiation-free.OBJECTIVE:To investigate the influencing factors of vulnerable carotid plaque in the high-risk stroke population based on clinical baseline characteristics and carotid ultrasound parameters,and to develop a Nomogram prediction model based on independent risk factors.METHODS:A total of 180 patients who were identified to be at high risk of stroke by stroke screening at Fuzhou First People's Hospital from November 2021 to November 2023 were retrospectively selected as the study objects,and the patients were divided into a modeling set (n=126) and a validation set (n=54)at a ratio of 7∶3. According to the results of carotid artery ultrasound,the subjects in the modeling set were divided into a vulnerable plaque group (n=54) and a non-vulnerable plaque group (n=72). Independent risk factors were obtained by multi-factor Logistic regression,and a Nomogram model was constructed. Decision curves were drawn using R language to evaluate the clinical benefit of the model. The predictive efficacy of the model was tested by receiver operating characteristic curve and calibration curve,and the case data of the validation set were analyzed for external validation.RESULTS AND CONCLUSION:Multivariate Logistic regression results showed that age,family history of stroke,maximum carotid plaque thickness,carotid plaque quantity,urine microalbumin,urine microalbumin/creatinine ratio were associated with vulnerable carotid plaques in patients at high risk of stroke (P<0.05). The area under curve of the established Nomogram model was 0.917,and the sensitivity and specificity were 79.6％ and 91.7％,respectively. The results of decision curve showed that the potential clinical benefit of this model was considerable and its usability was high. The calibration curve results showed that the model had good prediction accuracy. The verification set results showed that the external prediction performance of the model was good. To conclude,age,family history of stroke,and maximum carotid plaque thickness in the high-risk population are all factors that influence this prediction model. This Nomogram based on these independent risk factors can provide a powerful reference for the clinical treatment of this high-risk population.

Objective To explore the effect of a self-developed augmented multi-task sensory exer-cise intervention on perceptual-motor skills and motor coordination in children with developmental coor-dination disorder(DCD).Methods Twenty-four DCD children aged 6～7 years were included and ran-domly divided into a control group(n=12)and an experimental group(n=12).Both groups maintained their daily physical activities and took P.E.classes in school,while the experimental group additional-ly underwent a multi-task somatosensory motor intervention consisting of 3 stages.Each stage lasted for 4 weeks,3 sessions per week,with progressively increased difficulty.A self-designed data process-ing module of the somatosensory intervention system was used to collect the scores of each task(i.e.,sensory-motor evaluation),and the changes in scores of each task at each stage were analyzed.More-over,before and after the intervention,the motor coordination ability was assessed using the Move-ment Assessment Battery for Children-Second Edition(MABC-2),and the intra-and inter-group dif-ferences in MABC-2 scores were analyzed.Two weeks after the intervention,the experimental group conducted 3 sessions of motor relearning at the difficulty level of the 3rd stage to examine the effects of motor retention and relearning.Results 1)The experimental group showed a significant increase in their scores on all tasks from T1 to T5 during the enhanced multi-task somatosensory training of all the three stages(P<0.001,P<0.05).2)After the kinesthetic exercises,the experimental group had sig-nificantly higher abilities in fine motor skills,positioning&grasping and body balance compared to the control group(P<0.05),with relatively greater effect on threading beads,drawing traces,tossing and catching bags,single-leg balance,tiptoe walking and two-legged hopping(η2≥0.114).3)In the assessment of motor skill retention and relearning,the T1～T4 scores in the first retest were lower than the previous final ones(P<0.05),with no significant difference from those at the end of the second stage,but showing significantly higher T1 and T5 scores.Moreover,all the T1～T5 scores reached the level measured at the previous end of stage three after three sessions of relearning.Conclusion The augmented multi-task somatosensory practice based on perception-motor skills theory can enhance the perception-motor skills and motor coordination ability of the DCD children,with good motor skill reten-tion and recovery effectiveness after such intervention.

Objective:To investigate the awareness of clinical practice guidelines (referred to as "guidelines") and experts consensus (referred to as "consensus") among otorhinolaryngology head and neck surgery medical staff, and to analyze the effectiveness of the ninth guideline methodology workshop.Methods:Self-designed survey questionnaires were used to conduct two surveys among otorhinolaryngology head and neck surgery medical staff who participated in the ninth guideline methodology workshop held in Chengdu from Jannuary 10 to 11, 2025, both before and after the training, to assess their awareness and knowledge of guideline and consensus development methodology. The effectiveness of the training was evaluated using the paired chi-square test.Results:A total of 77 peoples (95.06%), who participated in the ninth guideline methodology workshop, completed the survey questionnaires both before and after the training. One-third of the respondents reported a relatively good to very good understanding of guideline and consensus development. The overall methodology of the guidelines and consensus they had participated in developing still showed room for improvement. After the methodology training, the score rate for each test question significantly increased compared to before the training ( P<0.05), and the distribution trend of the total scores changed markedly (Before the training, 71 people scored less than 60 points, 4 people scored 60 points, and 2 people scored 70 points. After the training, only 1 person scored less than 60 points, 1 person scored 60 points, and 75 people scored between 70 and 100 points, of which 21 people scored 100 points). Conclusion:The awareness of guideline and consensus development methodology among otorhinolaryngology head and neck surgery medical staff still has room for improvement. The guideline methodology workshop can enhance participants′ mastery of guideline and consensus development methodology.

