Objective:To investigate the clinical phenotype and genetic characteristics of patients with Fabry disease caused by a GLA variant, IVS4+919G>A.Methods:It was a prospective study. Fabry disease screening was conducted among high-risk population in Ninghai from October 2021 to August 2023. Those children with decreased α-galactosidase enzyme activity<2.40 μmol/(L·h) or elavated Lyso-GL-3 level>1.10 μg/L in dried blood spot (DBS) method underwent GLA genetic testing for diagnosis confirmation. Meanwhile, family screening was carried out. A proband and his family members diagnosed with Fabry disease were research subjects. The clinical and genetic characteristics of patients with Fabry disease caused by the GLA variant (IVS4+919G>A) were analyzed.Results:The female proband aged 9.8 years with pain in both lower limbs as the initial symptom was found to have a heterozygous GLA variant IVS4+919G>A among 102 patients. In family screening, there were 4 family members (proband's father, elder sister, elder male cousin and elder female cousin) with Fabry disease and a family member (proband's fifth aunt) with a GLA variant. Among these 4 diagnosed family members, the elder male cousin of the proband, a boy aged 13.2 years had a heterozygous GLA variant, IVS4+919G>A with intermittent pain in both lower limbs as the initial symptom. The proband′s father had knee joint pain. The proband′s elder sister had decreased vision and his elder female cousin had no obvious symptoms. The proband′s fifth aunt with a GLA variant had decreased vision.Conclusions:High-risk screening in children and family screening are helpful for early diagnosis and treatment of Fabry disease. Neuropathic pain may be a early symptom in children with Fabry disease caused by the GLA variant, IVS4+919G>A.

Objective To observe the impact factors of the diagnostic accuracy of fine needle aspiration biopsy(FNAB)for papillary thyroid carcinoma(PTC).Methods Totally 468 patients with single PTC confirmed by postoperative pathology who underwent FNAB before surgery were enrolled.The impact of clinica,l ultrasonic and pathological features on the accuracy of FNAB diagnosis were analyzed.Results The accuracy of FNAB for diagnosing PTC was 71.37%(334/468).The maximum diameter and location of PTC were both impact factors of the diagnostic accuracy of FNAB.The maximum diameter of 0.7 cm was the optimal cutoff value of FNAB for diagnosing PTC,and the diagnostic accuracy of FNAB for PTC with the maximum diameter＜0.7 cm and those≥0.7 cm was 62.96%(119/189)and 77.06%(215/279),respectively.The diagnostic accuracy of FNAB for PTC located in the difficult and easy area of puncture was 52.53%(52/99)and 76.42%(282/369),respectively.The diagnostic accuracy of FNAB for PTC with the maximum diameter≥0.7 cm and located in the easy area,≥0.7 cm and located in the difficult area,＜0.7 cm and located in the easy area,＜0.7 cm and located in the difficult area was 80.43%(185/230),61.22%(30/49),69.78%(97/139)and 44.00%(22/50),respectively.Conclusion The maximum diameter and location of PTC were both impact factors of the diagnostic accuracy of FNAB.

Objective:To investigate the correlation between serum inflammatory markers and carotid plaque and its stability in patients with acute ischemic stroke (AIS).Methods:Patients with AIS admitted to Liaocheng Third People’s Hospital from June 2021 to April 2022 were prospectively enrolled. The demographic and relevant clinical data were collected. Color Doppler ultrasound was used to detect carotid artery plaques. The patients were divided into unstable plaque group, stable plaque group and non-plaque group according to plaque characteristics. The levels of serum hypersensitive C-reactive protein (hs-CRP), serum amyloid A (SAA) and interleukin (IL) -6 were detected and compared. Multivariate logistic regression analysis was used to determine the independent risk factors for carotid plaque and its stability. Results:A total of 201 patients with AIS were enrolled, including 87 patients (43.30%) in the non-plaque group, 57 (28.35%) in the stable plaque group, and 57 (28.35%) in the unstable plaque group. The proportion of patients with hypertension and previous stroke history, and hs-CRP, SAA and IL-6 levels in the unstable plaque group was significantly higher than those in the stable plaque group and the non-plaque group (all P<0.05). Multivariate logistic regression analysis showed that after adjusting for other confounding factors, the increased IL-6 level (odds ratio [ OR] 1.174, 95% confidence interval [ CI] 1.049-1.314; P=0.005) was an independent risk factor for the existence of stable plaques, while the previous stroke history ( OR 3.172, 95% CI 1.123-8.957; P=0.029) and the increased IL-6 level ( OR 1.367, 95% CI 1.107-1.687; P=0.004) were the independent risk factors for the existence of unstable plaques. Conclusion:The serum IL-6 level in patients with AIS increase significantly, which is closely associated with the formation and stability of carotid plaques.

