Zebrafish larvae are useful for identifying chemicals against lateral line (LL) hair cell (HC) damage and this type of chemical screen mainly focuses on searching for protectors against cell death. To expand the candidate pool of HC protectors, a self-built acoustic escape response (AER)-detecting system was developed to apply both low-frequency near-field sound transmission and AER image acquisition/processing modules. The device quickly confirmed the changed LL HC functions caused by most known ototoxins, protectors, and neural transmission modifiers, or knockdown of LL HC-expressing genes. With ten devices wired in tandem, five 'hit' chemicals were identified from 124 cyclin-dependent kinase inhibitors to partially restore cisplatin-damaged AER in less than a day. AS2863619, ribociclib, and SU9516 among the hits, protected the HCs in the mouse cochlea. Therefore, using free-swimming larval zebrafish, the self-made AER-detecting device can efficiently identify compounds that are protective against HC damage, including cell death and loss-of-function.
Animals ; Zebrafish ; Hair Cells, Auditory/physiology* ; Lateral Line System/cytology* ; Escape Reaction/physiology* ; Larva ; Mice ; Cisplatin/toxicity* ; Drug Evaluation, Preclinical/methods*

Microbial communities such as those residing in the human gut are highly diverse and complex, and many with important implications for health and diseases. The effects and functions of these microbial communities are determined not only by their species compositions and diversities but also by the dynamic intra- and inter-cellular states at the transcriptional level. Powerful and scalable technologies capable of acquiring single-microbe-resolution RNA sequencing information in order to achieve a comprehensive understanding of complex microbial communities together with their hosts are therefore utterly needed. Here we report the development and utilization of a droplet-based smRNA-seq (single-microbe RNA sequencing) method capable of identifying large species varieties in human samples, which we name smRandom-seq2. Together with a triple-module computational pipeline designed for the bacteria and bacteriophage sequencing data by smRandom-seq2 in four human gut samples, we established a single-cell level bacterial transcriptional landscape of human gut microbiome, which included 29,742 single microbes and 329 unique species. Distinct adaptive response states among species in Prevotella and Roseburia genera and intrinsic adaptive strategy heterogeneity in Phascolarctobacterium succinatutens were uncovered. Additionally, we identified hundreds of novel host-phage transcriptional activity associations in the human gut microbiome. Our results indicated that smRandom-seq2 is a high-throughput and high-resolution smRNA-seq technique that is highly adaptable to complex microbial communities in real-world situations and promises new perspectives in the understanding of human microbiomes.
Humans ; Gastrointestinal Microbiome/genetics* ; Bacteriophages/physiology* ; High-Throughput Nucleotide Sequencing ; Sequence Analysis, RNA/methods* ; Bacteria/virology*

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Aim To observe the behavioral effects of exogenous allopregnanolone(ALLO)and its inhibitor finasteride on the receptive period(R)and non-recep-tive period(NR)of PMDD liver-qi inversion model rats and the expression of GABAARα4,GABAARδ mR-NA and protein effects to explore its pathogenesis.Methods The PMDD liver-qi reverse syndrome rat model was prepared.The rats were divided into the normal group R and NR(control-R,control-NR),model group R and NR(Model-R,Model-NR),nor-mal group R+ALLO and NR+ALLO(Control+A-R,Control+A-NR),and model group R+ALLO and NR+ALLO(Model+A-R,Model+A-NR),model group R+finasteride and NR+finasteride(Model+F-R,Model+F-NR).The elevated cross labyrinth ex-periment and social interaction experiment were used to detect the behaviors of rats;fluorescence quantitative PCR and immunofluorescence were used to detect the expression of GABAARα4 and 8 mRNA and protein in rat amygdala and hippocampus.Results In the be-havioral evaluation,in the NR period,in the elevated cross maze test and in the social interaction test,the rats in the model group had anxiety behavior and de-creased social communication ability(P＜0.05),while the rats in the Model+A group could effectively relieve anxiety symptoms and improve their social com-munication ability(P＜0.05),and the rats in the Model+F group had increased anxiety behavior and social disorder(P＜0.05).In fluorescence quantita-tive PCR and immunofluorescence experiments,the ex-pression of GABAARα4 subunit in the model group was up-regulated in the hippocampus(P＜0.01),and the expression of δ subunit was down-regulated(P＜0.01);the expression of GABAARα4 subunit in the a-mygdala and hippocampus of the Model+A group de-creased(P＜0.01),and the expression of δ subunit increased in the hippocampus(P＜0.01).Conclu-sions The abnormal expression of GABAARα4 and 8 subunits mediated by ALLO improves the anxiety symptoms and social interaction ability of PMDD,which is the pathogenesis of PMDD liver-qi reverse syndrome,and provides basis and support for subse-quent exploration of the pathogenesis of PMDD liver-qi reverse syndrome.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

