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.

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.

Objective:To confirm the potential etiological factors of congenital aortic stenosis(AS)by genetic analysis on prenatal diagnostic results of the fetus with AS.Methods:Amniocentesis for chromosomal G-band karyotyping combinated with single nucleotide polymorphism array(SNP-array)analysis was conducted on the amniotic fluid collected from a 25-week pregnant woman diagnosed as"fetus AS";chromosome karyotyping was also performed on the peripheral blood of the fetal parents.Results:The fetal karyotype analysis showed a chimeric Y-chromosome isobaric double-adherent granules.The SNP-array analysis results revealed a 11.2 Mb duplication in the Yp11.31q11.21 region and a 14.8 Mb deletion in the Yq11.21q11.23 region.Both the parents presented a normal karyotype,suggesting it was a newfound mutation.After extensive genetic counseling,the pregnant woman and her family chose to terminate the pregnancy locally.Conclusion:The chromosomal karyotype of the chimeric Y-chromosome isobaric double-adherent granules may be a contributing factor to the AS phenotype in the male fetus.The combined use of chromosomal karyotyping and SNP-array analysis on the amniotic cells is instrumental in the early diagnosis of the disease.

Objective To construct HEK 293T cells that express tardigrade Dsup protein fused with green fluorescent protein copGFP in order to study the effect of Dsup protein on proliferation of HEK 293T cells.Methods The CRISPR/Cas9 gene knock-in system was constructed.The target gene fragments of Dsup,copGFP,EF1α and puromycin were amplified by PCR and inserted into pAAVS1-SFFV to construct the fusion vector of Dsup and copGFP,which was known as pAAVS1-SFFV-Dsup-copGFP-EF1α-Puro.pAAVS1-SFFV-Dsup-copGFP-EF1 α-Puro and pAAVS1-CRISPR-Cas9 vector were co-transfected into HEK 293T cells before Dsup gene was inserted into the AAVS1 region of HEK 293T cells via homologous recombination.The HEK 293T cells expressing Dsup gene were obtained following puromycin selection,flow cytometry sorting and genome identification.The expression of Dsup at mRNA and protein levels and proliferation-related genes(MCM2,MCM4,PCNA,Ki-67)were examined to investigate the effects of Dsup gene on the proliferation of HEK 293T-Dsup-copGFP cells.Results The pAAVS1-SFFV-Dsup-copGFP-EF1α-Puro recombinant vector was constructed,and the HEK 293T-Dsup-copGFP cells with Dsup gene inserted in the AAVS1 region were obtained,where both Dsup mRNA and protein were expressed.The cell proliferation rate of HEK 293T-Dsup-copGFP was higher than that of HEK 293T-Control-copGFP(P＜0.001).Further investigation revealed that the expressions of Ki-67 and MCM4 protein in HEK 293T-Dsup-copGFP were significantly higher than in the control group,indicating that the knock in of Dsup gene might enhance the proliferation ability of human cells by promoting the expression of Ki-67 and MCM4 protein.Conclusion A gene editing vector is constructed,and stable cell line HEK 293T-Dsup-copGFP for Dsup fusion expression with copGFP is established.The expression of Dsup gene in HEK 293T cells can promote cell proliferation,possibly by upregulating the expressions of Ki-67 and MCM4 protein.

OBJECTIVE: To explore the genetic basis for a child with Isolated sulfite oxidase deficiency (ISOD). METHODS: The child and her parents were subjected to targeted capture and next-generation sequencing. Pathogenicity of candidate variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). RESULTS: The child was found to harbor compound heterozygous variants of the SUOX gene, namely c.1200C>G (p.Tyr400*) and c.1406_1421delCCTGGCAGGTGGCTAA (p.Thr469Serfs*20), which were inherited from her mother and father, respectively. The c.1200C>G was a known pathogenic variant, while the c.1406_1421delCCTGGCAGGTGGCTAA was unreported previously and predicted to be a pathogenic variant (PVS1+PM2_Supporting +PM3) based on the guidelines from the American College of Medical Genetics and Genomics. CONCLUSION The compound c.1200C>G and c.1406_1421delCCTGGCAGGTGGCTAA variants of the SUOX gene probably underlay the pathogenesis of ISOD in this child. Above finding has expanded the spectrum of SUOX gene variants and provided molecular evidence for the clinical diagnosis and genetic counseling for this pedigree.
Child ; Female ; Humans ; Amino Acid Metabolism, Inborn Errors/genetics* ; Genetic Counseling ; Genomics ; High-Throughput Nucleotide Sequencing ; Mutation

Animals ; Antibodies, Neutralizing/biosynthesis* ; Antibodies, Viral/biosynthesis* ; Body Weight/immunology* ; COVID-19/virology* ; Disease Models, Animal ; Disease Progression ; Humans ; Immunohistochemistry ; Lung/virology* ; Male ; Mesocricetus ; Nasal Cavity/virology* ; RNA, Viral/immunology* ; SARS-CoV-2/pathogenicity* ; Severity of Illness Index ; Viral Load