Aim To investigate the effects of the fangchinoline derivative LYY-32 on the biological prop-erties of the BLM642-1290 DNA helicase,in order to lay a foundation for further research on its antitumor activity.Methods Fluorescence polarization assay,malachite green-phosphate and ammonium molybdate colorime-try,and fluorescein-labeled DNA gel electrophoresis experiments were conducted to study the effects of fangchinoline derivative LYY-32 on the DNA binding activity,ATPase activity,and DNA unwinding activity of BLM642-1290 DNA helicase.The effects of LYY-32 on the DNA unwinding activity of DNA helicase in cells were studied using fluorescent techniques and time-lapse microscopy.Ultraviolet spectral scanning was used to investigate the effects of LYY-32 on the confor-mation of the BLM642-1290 DNA helicase.Results At a concentration of 10 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to dsDNA was 53.17％.At a concentration of 5 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to ssDNA was 88.49％.The inhibition rate of LYY-32 on the ATPase activity of BLM642-1290 DNA he-licase was 89.3％at a concentration of 50 μmol·L-1.When the concentration of LYY-32 exceeded 5μmol·L-1,its inhibition rate on the DNA unwinding activity of BLM642-1290 DNA helicase was 100％.LYY-32 also significantly inhibited the DNA unwinding ac-tivity of DNA helicase in cells.However,LYY-32 had no effect on the conformation of BLM642-1290 DNA heli-case.Conclusion The DNA binding activity,AT-Pase activity,and DNA unwinding activity of BLM642-1290 DNA helicase could be significantly inhibi-ted by the fangchinoline derivative LYY-32.

Objective To study the immune regulatory effect of total flavonoids from houttuynia cordata on herpes simplex keratitis(HSK)mice and preliminarily explore its mechanism.Methods A surgical blade to mark the"#"character on the corneal epithelial layer of Balb/c mice and inoculate with I type herpes simplex virus(HSV-1)was used to construct an HSK model.The successfully identified HSK mice were randomly divided into model group,low(75 mg/kg)and high-dose(300 mg/kg)total flavonoids from houttuynia cordata groups,and high-dose total flavonoids from houttuynia cordata+toll like receptor(TLR)2 agonist Pam3CSK4(0.3 mg/kg)group.A control group was also established with 12 mice in each group.During the modeling and administration period,the corneal lesions in mice were observed daily using a slit-lamp microscope and scored.After administration,HE staining was used to observe the pathological changes of the mouse cornea.ELISA was used to detect the levels of interferon-γ(INF-γ),interleukin-2(IL-2),IL-4,and IL-6 in mouse serum.Western blot was used to detect the protein expression levels of TLR2,myeloid differentiation factor 88(MyD88),nuclear factor-kappaB p65(NF-κB p65)and p-NF-κB p65 in mouse corneal tissue.Results Compared with the control group,the model group mice showed corneal edema,ulcers,and neovascularization,with severe corneal damage and a large number of inflammatory cell infiltration.The serum levels of INF-γ and IL-2 significantly decreased,while the levels of IL-4 and IL-6 significantly increased(P<0.01).The protein expression levels of TLR2 and MyD88 and protein ratios of p-NF-κB p65/NF-κB p65 in corneal tissue significantly increased(P<0.01).Compared with the model group,the low and high dose of total flavonoids from houttuynia cordata groups showed improved corneal injury,the corneal lesion score significantly dereased(P<0.01).The serum levels of INF-γ and IL-2 significantly increased,while the levels of IL-4 and IL-6 significantly decreased(P<0.01).The protein expression levels of TLR2 and MyD88 and protein ratios of p-NF-κB p65/NF-κB p65 in corneal tissue significantly decreased(P<0.01).However,the TLR2 agonist Pam3CSK4 partially reversed the improvement effects of total flavonoids from houttuynia cordata on keratitis and immune imbalance in HSK mice.Conclusion The total flavonoids of houttuynia cordata can effectively improve corneal damage,regulate immune response,and suppress inflammation levels in HSK mice.Its mechanism of action may be related to the regulation of TLR2/NF-κB signaling pathway.

