Objective:To assess the feasibility and efficacy of hypofractionated radiotherapy with simultaneous integrated boost (HFRT-SIB) for patients with non-osteogenic spinal metastases who were not suitable for stereotactic body radiotherapy (SBRT).Methods:A totoal of 26 spinal metastatic lesions in 24 patients with non-osteogenic spinal metastases admitted to Beijing Luhe Hospital affiliated to Capital Medical University from March 2020 to April 2023 were retrospectively analyzed. In our institution, a higher-dose fractionated regimen for spinal metastases was introduced, at a dose of 3 Gy/f ×10 times (5 times a week, once a day) to the clinical target volume (CTV), and simultaneous integrated boost (SIB) of 4 Gy/f ×10 times (5 times a week, once a day) to the gross tumor volume (GTV). The primary endpoint was the overall relief (OR) rates of pain at 12 and 24 weeks post-radiotherapy, while secondary endpoints included the pain response time and duration of pain relief, the incidence of adverse events post-radiotherapy, and the 1-year overall survival (OS) rate. The differences before and after treatment were analyzed by Wilcoxon signed-rank test. OS was assessed using Kaplan-Meier method.Results:The median follow-up was 11.7 (8.0, 17.0) months. At 12 weeks post-radiotherapy, 92% (22/24) of patients achieved OR, and 81% (17/21) obtained OR at 24 weeks post-radiotherapy. The median pain response time was 4 (3, 5) d. At the last follow-up, 42% (10/24) of patients maintained pain relief for over 1 year, with a median duration of pain relief up to 11.0 (6.0, 16.9) months. The 1-year OS rate was 66.3%, and no patients experienced grade 3 or higher acute or chronic adverse events.Conclusion:HFRT-SIB can effectively alleviate pain, and achieve sustained pain control, and does not lead to severe adverse effects in patients with non-osteogenic spinal metastases.

Humans ; COVID-19/genetics* ; SARS-CoV-2/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; CRISPR-Cas Systems/genetics* ; RNA, Viral/genetics*

Humans ; Parkinson Disease/diagnosis* ; Machine Learning

Objective:To study the clinicopathological features, immunophenotype, molecular genetic characteristics and prognosis of renal cell carcinoma associated with TFEB gene rearrangement (TFEBr-RCC).Methods:Eight cases of TFEBr-RCC diagnosed at the West China Hospital of Sichuan University from 2014 to 2022 were collected for clinicopathological, immunohistochemical, fluorescence in situ hybridization and RNA sequencing analyses, with review of literature.Results:Six patients were male and two were female. The patient ages ranged from 25 to 50 years (mean: 34 years, median: 32 years). The tumors were present in the right kidney (3 cases) or the left kidney (5 cases). The maximum diameters of the tumors ranged from 4.0 cm to 18.5 cm, with an average of 8.5 cm. Histologically, majority of the cases (5/8) showed typical biphasic "pseudorosette" structure, while the remaining three cases demonstrated atypical morphology that was similar to epithelioid angiomyolipoma or clear cell renal cell carcinoma. Immunohistochemical study showed positivity of TFEB (8/8), PAX8 (8/8), MART-1 (7/7), and HMB45 (5/6). Interestingly, PD-L1 was variably expressed in all five tested cases. Staining for TFE3 in all cases was negative. TFEB translocation was verified in all 8 cases using TFEB fluorescence in situ hybridization. RNA sequencing showed MALAT1-TFEB gene fusion in 4 of the 5 tested cases (two of which showing novel MALAT1-TFEB fusion sites), and one case with a novel ACTB-TFEB gene fusion. Patient follow-ups ranged from 5 to 96 months (average 47 months). All patients were alive without recurrence or metastasis.Conclusions:TFEBr-RCC tends to occur in young adults and has a good prognosis. Histologically, most of the cases show characteristic biphasic structure, and some cases show epithelioid angiomyolipoma-like or clear cell RCC-like morphology. Immunohistochemical reactivity to TFEB, melanocytic markers and PD-L1 is characteristic. MALAT1-TFEB gene fusion is the most common molecular change, with variable fusion sites.

