Objective To study the complexity of helical tomotherapy plans for different anatomical sites and explore its correlations with dosimetric verification.Methods A total of 71 complexity metrics of the helical tomotherapy plans executed by Accuray?planning system v.5.1.9.2 for nasopharyngeal carcinoma(n=52),breast cancer(n=19),cervical cancer(n=52)and central nervous system cancer(n=37)were analyzed.The correlations between metrics were analyzed,and principal component analysis was used for dimensionality reduction.The global complexity score(normalized plan complexity score,nPCS)was calculated.The top-contributing complexity metrics within the first 10 principal components were extracted,and a correlation analysis with the gamma passing rate was conducted.Results There was no significant correlation between most metrics.The global complexity score was different for different sites,with the highest median nPCS and the most complex plan in the head and neck cancer.The correlation analysis between the global complexity score and gamma passing rate revealed that in the central nervous system plans,CFNS90 and EPSTV1_0 had strong correlations with gamma passing rate for 3%/2 mm criterion,and a significant correlation was found between CFNS90 and gamma passing rate for 3%/3 mm criterion.Conclusion Complexity scores can quantize the complexity of helical tomotherapy plans for different sites,and certain metrics are correlated with gamma passing rate.

Objective To study the complexity of helical tomotherapy plans for different anatomical sites and explore its correlations with dosimetric verification.Methods A total of 71 complexity metrics of the helical tomotherapy plans executed by Accuray?planning system v.5.1.9.2 for nasopharyngeal carcinoma(n=52),breast cancer(n=19),cervical cancer(n=52)and central nervous system cancer(n=37)were analyzed.The correlations between metrics were analyzed,and principal component analysis was used for dimensionality reduction.The global complexity score(normalized plan complexity score,nPCS)was calculated.The top-contributing complexity metrics within the first 10 principal components were extracted,and a correlation analysis with the gamma passing rate was conducted.Results There was no significant correlation between most metrics.The global complexity score was different for different sites,with the highest median nPCS and the most complex plan in the head and neck cancer.The correlation analysis between the global complexity score and gamma passing rate revealed that in the central nervous system plans,CFNS90 and EPSTV1_0 had strong correlations with gamma passing rate for 3%/2 mm criterion,and a significant correlation was found between CFNS90 and gamma passing rate for 3%/3 mm criterion.Conclusion Complexity scores can quantize the complexity of helical tomotherapy plans for different sites,and certain metrics are correlated with gamma passing rate.

OBJECTIVES: To explore the neuroprotective mechanism of electroacupuncture at the acupoints Baihui and Shenting in rats with cerebral ischemia-reperfusion (IR) injury. METHODS: Forty-eight male SD rats were equally randomized into sham operation group, cerebral IR model group, acupoint electroacupuncture group and non-acupoint acupuncture group. In the latter 3 groups, cerebral focal ischemic injury was induced using the Longa method; in the two electroacupuncture groups, electroacupuncture was performed either at the acupoints Baihui and Shenting or at non-acupoint sites for 7 days. The changes in neurological deficit scores, cerebral infarction volume, learning and memory function, pathologies in hippocampal CA1 area, neuronal and synaptic ultrastructures, and synaptic density of the rats were observed, and serum GABA level and mRNA and protein expressions of GABA_AR α1, CaMK II, SYN1 and PSD-95 in the hippocampal tissue were detected. RESULTS: Compared with those in cerebral IR model group, the rats receiving electroacupuncture at the acupoints, but not those with electroacupuncture at the non-acupoints, showed significantly decreased neurological deficit scores and cerebral infarction volume with shortened escape latency and increased platform crossings. Electroacupuncture at the acupoints significantly increased neuronal cell number, decreased the width of the synaptic gaps and increased density of synaptic bodies in the ischemic hippocampal CA1 area, resulting also in increased serum GABA levels and hippocampal expressions of GABA_ARα1, SYN1 and PSD-95 and lowered expression level of CaMK II. CONCLUSIONS Electroacupuncture at Baihui and Shenting improves learning and memory function of rats with cerebral IR injury possibly through a mechanism that promotes synaptic regeneration, upregulates hippocampal expressions of GABAAR α 1, SYN1 and PSD-95 and downregulates the expression of CaMK II.
Animals ; Electroacupuncture ; Reperfusion Injury/therapy* ; Male ; Rats ; Rats, Sprague-Dawley ; Brain Ischemia/therapy* ; Hippocampus/metabolism* ; Memory ; Learning ; Disks Large Homolog 4 Protein/metabolism* ; Synapses ; Acupuncture Points ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism* ; Receptors, GABA-A/metabolism* ; gamma-Aminobutyric Acid/metabolism*

