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.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective:To investigate the clinicopathological features of advanced-stage mycosis fungoides (MF).Methods:A retrospective case-series study was conducted. The clinical data of 5 cases diagnosed with advanced-stage MF in Chengdu Second People's Hospital between January 2015 and July 2023 were analyzed. The clinicopathological features of patients were summarized.Results:There were 2 males and 3 females in 5 MF patients, with the median age of 55 years (45-86 years) and the medical history of 2-16 years. The main symptoms were pruritus and erythema. The lesions were presented by erythema, scales, plaques, blisters, erosion, ulcers, pigmentation, nodules, and erythroderma. Histopathological examination showed different skin lesion patterns such as psoriasis-like, interfacial dermatitis, non-infectious granuloma, deep and shallow perivascular dermatitis, tumors. Among 5 patients, 1 case was mycosis fungoides bullosa, 2 cases were erythrodermic MF, 1 case was granulomatous MF, and 1 case was classical MF. Lymphocyte epidermis was found in 4 cases, cytoplasmic halos cells lined up along the basal layer of the epidermis and Pautrier microabscess were found in 3 cases, large-cell transformation was found in 1 case. Tumor cells were positive for CD3, CD4 and negative for CD8, CD56, ALK and CD20; EBER 1/2 hybridization in situ was negative. CD30 was positive in transformed large cells and T cell receptor gene rearrangement was positive. The tumor cells were detected in bone marrow and peripheral blood of 2 cases and in cerebrospinal fluid of 1 case. Head magnetic resonance imaging of 1 case indicated abnormal signal nodules in the right temporal region and the normal architecture of the lymph nodes in 2 cases was completed destroyed by malignant cells. TNMB stage: 2 cases were in stage Ⅱ B, 2 cases were in stage Ⅳ A2, and 1 case was in stage Ⅳ B. Interferon α-based systemic therapy was performed in 1 case, 2 cases received chemotherapy or combined with intrathecal injection and radiotherapy, and other 2 cases were not treated. All of them just achieved partial remission. Finally, 1 case died of sudden cardiac death, 2 cases died of lung infection, and 2 cases survived with tumors. Conclusions:Advanced-stage MF is presented with different skin lesion manifestations and histopathologic changes. Multidisciplinary combined management helps the diagnosis and treatment of MF.

Objective To explore the application value of mpMRI-TRUS multi-modal image fusion transperineal biopsy technique using electromagnetic needle tracking under local anesthesia combined with rapid paraffin-embedded section of small specimen in the diagnosis of prostate cancer.Methods The clinicopathological data of 138 patients with PI-RADS score≥3 who underwent mpMRI-TRUS image fusion transperineal biopsy using electromagnetic needle tracking under local anesthesia were retrospectively analyzed.AI technology was used to fuse mpMRI and TRUS multi-mode images,and two-core targeted biopsies were performed on suspicious lesions,followed by 12-core systematic biopsies.The specimens obtained from targeted biopsies were sent for rapid paraffin-embedded section pathological examination,and the detection rates of csPCa were compared.Results The detection rate of csPCa in 138 patients was 71.01% .The detection rates of csPCa in targeted biopsies and systematic biopsies were 62.32% and 70.29%,respectively(P=0.20).The detection rate of combined biopsies was higher than those of targeted biopsies and systematic biopsies,but the difference was not statistically significant(P>0.05).The detection rates of csPCa in targeted biopsies,systematic biopsies,and combined biopsies in patients with PI-RADS score 3 were 30.95%,38.10%,and 40.48%,respectively;and the percentages were 52.94%,61.76%,and 61.76% in patients with PI-RADS score 4,respectively;and the percentages were 90.32%,96.77%,and 96.77% in patients with PI-RADS score 5,respectively,without statistically significant difference(all P>0.05).In the subgroups with PI-RADS scores of 3,4,and 5,the missed diagnosis rates of csPCa by targeted biopsies were 23.53%,14.29%,and 6.67%,respectively.Conclusion For patients with suspected prostate cancer and PI-RADS v2.1 score≥3,transperineal biopsy using electromagnetic needle tracking combined with rapid paraffin-embedded section of small specimen can obtain pathological results rapidly and has good diagnostic accuracy.However,combined biopsy is still the most suitable method for the diagnosis of prostate cancer at present.