Objective:To observe the changes of macular visual function after myopic foveoschisis (MF) and pars plana vitrectomy (PPV) combined with internal limiting membrane peeling and air filling.Methods:A single-center, retrospective study. From October 2018 to October 2019, 29 MF inpatients (32 eyes) in Tianjin Eye Hospital were included in this study. There were 3 males (4 eyes) and 26 females (28 eyes). The age was 63.00±3.45 years old. Equivalent spherical lens degree was -14.16±2.54 D, and axial length was 29.14±1.04 mm. Among them, 3 patients (3 eyes) had lamellar macular holes. All eyes underwent standard pars plana three-channel 25G PPV combined with internal limiting membrane peeling and air filling. Before surgery and at 1, 3, and 6 months after surgery, macular microperimetry was performed with a macular integrity assessment instrument, and the mean retinal sensitivitie (MS) within 10° of the macula, fovea 2° and 4° fixation rates (P1, P2), 63% and 95% bivariate contour ellipse area (BCEA) were recorded. The comparison of MS, P1, P2, 63%BCEA and 95%BCEA at different times before and after surgery was performed by paired t test; the comparison of fixation stability rate was performed by χ 2 test. Results:Compared with before surgery, there were significant differences in the improvement of MS in affected eyes at 1, 3 and 6 months after surgery ( t=-2.208, -3.435,-4.919; P=0.038, 0.002, 0.000). In the pairwise comparison at different times after surgery, only 6 months after surgery and 1 month after surgery were significantly different ( P=0.036). Compared with the preoperative P1, P2, 63%BCEA and 95%BCEA, the P1 and P2 of the eyes gradually increased after surgery, while the 63%BCEA and 95%BCEA gradually decreased, however, the difference was not statistically significant (P1: t=-1.595,-1.698,-1.966; P=0.125, 0.104, 0.062. P2: t=-1.622,-1.654,-1.707; P=0.119, 0.112, 0.102. 63%BCEA: t=1.410, 1.409, 1.553; P=0.172, 0.173, 0.135. 95%BCEA: t=1.412, 1.408, 1.564; P=0.172, 0.173, 0.132). Six months after surgery, all the eyes underwent anatomical repositioning of the macular area, and no serious complications such as full-thickness macular hole and macular hole retinal detachment were found. Conclusions:PPV with internal limiting membrane peeling and air filling is an effective and safe method for MF, and the macular function improved significantly within 6 months postoperatively.

We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with low-risk gestational trophoblastic neoplasia (GTN). In this trial (NCT01823315), 276 patients were analyzed. Patients were allocated to three initiated regimens: single-course methotrexate (MTX), single-course MTX + dactinomycin (ACTD), and multi-course MTX (control arm). The primary endpoint was the complete remission (CR) rate by initial drug(s). The primary CR rate was 64.4% with multi-course MTX in the control arm. For the single-course MTX arm, the CR rate was 35.8% by one course; it increased to 59.3% after subsequent multi-course MTX, with non-inferiority to the control (difference -5.1%,95% confidence interval (CI) -19.4% to 9.2%, P = 0.014). After further treatment with multi-course ACTD, the CR rate (93.3%) was similar to that of the control (95.2%, P = 0.577). For the single-course MTX + ACTD arm, the CR rate was 46.7% by one course, which increased to 89.1% after subsequent multi-course, with non-inferiority (difference 24.7%, 95% CI 12.8%-36.6%, P < 0.001) to the control. It was similar to the CR rate by MTX and further ACTD in the control arm (89.1% vs. 95.2%, P =0.135). Four patients experienced recurrence, with no death, during the 2-year follow-up. We demonstrated that chemotherapy initiation with single-course MTX may be an alternative regimen for patients with low-risk GTN.
Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Dactinomycin/adverse effects* ; Female ; Gestational Trophoblastic Disease/drug therapy* ; Humans ; Methotrexate/therapeutic use* ; Pregnancy ; Retrospective Studies

Comorbidities will inevitably lead to an increase in the number of medications used and adverse drug reaction events in elderly patients.Therefore, it is urgent to implement precision medicine in the elderly population.pharmacogenomic testing can increase the opportunity of individualized drug selection for elderly patients, reduce the risk of adverse drug reactions, reduce the cost-effectiveness ratio of medication, improve elderly patients' medication compliance, and thus reduce their readmission rate.Therefore, it is necessary to promote pharmacogenetic testing for elderly patients with comorbidities and polypharmacy, so as to provide measures for the implementation of personalized medicine in the elderly.

Objective:To verify the value of whole genomic copy number variation (WGCNV) detection and scoring system in the diagnosis and prognosis of lung adenocarcinoma.Methods:Seventy-six lung adenocarcinoma specimens including ninety-one tumor samples and twenty adjacent non-tumor lung tissue samples were collected using Laser capture microdissection (LCM). Whole genomic amplification (WGA) was used to enrich DNA and construct a sequencing library for next generation sequencing (NGS). Changes of larger than 5Mb CNV in this study were analyzed and scored. The nuclear grading and score of tumor cells in the surgery and pleural effusion cytology of lung adenocarcinoma specimens were evaluated separately. For each case, we evaluated (1) nuclear size, (2) mitotic counts, (3) nuclear atypia, (4) atypical mitoses. The data of disease-free survive (DFS) and overall survive (OS) were collected for assessing the prognostic value of WGCNV score. Meanwhile, receiver operating characteristic (ROC) and area under curve (AUC) were used to define a cut-off value and evaluate the diagnostic significance in lung adenocarcinoma.Results:The WGCNV scores of twenty adjacent non-tumor lung tissue samples were treated as normal control and all of WGCNV scores of tumor samples range from 0 to 9.95, the median score was 2.7. The WGCNV scores were divided into three groups: low score group <1.74, medium score grade 1.74~4.23, high score grade >4.23. The WGCNV score was positively associated with the nuclear grade scoring ( r=0.780 90, P<0.001). The result for evaluation of prognostic value of the WGCNV scores showed that comparing with low WGCNV score group, Hazard Ratio (HR) of medium score group was 4.11 (95% CI=0.72~23.57) and high score group was 2.07 (95% CI=0.30~14.12). These results suggested that the risks of the medium and high WGCNV score group elevated. According to the analysis results of ROC curve, when the cut off value was 0.01, the sensitivity and specificity for lung adenocarcinoma diagnosis were 97.8% and 95.0% respectively, the positive predictive value (PPV) and negative predictive value (NPV) were 99.0% and 90.1%, respectively, the AUC was 0.981. In the differentiation of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) group and invasive adenocarcinoma group, when the cut off value was 1.8, the sensitivity and specificity between the two groups were 78.1% and 94.4%, and the PPV and NPV were 98.0% and 52.0%, respectively, the AUC was 0.896. Conclusion:This study verifies that WGCNV scoring system has a potential diagnostic and prognostic value in lung adenocarcinoma.

