Objective To explore the risk signals of niraparib and provide references for rational and safe clinical medication.Methods Niraparib-related adverse drug events(ADEs)reports from Q1 2017 to Q2 2023 were extracted from the US FDA Adverse Event Reporting System(FAERS)database.Risk signals were identified using the reporting odds ratio(ROR),proportional reporting ratio(PRR),Bayesian confidence propagation neural network(BCPNN),and multi-item gamma Poisson shrinker(MGPS)methods.The Risk signals were described and classified by preferred system organ classes(SOCs)and preferred terms(PTs)from the Medical Dictionary for Regulatory Activities(MedDRA)version 26.1,and the occurrence of niraparib-related ADEs was also analyzed.Results A total of 16,961 ADE reports with niraparib as the primary suspected drug were extracted.Through screening and analysis,32 PTs were identified involving 11 SOCs,which were largely consistent with the information in the drug label.However,suspicious signals not mentioned in the label,including neuropathy peripheral,decreased red blood cell count,reduced hematocrit,dehydration,and hot flashes,require further attention.The median occurrence time was 22 days(IQR 2-98 days),and the Weibull distribution test indicated an early failure-type curve.Conclusion When using niraparib,particularly in early stages of treatment,it is essential to monitor not only the ADEs mentioned in the drug instructions,such as decreased platelet count,nausea and fatigue,but also to pay close attention to the ADEs not included in the instructions,such as peripheral neuropathy and decreased red blood cell count,which exhibit strong signal values,to ensure patient medication safety.

BACKGROUND:Kinesio taping has been widely used as a means of sports protection,but its role as a means to correct abnormal biomechanical changes of the lower limbs during side-step cutting remains unclear. OBJECTIVE:To analyze and compare the changes in lower limb kinematics and dynamics when the subjects complete the side-step cutting of the knee joint under the conditions of kinesio taping,placebo taping and blank control. METHODS:Thirty-nine male college students majoring in basketball were recruited as subjects.Each subject was tested with kinesio taping,placebo taping or no taping.The mechanical correction method was used to patch the dominant knee joint of each subject.The run-up speed of 4.5-5.5 m/s was selected to complete the 45° side-step cutting motion,and the kinematics and kinetics data were collected synchronously by the three-dimensional dynamic capture system and the force measuring platform.The kinematics and kinetics parameters at the moment of initial touchdown and peak ground reaction force were selected for data analysis.SPSS 27.0 software was used for statistical analysis of the test data. RESULTS AND CONCLUSION:Kinematic indexes:compared with no taping and placebo taping,the hip abduction and knee valgus angles at the initial touchdown moment were significantly decreased when kinesio taping was used(P<0.05);at the moment of peak lateral ground reaction force,the angles of hip abduction,knee valgus and ankle plantar flexion decreased significantly(P<0.05),and the knee flexion angle was significantly increased(P<0.05).Kinetic indexes:Compared with no taping,both kinesio taping and placebo taping significantly reduced hip abduction and external rotation torque,knee valgus and external rotation torque at the moment of initial touchdown(P<0.05),and significantly reduced peak vertical ground reaction force and peak horizontal backward ground reaction force(P<0.05);in addition,kinesio taping significantly reduced peak lateral ground reaction force compared with no taping and placebo taping(P<0.05).These results indicate that kinesio taping of the knee joint may improve some kinematic and kinetic indexes associated with lower limb injury risk factors during the completion of the side-step cutting in basketball specialized college students to some extent,and may have a positive effect on the prevention of injury during the side-step cutting.In addition,the trends in the effects of placebo taping and kinesio taping on the knee joint are more consistent in terms of changes in some indexes,suggesting that there may be a placebo effect on the mechanism of action of kinesio taping.