Objective To explore the effect and safety of magnetic resonance imaging and transrectal ultrasound (mpMRI-TRUS) image fusion targeted transperineal biopsy technique using electromagnetic needle tracking under local anesthesia. Methods We retrospectively analyzed the clinical and pathological data of 81 patients with mpMRI-TRUS image fusion targeted transperineal prostate biopsy using electromagnetic needle tracking under local anesthesia. Visual analog scale (VAS) and visual numeric scale (VNS) were used to evaluate the pain level and satisfaction of patients during prostate biopsy (VAS-1 and VNS-1), one hour after puncture (VAS-2 and VNS-2), and one day after surgery (VAS-3 and VNS-3). The perioperative clinical data and tumor positive rate of postoperative biopsy were recorded. Results The average prostate volume of 81 patients was 53.39±29.46 cm³. The PSA values of patients with PI-RADS scores of 2, 3, 4, and 5 were 9.14±2.31, 9.95±4.10, 14.77±6.36, and 32.17±24.39 ng/ml, respectively. The scores of VAS-1, VAS-2, and VAS-3 were 1.70±0.73, 1.16±0.58, and 0.53±0.55, respectively; the scores of VNS-1, VNS-2, and VNS-3 were 2.74±0.44, 3.69±0.46, and 3.84±0.37, respectively. The average surgical time was 17.47±3.44 minutes. Postoperative pathological results showed that the tumor positive rate of targeted prostate biopsy was 64.20%. According to the PI-RADS score for subgroup analysis, the tumor positive rates of patients with PI-RADS scores of 2, 3, 4, and 5 were 21.43%, 44.44%, 61.11%, and 96.77%, respectively. After transperineal prostate biopsy, gross hematuria occurred in 19.75% patients, and urinary retention occurred in 3.70%. The latter were relieved after symptomatic treatment. All patients did not experience complications, such as perineal puncture area hematoma, urinary tract infection, hematospermia, hematoma in perineal puncture area, urinary tract infection, hematospermia, vagus nerve reaction, or septic shock. Conclusion For suspected prostate cancer patients, mpMRI-TRUS image fusion targeted transperineal biopsy technique using electromagnetic needle tracking under local anesthesia is a feasible and easily tolerated surgical procedure. It has good safety and high tumor positive-detection rate, indicating that this technique is worthy of further clinical promotion and application.

Objective To investigate the effect of dexmedetomidine on renal function in patients with septic-associated acute kidney injury(SAKI).Methods A prospective cohort study was conducted in 180 patients with sepsis admitted to ICU in the Second Affiliated Hospital of Guangdong Medical University from October 2021 to April 2023.According to the principle of randomized controlled trials,60 non-acute kidney injury(AKI)patients were divided into S-D group(n = 30,dexmedetomidine + conventional treatment)and S group(n = 30,conventional treatment),and the occurrence and disease score of AKI after treatment were compared between the two groups.A total of 120 AKI patients were divided into SA-D-RT group(n = 30,dexmedetomidine + blood purification + conven-tional treatment),SA-D group(n = 30,dexmedetomidine + conventional treatment),SA-RT group(n = 30,blood purification + conventional treatment)and SA group(n = 30,conventional treatment).Renal function,inflammatory factor level and disease change of the four groups were compared after treatment.Results After treatment,the inci-dence of AKI in S-D group was lower than that in S group,and the APACHEII score and SOFA score in S-D group were lower than those in S group on the 7th day after treatment(P<0.05).After 7 days of treatment,the level of Scr,BUN and CysC in the 4 groups was significantly lower than that on the 1st and 3rd day,and those in the SA-D-RT group were lower than those in the SA-D group,SA-RT group and SA group(P<0.05).After 7 days of treatment,the level of CRP,PCT,TNF-α,IL-6 and IL-1β in four groups was significantly decreased compared with on the 1st and 3rd day,and the level of CRP,PCT,TNF-α,IL-6 and IL-1β in SA-D-RT group was lower than that in SA-D group,SA-RT group and SA group(P<0.05).After 7 days of treatment,the APACHEII score and SOFA score of the four groups were significantly lower than on the 1st and 3rd day,and the scores of the SA-D group were lower than those of the SA-D group,the SA-RT group and the SA group(P<0.05).Conclusion Dexmedetomidine can effectively reduce the incidence of AKI,affect the expression level of renal function markers and inflammatory factors in serum of SAKI patients,and improve the condition of patients.