Objective:To verify the value of whole genomic copy number variation (WGCNV) detection and scoring system in the diagnosis and prognosis of lung adenocarcinoma.Methods:Seventy-six lung adenocarcinoma specimens including ninety-one tumor samples and twenty adjacent non-tumor lung tissue samples were collected using Laser capture microdissection (LCM). Whole genomic amplification (WGA) was used to enrich DNA and construct a sequencing library for next generation sequencing (NGS). Changes of larger than 5Mb CNV in this study were analyzed and scored. The nuclear grading and score of tumor cells in the surgery and pleural effusion cytology of lung adenocarcinoma specimens were evaluated separately. For each case, we evaluated (1) nuclear size, (2) mitotic counts, (3) nuclear atypia, (4) atypical mitoses. The data of disease-free survive (DFS) and overall survive (OS) were collected for assessing the prognostic value of WGCNV score. Meanwhile, receiver operating characteristic (ROC) and area under curve (AUC) were used to define a cut-off value and evaluate the diagnostic significance in lung adenocarcinoma.Results:The WGCNV scores of twenty adjacent non-tumor lung tissue samples were treated as normal control and all of WGCNV scores of tumor samples range from 0 to 9.95, the median score was 2.7. The WGCNV scores were divided into three groups: low score group <1.74, medium score grade 1.74~4.23, high score grade >4.23. The WGCNV score was positively associated with the nuclear grade scoring ( r=0.780 90, P<0.001). The result for evaluation of prognostic value of the WGCNV scores showed that comparing with low WGCNV score group, Hazard Ratio (HR) of medium score group was 4.11 (95% CI=0.72~23.57) and high score group was 2.07 (95% CI=0.30~14.12). These results suggested that the risks of the medium and high WGCNV score group elevated. According to the analysis results of ROC curve, when the cut off value was 0.01, the sensitivity and specificity for lung adenocarcinoma diagnosis were 97.8% and 95.0% respectively, the positive predictive value (PPV) and negative predictive value (NPV) were 99.0% and 90.1%, respectively, the AUC was 0.981. In the differentiation of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) group and invasive adenocarcinoma group, when the cut off value was 1.8, the sensitivity and specificity between the two groups were 78.1% and 94.4%, and the PPV and NPV were 98.0% and 52.0%, respectively, the AUC was 0.896. Conclusion:This study verifies that WGCNV scoring system has a potential diagnostic and prognostic value in lung adenocarcinoma.

Objective To analyze the relationship between blood glucose,blood lipid and body mass index (BMI) in elderly patients with hypertension.Methods Form January 2016 to December 2017,376 hypertensive patients over 65 year old in Jinan city were enrolled in this study.The sex,age,BMI,fasting blood glucose and blood lipid were investigated and tested.The prevalence of coronary heart disease and diabetes mellitus in hypertensive patients were investigated,and the relationship between BMI and blood glucose,blood lipid and liver function index were explored.Results Of 376 hypertensive patients,the detection rate of diabetes mellitus was 21.01％ (79/376),221 cases were diagnosed with coronary heart disease,with the detection rate of 58.78％.With the rise of BMI,fasting blood glucose showed an upward trend.Person correlation analysis showed that there was a significant positive correlation between BMI and fasting blood glucose(r =0.167,P =0.003).The difference between TG and TC in different BMI groups was statistically significant(FTG =12.48,P ＜ 0.001;Frc =4.83,P ＜ 0.001).The content of alanine transaminase in the overweight group and obese group was significantly higher than that in the normal body weight group,the difference was statistically significant(F =5.24,P =0.005).Conclusion For elderly hypertensive patients,it is urgent to test blood glucose and coronary heart disease screening.For people over the age of 65,obesity is still an important risk factor for hyperlipidemia and hyperglycemia.Therefore,body weight control is needed in elderly patients with hypertensive.