ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

Objective:To investigate the clinical effects of adjustable external fixation traction combined with arthroscopic microfracture in the treatment of osteochondral lesions of the talus (OLT).Methods:A retrospective study was conducted to analyze the data of 27 OLT patients who had been treated at Department of Orthopedics, Beijing Rehabilitation Hospital from May 2017 to March 2022. There were 16 males and 11 females, aged (32.4±7.2) years. Lesion site: 23 medial and 4 lateral cases; Hepple staging: 7 cases at stage Ⅰ, 15 cases at stage Ⅱ, and 5 cases at stage Ⅲ; disease duration: (10.6±3.3) months. All the patients were treated by adjustable external fixation traction combined with arthroscopic microfracture. Recorded were the patients' visual analogue scale (VAS) pain scores and American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores at 6 months and 12 months after surgery, levels of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor- α (TNF- α) at 1 month after surgery, lesion area at 12 months after surgery, and incidence of complications. Results:The follow-up time for this cohort was (16.2±6.7) months. The AOFAS score was (61.52±6.75) points before surgery, (84.15±5.56) points at 6 months after surgery and (95.67±4.30) points at 12 months after surgery. The VAS score was (5.88±1.02) points before surgery, (2.12±0.48) points at 6 months after surgery and (0.66±0.36) points at 12 months after surgery. The two-by-two comparisons between the 3 time points for the above items were statistically significant ( P<0.05). IL-1 was (32.37±6.64) pg/mL, IL-6 (34.04±7.12) pg/mL, and TNF- α (17.89±4.96) ng/L at 1 month after surgery in the 27 patients, all of which were significantly lower than their preoperative levels [(96.63±14.80) pg/mL, (102.33±20.42) pg/mL, and (54.48±9.33) ng/L] ( P<0.05). The lesion area was (28.66±6.52) mm 2 at 12 months after surgery, significantly smaller than the value before surgery [(128.52±11.32) mm 2] ( P<0.05). Infection at the adjustable external fixation needle track occurred in 1 patient and lower limb thrombosis in 2 patients. Conclusion:In the treatment of OLT, adjustable external fixation and traction combined with arthroscopic microfracture can achieve satisfactory results and improve symptoms for the patients.

Abstract: Objective　To genotype and analyze whole genomic features of Coxsackievirus B3 (CVB3) isolated in Tianjin, to improve evolution information of CVB3 virus in Tianjin, and to provide basis for surveillance and early warning of related diseases. Methods　Viral RNA was extracted from five CVB3 strains isolated in Tianjin, whole genome sequence of the virus was amplified by RT-PCR and sequenced by next-generation sequencing method, and phylogenetic and recombinant analysis were carried out. Results　The open reading frame 1(ORF) of the five CVB3 strains contained 6 555 nucleotides and encoded 2 185 amino acids, and ORF2 was composed of sequences encoding 68 amino acids. The nucleotide sequence similarity ranged from 78.3%-100%, and the amino acid sequence similarity ranged from 95.7%-100%. Compared with the CVB3 prototype strain, the nucleotide sequence similarity of the five viruses was between 78.2%-79.1%, and the similarity of amino acid sequences was 94.9%-95.3%. All five viruses exhibited a T151A mutation on the VP2 protein. Additionally, the encephalitis isolate showed a K158E mutation on the VP2 protein, while one of the sewage isolates had a C234T mutation in 5' noncoding region. The five strains belonged to two different genotypes, among which the encephalitis isolate in 2016 belonged to the D genotype, while the sewage isolates in 2021 belonged to the E genotype. This is also the first report of E genotype CVB3 in northern China. The CVB3 strain may have recombinant events in non-structural protein regions, in which encephalitis isolate may recombine with a Coxsackievirus B5 (CVB5) strain, while sewage isolates may have recombinant events with a strain of ECHO virus 18 (E18). Conclusions　The CVB3 isolates in Tianjin belong to D and E genotypes, and recombination events may exist in non-structural protein region of the viral genome. The results of CVB3 virus genome analysis in sewage suggests presence of CVB3 infection in the population of Tianjin, and its epidemic dominant genotype may have changed.

