Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

Neoadjuvant therapy for hepatocellular carcinoma is the frontier and hot topic in the current field of liver cancer research.The fundamental purpose is to reduce the risk of postoperative recurrence through standardized preoperative treatment methods.From the attempts of Transcatheter Arterial Chemoembolization monotherapy for neoadjuvant therapy for hepatocellular carcinoma to systematic treatment represented by"targeted combined with immunotherapy",the latter has become the most promising neoadjuvant strategy due to its high objective response rate and potential to induce pathological complete remission.However,the field still faces challenges such as lack of evidence of overall survival benefit in Phase Ⅲ randomized controlled trials,treatment-related adverse reactions that may lead to delay in surgery,optimal population screening,and timing of surgery.This article aims to briefly discuss the current research status of the application of neoadjuvant therapy in resectable hepatocellular carcinoma,explore relevant diagnosis and treatment concepts,and further understand neoadjuvant therapy.

Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

Neoadjuvant therapy for hepatocellular carcinoma is the frontier and hot topic in the current field of liver cancer research.The fundamental purpose is to reduce the risk of postoperative recurrence through standardized preoperative treatment methods.From the attempts of Transcatheter Arterial Chemoembolization monotherapy for neoadjuvant therapy for hepatocellular carcinoma to systematic treatment represented by"targeted combined with immunotherapy",the latter has become the most promising neoadjuvant strategy due to its high objective response rate and potential to induce pathological complete remission.However,the field still faces challenges such as lack of evidence of overall survival benefit in Phase Ⅲ randomized controlled trials,treatment-related adverse reactions that may lead to delay in surgery,optimal population screening,and timing of surgery.This article aims to briefly discuss the current research status of the application of neoadjuvant therapy in resectable hepatocellular carcinoma,explore relevant diagnosis and treatment concepts,and further understand neoadjuvant therapy.

Mechanosensitive channels (MSCs) are special membrane proteins that can convert mechanical stimulation into electrical or chemical signals. These channels have become potential targets for ultrasonic neuromodulation due to their properties. The good spatial resolution and focusing effect of ultrasound make it theoretically possible to achieve non-invasive whole-brain localization. Therefore, ultrasonic neuromodulation is a promising method for performing physical neuromodulation and treating neurological disorders. To date, only a few ion channels have been reported to be activated by ultrasound, while recent research has identified more channels with mechanosensitive properties. Moreover, the opening process and mechanism of MSCs under ultrasound excitation remain unknown. This review provides an overview on recent research advances and applications in MSCs, including large conductance mechanosensitive channels, transient receptor potential channels, degenerated protein/epithelial sodium channels, two-pore potassium channels, and piezo channels. These findings will facilitate future studies and applications of ultrasonic neuromodulation.
Ultrasonics ; Ion Channels/metabolism*

Anaplastic lymphoma kinase (ALK) is the most common fusion gene involved in non-small cell lung cancer (NSCLC), and remarkable response has been achieved with the use of ALK tyrosine kinase inhibitors (ALK-TKIs). However, the clinical efficacy is highly variable. Pre-existing intratumoral heterogeneity (ITH) has been proven to contribute to the poor treatment response and the resistance to targeted therapies. In this work, we investigated whether the variant allele frequencies (VAFs) of ALK fusions can help assess ITH and predict targeted therapy efficacy. Through the application of next-generation sequencing (NGS), 7.2% (326/4548) of patients were detected to be ALK positive. On the basis of the adjusted VAF (adjVAF, VAF normalization for tumor purity) of four different threshold values (adjVAF < 50%, 40%, 30%, or 20%), the association of ALK subclonality with crizotinib efficacy was assessed. Nonetheless, no statistical association was observed between median progression-free survival (PFS) and ALK subclonality assessed by adjVAF, and a poor correlation of adjVAF with PFS was found among the 85 patients who received first-line crizotinib. Results suggest that the ALK VAF determined by hybrid capture-based NGS is probably unreliable for ITH assessment and targeted therapy efficacy prediction in NSCLC.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Anaplastic Lymphoma Kinase/therapeutic use* ; Crizotinib/therapeutic use* ; Lung Neoplasms/pathology* ; Protein Kinase Inhibitors/pharmacology* ; Gene Frequency