Objective:To translate Evidence-based Practice-knowledge, attitude, application, anticipated future use (EBP-KAPF) scale into Chinese, and evaluate its reliability and validity.Methods:The Chinese version of the EBP-KAPF scale was determined through translation, adaptation, recall, review and pre-investigation. From July to August 2022, 250 clinicians from 28 provinces (autonomous regions and municipalities directly under the Central Government) were selected by using the convenience sampling method. A self-made questionnaire was used to investigate the EBP-KAPF scale in Chinese to investigate the EBM ability of clinicians, including the basic information of the respondents, the learning and use of Evidence-based medicine courses and related software. The item analysis, validity and reliability evaluation of the Chinese version of the EBP-KAPF scale were performed.Results:The Chinese version of the EBP-KAPF scale included 26 items in four dimensions: knowledge mastery, attitude, personal application and future use. A total of 265 questionnaires were sent out (including self-made questionnaires and the Chinese version of the EBP-KAPF scale), and 250 effective questionnaires were obtained, with a total effective rate of 94.3%. The total score of the Chinese version of the EBP-KAPF scale was (102.85±17.48) points, and the scores of knowledge mastery, attitude, personal application and future use sub-scales were (27.22±4.47), (13.56±7.70), (20.07±6.78), and (42.00±9.00) points, respectively. Except for item 16, all items were correlated with the total score of the scale, and the correlation coefficient ranged from 0.456 to 0.828. After item 16 was deleted, the determination values of the remaining 25 items ranged from 4.287 to 18.262 ( P<0.001). After item was removed one by one, the Cronbach′s α coefficient of the scale ranged from 0.870 to 0.888. After item 16 was removed, the Chinese version of the 25-item EBP-KAPF scale had good content validity, structural validity and discriminant validity. The content validity index (I-CVI) at the item level ranged from 0.875 to 1.000, and the content validity index at the overall agreement scale level was 0.615. The average S-CVI values were 0.952, and the probability of correction ( K*) values were 0.87 to 1.00. The results of confirmatory factor analysis showed that the structure fit was good [comparative fit index (CFI)=0.962, Tucker-Lewis index (TLI)=0.957, root mean square error of approximation (RMSEA)=0.060, χ2/ df=1.889]. Discriminant validity analysis showed that there were statistically significant differences in the EBP-KAPF scores among clinicians of different ages, evidence-based medicine course learning and related software use ( P<0.05). After item 16 was removed, the Cronbach′s α coefficient of the Chinese version of the EBP-KAPF scale was 0.893, and the Guttman half coefficients of each dimension were 0.915, 0.901, 0.812 and 0.906, respectively. The correlation coefficients were 0.902-0.982, 0.507-0.953, 0.517-0.744 and 0.632-0.986, respectively. Conclusion:The Chinese version of the EBP-KAPF scale is simple, easy to understand, unambiguous, and has good validity and reliability.

Objective To explore the efficacy and safety of multi-parametric magnetic resonance imaging and transrectal ultrasonography(mpMRI-TRUS)fusion targeted transperineal biopsy(TPB)under local anesthesia(LA)with"one-plane three-point"dual probe ultrasound localization.Methods Clinical data of 134 suspected prostate cancer(PCa)patients treated with this method in our hospital during Jan.and Sep.2023 were retrospectively analyzed.The same doctor applied visual analog scale(VAS)and visual digital scale(VNS)to evaluate the pain level and satisfaction of patients during TPB(VAS-1 and VNS-1)and 1 hour after TPB(VAS-2 and VNS-2),and recorded the perioperative clinical data and detection rate of clinically significant prostate cancer(csPCa).Results VAS-1 score was(1.60±0.68)and VAS-2 score was(1.13±0.55);VNS-1 score was(2.84±0.41),and VNS-2 score was(3.74±0.44).The operation time was(16.12±3.35)minutes.The postoperative pathological results showed that the detection rate of csPCa was 65.67％(88/134).According to the PI-RADS score in subgroup analysis,the detection rates of patients with PI-RADS scores of 2,3,4,and 5 were 23.08％(6/26),52.94％(18/34),62.50％(15/24)and 98.00％(49/50),respectively.After TPB,gross hematuria occurred in 20.90％(28/134)patients,and urinary retention occurred in 4.00％(5/125)patients,which were relieved after symptomatic treatment.No complications such as perineal puncture area hematoma,urinary tract infection,hematospermia,vagal nerve reaction,and septic shock occurred.Conclusion The mpMRI-TRUS fusion targeted TPB under LA with"one-plane three-point"dual probe ultrasound localization provides a feasible and tolerable surgical procedure for suspected PCa patients with a high detection rate of csPCa,which is worthy of further clinical promotion and application.