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

Objective To conduct hazard vulnerability analysis(HVA)in a blood bank,aimed to identify high-risk e-vents and optimize emergency management measures.Methods The risk event evaluation index system was established by referring to the Kaiser model and the situation of Guangzhou Blood Center,and risk events were ranked by risk matrix and Borda count.Results The top five events with the highest risk values identified by Kaiser model were information system e-mergencies(39.61％),extreme weather(38.03％),major public sentiment(37.86％),public health events(37.37％)and policy changes(37.24％).The results of risk matrix and Borda count revealed 1 extremely high-risk indicator as information system emergency,5 high-risk indicators with the highest risk being major public sentiment,11 medium-risk indicators with the highest risk being major medical disputes and 1 low-risk indicator as external fires.Conclusion Conducting HVA in combination with the actual situation of blood banks can effectively identify high-risk events and provide theoretical basis for improving emergency management measures.

Objective To investigate the mechanisms of microRNA-211-5p (miR-211-5p) in regulation of proliferation, apoptosis, migration, invasion, and collagen synthesis of human hypertrophic scar fibroblasts (HSFBs) via the transforming growth factor (TGF)-β1/Smad homolog 2 (Smad2) signaling pathway. Methods HSFBs were randomly divided into control, miR-NC, miR-211-5p mimic, anti-miR-211-5p, and miR-211-5p mimic + SB431542 (TGF-β1/Smad2 signaling pathway inhibitor) groups. After 72 hours of continuous culture, quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to detect miR-211-5p expression, western blot was employed to assess TGF-β1 and Smad2 protein levels, methyl-thiazoldiphenyl-tetrazolium (MTT) assay was performed to measure cell proliferation, flow cytometry was utilized to analyze apoptosis rates, Transwell chambers were applied to evaluate cell invasion and migration, and western blot was again utilized to quantify type I collagen (Col-Ⅰ) and type Ⅲ collagen (Col-Ⅲ) protein expressions. An animal model of hypertrophic scars was established in rats using a constant temperature and pressure electric scalding apparatus. Following successful modeling, rats in each group received tail vein injections of miR-NC or miR-211-5p mimic. Scar healing was assessed, and histopathological changes in scar tissue were observed via hematoxylin and eosin (HE) staining. Results Compared with the control and miR-NC groups, the miR-211-5p mimic group exhibited increased miR-211-5p, TGF-β1, and Smad2 protein expressions, enhanced cell proliferation, reduced invasion and migration capabilities, decreased apoptosis rates, and elevated Col-Ⅰ and Col-Ⅲ protein expressions (P < 0.05). Conversely, the anti-miR-211-5p group displayed opposite trends, and significant differences were observed between the anti-miR-211-5p and miR-211-5p mimic groups for the aforementioned indicators (P < 0.05). Compared to the miR-NC group, the miR-211-5p mimic group had higher scar healing rates and fibroblast counts (P < 0.05). Compared to the miR-211-5p mimic group, the miR-211-5p mimic + SB431542 group showed reduced TGF-β1, Smad2 protein expressions, and weakened cell invasion and migration capabilities (P < 0.05). Conclusion MiR-211-5p may regulate proliferation, apoptosis, migration, invasion, and collagen synthesis of HSFBs by activating the TGF-β1/Smad2 signaling pathway.

Objective:By analyzing the clinical phenotypic characteristics and gene sequences of two patients with Treacher Collins syndrome（TCS）, the biological causes of the disease were determined. Then discuss the therapeutic effect of hearing intervention after bone bridge implantation. Methods:All clinical data of the two family members were collected, and the patients signed the informed consent. The peripheral blood of the proband and family members was extracted, DNA was extracted for whole exome sequencing, and Sanger sequencing was performed on the family members for the mutation site.TCOF1genetic mutations analysis was performed on the paitents. Then, the hearing threshold and speech recognition rate of family 2 proband were evaluated and compared under the sound field between bare ear and wearing bone bridge. Results:In the two pedigrees, the probands of both families presented with auricle deformity, zygomatic and mandibular hypoplasia, micrognathia, hypotropia of the eye fissure, and hypoplasia of the medial eyelashes. The proband of Family 1 also presents with specific features including right-sided narrow anterior nasal aperture and dental hypoplasia, which were consistent with the clinical diagnosis of Treacher Collins syndrome. Genetic testing was conducted on both families, and two heterozygous mutations were identified in the TCOF1 gene: c. 1350_1351dupGG（p. A451Gfs*43） and c. 4362_4366del（p. K1457Efs*12）, resulting in frameshift mutations in the amino acid sequence. Sanger sequencing validation of the TCOF1 gene in the parents of the proband in Family 1 did not detect any mutations. Proband 1 TCOF1 c. 1350_1351dupGG heterozygous variants have not been reported previously. The postoperative monosyllabic speech recognition rate of family 2 proband was 76%, the Categories of Auditory Performance（CAP） score was 6, and the Speech Intelligibility Rating（SIR） score was 4. Assessment using the Meaningful Auditory Integration Scale（MAIS） showed notable improvement in the patient's auditory perception, comprehension, and usage of hearing aids. Evaluation using the Glasgow Children's Benefit Inventory and quality of life assessment revealed significant improvements in the child's self care abilities, daily living and learning, social interactions, and psychological well being, as perceived by the parents. Conclusion:This study has elucidated the biological cause of Treacher Collins syndrome, enriched the spectrum of TCOF1 gene mutations in the Chinese population, and demonstrated that bone bridge implantation can improve the auditory and speech recognition rates in TCS patients.
Child ; Humans ; Mandibulofacial Dysostosis/genetics* ; Quality of Life ; Speech ; Parents ; Mutation ; Nuclear Proteins/genetics* ; Phosphoproteins/genetics*