Objective    To study the feasibility and safety of CT-guided preoperative Hookwire localization of pulmonary nodules in clinical application. Methods    Clinical data of 102 patients who were scheduled to undergo surgical treatment for pulmonary nodules from June 2015 to April 2020 in the North Ward of Thoracic Surgery Department of Ruijin Hospital were retrospectively analyzed. There were 38 males and 64 females, aged 23-82 (53.2±12.8) years. Results    All 102 patients with pulmonary nodules underwent CT-guided preoperative Hookwire localization successfully, with a localization success rate of 100.0%. The localization time was 27.0 (11-67) min; the number of times to adjust the angle during the positioning process was 6.9 (3-14); the needle depth of the positioning needle was 41.5 (16.3-69.1) mm. A total of 48 (47.1%) patients had a small amount of bleeding in the lung tissue in the positioning area after positioning; 53 (51.9%) patients had a small amount of pneumothorax after positioning; 16 (15.7%) patients were found that the positioning needle completely shedded from the lung tissue in the subsequent surgery. One patient was transferred to open thoracotomy because of extensive dense adhesion in the thorax, and the remaining 101 patients were operated on under thoracoscopy. Postoperative pathology showed that 5 (4.9%) patients were adenocarcinoma in situ, 28 (27.5%) were microinvasive adenocarcinoma, 36 (35.3%) patients were invasive carcinoma and 32 (31.3%) patients were benign lesions. No patients had complications or adverse events related to preoperative positioning. Conclusion    Pre-operative CT-guided localization of Hookwire intrapulmonary nodules is safe and effective, and can meet the intraoperative localization needs of thoracic surgeons in most clinical situations, and is not inferior to other preoperative localization methods currently used in clinics.

Objective:To explore the role and molecular mechanism of trophoblastic cell surface antigen 2 (Trop2) in the invasion and migration of ovarian cancer.Methods:Through the data mining of Cancer Cell Line Encyclopedia and TCGA database, the clinical significance of Trop2 expression was analyzed. Western blot was used to detect Trop2 protein expression in ovarian cancer cell lines including A3O, A1780 and SKOV3. SKOV3 cells were used to construct Trop2-short hairpin RNA (shRNA) cell model. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to detect the SKOV3 mRNA expression in SKOV3-shRNA and SKOV3-NC cells. Cell counting kit-8 (CCK8) was used to detect the proliferation of SKOV3-shRNA cells and SKOV3-NC cells. Flow cytometry was used to detect cell cycle and apoptosis in two groups of cells. Transwell array was used to detecte the invasion and migration of SKOV3-shRNA cells and SKOV3-NC cells. Western blot was used to detect the protein expressions of AKT, p-AKT, β-catenin, caspase3, bcl-2, E-cadherin and vimentin.Results:Trop2 mRNA highly expressed in ovarian cancer, and was related to the tumor stage and patient survival. Compared with A3O cells, Trop2 overexpressed in A1780 and SKOV3 cells ( P<0.05). The relative expression levels of Trop2 mRNA in SKOV3-NC group and SKOV3-shRNA group were 1.18±0.24 and 0.42±0.08, with statistically significant difference ( P<0.05). The results of CCK-8 array showed that the cell viability of SKOV3-NC group was significantly higher than that of SKOV3-shRNA group ( P<0.05). The proportion of G 0/G 1 cells in SKOV3-NC and SKOV3-shRNA groups were (38.67±4.22)% and (60.24±8.17)%, respectively. G 0/G 1 arrest was observed in SKOV3-shRNA cells ( P<0.05). The apoptosis rate of SKOV3-shRNA group was (26.32±1.81)%, significantly higher than (6.54±1.32)% of SKOV3-NC group ( P<0.05). The number of migrating SKOV3 cells in the SKOV3-shRNA and SkOV3-NC groups were 1 255.83±108.44 and 1 679.71±213.92, while the number of invading cells were 242.49±52.09 and 473.54±73.11, respectively. Compared with the SKOV3-NC group, the number of migrating and invading SKOV3-shRNA group was significantly reduced (all P<0.05). The expressions of p-AKT2, Bcl-2, vimentin and β-catenin were down-regulated, and the expressions of caspase 3 and E-cadherin were up-regulated in SKOV3-shRNA cells. There was no significant change in the total protein level of AKT. Conclusions:Trop2 expression is related to ovarian cancer stage and postoperative survival. Trop2 can promote ovarian cancer cell proliferation and metastasis by activating the AKT/β-catenin signaling pathway and knockdown of Trop2 inhibits the progression of ovarian cancer.

