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.

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

The complement system is a self-protection mechanism of the human body. The abnormal activation of the complement system is involved in the occurrence and development of various diseases. The application of complement inhibitors in many rare diseases was a milestone in leading to the progress of such disease as paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and others. Recently, the application of complement inhibitors has gradually expanded to other complement-related diseases. This review summarizes the literature on the current application of complement inhibitors in rare diseases and looks into the prospects of the application in the rare diseases.

Objective:To evaluate the performance of the Cepheid Xpert Xpress Flu/RSV assay (Xpert) in the detection of children infected with influenza virus (Flu) or respiratory syncytial virus (RSV).Methods:Nasopharyngeal specimens were collected from children who showed symptoms of respiratory infection and tested FluA, FluB and RSV by Xpert and sequencing assay respectively side by side. Discordant result were tested with a laboratory-developed real-time PCR for resolution.Results:A total of 388 nasopharyngeal swabs (NAPs) from children with acute respiratory tract infection were analyzed and the result showed 91.75-94.85% agreement between two tests. The sensitivity of FluA, FluB and RSV detected by Xpert and sequencing assay were 99.21% (125/126) vs. 92.86% (117/126), 100.00% (109/109) vs. 84.40% (92/109) and 100.00% (52/52) vs. 40.38% (21/52), respectively. The specificity of FluA, FluB and RSV detected by Xpert were all lower than that of the sequencing assay: 95.42% (250/262) vs 99.24% (260/262), 99.28% (277/279) vs 99.64% (278/279) and 99.70% (335/336) vs 100.00% (336/336). The positive predictive values (PPV) of FluA, FluB and RSV detected by Xpert were lower than those of the sequencing assay: 91.30% (126/138) vs. 98.33% (118/120), 98.18% (108/110) vs. 98.92% (92/93) and 98.11% (52/53) vs. 100.00% (21/21), respectively. The negative predictive values (NPV) of FluA, FluB and RSV detected by Xpert were higher than those of the sequencing assay: 99.60% (251/252) vs. 96.67% (261/270), 99.64% (279/280) vs. 94.27% (280/297) and 100.00% (337/337) vs. 91.60% (338/369).Conclusions:The Cepheid Xpert Xpress Flu/RSV assay is a sensitive, reliable and rapid assay for the detection of FluA, FluB and RSV in pediatrics.

Objective:To investigate the expression of iron-regulating erythroid factors in different types of erythropoiesis disorders.Methods:From January 2016 to November 2019, the plasma concentrations of iron-regulating erythroid factors were measured by ELISA methods in 47 patients with different types of erythropoiesis disorders. The adaptation orientation of iron-regulating erythroid factor expression with bone marrow erythropoiesis activities (represented by bone marrow-nucleated erythrocytes ratio) was analyzed.Results:The median plasma growth differentiation factor (GDF) 15 levels in patients with polycythemia vera (PV) , pure red cell aplasia (PRCA) , autoimmune hemolytic anemia (AIHA) , and myelodysplastic syndrome (MDS) were 266.01 ng/L (112.40, 452.37) , 110.63 ng/L (81.41, 220.42) , 52.11 ng/L (32.61, 171.66) , and 276.53 (132.16, 525.70) ng/L, respectively, which were significantly higher than those in normal patients with 37.45 (19.65, 57.72) ng/L (all P < 0.01) . The plasma TWSG1 expression levels were not significantly different in patients with PV, PRCA, AIHA, and MDS from those of normal patients (P>0.05) . The median plasma GDF11 level in PV was 74.75 (10.95, 121.32) ng/L, which was significantly higher than 36.90 (3.38, 98.34) ng/L in normal control subjects ( P<0.01) . However, no statistical differences were observed in the other three subjects ( P>0.05) . The median plasma erythroferrone (ERFE) levels in AIHA and PV were 121.76 ng/L (68.12, 343.11) and 129.63 (47.02, 170.03) ng/L, respectively, with the highest level in AIHA in all the studied types of erythropoiesis disorders. The bone marrow-nucleated erythrocytes ratio was significantly and positively correlated with ERFE ( r=0.458, P=0.001) but not with GDF15 ( r=-0.163, P=0.274) , GDF11 ( r=0.120, P=0.421) , and TWSG1 ( r=-0.166, P=0.269) . Conclusion:The expression profile of iron-regulating erythroid factors is not exactly the same in different types of erythropoiesis disorders. ERFE demonstrated the highest correlation with erythropoiesis activities.