OBJECTIVES: To analyze the results of neonatal screening for congenital hypothyroidism (CH) and hyperphenylalaninemia (HPA) in Zhejiang province from 1999 to 2022. METHODS: A total of 11 922 318 newborns were screened from September 1999 and December 2022 in Zhejiang province. The blood thyroid stimulating hormone (TSH) levels were measured by a fluorescence method and blood phenylalanine (Phe) levels were measured by fluorescence method or tandem mass spectrometry. TSH≥9 μIU/mL was considered positive for CH, while Phe>120 μmol/L and/or Phe/Tyr ratio>2.0 were considered positive for HPA. The positive newborns in screening were recalled, and the gene variations were detected by high-throughput sequencing and MassARRAY tests. RESULTS: The overall neonatal screening rate during 1999-2022 was 89.41% (11 922 318/13 333 929) and the screening rate was increased from 6.46% in 1999 to 100.0% in 2022. A total of 8924 cases of CH were diagnosed among screened newborns with an incidence rate of 1/1336. A total of 563 cases of HPA were diagnosed, including 508 cases of classic phenylketonuria (cPKU) and 55 cases of tetrahydrobiopterin deficiency (BH4D), with an incidence rate of 1/21 176. Ninety-seven out of 8924 cases of CH underwent genetic analysis. Gene mutations were detected in 9 CH related genes, the highest frequency mutations were found in DUOX2 gene (69.0%) with c.3329G>A (p.R1110Q) (18.2%) and c.1588A>T (p.K530X) (17.3%) as the hotspot mutations. There were 81 PAH gene variants detected in a total of 250 cases of cPKU, and c728G>A (p.R243Q) (24.4%), c.721C>T (p.R241C) (15.0%) were the hotspot mutations. Meanwhile 7 novel variants in PAH gene were detected: c.107C>A (p.S36*), c.137G>T (p.G46V), c.148A>G(p.K50E), c.285C>T (p.I95I), c.843-10delTTCC, exon4-7del and c.1066-2A>G. There were 12 PTS gene variants detected in 36 cases of BH4D, and c.259C>T (p.P87S) (31.9%) was the hotspot mutation. CONCLUSIONS The incident of CH has increased from 1999 to 2022 in Zhejiang province, and it is higher than that of national and global levels; while the incidence of HPA is similar to the national average. DUOX2 gene variation is the most common in CH patients; c.728G>A (p.R243Q) is the hotspot mutation in cPKU patients, while c.259C>T (p.P87S) is the hotspot mutation in BH4D patients.
Humans ; Infant, Newborn ; Neonatal Screening ; Dual Oxidases ; Congenital Hypothyroidism/genetics* ; Phenylketonurias/genetics* ; Thyrotropin

Objective:To investigate the clinical effects of tibial transverse bone transport assisted by nose ring drainage (NRD) in the treatment of foot and ankle chronic osteomyelitis.Methods:A retrospective study was conducted to analyze the data of 32 patients with foot and ankle chronic osteomyelitis who had been treated at Department of Orthopedics, Beijing Rehabilitation Hospital from March 2013 to February 2022. The patients were assigned into a study group and a control group. In the control group, there were 12 males and 3 females, aged (39.5±8.8) years. The osteomyelitis was located at the distal tibia in 4 cases, at the talus in 1 case, at the calcaneus in 2 cases, at the midfoot in 4 cases and at the forefoot in 4 cases. According to the Crerny-Mader classification, there were 5 cases of type Ⅰ and 10 cases of type Ⅱ. The control group was treated with Ilizarov transverse tibial bone transport in combination with thorough debridement and anti-infection therapy. In the study group, there were 12 males and 5 females, aged (42.3±13.4) years. The osteomyelitis was located at the distal tibia in 4 cases, at the talus in 1 case, at the calcaneus in 3 cases, at the midfoot in 5 cases and at the forefoot in 4 cases. According to the Crerny-Mader classification, there were 7 cases of type Ⅰ and 10 cases of type Ⅱ. The study group was treated with NRD drainage in addition to the procedures in the control group. The curative effects were evaluated by comparing the cure, recurrence, amputation (toe amputation), antibiotic use time, wound healing time, relevant inflammatory indicators [WBC, neutrophil percentage (NEU), erythrocyte sedimentation rate (ESR), procalcitonin, interleukin-6 (IL-6), C-reactive protein (CRP)], and postoperative functional recovery between the 2 groups.Results:The 2 groups were comparable because there was no statistically significant difference in the general data between them ( P>0.05). The follow-up period was (36.0±9.8) months. There was no significant difference between the 2 groups in the cure or amputation (toe amputation) ( P>0.05), but the recurrence rate in the study group was significantly lower than that in the control group ( P<0.05). The antibiotic use time [(20.7±3.6) d] and wound healing time [(88.3±17.1) d] in the study group were significantly shorter than those [(37.9±6.5) d and (102.2±22.6) d] in the control group ( P<0.05). The ESR, IL-6 and CRP at 1 week after operation in the study group were significantly lower than those in the control group ( P<0.05), but there was no significant difference between the 2 groups in the WBC, NEU or PCT at 1 week after operation ( P>0.05). There was no significant difference either in the inflammatory indicators between the 2 groups at 1 month after operation ( P>0.05). In all patients, the inflammatory indicators like WBC, NEU, ESR, PCT, IL-6 and CRP at 1 week and 1 month after operation were significantly better than those before operation, and the Maryland foot functional score at 12 months after operation was significantly higher than the preoperative one ( P<0.05). There was no significant difference between the 2 groups in the Maryland foot functional score at 12 months after operation ( P>0.05). Conclusion:In the treatment of foot and ankle chronic osteomyelitis, compared with the Ilizarov transverse tibial bone transport, our tibial transverse bone transport assisted by NRD can achieve satisfactory therapeutic effects, shorten antibiotic use time and treatment cycle, and reduce recurrence rate.