Objective:To explore the role and molecular mechanism of trophoblastic cell surface antigen 2 (Trop2) in the invasion and migration of ovarian cancer.Methods:Through the data mining of Cancer Cell Line Encyclopedia and TCGA database, the clinical significance of Trop2 expression was analyzed. Western blot was used to detect Trop2 protein expression in ovarian cancer cell lines including A3O, A1780 and SKOV3. SKOV3 cells were used to construct Trop2-short hairpin RNA (shRNA) cell model. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to detect the SKOV3 mRNA expression in SKOV3-shRNA and SKOV3-NC cells. Cell counting kit-8 (CCK8) was used to detect the proliferation of SKOV3-shRNA cells and SKOV3-NC cells. Flow cytometry was used to detect cell cycle and apoptosis in two groups of cells. Transwell array was used to detecte the invasion and migration of SKOV3-shRNA cells and SKOV3-NC cells. Western blot was used to detect the protein expressions of AKT, p-AKT, β-catenin, caspase3, bcl-2, E-cadherin and vimentin.Results:Trop2 mRNA highly expressed in ovarian cancer, and was related to the tumor stage and patient survival. Compared with A3O cells, Trop2 overexpressed in A1780 and SKOV3 cells ( P<0.05). The relative expression levels of Trop2 mRNA in SKOV3-NC group and SKOV3-shRNA group were 1.18±0.24 and 0.42±0.08, with statistically significant difference ( P<0.05). The results of CCK-8 array showed that the cell viability of SKOV3-NC group was significantly higher than that of SKOV3-shRNA group ( P<0.05). The proportion of G 0/G 1 cells in SKOV3-NC and SKOV3-shRNA groups were (38.67±4.22)% and (60.24±8.17)%, respectively. G 0/G 1 arrest was observed in SKOV3-shRNA cells ( P<0.05). The apoptosis rate of SKOV3-shRNA group was (26.32±1.81)%, significantly higher than (6.54±1.32)% of SKOV3-NC group ( P<0.05). The number of migrating SKOV3 cells in the SKOV3-shRNA and SkOV3-NC groups were 1 255.83±108.44 and 1 679.71±213.92, while the number of invading cells were 242.49±52.09 and 473.54±73.11, respectively. Compared with the SKOV3-NC group, the number of migrating and invading SKOV3-shRNA group was significantly reduced (all P<0.05). The expressions of p-AKT2, Bcl-2, vimentin and β-catenin were down-regulated, and the expressions of caspase 3 and E-cadherin were up-regulated in SKOV3-shRNA cells. There was no significant change in the total protein level of AKT. Conclusions:Trop2 expression is related to ovarian cancer stage and postoperative survival. Trop2 can promote ovarian cancer cell proliferation and metastasis by activating the AKT/β-catenin signaling pathway and knockdown of Trop2 inhibits the progression of ovarian cancer.

The purpose of this paper is to investigate the altered brain areas activated in functional magnetic resonance imaging before and after escitalopram antidepressant treatment in patients with major depressive disorder. Functional magnetic resonance studies showed abnormal activity in brain regions such as prefrontal cortex， cingulate cortex and striatum in patients prior to treatment， meantime， the abnormal activation of anterior cingulate， dorsolateral prefrontal and thalamus reflected the outcomes of escitalopram antidepressant therapy. Following the treatment with escitalopram， the fMRI activation of brain areas returned to normal， and those changes were significantly correlated with the improvement of depressive symptoms. So this paper provides a review of the brain functional activity changes in patients with major depressive disorder before treatment and at different time point of medication， as well as the correlation between altered brain functional activity and clinical symptoms.

