Objective:To investigate the necessity of internal fixation of the fibular fracture in the treatment of degree Ⅱ ankle supination-external rotation injury by the Dias-Tachdjian classification in children.Methods:A retrospective study was conducted to analyze the data of 69 children with ankle fracture (degree Ⅱ ankle supination-external rotation injury by the Dias-Tachdjian classification) who had been treated at Department of Orthopedic Trauma, The People's Hospital of Weifang and Department of Pediatric Orthopedics, Tianjin Hospital from January 2015 to October 2021. There were 41 males and 28 females with an age of (10.1±1.4) years, and 37 left and 32 right sides affected. The patients were divided into 2 groups according to whether internal fixation of the fibular fracture was performed. Group A consisted of 21 cases with fibular internal fixation and group B of 48 cases without fibular internal fixation. The preoperative data, operation time and operation expenses were recorded and compared between the 2 groups. At the last follow-up, the anteroposterior and lateral radiographs of bilateral full length lower limbs and ankle joints were taken; the lateral distal tibial angle (LDTA) and the anterior distal tibial angle (ADTA) on the affected side, and the disparity between bilateral ankle tibiotalar angles were measured; ankle function was assessed according to the ankle-hindfoot score of American Association of Foot and Ankle Surgery (AOFAS); the occurrence of premature physeal closure (PPC) was recorded.Results:There was no significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (19.5±4.1) months. At the last follow-up, the LDTA on the affected side was 89.6° (87.9°, 90.5°) in group A and 88.6°±1.9° in group B; the ADTA on the affected side was 80.9° (79.0°, 81.4°) in group A and 80.0° (78.6°, 81.2°) in group B; the disparity between bilateral ankle tibiotalar angles was 1.1°±0.5° in group A and 1.2°±0.5° in group B; the AOFAS ankle-hindfoot score was (89.5±5.2) points in group A and 89.0 (87.0, 92.0) points in group B. There was no statistically significant difference between the 2 groups in the above items ( P>0.05). The incidence of PPC was, respectively, 14.3% (3/21) and 14.6% (7/48) in groups A and B, showing no statistically significant difference ( P>0.05). Conclusions:In the treatment of degree Ⅱ ankle supination-external rotation injury in children, internal fixation of the fibular fracture has no significant effect on the imaging angles or the function of the ankle joint. After anatomic reduction of the distal tibia, the fibular fracture can be treated without internal fixation to reduce operational trauma, shorten operation time and reduce operation expenses.

Objective:To understand the epidemiological and etiological characteristics of hand-foot-mouth disease (HFMD) in the Nanshan District of Shenzhen City from 2019 to 2022 and to provide a scientific basis for HFMD prevention in the area.Methods:Epidemiological data on HFMD in Shenzhen Nanshan District from 2019 to 2022 in the China Information System for Disease Control and Prevention were analyzed using descriptive research methods.Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to analyze the etiology characteristics of clinical specimens from HFMD patients. The VP1 gene of the dominant pathogen coxsackievirus A6 (CV-A6) was amplified and sequenced. SepMan Pro of DNASTAR software was used for sequence assembly and MegAlign was used for nucleotide homology analysis.Results:A total of 13 195 HFMD cases were reported in Shenzhen Nanshan District from 2019 to 2022, with an average annual incidence rate of 186.18/100, 000. Summer and autumn are the main onset seasons and children under 7 years old were the main population, accounting for 93.1%. The male-to-female ratio is 1.44∶1. A total of 451 clinical HFMD specimens were detected in the laboratory, including 403 positive (87.36%) and 48 negative (10.64%). The main pathogens were CV-A6 (63.03%), coxsackievirus A16 (CV-A16) (27.79%), coxsackievirus A4 (CV-A4) (4.71%), coxsackievirus A10 (CV-A10) (1.99%), Echovirus 11 (Echo-11) (0.25%), and uncertain type accounted for 2.23%, with no detection for enterovirus71 (EV71) type. The nucleotide homology of the 13 CV-A6 strains ranged from 94.0%?99.6%, and the nucleotide homology with the prototype strain Gdula ranged 84.1%?85.8%. The results of phylogenetic tree showed that all 13 CV-A6 strains in Nanshan District were of the D3a genotype.Conclusions:FHFMD in Nanshan District of Shenzhen City in 2019-2022 shows obvious differences in population and time distribution. Therefore, it is necessary to strengthen publicity and education on HFMD prevention and control in the summer and fall seasons and among key populations. CV-A6 and CV-A16 are the dominant strains of HFMD in Nanshan District, Shenzhen in recent years, so the monitoring of the dominant strains should be improved.