Objective:To translate Evidence-based Practice-knowledge, attitude, application, anticipated future use (EBP-KAPF) scale into Chinese, and evaluate its reliability and validity.Methods:The Chinese version of the EBP-KAPF scale was determined through translation, adaptation, recall, review and pre-investigation. From July to August 2022, 250 clinicians from 28 provinces (autonomous regions and municipalities directly under the Central Government) were selected by using the convenience sampling method. A self-made questionnaire was used to investigate the EBP-KAPF scale in Chinese to investigate the EBM ability of clinicians, including the basic information of the respondents, the learning and use of Evidence-based medicine courses and related software. The item analysis, validity and reliability evaluation of the Chinese version of the EBP-KAPF scale were performed.Results:The Chinese version of the EBP-KAPF scale included 26 items in four dimensions: knowledge mastery, attitude, personal application and future use. A total of 265 questionnaires were sent out (including self-made questionnaires and the Chinese version of the EBP-KAPF scale), and 250 effective questionnaires were obtained, with a total effective rate of 94.3%. The total score of the Chinese version of the EBP-KAPF scale was (102.85±17.48) points, and the scores of knowledge mastery, attitude, personal application and future use sub-scales were (27.22±4.47), (13.56±7.70), (20.07±6.78), and (42.00±9.00) points, respectively. Except for item 16, all items were correlated with the total score of the scale, and the correlation coefficient ranged from 0.456 to 0.828. After item 16 was deleted, the determination values of the remaining 25 items ranged from 4.287 to 18.262 ( P<0.001). After item was removed one by one, the Cronbach′s α coefficient of the scale ranged from 0.870 to 0.888. After item 16 was removed, the Chinese version of the 25-item EBP-KAPF scale had good content validity, structural validity and discriminant validity. The content validity index (I-CVI) at the item level ranged from 0.875 to 1.000, and the content validity index at the overall agreement scale level was 0.615. The average S-CVI values were 0.952, and the probability of correction ( K*) values were 0.87 to 1.00. The results of confirmatory factor analysis showed that the structure fit was good [comparative fit index (CFI)=0.962, Tucker-Lewis index (TLI)=0.957, root mean square error of approximation (RMSEA)=0.060, χ2/ df=1.889]. Discriminant validity analysis showed that there were statistically significant differences in the EBP-KAPF scores among clinicians of different ages, evidence-based medicine course learning and related software use ( P<0.05). After item 16 was removed, the Cronbach′s α coefficient of the Chinese version of the EBP-KAPF scale was 0.893, and the Guttman half coefficients of each dimension were 0.915, 0.901, 0.812 and 0.906, respectively. The correlation coefficients were 0.902-0.982, 0.507-0.953, 0.517-0.744 and 0.632-0.986, respectively. Conclusion:The Chinese version of the EBP-KAPF scale is simple, easy to understand, unambiguous, and has good validity and reliability.

Objective:To investigate influences of echinacoside(ECH)on myocardial cell apoptosis,inflammatory injury and mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription 3(STAT3)signaling pathway in rats with coronary heart disease(CHD).Methods:A total of 12 SD rats were taken as control group(NC group),48 CHD rat models were successfully constructed,and randomly divided into model(Model)group,ECH group(50 mg/kg),mTOR activator MHY1485 group(10 mg/kg),ECH+MHY1485 group(50 mg/kg ECH+10 mg/kg MHY1485).After 4 weeks,electrocardiogram was recorded through biological function experimental system.Kits were used to detect myocardial C-reactive protein(CRP)and IL-6 levels.Myocardial pathology and apoptosis were measured by HE and TUNEL staining.qRT-PCR was used to detect myocardial Bcl-2,Bax mRNA expressions.Western blot was used to detect myocardial mTOR/STAT3 pathway protein expression.Results:Compared with NC group,Model group rats had obvious necrosis,edema and inflammatory cell infiltration,ST segment deviation,IL-6,CRP levels,cardiomyocyte apoptosis rate,Bax mRNA expression,mTOR and p-STAT3/STAT3 protein levels were significantly increased(P<0.05),Bcl-2 mRNA expression was significantly decreased(P<0.05).Compared with Model group,myocardial injury in ECH group was alleviated,ST segment shift,IL-6,CRP levels,cardiomyocyte apoptosis rate,Bax mRNA expression,mTOR and p-STAT3/STAT3 protein levels were were significantly decreased(P<0.05),Bcl-2 mRNA expression was significantly increased(P<0.05).The above indexes of MHY1485 group rats showed opposite trend.MHY1485 eliminates beneficial effects of ECH on CHD rats.Conclusion:ECH may reduce myocardial inflammatory injury and apoptosis in CHD rats by down-regulating mTOR/STAT3 pathway.