Objective To investigate the clinical significance of serum S100 calcium binding protein(S100 A4)and S100A12 in patients with severe traumatic brain injury(sTBI).Methods A total of 147 sTBI pa-tients admitted to Handan Central Hospital from March 2021 to March 2023 were selected as the sTBI group,and 50 healthy subjects who underwent physical examination in Handan Central Hospital during the same pe-riod were selected as the control group.The correlation between S100A4,S100A12 levels and brain injury markers and the influencing factors of early death in sTBI patients were analyzed,and the predictive value of serum S100A4 and S100A12 for early death in sTBI patients was studied.Results The serum levels of S100A4,S100A12,myelin basic protein(MBP),S100B and neuron specific enolase(NSE)in sTBI group were significantly higher than those in control group(P＜0.05).The serum levels of S100A4 and S100A12 were positively correlated with MBP,NSE and S100B in sTBI patients(P＜0.05).Multivariate Logistic regression analysis showed that decreased Glasgow coma scale(GCS)score on admission and increased serum levels of S100A4,S100A12,MBP,NSE and S100B were risk factors for early death in sTBI patients(P＜0.05).Receiv-er operating characteristic curve showed that the combination of serum S100A4 and S100A12 with GCS score,MBP,NSE and S100B was superior to any single detection in predicting early death in sTBI patients.Conclu-sion The serum levels of S100A4 and S100A12 are increased in sTBI patients,which are related to the aggra-vations of brain injury and early death.The combined detection of S100A4 and S100A12 has a good predictive value for early death in sTBI patients.

Objective The reliability and validity of the SGGC-Net-based motion capture system(SGGC-Net system)and SIMI system for parsing walking gait were compared using a three-dimensional(3D)motion capture system(Vicon)with marker points as a reference standard.Methods Thirty healthy college students were recruited,and their gait characteristics while walking on a treadmill were analyzed.Kinematic data were collected using the Vicon system,and video data were collected synchronously using four cameras to obtain the right shoulder,elbow,hip,knee,and ankle joint angles.Reliability was assessed using intraclass correlation coefficients(ICCs)with 95％confidence intervals and standard error of measurement(SEM).Validity was assessed using multiple correlation coefficients(MCCs)and root mean square errors(RMSEs).Results The ICCs of the maximum and minimum 3D coordinate angles of the upper and lower limb joints of the SGGC-Net system ranged from 0.798-0.990 with an SEM of 0.04°-0.95°,and the ICCs of the SIMI system ranged from 0.650-0.967,with an SEM of 0.31°-1.24°.The ICCs of the SGGC-Net system were higher than those of the SIMI system for all joint angles except for the minimum hip and maximum knee angles.Compared to the joint angle curves derived from the SIMI system,the MCCs of the curves derived from the SGGC-Net system ranged from 0.945-0.996,with RMSEs of 1.44°-4.65°,and the multiple correlation coefficients of the SIMI system ranged from 0.815-0.986,with RMSEs of 2.56°-9.99°.The MCCs of the SGGC-Net system were greater than those of the SIMI system at all angles except for the ankle joint.The RMSEs of the SGGC-Net system were smaller than those of the SIMI system at all angles except for the ankle joints.Conclusions The SGGC-Net system has better reliability and validity than the SIMI system in most of the variables,and it has better repeatability and accuracy in analyzing walking gait.It can be applied to motion capture environments without marker points,such as technical analysis of athletes'movements and clinical gait analysis of special populations.