Novel coronavirus Omicron variant infection can cause severe illness and even death in certain populations. Omicron variant infection may lead to systemic inflammatory response, coagulation disorder, multi-organ dysfunction and other pathophysiological changes, which are different from other Novel coronavirus variants to a certain extent, so therapeutic strategies should not be the same. The National Medical Center for Major Public Health Events invited experts in fields of infectious diseases, respiratory medicine, intensive care, pediatrics and fever clinic to develop this quick guideline based on the current best evidence and extensive clinical practices. This quick guideline aims to standardize the diagnosis and treatment of novel coronavirus Omicron infection, and to improve the disease management abilities of clinicians.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems

Objective:To investigate the clinical features of the initial phase of acute osteomyelitis in children with skin and soft tissue infection as the main sign.Methods:The clinical data of 154 children with skin and soft tissue infections as the main sign from July 2017 to February 2023 were retrospectively analyzed. According to MRI, 48 children with no signs of osteomyelitis and only simple skin and soft tissue infection were included in the non-osteomyelitis group, including 28 boys and 20 girls, aged 38.50 (12.00, 93.00) months; 106 children with acute osteomyelitis with skin and soft tissue infection as the main sign were included in the osteomyelitis group, including 65 boys and 41 girls, aged 49.50 (17.50, 87.00) months. The disease course, maximum body temperature at onset, inflammatory indicators (including white blood cell count, neutrophil count, C-reactive protein, erythrocyte sedimentation rate) examined within 24 h after admission were compared between the two groups, and receiver operating characteristic (ROC) curve was used to evaluate the efficacy of each index in diagnosing osteomyelitis.Results:The white blood cell counts in the non-osteomyelitis group and osteomyelitis group were 13.72 (10.19, 19.19) ×10 9 /L and 14.74 (10.63, 18.67) ×10 9 /L, and the neutrophil counts were 7.79 (5.62, 11.91) ×10 9 /L and 9.58 (5.77, 13.67) ×10 9 /L, the difference was not statistically significant ( Z=-0.68, P=0.495; Z=-1.24, P=0.216). The course of disease in the non-osteomyelitis group and osteomyelitis group was 5.00 (3.00, 7.00) d and 5.50 (4.00, 9.00) d ( Z=-2.03, P=0.042), and the maximum body temperature at the onset of the disease was 38.50 (36.65, 39.00) ℃ and 39.00 (38.50, 40.00) ℃ ( Z=-3.72, P<0.001), C-reactive protein was 23.26 (8.16, 47.67) mg/L and 69.27 (26.28, 111.03) mg/L ( Z=-4.52, P<0.001), erythrocyte sedimentation rate was 35.00 (24.25, 53.00) mm/1 h and 61.00 (43.00, 78.00) mm/1 h ( Z=-5.06, P<0.001), the differences were statistically significant. The proportion of patients with increased C-reactive protein was 70.8% (34/48) and 92.5% (98/106) in non-osteomyelitis group and osteomyelitis group, the proportion of patients with increased erythrocyte precipitation rate was 81.3% (39/48) and 100% (106/106), and the proportion of patients with fever was 66.7% (32/48) and 100% (106/106), respectively, the difference was statistically significant (χ 2=12.61, P<0.001; χ 2=21.11, P<0.001; χ 2=39.43, P<0.001). The sensitivity, specificity and area under the curve of osteomyelitis were 84.0%, 33.3% and 0.602, respectively. The maximum body temperature at onset was 99.1%, 35.4% and 0.687, and the C-reactive protein was 57.6%, 85.4% and 0.728, respectively. Erythrocyte sedimentation rates were 84.0%, 56.3% and 0.755, respectively. Multivariate logistic regression analysis indicated that the maximum body temperature was >37.6 ℃ [ OR=22.54, 95% CI (2.66, 190.81)] and C-reactive protein was >54.59 mg /L [ OR=4.23, 95% CI (1.63, 11.01)] was an independent risk factor for predicting osteomyelitis with skin and soft tissue infection as the main sign. Conclusion:Compared to simple skin and soft tissue infections, children with osteomyelitis had a higher proportion of fever, elevated C-reactive protein, and elevated erythrocyte sedimentation rate, a longer duration of illness, and higher elevations in temperature, C-reactive protein, and erythrocyte sedimentation rate. Length of onset, maximum body temperature at onset, C-reactive protein and erythrocyte sedimentation rate had certain diagnostic efficacy in determining the tendency of skin soft tissue infection to osteomyelitis. Maximum body temperature >37.6 ℃ and C-reactive protein >54.59 mg/L may independently predict the possibility of skin soft tissue infection as osteomyelitis, and prompt Magnetic Resonance Imaging is recommended for early diagnosis and treatment in such children.