OBJECTIVE：To compare the chemical compo sition difference in methanol and petroleum ether fraction from Curcuma longa of different habitats. METHODS ：The ultrasonic method was used to extract C. longa from 7 defferent producingareas（S1-S7），and methanol and petroleum ether fraction were obtained and calculated yield. The curcumin compounds in methanol fraction were determined by LC-MS ；The chemical components in petroleum ether fraction were analyzed by GC-MS ， and the relative percentage content was determined by peak area normalization method after determining its structure by comparing NIST 2005 standard mass spectra and Wiley 275 standard mass spectra. SPSS 25.0 software was used for principle component analysis（PCA）and cluster analysis of relative percentage content of common components in petroleum ether fraction from C. longa of different habitats. At the same time ，the influence of latitude of the habitats on the content of total tumerone （by tumerone and ar-tumerone ）was analyzed. RESULTS ：The yield of methanol fraction were 1.35％-8.90％ from C. longa of 7 habitats；the yield of petroleum ether fraction were 0.81％-4.90％，which were the highest in C. longa from Longyan of Fujian Province. There was no significant difference in the relative content of curcumin compounds（reference peak area ）from S 1，S3-S7，which was in descending order as follows as curcumin ＞desmethoxycurcumin＞bisdemethoxycurcumin. There was slightly different in curcumin compounds of C. longa from S 2，mainly manifesting as the content of bisdemethoxycurcumin was higher than that from other producing areas. Totally 48 chemical compositions were identified from petroleum ether fraction in C. longa from different habitats ， mainly being sesquiterpenoids and monoterpenoids. 23，10，15，18，11，14，15 chemical compositions were identified from S1-S7，accounting for 94.49％，96.09％，95.66％，98.98％，99.24％，89.05％ and 97.27％. There were 4 common compositions in C. longa from different habitats ，which were tumerone （17.90％-43.07％），ar-tumerone（6.97％-33.66％），（6R，7R）-bisabolone （1.60％-4.28％），curlone（6.80％-20.63％）. PCA analysis showed that accumulative contribution rate of former 6 principle components was 100％. Cluster analysis showed that S1，S2， S6 was clustered into a category ，respecrively；and others intoa category. Total content of total tumerone decreased first and then increased as the increase of latitude ，which was the highest in Mianyang of Sichuan province （64.28％）and the lowest in Zhangzhou of Fujian province （26.92％）. CONCLUSIONS ： There are difference in composition and content of methanol and petroleum ether fractions in C. longa from different habitats.