Objective:To evaluate the performance of machine learning (ML) based on automated breast volume scanner (ABVS) radiomics in distinguishing benign and malignant BI-RADS 4 lesions.Methods:Between May to December 2020, patients with BI-RADS 4 lesions from the Affiliated Hospital of Southwest Medical University (Center 1) and Guangdong Provincial Hospital of Traditional Chinese Medicine (Center 2) were prospectively collected and divided into training cohort (Center 1) and external validation cohort (Center 2). The radiomics features of BI-RADS 4 lesions were extracted from the axial, sagittal and coronal ABVS images by MaZda software. In the training cohort, 7 feature selection methods and thirteen ML algorithms were combined in pairs to construct different ML models, and the 6 models with the best performance were verified in the external validation cohort to determine the final ML model. Finally, the diagnostic performance and confidence (5-point scale) of radiologists (R1, R2 and R3, with 3, 6 and 10 years of experience, respectively) with or without the model were evaluated.Results:①A total of 251 BI-RADS 4 lesions were enrolled, including 178 lesions (91 benign, 87 malignant) in the training cohort and 73 lesions (44 benign, 29 malignant) in the external validation cases. ②In the training cohort, the 6 ML models (DNN-RFE, AdaBoost-RFE, LR-RFE, LDA-RFE, Bagging-RFE and SVM-RFE) had the best diagnostic performance, and their AUCs were 0.972, 0.969, 0.968, 0.968, 0.967 and 0.962, respectively. ③In the external validation cohort, the DNN-RFE still had the best performance with the AUC, accuracy, sensitivity, specificity, PPV and NPV were 0.886, 0.836, 0.934, 0.776, 86.8% and 82.5%, respectively. ④Before model assistance, R1 had the worst diagnostic performance with the accuracy, sensitivity, specificity, PPV and NPV were 0.680, 0.750, 0.640, 57% and 81%, respectively. After model assistance, the diagnostic performance of R1 was significantly improved ( P=0.039), and its diagnostic sensitivity, specificity, accuracy, PPV and NPV improved to 0.730, 0.810, 0.930, 68% and 94%; while the improvement of R2 and R3 were not significantly ( P=0.811, 0.752). Meanwhile, the overall diagnostic confidence of the 3 radiologists increased from 2.8 to 3.3 ( P<0.001). Conclusions:The performance of ML based on ABVS radiomics in distinguishing between benign and malignant BI-RADS 4 lesions is good, which may improve the diagnostic performance of inexperienced radiologists and enhance diagnostic confidence.