Since 2010, the incidence of severe fever with thrombocytopenia syndrome (SFTS) has been increased. Owing the progress in diagnosis and treatment, the overall mortality of SFTS in China has decreased, while the mortality in critical SFTS patients is still high. In order to provide guidance and working procedures for clinicians to diagnose and treat critical SFTS, the National Medical Center for Major Public Health Events invited experts to discuss and formulate this consensus based on their experience and up-to-date knowledge on SFTS.

Excessive theta (θ) frequency oscillation and synchronization in the basal ganglia (BG) has been reported in elderly parkinsonian patients and animal models of levodopa (L-dopa)-induced dyskinesia (LID), particularly the θ oscillation recorded during periods when L-dopa is withdrawn (the off L-dopa state). To gain insight into processes underlying this activity, we explored the relationship between primary motor cortex (M1) oscillatory activity and BG output in LID. We recorded local field potentials in the substantia nigra pars reticulata (SNr) and M1 of awake, inattentive resting rats before and after L-dopa priming in Sham control, Parkinson disease model, and LID model groups. We found that chronic L-dopa increased θ synchronization and information flow between the SNr and M1 in off L-dopa state LID rats, with a SNr-to-M1 flow directionality. Compared with the on state, θ oscillational activity (θ synchronization and information flow) during the off state were more closely associated with abnormal involuntary movements. Our findings indicate that θ oscillation in M1 may be consequent to abnormal synchronous discharges in the BG and support the notion that M1 θ oscillation may participate in the induction of dyskinesia.

Objective To investigate the mechanism of improvement of gait behavior in PD rat models by low frequency electrical stimulation of pedunculopontine tegmental nucleus (PPTN) by optogenetics method. Methods (1) Twenty-four healthy adult male SD rats were randomly divided into a sham-operated group 1, a lesion group 1 and a photoactivation group (n=8); normal saline was injected into the right medial frontal tract (MFB) of the sham-operated group 1; 6-hydroxydopamine (6-OHDA) was injected into the lesion group 1 and photoactivation group to induce PD models; two weeks after modeling, injection of adeno-associated virus hsynapsin-ChR2-mcherry into the right PPTN of the three groups was performed, and the photoactivation group received blue-ray stimulation by implanting optical fibers into the PPTN at the same time. (2) Twenty-four healthy adult male SD rats were randomly divided into a sham-operated group 2, a lesion group 2 and a photoinhibition group (n=8);normal saline was injected into right MFB of the sham-operated group 2; 6-OHDA was injected into the lesion group 2 and photoinhibition group to induce PD models; two weeks after modeling, injection of adeno-associated virus hsynapsin-NpHR-mcherry into the right PPTN of the three groups was performed, and the photoinhibition group received yellow-ray stimulation by implanting optical fibers into the PPTN at the same time. (3) Three weeks after injection of adeno-associated virus, Catwalk gait analysis was used to assess the behavioral ability of rats in each group. Results (1) As compared with the sham-operated group 1, lesion group 1 had significantly increased front claw spacing and back front claw spacing, and significantly decreased stride length and pressure of damaged lateral and contralateral limbs, and significantly decreased swing speed of contralateral limb (P<0.05); as compared with those in the lesion group 1, the front claw spacing and back claw spacing were significantly shortened, and stride length and pressure of damaged lateral and contralateral limbs were statistically increased in the photoactivation group (P<0.05). (2) As compared with the sham-operated group 2, lesion group 2 had significantly increased front claw spacing and back front claw spacing, significantly decreased stride length of damaged lateral limb, and significantly decreased pressure and swing speed of damaged lateral and contralateral limbs (P<0.05); no significant differences were noted on the front claw spacing and back front claw spacing, pressure and swing speed of damaged lateral and contralateral limbs between lesion group 2 and photoinhibition group (P>0.05). Conclusion The mechanism of low frequency electrical stimulation of PPTN improving gait behavior of PD rat models is related to activation of PPTN neurons.