Objective To evaluate the effects of spinal manipulation therapy (SMT) on chronic nonspecific neck pain (CNSNP) by using World Health Organization Family International Classifications (WHO-FICs). Methods Randomized controlled trials (RCTs) about the effects of SMT on CNSNP were searched from PubMed, Web of Science, Cochrane Library, EMBASE, EBSCO, CBM and CNKI from database establishment to December 31st, 2021. At least two researchers extracted the data. Cochrane bias risk assessment tool and Physiotherapy Evidence Database Scale were used to evaluate the quality of the included articles. Revman 5.4 software and Stata 16.0 software were used for meta-analyses and publication bias analysis respectively. Results A total of 15 RCTs that represented 1 067 participants were evaluated. In terms of body functions, compared with the control group, SMT significantly reduced Visual Analog Score for pain (MD = -0.85, 95%CI -1.06 to -0.63, P < 0.00001) and Numerical Rating Scale (MD = -0.92, 95%CI -1.29 to -0.55, P < 0.001), increased pressure pain thresholds (SMD = 0.67, 95%CI 0.47 to 0.86, P < 0.001), cervical range of motion (ROM) of flexion/extension (SMD = 0.51, 95%CI 0.33 to 0.68, P < 0.001) and rotation (SMD = 0.20, 95%CI 0.01 to 0.38, P = 0.04), improved root mean square of cervical muscles electromygraphy (MD = 2.17, 95%CI 0.06 to 4.29, P = 0.04), but not significantly in cervical ROM of lateral flexion (SMD = 0.19, 95%CI -0.00 to 0.38, P = 0.06), cervical strength (SMD = -0.18, 95%CI -0.84 to 0.49, P = 0.60) and endurance (SMD = 0.18, 95%CI -0.39 to 0.75, P = 0.53). In term of activities and participation, SMT significantly improved cervical disability (MD = -0.96, 95%CI -1.55 to -0.38, P = 0.001), but not significantly in health status of patients with CNSNP (SMD = 0.08, 95%CI -0.03 to 0.20, P = 0.15). Conclusion SMT could improve pain intensity, pain sensitivity, cervical ROM and disability in patients with CNSNP, but its efficacy on muscle function, proprioception and health status is unclear.

Objective:To analyze the gene variants in patients with primary distal renal tubular acidosis (dRTA), and explore the correlation between the genotype and phenotype.Methods:The Sanger direct sequencing or whole-exome sequencing was used to identify causal variants and the variation pathogenicity was evaluated according to 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines in 44 dRTA patients (37 families) diagnosed in the Affiliated Qingdao Municipal Hospital of Qingdao University and the Affiliated Hospital of Qingdao University from April 2010 to September 2020. The clinical features of the patients were summarized, and the correlation between the genotype and phenotype was investigated.Results:Seven variants of SLC4A1 gene, 17 variants of ATP6V0A4 gene, and 15 variants of ATP6V1B1 gene were identified in 44 patients with dRTA, and of which 11 variants were new ones. According to ACMG guidelines, the pathogenic, likely pathogenic, benign variants among the 39 variants were 22, 16 and 1, respectively. Nine patients were autosomal dominant hereditary dRTA caused by SLC4A1 gene mutation, 4 patients with autosomal recessive hereditary dRTA complicated with Southeast Asian ovalocytosis and anemia were caused by SLC4A1 gene mutation, and 14 patients caused by ATP6V0A4 gene mutation and 8 patients caused by ATP6V1B1 gene mutation were autosomal recessive hereditary dRTA; Two children with dRTA were found to carry one monoallelic defect in ATP6V1B1, and no causal gene mutation was identified in 7 patients. One patient showed incomplete dRTA, and the other 43 patients showed complete dRTA. The prevalence of sensory neural hearing loss caused by ATP6V0A4 and ATP6V1B1 mutation were 2/14 and 6/10 respectively. The frequency of chronic kidney disease in adults, children and infants were 4/4, 2/4, and 1/36, separately. After the drug treatment based on potassium citrate and sodium citrate, the growth and development (28/40) and electrolyte disturbance (41/44) of most patients were significantly improved. Conclusions:The present study has identified 39 variants of SLC4A1, ATP6V0A4 and ATP6V1B1 genes in 44 patients with dRTA, including 11 novel ones. There is a close relationship between genotype and phenotype in dRTA patients and most patients' conditions were improved after proper treatment. This study enriches the human gene mutation database and provides valuable references for diagnosis, treatment and genetic counseling in patients with dRTA.