Objective:Lung ultrasound (LUS) has been used in the diagnosis of neonatal respiratory distress syndrome(RDS) successfully, but there have been no multicenter prospective studies to verify its reliability or determine how to grade RDS with LUS findings.This study aimed to discuss the necessity and feasibility of using LUS findings to determine RDS grades through a multicenter prospective study.Methods:Every researcher participated in the National Neonatal Lung Ultrasound Training Course and receiving 3-6 months of lung ultrasound system training at the National Neonatal Lung Ultrasound Training Center.Patients between June 2018 and May 2020 who met the RDS ultrasound diagnostic criteria and had full available clinical data were included in this study.The LUS examination was completed immediately after the patients were admitted to the hospital.Some of them also underwent chest X-ray examination.Arterial blood gas analysis was completed immediately before or after the LUS ultrasound examination.RDS grading was performed according to the LUS findings and whether the patient had serious complications.Results:A total of 275 qualifying cases were included in this study, which included 220 premature infants and 55 full-term infants, and the primary RDS occurred in 117 cases (42.5%), and secondary RDS occurred in 158 cases (57.5%). LUS manifestations of RDS patients can be divided into three categories: (1)A ground-glass opacity sign: which could be found among 50 infants when they were admitted to the hospital (that was, at their first LUS examination). Twenty-eight of these infants were considered to have wet lungs and were not sent for special management on admission, but LUS showed typical snowflake-like lung consolidation within 0.5 to 4 hours.Twenty-two of them were given mechanical ventilation with exogenous pulmonary surfactant; Eighteen cases were controlled within 6-12 hours, but the lung lesions became more severe in the other 4 infants (due to severe intrauterine infection). (2)Snowflake-like lung consolidations: the first LUS on admission showed typical snowflake-like lung consolidation involving areas ranging from 1-2 intercostal spaces to 12 lung divisions in 204 cases.Thirty-eight infants among them the lung consolidation only had involvement of 1-2 intercostal spaces at the time of admission; Fifteen of them received invasive respiratory support and recovered within 4-12 hours.Twelve patients received noninvasive respiratory support; Seven of them recovered, while five cases developed severe lung illness.The remaining 11 patients who were not given any form of ventilator support developed severe conditions within 1-4 hours.Thirty of them showed snowflake signs involving 12 lung regions at admission.The remaining 136 patients had lung consolidation degree between the two degree above condition.(3)Snowflake-like sign with complications: Twenty-one patients had severe complications such as pneumothorax, pulmonary hemorrhage or/and persistent pulmonary hypertension of the newborn or large area atelectasis, etc, although snowflake lung consolidation did not involve all lung regions.Conclusion:(1) LUS is reliable and accurate for diagnosing RDS.RDS has the same characteristics on ultrasound for both preterm and full-term infants, both primary and secondary RDS.(2) To facilitate the management of RDS, it is necessary to classify RDS according to the ultrasound findings and the presence of severe complications.(3) Based on the results of this study, it is recommended that RDS can be divided into mild, moderate and severe degrees.The exact standards for grading are as follows: Mild RDS: the early stage of RDS, in which lung consolidation shows as a ground-glass opacity sign on ultrasound; Moderate RDS: lung consolidation shows a snowflake sign on ultrasound, not all of the lung fields are involved; Severe RDS meets one or more of the following criteria: lung consolidation shows as a snowflake sign on ultrasound and all lung regions are involved, or regardless of its degree and extent, lung consolidation has caused serious complications, such as pulmonary hemorrhage, pneumothorax, persistent pulmonary hypertension of the newborn, or/and a large area of pulmonary atelectasis.

The purpose of this study was to investigate the NOAEL of the nickel ion and provide with basic data for the biological evaluation of those medical devices containing nickel. Five groups SD rats were repeatedly exposed during 14 d respectively to nickel at first stage doses of 4.9, 3.7, 2.5 mg/(kg.d), and the second stage doses of 1.2, 0.25 mg/(kg.d) by the intravenous route. The results showed that the NOAEL of nickel ion is 0.25 mg/(kg.d) for SD rats, and the result was verified by subchronic systemic toxicity test of nickel alloy. The threshold of toxicological concern (TTC) of nickel is 150 μg/d (based on application of 100-fold uncertainty factor and a body weight of 60 kg)deduced by these data.
Animals ; Equipment and Supplies/adverse effects* ; Nickel/toxicity* ; No-Observed-Adverse-Effect Level ; Rats ; Rats, Sprague-Dawley ; Risk Assessment

Objective:To evaluate a multiplex fluorescent probe real-time PCR kit in the viral pathogen detection among children with acute lower respiratory tract infections.Methods:This study used multiplex fluorescent probe real-time PCR method to detect viral pathogens in 300 nasopharyngeal swabs from children with acute lower respiratory tract infection in Beijing Children′s Hospital (influenza A/B virus, respiratory syncytial virus, adenovirus, parainfluenza virus type I and parainfluenza virus type ⅡI), and liquid chip method was used for comparison. In addition, 136 positive-nasopharyngeal aspirates determined by immunofluorescence test were verified by the multiplex fluorescent probe real-time PCR method .Results:For the 300 nasopharyngeal swabs, 173 and 159 were determined positive by real-time PCR and liquid chip kit, respectively. In addition, real-time PCR method found 22 cases of mixed infection samples with two or more viral pathogens compared with the immunofluorescence method .Conclusions:The multiplex fluorescent probe real-time PCR method has high sensitivity and specificity, and has good application value for the detection of children′s acute lower respiratory tract viral pathogens.