Objective: To solve the problems of low throughput of current cell migration research methods，which was difficult to establish a stable concentration gradient and observe cell migration behavior in real time，a six-channel array microfluidic chip was designed in this paper． Methods : In this paper，a six-channel array microfluidic chip is designed．Firstly，multiphysics modeling and numerical simulation were performed using the finite element analysis software COMSOL Multiphysics 5．5 to analyze the flow behavior of the main pipeline of cell migration. Then，the throughput advantage of the device was verified by testing the chemotaxis response of healthy human neutrophils to different types of chemokine gradients in this microfluidic chip．Subsequently，by analyzing the migration rate of neutrophils in 6 patients with type II diabetes mellitus and 3 healthy people，the clinical applicability of the annular six-channel array microfluidic chip was further verified．Finally，the Pearson coefficient was used to analyze the correlation between neutrophil chemotaxis function and some physiological indicators in patients with diabetes. Results: The concentration gradient data inside the pipeline simulated by the simulation software was compatible with the real-time fluorescence test data of the pipeline．The average migration rate of healthy human neutrophils was (0．21 ± 0．01 ) μm / s in 100 nmol / L interleukin-8 ( IL-8 ) environment and (0．22 ± 0．01 ) μm / s in 100 nmol / L N-Formyl-Met-Leu-Phe ( fMLP) environment． In the comparison of neutrophil migration experiments between healthy people and diabetic patients，the chemotaxis rate of neutrophils in healthy people was (0．19 ± 0．01) μm / s ，and the neutrophil chemotaxis rate in diabetic patients was (0. 15 ± 0. 02 ) μm / s． Correlation analysis showed that neutrophil migration rate in patients with type II diabetes mellitus was inversely correlated with glycated hemoglobin． Conclusion The high-throughput microfluidic chip proposed in this paper allowed rapid and selective detection of cell migration characteristics at the single-cell level，and it could be used as a new tool for cell migration research.

Objective: To evaluate the quality of tandem mass spectrometry (MSMS) screening for neonatal inherited metabolic diseases in Zhejiang Province from 2009 to 2021. Methods: The data pertaining to MSMS screening for neonatal inherited metabolic diseases in Zhejiang Province from 2009 to 2021 were collected from the database created by Zhejiang Provincial Center for Neonatal Disease Screening. The percentage of MSMS screening, percentage of recall of suspected screening-positive infants and incidence of neonatal inherited metabolic diseases were analyzed retrospectively to evaluate the quality of MSMS screening for inherited metabolic diseases. Results: A total of 4 706 916 newborns were screened among 8 297 039 live births by MSMS in Zhejiang Province from 2009 to 2021, and the percentage of MSMS screening increased from 5.48% to 97.54%, with a mean percentage of 56.73%. Of 46 838 suspected screening-positive infants, 45 527 infants were recalled, and the percentage of recall increased from 94.57% to 98.62%, with a mean percentage of 97.20%. A total of 1 038 infants were definitively diagnosed with inherited metabolic diseases in Zhejiang Province from 2009 to 2021, with an overall incidence rate of 1/4 535, and the incidence rates of amino acid metabolic disorder, fatty acid oxidation metabolic disorder and organic acid metabolic disorder were 1/11 767, 1/13 763 and 1\15 902, respectively. Of the 11 cities in Zhejiang Province, the highest percentage of tandem mass spectrometry screening for inherited metabolic diseases was found in Hangzhou City (83.01%), and the highest percentage of recall of suspected screening-positive infants was se en in Zhoushan City (99.08%). Conclusions A high percentage of MSMS screening for neonatal inherited metabolic diseases was observed in Zhejiang Province from 2009 to 2021; however, there was a region-specific percentage of screening, and the recall of suspected screening-positive infants remains to be improved.

Abstract Neonatal disease screening is a major tool for prevention of birth defects, and monitoring and evaluation of neonatal disease screening facilitates the improvements in screening quality and efficiency. A strict quality control of screening, diagnosis, treatment and follow-up of neonatal diseases is performed in Zhejiang Provincial Center for Quality Control of Neonatal Disease Screening. In this study, the data pertaining to screening of neonatal inherited metabolic diseases, hearing loss and congenital heart diseases were collected in Zhejiang Province from 2018 to 2020, and the screening rate, recall rate of suspected screening-positive neonates, and detection rate of diseases were calculated to assess the quality of neonatal disease screening. The screening rate and recall rate of neonatal inherited metabolic diseases, hearing loss and congenital heart diseases were high in Zhejiang Province, and the detection of screened diseases was stable, indicating a high overall quality of neonatal disease screening. Increasing the impact of neonatal disease screening and consolidating the screening achievements should be given a high priority during the future quality control of neonatal disease screening in Zhejiang Province.