Objective:To establish a disk (CD) microfluidic chip detection platform for the rapid detection of CALR-1 and CALR-2 mutations in patients with cerebral infarction, and summarize its clinical application value.Methods:Based on microfluidic technology and loop mediated isothermal amplification technology, a CD microfluidic chip detection platform for simultaneous detection of CALR-1 and CALR-2 gene mutations were established, and the sensitivity, specificity, repeatability and accuracy of the platform were verified. A total of 124 patients with cerebral infarction treated in Huashan Hospital, Shanghai Medical College, Fudan University from November 2019 to March 2021 were prospectively selected into the experimental group; and 80 healthy subjects were included in the control group. The CALR-1 and CALR-2 gene mutations in anticoagulant peripheral blood samples were detected by the CD microfluidic chip. Each chip could detect 4 samples at the same time and synchronously detect 3 indexes of each sample. The detection results could be obtained after isothermal amplification for 40 min. At the same time, sequencing method was used to verify the test results, and the consistency of the results of the two detection methods was compared.Results:Using this CD microfluidic chip platform, the synchronous amplification of 3 indexes in the sample could be completed within 40 min without the need of thermal circulation, and the whole detection process of the sample could be completed within 60 min. For samples with a high concentration of target nucleic acid, typical positive signals could be visualized after amplification for 10 min, and the test results would be available within 30 minutes after receiving the samples. The detection sensitivity of CD microfluidic chip method for CALR-1 and CALR-2 mutation load concentration was 1.0% and 0.5% respectively. Nonspecific amplification was not observed for the non-target nucleic acid samples, indicating the high specificity of this method. The coincidence rates of intra and inter batch repeatability were 100% (20/20) respectively. Two samples with CALR gene mutation were found in the cerebral infarction group, both of which were CALR-1 mutations (L367fs*46). There was no CALR-1 or CALR-2 mutation in the control group. The detection results of CD microfluidic chip method were completely consistent with the sequencing verification results (100% [204/204]).Conclusions:The CD microfluidic chip method could be used for the detection of CALR-1 and CALR-2 gene mutations in clinical samples of patients with cerebral infarction. This method has the advantages of high detection sensitivity, good detection specificity, fast detection speed and high detection flux, which is helpful to clarify the etiology of patients with cerebral infarction.

Objective:To study the repair effects of bone marrow mesenchymal stem cells (BMSCs) injection via the caudal vein on the nerve cells in the spinal cord tissue of rats with acute spinal cord injury.Methods:Sixty Sprague-Dawley male rats were divided into sham operation group, model group and BMSCs group using the random number table method, with 20 rats in each group. The Allen's method was used in the model group and BMSCs group to construct the rat models of a spinal cord injury model. Rats in the sham operation group did not undergo spinal cord injury and only received surgical exposure. 24 hours after the establishment of the model, rats in the BMSCs group were received 0.2 ml BMSCs single cell suspension (2 ×10 6 cells) via tail vein injection. Rats in the sham operation group and model group were received the same volume of 0.2 ml Sodium chloride solution via tail vein injection. The motor function of the rats on the 1st, 4th, 7th, 15th and 30th day after modeling was recorded by Basso-Beattie-Bresnahan (BBB) scoring method. The contents of inflammatory factors tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-β) and Prostaglandin E 2 (PGE 2) in spinal cord tissue of rats were detected by enzyme-linked immunosorbent assay (ELASA) on the 30th day after modeling. Hematoxylin-eosin staining was used to observe the pathological changes of rat spinal cord tissue. Nissl staining was used to analyze the changes of Nissl bodies and neuron cells in rat spinal cord tissue. Result:Compared with the model group, the BBB scores of the BMSC group were significantly increased on the 7 (5.68±0.82 vs 1.82±0.84), 15 ( 10.25±1.55 vs 3.38±0.88) and 30 (13.25±2.36 vs 5.83±1.36) days after modeling, and the differences were statistically significant (all P<0.01). Compared with the model group, the levels of TNF-α, IL-1β and PGE 2 in the spinal cord tissue of the BMSCs group were significantly lower than those in the model group on the 30 days after modeling (all P<0.01). Besides, the spinal cord tissue injury was significantly reduced, and the number of neurons and Nissl bodies in the BMSCs group were also significantly higher than those in the model group (all P<0.01). Conclusions:BMSCs injection via the caudal vein can significantly ameliorate acute spinal cord injury in rats. BMSCs may accelerate the repair of nerve cells in acute spinal cord injury tissue and further promote the recovery of motor function in rats with acute spinal cord injury through the regulation of TNF-α, IL-1β, PGE 2 inflammatory factors.