Objective:To analyze the epidemiological and etiological characteristics of sever fever with thrombocytopenia syndrome (SFTS) cases in Henan province during 2017-2020.Methods:Descriptive epidemiology method was used to analyze the characteristics of SFTS cases in Henan during 2017-2020. Patients' sera in acute phase were collected and tested using real-time fluorescence RT-PCR. The S segment complete sequences of the isolated sever fever with thrombocytopenia syndrome virus (SFTSV) strains were amplified and homology analysis was performed to construct the phylogenetic tree.Results:A total of 1 767 SFTS cases, including 1 000 suspected cases and 767 confirmed cases, were reported in Henan during this period, and 11 cases, including 3 suspected cases and 8 confirmed cases died, the case fatality rate was 0.62% (11/1 767). The incidence decreased year by year. The cases were distributed in 28 counties of 6 cities, and 1 681 cases were reported in Xinyang, accounting for 95.13% (1 681/1 767) of the total. The cases mainly occurred from April to October, accounting for 96.10% (1 698/1 767) of the total. The incidence in males (0.38/100 000) was significantly lower than that in females (0.54/100 000) ( χ 2=54.855, P<0.001). Up to 93.44% (1 651/1 767) of the cases were aged between 40 and 84 years. Farmers accounted for 96.10% (1 698/1 767) of the total cases. One family cluster outbreak occurred in 4 years. A total of 1 110 samples were detected by Henan CDC, in which 435 were SFTS virus positive with an average positive rate of 39.19% (435/1 110). The differences in positive rates of SFTS virus among different years were significant ( χ2=25.405, P<0.001). The sequence homology of complete S segment of the 39 SFTS virus strains ranged from 94.76% to 99.82%. The genetic evolution analysis on the complete S segment of the 39 SFTS virus strains showed that 34 strains belonged to genotype A, 2 strains belonged to genotype B, and 3 strains belonged to genotype D. Conclusions:The incidence of SFTS in Henan was sporadic, and decreased year by year. SFTS had obvious regional and seasonal characteristics, and the area affected by SFTS expanded. The incidence of SFTS was high in elderly female farmers, and the positive rate of SFTS virus varied greatly in different years. The main type of SFTS virus in Henan was genotype A, but the etiological surveillance is still needed.

Objective:To identify the viral etiologies and epidemic characteristics of acute respiratory infection (ARI) in Fuzhou.Methods:The information and respiratory tract specimens of ARI cases from three different types of hospitals in Fuzhou were collected in 2019. Real-time quantitative fluorescent PCR (Polymerase Chain Reaction, PCR) was uesd to detect adenovirus (AdV) and human bocavirus (HBoV), Real-time quantitative fluorescent RT-PCR (Reverse Transcription-PCR, RT-PCR) was used to detect influenza virus A/B (IFV-A/B), respiratory syncytial virus (RSV), parainfluenza virus 1-4 (PIV-1~4), human metapneumovirus (HmpV), coronavirus (CoV)-229E/OC43/HKU1/NL63 and rhinovirus (RV). Chi-square test and Fisher exact test were used to analyze the epidemiological characteristics of ARI cases. Results:Of the 726 ARI cases enrolled, 316 (43.53%) were positive for at least one viral pathogen, of which, 40 cases had dual infection and 9 had triple infection. The viral infection rates in different age groups were significantly different. The main viral pathogens in ARI in Fuzhou in 2019 were IFVs (12.40%), followed by Adv (10.61%), RV (8.82%), and RSV (5.51%). The AdV infection was more common in male ARI cases, and IFV-B, PIV, RSV, RV, and AdV were identified more commonly in children. In addition, the infection with IFVs, RSV, and RV had obvious seasonality.Conclusions:The main pathogens of ARI cases in Fuzhou in 2019 include IFVs, AdV, RV, RSV, etc. The infection of respective virus in ARI cases represent different age-distribution and seasonality.

OBJECTIVE: To investigate the relationship between sleep parameters and suicidal ideation in patients with late-life depression (LLD). METHODS: Seventy-seven LLD patients over 60 years old from Sir Run Run Shaw Hospital of Zhejiang University during July 2017 and July 2018 were included in the study. All patients were assessed with Hamilton Depression Rating Scale (HAMD) and polysomnography (PSG) overnight. The suicidal score of item 3 in HAMD (HAM-D3)was used to define whether there was a suicidal ideation. Participants were subsequently grouped according to endorsement of presence (HAM-D3 score ≥1, =46) versus absence (HAM-D3 score=0, =31) of suicidal ideation symptoms. The sleep efficiency, total sleep time, wakefulness after sleep onset, rapid eye movement percent/latency, and non-rapid eye movement sleep stages 1-3 (N1-N3) were assessed. ANOVA analyses were conducted to explore the correlation of sleep parameters with suicidal ideation between the groups with and without suicidal ideation. In model 1, the HAM-D3 constituted the independent variable in separate ANOVA tests; in model 2 the impact of depressive symptoms were assessed as a covariate with sleep parameters. RESULTS: There was less stage N3 [(55±41)min, =-4.731, <0.05] and the reduced percentage of N3 [(15±11)%, =-4.194, <0.05] in LLD patients with suicidal ideation, compared with the LLD patients without suicidal ideation [(104±49) min, (26±11)%]. Correlation analyses revealed that there was a significant correlation between the suicidal ideation and the percentage of stage N3 and sleep time of stage N3 (both <0.05). CONCLUSIONS Suicidal ideation is associated with less N3 sleep in LLD patients.