Objective To study the effect of psoralen isoflavone on the treatment of PC12 cells injured by Aβ and the mechanism on the effect of the psoralen isoflavones on the expression of related proteins. Methods The PC12 cells were divided into blank group, model group, E2 group, and psoralen isoflavones group by random number table method, In addition to the blank group the rest of each group culture medium were added 20μmol/L of Aβ25-35 modeling, The E2 group was added to the 10-3μmol/L oestrogen and psoralen isoflavones group for the intervention of 102-10-6 μmol/L.The proliferation rate of PC12 cells was detected by MTT assay, and the expression of APP, BACE1, ERβ, p-ERK and Aβ protein was detected by Western Blot. Results Compared with the model group, the proliferation of PC12 cells induced by 10-1μmol/L of psoralen isoflavone increased (101％ vs. 52％, P<0.01); The expression of p-ERK (0.751± 0.066 vs. 0.364 ± 0.015), ERβ(0.756 ± 0.105 vs. 0.337 ± 0.045) increased significantly (P<0.01); APP (0.382 ± 0.039 vs. 0.479 ± 0.015), BACE1 (0.517 ± 0.024 vs. 0.622 ± 0.029), Aβ (0.430 ± 0.032 vs. 0.581 ± 0.030) expression amount were significantly lower (P<0.05). Conclusions Psoralen isoflavones have a certain therapeutic effect on PC12 cells injured by Aβ.

Objective To investigate the potential of substrate elasticity in regulating rapid differentiation of HepaRG cells into hepatocyte-like cells ,and further provide hepatocytes for bioartificial liver. Methods The substrate elasticity was divided into 4 groups. The expressions of albumin(ALB)were detected by albumin-green fluorescent protein-reporter system (ALB-GFP-reporter system) and Image J software;the cell morphology was observed by microscope and the amounts of cell were detected by cell Titer-Blue cell viability assay kit (alamar blue). Results The results of ALB showed that at the 4th hour,the expressions of ALB inside the HepaRG cells between 4s group and 8s group,16 s group and Glass group were not statistically different (t = 0.791,1.389, 2.481,P>0.05);at the 4th day,the expressions of 4s group had statistical differences in comparison with those of 16s group and Glass group(t = 12.41,12.52,P < 0.05),but not statistical difference when compared with those of 8s group(t = 2.603,P > 0.05);at the 7th day,the expressions of 4s group were statistically different from those of 8s group,16s group and Glass group(t=3.266,6.725,8.005,P<0.05). The microscope showed that only a typical epithelial morphology was observed before differentiation ,then hepatocyte-like cells and bile duct-like cell were observed at differentiated phases. The alamar blue showed that at the 4th and the 7th day,the cell number of 4s group were not statistically different from that of 8s group,16s group and Glass group(P >0.05). Conclusion Soft substrate can promote differentiation of HepaRG cells.