Objective To observe the value of non-parallel transmission(non-PTX)reduced field-of-view(rFOV)echo planar imaging(EPI)sequence applied in diffusion weighted imaging(DWI)for displaying prostate lesions.Methods Conventional EPI-DWI and non-PTX rFOV-EPI-DWI were prospectively acquired in 30 patients with prostate lesions,including 22 cases of prostatic hyperplasia and 8 cases of prostate cancer.Subjective scoring of imaging quality,as well as objective evaluation on indexes including signal-to-noise ratio(SNR),contrast ratio(CR),contrast-to-noise ratio(CNR)and lesions'apparent diffusion coefficient(ADC)values were performed and compared between two kinds of DWI.Results The subjective score of non-PTX rFOV-EPI-DWI was higher than that of conventional EPI-DWI(P＜0.001).SNR,CR,CNR of non-PTX rFOV-EPI-DWI and lesions'ADC values measured on non-PTX rFOV-EPI-DWI were all higher than those of conventional EPI-DWI(all P＜0.05).Conclusion non-PTX rFOV-EPI DWI could display prostate lesions better than conventional EPI-DWI.

ObjectiveTo investigate the optimal ratio of goat horn replacing antelope horn in Fufang Lingjiao Jiangya pills and the blood pressure-lowering mechanism of this medicine. MethodsThe blood pressure-lowering efficacy of Fufang Lingjiao Jiangya pills with varying proportions of goat horn replacing antelope horn was evaluated on spontaneous hypertensive rats （SHR）. In this experiment， 50 SHR rats were randomly grouped as follows： model （n=8）， captopril （0.01 g·kg^-1） （n=6）， low-dose blank Fufang Lingjiao Jiangya pills （0.342 g·kg^-1） （n=6）， high-dose blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1） （n=6）， low-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， high-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）， low-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， and high-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）. Additionally， 8 WKY rats were used as the normal group. Drugs were administered by gavage for 4 weeks while an equal volume of distilled water was administered for the normal and model groups. Blood pressure was measured before administration， 3 h post administration， and biweekly thereafter. In the experiment for Fufang Lingjiao Jiangya pills with goat horn replacing antelope horn in different proportions， 48 SHR rats were randomly grouped as follows： model， blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1）， antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1）， 2× goat horn-containing Fufang Lingjiao Jiangya pills （0.824 g·kg^-1）， 4× goat horn Fufang Lingjiao Jiangya pills （0.969 g·kg^-1）， and 6× goat horn Fufang Lingjiao Jiangya pills （1.112 g·kg^-1）. The normal group included 8 WKY rats， and the normal group and model group received an equal volume of distilled water. The treatment lasted for 2 weeks， and blood pressure was recorded at various time points （pre-administration， 3 h post administration， and on days 4， 7， 10， and 14 of administration）. Serum levels of angiotensin-converting enzyme （ACE）， angiotensin Ⅱ（Ang Ⅱ）， renin， and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay. Histopathological changes in the heart， kidney， and thoracic aorta were observed by hematoxylin-eosin staining. The protein levels of ACE2， angiotensin Ⅱ type 1 receptor （AT1R）， and angiotensinogen （AGT） in the kidney tissue were determined by Western blot， while the expression of nuclear factor （NF）-κB p65 and Toll-like receptor 4 （TLR4） in the thoracic aorta tissue was assessed by immunohistochemistry. ResultsCompared with the model group， all treatment groups showed lowered blood pressure （P<0.05， P<0.01）， and the 6× goat horn-containing Fufang Lingjiao Jiangya pills group showed consistent blood pressure-lowering effect with the antelope horn-containing Fufang Lingjiao Jiangya pills group. Compared with the normal group， the model group showed elevated serum levels of ACE， Ang Ⅱ， renin， and IL-6， while the elevations were declined in the Fufang Lingjiao Jiangya pills groups （P<0.05， P<0.01）. Pathological changes in the heart， kidney， and thoracic aorta were alleviated in all the treatment groups， with the 6× goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups exhibited the best effect. Western blot and immunohistochemistry results showed that all the treatment groups exhibited down-regulated protein levels of AT1R， AGT， NF-κB p65， and TLR4 and up-regulated protein levels of ACE2 （P<0.05， P<0.01） compared with model group， with the 6×goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups showcasing the best effect. ConclusionReplacing antelope horn with 6×goat horn in Fufang Lingjiao Jiangya pills can achieve consistent blood pressure-lowering effect with the original prescription. The prescription may exert the effect by inhibiting the renin-angiotensin-aldosterone system （RAAS） and TLR4/NF-κB signaling pathways.