BACKGROUND:Disseminated intravascular coagulation(DIC)is associated with increased mortality in sepsis patients.In this study,we aimed to assess the clinical ability of sepsis-induced coagulopathy(SIC)and sepsis-associated coagulopathy(SAC)criteria in identifying overt-DIC and pre-DIC status in sepsis patients. METHODS:Data from 419 sepsis patients were retrospectively collected from July 2018 to December 2022.The performances of the SIC and SAC were assessed to identify overt-DIC on days 1,3,7,or 14.The SIC status or SIC score on day 1,the SAC status or SAC score on day 1,and the sum of the SIC or SAC scores on days 1 and 3 were compared in terms of their ability to identify pre-DIC.The SIC or SAC status on day 1 was evaluated as a pre-DIC indicator for anticoagulant initiation. RESULTS:On day 1,the incidences of coagulopathy according to overt-DIC,SIC and SAC criteria were 11.7％,22.0％and 31.5％,respectively.The specificity of SIC for identifying overt-DIC was significantly higher than that of the SAC criteria from day 1 to day 14(P＜0.05).On day 1,the SIC score with a cut-off value＞3 had a significantly higher sensitivity(72.00％)and area under the curve(AUC)(0.69)in identifying pre-DIC than did the SIC or SAC status(sensitivity:SIC status 44.00％,SAC status 52.00％;AUC:SIC status 0.62,SAC status 0.61).The sum of the SIC scores on days 1 and 3 had a higher AUC value for identifying the pre-DIC state than that of SAC(0.79 vs.0.69,P＜0.001).Favorable effects of anticoagulant therapy were observed in SIC(adjusted hazard ratio[HR]=0.216,95％confidence interval[95％CI]:0.060-0.783,P=0.018)and SAC(adjusted HR=0.146,95％CI:0.041-0.513,P=0.003). CONCLUSION:The SIC and SAC seem to be valuable for predicting overt-DIC.The sum of SIC scores on days 1 and 3 has the potential to help identify pre-DIC.

Objective To compare the external morphological characteristics and movement patterns between Schistosoma japonicum and S. sinensis cercariae. Methods S. japonicum and S. sinensis cercariae were heat-fixed, and well-extended cercariae, of 50 each species, were randomly selected for measurement of body length, body width, tail stem length, and tail fork length. The external morphological characteristics of S. japonicum and S. sinensis cercariae were compared. In addition, S. japonicum-infected Oncomelania snails and S. sinensis-infected Tricula snails were observed under a microscope and the movement patterns of S. japonicum and S. sinensis cercariae were compared. Results The mean body length, body width, tail stem length, and tail fork length were (0.16 ± 0.01), (0.05 ± 0.01), (0.14 ± 0.01) mm and (0.06 ± 0.01) mm for S. japonicum cercariae, and (0.13 ± 0.01), (0.05 ± 0.01), (0.13 ± 0.01) mm and (0.06 ± 0.01) mm for S. sinensis cercariae, respectively, and there were significant differences in terms of cercaria body length (t = 14.583, P < 0.05) and tail stem length (t = 3.861, P < 0.05), while no significant differences were seen in terms of body width (t = 0.896, P > 0.05) or tail fork length (t = −0.454, P > 0.05). Microscopy revealed that the tails of both S. japonicum and S. sinensis cercariae swung from side to side and there was no significant difference in their movement pattern. Conclusion S. sinensis and S. japonicum cercariae share highly similar external external morphological characteristics and movement patterns.