Objective To investigate the eftect of radiation dose of dual-source computed tomography (CT) dual energy single-phase enhanced scan in patients with esophageal cancer.Methods The prospective study was conducted.The clinicopathological data of 56 patients with esophageal cancer who were admitted to the Lishui Hospital of Zhejiang University between January 2015 and December 2016 were collected.All the patients were divided into the experimental group (undergoing dual-source CT dual energy single-phase enhanced scan) and control group (undergoing dual-phase CT enhanced scan) bv randomised block method.TNM classification of esophageal cancer (Seventh Edition) published by American Joint Committee on Cancer (AJCC) was used as a standard TNM staging.Two observers independently read films.All the patients underwent radical resection of esophageal cancer or palliative surgery,and then received adjuvant radiochemotherapy.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival of patients up to March 2017.Observation indicators:(1) consistencies of T staging,N staging and M staging;(2) accuracies of T staging,N staging and M staging (pathological results as a gold standard);(3) radiation dose of CT scan;(4) treatment and follow-up situations.The Kappa test was used for evaluating the consistency,κ≥0.75 as a good consistency,0.40≤κ＜0.75 as a normal consistency and κ＜0.40 as a poor consistency.Comparisons of count data and ratio were done by the chi-square test.Comparisons of measurement data were analyzed by the t test.Results A total of 50 patients were enrolled in the study,including 25 in the experimental group and 25 in the control group.(1) Consistencies of T staging,N staging and M staging:all the 50 patients finished successfully CT scans.Two observers considered that consistencies of T staging,N staging and M staging in the 2 groups were normal (κ =0.452,0.618,0.729,P＜0.05).Consistencies of N staging and M staging were superior to T staging.(2) The pathological results were used as a gold standard.Accuracies of T staging,N staging and M staging in the experimental and control groups were 72％,76％ and 88％,84％ and 92％,88％,respectively,with no statistically significant difference between the 2 groups (x2 =0.10,0.37,0.50,P＞0.05).(3) Radiation dose of CT scan:volume CT dose index (CTDIvol),dose length production (DLP) and effective radiation dose (E) were (10.35±2.01) mGy,(400.63± 34.13) mGy · cm,(5.61 ± 0.47) mSv in the experimental group and (3.55 ± 0.60)mGy,(140.66± 10.89) mGy · cm,(1.98±0.17) mSv in the control group,respectively.There were statistically significant differences in CTDIvol and E between the 2 groups (t =16.23,36.30,P＜0.05).(4) Treatment and follow-up situations:of 50 patients,43 patients received treatments,including 32 undergoing radical resection (11 receiving postoperative adjuvant chemotherapy),6 undergoing palliative surgery,3 receiving single radiotherapy and 2 receiving single chemotherapy.Thirty-six of 43 patients were followed up for 3-18 months,with a median time of 6 months.During follow-up,1-year survival rate was 61.1％.Conclusion Dual-source CT dual energy single-phase enhanced scan in patients with esophageal cancer cannot reduce accuracy of TNM staging,but decreased effectively radiation dose.

Objective To explore the clinical value of CT-guided radiofrequency ablation (RFA) and imaging follow-up for patients with osteoid osteoma.Methods Thirty-seven patients with osteoid osteomas were selected.Their tumors occurred mainly in the femur and tibia (16/37,13/37) with local pain aggravated at night in 32 of the cases.They were treated with CT-guided RFA.One week,1 month and 3 months after the surgery,CT and MRI examinations were conducted to observe the density of the ablated area,any density (signal) changes and the recovery of adjacent tissues.A visual analogue scale (VAS) was used to assess the perceived pain of the patients.Results All of the patients went through the operation successfully and resumed unrestricted normal activity within 2 d to 1 week without complications.Field CT showed a low density of bone defects one month after the ablation,with the bone defect narrowing and peripheral thickened reactive bone thinning slightly 2 months later.One week after the RFA treatment the MRI's T2WI signal was lower than before the treatment and the T1WI signal was low.One month after the RFA the T2WI high signal of 20 of the patients (54.1％) had decreased and the T1WI low signal had narrowed compared to one week after the operation.The signals of the other 17 cases (45.9％) had returned to normal.Three months after the operation the T2WI high signal of 10 of the 20 patients (27％) had decreased further and their T1 WI low signal had also narrowed further compared to one month after the operation,with a total of 27 then normal.After the operation,the average VAS score decreased significantly compared to before the operation.Conclusion CT-guided RFA is a safe and effective minimally invasive method for the treatment of osteoid osteoma.Dynamic imaging is very useful for assessing the therapeutic effect in the short term.