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 genetic basis for a girl with primary microcephaly and growth retardation. METHODS: A girl who was admitted to Guangdong Maternal and Child Health Care Hospital in was selected as the study subject. Peripheral blood samples were collected from the child and her parents. Trio whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethnics Committee of Guangdong Maternal and Child Health Care Hospital (Ethics No. 202201278). RESULTS: DNA sequencing revealed that the child has harbored compound heterozygous variants of the WDR62 gene, including a frameshifting c.2963delC (p.Pro988Argfs*80) variant in exon 24 which was inherited from the unaffected father, and a nonsense c.3163G>T (p.Glu1055*) variant in exon 26, which was inherited from her unaffected mother. Both variants were predicted to affect the reading frame of the WDR62 gene. CONCLUSION Based on the clinical manifestations, results of genetic testing and pedigree analysis, the compound heterozygous variants were predicted to underlay the pathogenesis of microcephaly and growth retardation in this child. Above discovery has expanded the mutational spectrum for WDR62-associated Primary microcephaly type 2, and facilitated genetic counseling for the family.
Female ; Humans ; Cell Cycle Proteins ; Heterozygote ; Microcephaly/genetics* ; Mutation ; Nerve Tissue Proteins/genetics* ; Pedigree

OBJECTIVE: To explore the clinical and genetic characteristics of five fetuses with Harlequin ichthyosis (HI). METHODS: Five fetuses with HI diagnosed at Guangdong Women and Children Hospital between 2017 and 2024 were selected as study subjects. Clinical and laboratory data were collected and reviewed. Whole exome sequencing (WES) was carried out, and candidate variants were verified by bioinformatic analysis. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 202401024). RESULTS: The five fetuses had presented with ectropion, eclabium and contracture and flexion of fingers and toes. WES revealed that all had harbored compound heterozygous or homozygous variants of the ABCA12 gene. Among the eight types of variants, five were unreported previously. CONCLUSION The compound heterozygous or homozygous variants of the ABCA12 gene probably underlay the HI in the five fetuses. Clinicians should be vigilant about the possibility of HI in fetus with ectropion, eclabium, and contracture and flexion of fingers and toes.
Humans ; Ichthyosis, Lamellar/genetics* ; Female ; ATP-Binding Cassette Transporters/genetics* ; Pregnancy ; Genotype ; Phenotype ; Exome Sequencing ; Fetus ; Mutation ; Male ; Adult

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 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 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 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 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.