Objective:To explore the effect of metastatic lymph node ratio (MLR) on the prognosis of adjuvant radiotherapy for stage-Ⅲ gastric cancer patients with no more than 15 lymph nodes dissection.Methods:According to the inclusion and exclusion criteria, a total of 590 patients diagnosed with stage-Ⅲ gastric cancer (excluding adenocarcinoma of esophagogastric junction) were included in this study from the SEER database between 2010 and 2016. No more than 15 lymph nodes were examined in all patients. Among them, 291 patients received surgery combined with adjuvant chemotherapy (surgery + chemotherapy group), and 299 patients received surgery combined with adjuvant radiochemotherapy (surgery + radiochemotherapy group). These two groups were treated with 1∶1 propensity score matching (PSM). We retrospectively analyzed the effect of MLR on prognosis of stage-Ⅲ gastric cancer patients with no more than 15 lymph nodes dissection, and evaluated the significance of postoperative adjuvant radiotherapy among patients with different MLR.Results:According to the analysis result of area under curve (ROC), 0.5 was defined as the best cut-off point of MLR. In the two groups of patients with stage-Ⅲ gastric cancer included in the study, the median survival time was 23 months in the surgery + radiochemotherapy group, and the 1 -, 3 -, and 5-year overall survival (OS) ratio were 77.1%, 33.2% and 22.8%, respectively. The median survival time was 21 months in the surgery + chemotherapy group, and the 1 -, 3 -, and 5-year OS ratio were 72.2%, 33.6% and 23.1%, respectively. There was no statistically significant difference between the two groups in OS. The result of subgroup analysis showed that there was no statistically significant difference in OS between the surgery + radiochemotherapy group and the surgery + chemotherapy group among patients with MLR≤0.5, while OS of the surgery + radiochemotherapy group was significantly better than the surgery + chemotherapy group among patients with MLR>0.5( χ2=8.542, P < 0.05). Multivariate Cox regression analysis showed that race, T stage, N stage, MLR and adjuvant radiotherapy were the important factors affecting OS of stage-Ⅲ gastric cancer patients with no more than 15 lymph nodes dissection( Wald=8.544, 7.547, 10.925, 18.047, 10.715, P < 0.05). After PSM, there was no statistically significant difference in OS between the two groups. The result of subgroup analysis showed that there was no statistically significant difference in OS between the surgery + radiochemotherapy group and the surgery + chemotherapy group among patients with MLR≤0.5, while OS of the surgery + radiochemotherapy group was significantly better than the surgery + chemotherapy group among patients with MLR>0.5( χ2=6.944, P < 0.05). Multivariate Cox regression analysis showed that race, T stage, N stage, MLR and adjuvant radiotherapy were the important factors affecting OS of stage-Ⅲ gastric cancer patients with no more than 15 lymph nodes dissection ( Wald=7.154, 8.023, 7.744, 17.016, 4.149, P < 0.05). The result of prognosis analysis of two groups before and after PSM were consistent. Conclusions:MLR is an important prognostic factor for stage-Ⅲ gastric cancer patients with no more than 15 lymph nodes dissection. The OS of patients with MLR ≤ 0.5 can′t benefit from postoperative adjuvant radiotherapy, while patients with MLR > 0.5 should be advised to receive postoperative adjuvant radiotherapy to improve the prognosis.