The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon-intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.
Humans ; Membrane Proteins/genetics* ; Pituitary Neoplasms/genetics* ; Biomarkers

Autism spectrum disorder (ASD) is a neurodevelopmental disorder.Its typical symptoms include social disorder, stereotyped behavior and restrictive interest.In addition, sensory abnormality is also a common symptom of ASD individuals.Pre-attentive processing is an automatic cognitive process that takes place before attention and is independent of consciousness, which reflects the ability to automatically detect changes in the environment of brain.Many researches show that the sensory abnormality and social ability disorder in ASD patients may be related to the defects in the pre-attentive processing stage.Mismatch negativity (MMN) is the most commonly used indicator of pre-attentive processing.ASD individuals show abnormal MMN in response to both social and non-social stimulus.Among them, the pre-attentive processing defect of non-social stimuli in ASD individuals is manifested as the amplitude or latency of MMN induced by single tones, voice or visual stimuli, which is different from that of normal people.The pre-attentive processing defect of social stimuli in ASD individuals is manifested as the amplitude or latency of MMN induced by emotional voice and emotional face, which is different from that of normal people.This result not only helps to find the physiological mechanism of sensory and social disorders in ASD individuals, but also provides theoretical support for MMN as an auxiliary diagnostic index of ASD.Future research on the pre-attentive processing of ASD individuals should pay more attention to enriching the research paradigms of MMN and adopting more kinds of social stimuli.At the same time, the influence of ASD genetic factors on MMN can also be one of the concerns of future research.

Objective:To examine whether the mixed infection rate in pertussis infants is significantly higher than that in non-pertussis infants with respiratory tract infection, to explore the mixed infection pathogen distribution in pertussis infants, and to provide reference for clinical diagnosis and treatment.Methods:A case-control study was conducted on 118 nasopharyngeal swabs collected from infants who applied for clinical pertussis etiological testing (culture and specific nucleic acid detection of Bordetella pertussis) in Beijing Children′s Hospital, Jiaxing Maternity and Child Health Care Hospital and Wuhu No.1 People′s Hospital from August 2018 to January 2021.According to the pertussis etiological testing results, the patients were divided into the pertussis group (65 cases) and non-pertussis group (53 cases). Thirty-three pairs of cases were matched according to age, onset season and city.All nasopharyngeal swabs were tested for infections of other pathogens using FilmArray RP2, which can detect 21 respiratory infection pathogens.The mixed infection rate was compared between groups by Chi- square test. Results:According to the FilmArray RP2 test results, 56.9%(37/65) cases in pertussis group and 15.1%(8/53) cases in the non-pertussis group were positive for multiple pathogens, and the difference was statistically significant ( χ2=21.651, P<0.001). The top 5 mixed infection pathogens in pertussis infants were human rhinovirus/enterovirus (HRV/EV) (38.5%, 25/65), parainfluenza virus (PIV) (18.5%, 12/65), respiratory syncytial virus (RSV) (10.8%, 7/65), coronavirus (Cov) (10.8%, 7/65), and adenovirus (ADV) (7.7%, 5/65). The mixed infection rates of the pertussis group in spring, summer, autumn and winter were 46.2% (6/13), 58.3%(14/24), 55.6%(5/9), and 63.2%(12/19), respectively.Comparison of matched and unmatched cases achieved similar results. Conclusions:Among clinical suspected pertussis infant specimens, the mixed infection rate in confirmed cases is tremendously higher than that in non-pertussis infants.The main mixed infection pathogens in pertussis infants are HRV/EV, PIV, RSV, Cov, and ADV.Mixed infection in pertussis children commonly occurs in four seasons, with the highest incidence in winter.