The research and development of chronic hepatitis B (CHB) therapeutic drugs has been undergoing rapid development in recent years in order to achieve the World Health Organization's goal of eliminating viral hepatitis as a major public health threat by 2030. The focus of early stage clinical trials (including the first human trial) is the selection of subjects, study design, dose selection, administration method, dose escalation, monitoring, observation and reporting procedures for adverse events/reactions (tolerability evaluation), and criteria for subjects to continue and discontinue administration. Therefore, quantitative pharmacology knowledge is required to analyze the relationship between in vivo drug exposure, efficacy and adverse reactions, and the inclusion of exploratory indicators such as HBV RNA, hepatitis B virus core-related antigen (HBcrAg), etc., to analyze the mechanism and target of innovative drugs and the efficacy of cccDNA in anti-hepatocytes. On the other hand, Phase II-III clinical trials prioritize the optimal dose, efficacy and safety indicators to verify the efficacy and safety of new drugs in a wider range of subjects. This paper refers to the relevant domestic and foreign literature, combined with the author's practical experience in early clinical research, and then briefly introduces the clinical issues that should be paid attention to in the design of clinical trials of CHB innovative drugs.

Objective To investigate the prevalence of Mycoplasma pneumoniae ( Mp) infection in children in Hengyang from 2013 to 2016 and to analyze the p1 genotypes of the isolated Mp strains by using polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP) , nested polymerase chain reaction (nPCR) and rapid-cycle polymerase chain reaction (Rapid-Cycle PCR).Methods Throat swab samples of children with acute respiratory tract infection were collected from four hospitals in Hengyang , Hu-nan Province from 2013 to 2016.Mp strains in these samples were identified by PCR amplification of the 16S rRNA gene.PCR-RFLP, nPCR and Rapid-Cycle PCR were performed for Mp p1 genotyping in order to fur-ther analyze the genotypes of Mp strains circulating in Hengyang .Results A total of 109 clinical strains of Mp were identified from the 984 throat swab samples .The sensitivities of PCR-RFLP and nPCR for genoty-ping MP strains were both 100％, while that of rapid-Cycle PCR was 98 .17％.All of the three methods showed 100％specificity for genotyping.Of all isolated Mp strains, 78.90％ were p1 gene type Ⅰ and 21.10％were p1 gene typeⅡ(t=93.239, P=0.01).From 2013 to 2016, the annual isolation rates of p1 gene type Ⅰ and type Ⅱ strains were 93.10％, 87.5％, 76.92％, 65.79％ and 6.90％, 12.5％, 23.08％, 34.21％, respectively.The rate of Mp p1 gene type Ⅰinfection decreased over year , while that of p1 gene type Ⅱinfection increased gradually .Conclusion PCR-RFLP, nPCR and rapid-Cycle PCR are reliable for genotyping of Mp p1 gene.The predominant genotype of Mp strains circulating in Hengyang is p 1 gene type Ⅰ, but the incidence of p 1 gene type Ⅱinfection gradually increases from 2013 to 2016 .

Objective To explore the characteristics regarding temporal,spatial and spatiotemporal distribution on severe fever with thrombocytopenia syndrome (SFTS) in Henan province.Methods Surveillance data related to SFTS was collected in Henan province,from year 2014 to 2016.Descriptive method was used to analyze the distribution of SFTS.1.7.0 software related to the Public health geographic information system (PHGIS),was applied to draw the spatial distribution map of SFTS.Chi-square test was used to compare the different incidence rates.Results A total of 2 781 SFTS cases,including 34 deaths,were reported in Henan province from 2014 to 2016,with an average annual fatality rate as 1.22％.There were statistically significant differences for the incidence rates of SFTS between different years (P＜0.01).Cases were mainly concentrated from April to October,which accounted for 96.66％ of the total number,with the incidence peak seen in May.Incidence rates of SFTS in spring,summer,autumn were higher than that in winter.The cases were scattering around in 26 counties of 8 cities.Xinyang city reported 2 714 cases,accounting for 97.59％ of the total number of cases in the province.The average annual incidence rate in Xinyang city was 17.22 per 100 000,much higher than that for the whole Henan province (0.98 per 100 000),with statistically significant difference (P＜0.01).Six counties reported having death cases,that accounted for 23.08％ of the total number of counties,reported to have death cases.Two kinds of incidence patterns of SFTS were noticed in Henan province,with aggregation in some local regions or sporadic in individual counties.The number of counties with reporting cases increased annually.The epidemic area was expanding and gradually spreading from south to north areas of the province.Conclusions SFTS was characterized with both temporal and spatial clusters in Henan province.Effective prevention and control measures should be made in accordance with the spatiotemporal distribution and the trend on SFTS.