Objective:To analyze the epidemiological characteristics of geriatric hip fractures.Methods:This study retrospectively analyzed the clinical characteristics of 2 054 elderly patients with hip fracture aged 60 years and over who were admitted to Beijing Hospital from January 2011 to December 2020.The epidemiological characteristics of geriatric hip fractures were analyzed from the aspects of age, gender, fracture type, length of stay, surgical method and surgical complications.Results:The total number of hip fractures patients admitted from 2011 to 2020 showed a general upward trend in quantity.Among them, there were 1 177 femoral neck fractures(57.3%, 1 177/2 054), and 877 intertrochanteric femoral fractures(42.7%, 877/2 054)with statistical differences in the distribution of fracture types between patients at different ages( χ2=61.727, P<0.001). A total of 1 839 patients chose surgical treatment, accounting for 89.5% of the total number of patients.Artificial femoral head arthroplasty was the most common operation mode for patients with femoral neck fractures(783 cases, 75.4%).534 patients with intertrochanteric femoral fractures(66.8%)were treated with closed reduction and femoral intramedullary nailing.There was a statistically significant difference in operation modes among different fracture types( χ2=1 480.800, P<0.001). The length of hospital stay in patients with femoral neck fracture was(14.2±8.3)days, which was significantly longer than in patients with femoral neck fracture(13.2±10.9)days( t=2.417, P=0.016). There was no significant difference in the time from admission to operation between the two groups[(5.7±3.5)days vs.(5.4±3.3)days]( t=1.954, P=0.051). Among all the comorbidities of hip fracture patients, the top 5 diseases were cardiovascular system diseases(2 001 cases, 97.4%), nervous system diseases(1 105 cases, 53.8%), endocrine system diseases(814 cases, 39.6%), skeletal and muscular system diseases(623 cases, 30.3%), digestive system diseases(472 cases, 23.0%).1 485 patients(72.3%)had 3 or more comorbidities. Conclusions:Hip fractures in the elderly have some epidemiological distribution characteristics in terms of age, gender, length of hospitalization, injury mechanism and comorbidities, which is conducive to further improve the prevention and treatment strategies for hip fractures and promote the rational allocation of medical resources.

Issues caused by maxillofacial tumours involve not only dealing with tumours but also repairing jaw bone defects. In traditional tumour therapy, the systemic toxicity of chemotherapeutic drugs, invasive surgical resection, intractable tumour recurrence, and metastasis are major threats to the patients' lives in the clinic. Fortunately, biomaterial-based intervention can improve the efficiency of tumour treatment and decrease the possibility of recurrence and metastasis, suggesting new promising antitumour therapies. In addition, maxillofacial bone tissue defects caused by tumours and their treatment can negatively affect the physiological and psychological health of patients, and investment in treatment can result in a multitude of burdens to society. Biomaterials are promising options because they have good biocompatibility and bioactive properties for stimulation of bone regeneration. More interestingly, an integrated material regimen that combines tumour therapy with bone repair is a promising treatment option. Herein, we summarized traditional and biomaterial-mediated maxillofacial tumour treatments and analysed biomaterials for bone defect repair. Furthermore, we proposed a promising and superior design of dual-functional biomaterials for simultaneous tumour therapy and bone regeneration to provide a new strategy for managing maxillofacial tumours and improve the quality of life of patients in the future.
Biocompatible Materials ; Bone Regeneration ; Bone and Bones ; Humans ; Quality of Life

Objective:To analysis effectiveness of the "14 plus 7 day quarantine" and "nucleic acid plus total antibody testing" strategy (combined screening strategy) for screenin the imported patients with COVID-19 in Xiamen.Methods:The study populations were overseas travelers arriving in Xiamen from March 17 to December 31, 2020, and overseas travelers who had quarantine outside Xiamen for less than 21 days from July 18 to December 31, 2020. Data were collected and analyzed on the timing of detection, pathways, and test results of the imported patients with COVID-19 after implementing combined screening strategy.Results:A total of 304 imported patients with COVID-19 were found from 174 628 overseas travelers and 943 overseas travelers from other cities. A total of 163 cases (53.6%) were diagnosed by multitime, multisite intensive nucleic acid testing after positive finding in total antibody testing. Among them, 27 (8.9%) were first positive for nucleic acid in 14 plus 7 day quarantine and 136 were first positive for nucleic acid in 14-day quarantine. Only 8 of these individuals were tested positive for nucleic acid after positive total antibody testing. The other 128 individuals were tested positive for nucleic acid after being negative for average 2.3 times (maximum of 6 times). Aditional 155 cases might be detected by using the combined "14 plus 7 day quarantine" and " nucleic acid plus total antibody testing" strategy compared with "14-day quarantine and nucleic acid testing" strategy, accounting for 51.0% of the total inbound infections. So the combined screening strategy doubled the detection rate for imported patients with COVID-19. No second-generation case caused by overseas travelers had been reported in Xiamen as of February 26, 2021.Conclusions:Xiamen's combined screening strategy can effectively screen the imported patients with COVID-19 who were first positive for nucleic acid after 14 day quarantine. Compared with "14 day quarantine and nucleic acid testing", the combined screening strategy improved detection rate and further reduced the risk of the secondary transmission caused by the imported patients with COVID-19.

OBJECTIVETo investigate the associations of occupational, educational and residential factors with the outcomes of in vitro fertilization -embryo transfer (IVF-ET).

METHODSA retrospective analysis was conducted among 3998 patients undergoing the first treatment with IVF-ET and 3064 perinatal infants in our center between January, 2010 and June, 2014. The relation of the patients' occupation, educational background, and residence registry with IVF-ET outcomes was analyzed.

RESULTSThe risk of abortion in the first trimester was significantly higher in female patients engaged in agriculture (OR=4.319, P=0.047). Occupation and educational background of the patients and their spouse were related with the incidence of ectopic pregnancy following IVF-ET. The total incidence rate of perinatal birth defects was 2.1% in this cohort, and was the highest in Shenzhen (5.5%) but this difference was not statistically significant (P>0.05).

CONCLUSIONThe patients' occupation and educational background are related with the outcomes of IVF-ET, suggesting the importance of health education and prenatal examination.

Abortion, Spontaneous ; Educational Status ; Embryo Transfer ; Female ; Fertilization in Vitro ; Humans ; Incidence ; Infant ; Occupations ; Pregnancy ; Pregnancy Outcome ; Pregnancy, Ectopic ; Residence Characteristics ; Retrospective Studies