Objective:To investigate the effect of chemotherapy combined with postoperative adjuvant radiotherapy on the overall survival (OS) of early and advanced (Ⅰ-Ⅱ A and Ⅱ B-Ⅳ) small cell neuroendocrine carcinoma of the cervix (SCNEC)patients and analyze the prognostic factors. Methods:The Surveillance, Epidemiology and End Result (SEER) database was used to search and screen out 269 SCNEC patients who received chemotherapy from 2004 to 2016. These patients were divided into four groups according to different treatment regimens: chemotherapy + postoperative radiotherapy group, chemotherapy + surgery group, chemotherapy + radiotherapy group and chemotherapy-alone group. Kaplan-Meier curve was utilized to compare the OS of SCNEC patients with stage Ⅰ-Ⅱ A and Ⅱ B-Ⅳ with different treatment regimens. Log-rank test and Cox regression analysis were used to evaluate significant clinicopathological factors on prognosis. Results:For patients with stage Ⅰ-Ⅱ A, the 5-year OS rate of chemotherapy + postoperative radiotherapy group, chemotherapy + surgery group, chemotherapy + radiotherapy group and chemotherapy-alone group were 39.9%, 71.7%, 24.5% and 0, respectively. Among patients with stage Ⅰ-Ⅱ A, chemotherapy + surgery group had a better prognosis ( HR 0.403, 95% CI: 0.112-1.112, P=0.047) than chemotherapy + postoperative radiotherapy group. For stage Ⅱ B-Ⅳ patients, the 5-year OS rate of the chemotherapy + postoperative radiotherapy group, chemotherapy + surgery group, chemotherapy + radiotherapy group and chemotherapy-alone group were 35.2%, 24.3%, 17.7% and 0, respectively. Among patients with stage Ⅱ B-Ⅳ, chemotherapy + surgery group, chemotherapy + radiotherapy group and chemotherapy-alone group all had worse prognosis ( HR 1.726, 95% CI: 0.944-3.157; HR 1.605, 95% CI: 0.968-2.661; HR 5.632, 95% CI: 3.143-10.093, P<0.05) than chemotherapy + postoperative radiotherapy group, respectively. In addition, the patients whose age ≤60 years old and tumor diameter<4 cm had a worse prognosis compared to those older than 60 years old ( HR 7.868, 95% CI: 3.032-20.415; HR 1.465, 95% CI: 1.006-2.435, P<0.05)and tumor diameter≥4 cm ( HR 2.576, 95% CI: 1.056-6.287; HR 1.965, 95% CI: 1.026-3.766, P<0.05). Conclusions:Chemotherapy combined with postoperative adjuvant radiotherapy can′t improve the OS of patients with early (Ⅰ-Ⅱ A) SCNEC, but can significantly improve the OS of advanced (Ⅱ B-Ⅳ) patients. Age, tumor size and treatment regimens are independent risk factors.

Objective To investigate the application of CT image and cone beam computed tomography (CBCT) image registration based on 3D Slicer software in image-guided radiotherapy for uterine cervical neoplasms. Methods Based on 3D Slicer software and Slicer RT toolkit, 10 positioning CT images and 50 CBCT images of 10 patients with uterine cervical neoplasms in Henan Provincial People's Hospital between January 2018 and October 2018 had rigid registration and b-spline deformation registration respectively. The dice similarity coefficient (DSC) and Hausdorff distance (HD) of the bladder, rectum, femoral head, spinal cord, and body of CT-CBCT images were compared by using paired t-test before and after the registration. Results Pre-registration, rigid registration and after b-spline deformation registration of CT images and CBCT images, the DSC in the bladder (0.459±0.177, 0.528±0.184, 0.542±0.187, respectively), the rectum (0.564±0.141, 0.632±0.091, 0.684±0.097, respectively), the femoral head (0.695±0.088, 0.833± 0.030, 0.865±0.027, respectively), the spinal cord (0.587±0.119, 0.746±0.085, 0.834±0.032, respectively) and the body surface (0.922±0.013, 0.948±0.011, 0.959±0.009, respectively) showed an increased trend; HD in the bladder (12.8±7.2, 12.2±7.1, 11.7±7.3, respectively), the rectum (5.0±1.8, 4.4±1.2, 3.4±1.2, respectively), the femoral head (3.6±1.2, 1.8±0.5, 1.5 ±0.5, respectively), the spinal cord (4.0 ±1.0, 2.7 ±1.3, 1.8 ±0.5, respectively) and the body surface (6.3±2.1, 5.2±2.0, 4.3±2.0, respectively) showed a decreased trend. The differences of pairwise comparison in the same parts were statistically significant (all P < 0.05). Conclusions Both rigid registration and b-spline deformation registration of CT-CBCT images based on 3D Slicer softwarecan improve the radiotherapy accuracy of uterine cervical neoplasms, and b-spline deformation registration has more significant advantages.