Objective To analyze the virus subtypes, molecular evolutional and molecular transmission network features of the first confirmed mpox case in Huai’an City, Jiangsu Province, so as to provide insights into understanding of the transmission and evolution dynamics of mpox virus and formulation of the mpox control strategy in the city. Methods Genomic DNA was extracted from swabs of the first confirmed mpox case’s skin lesions in Huai’an City, and the amplicon sequencing library was constructed using the hypersensitive mpox virus whole-genome capture kit. High-throughput sequencing was performed using the GridION X5 nanopore sequencer on the Nanopore sequencing platform, and single nucleotide polymorphism (SNP) analysis of mpox virus genome sequences was performed following sequence assembly. In addition, phylogenetic analysis, genetic genealogy and molecular traceability analysis were performed. Results The virus whole genome sequence of the first confirmed mpox case was successfully obtained by high-throughput sequencing, with a full length of 197 182 bp, and was named hMpxV/China/JS-HA01/2023, which belonged to the clade IIb (West African clade) lineage B.1.3. Compared with the mpox virus reference sequence MPXV-M5312_HM12_Rivers-001 (GenBank accession number: NC_063383), the genome sequence of the Huai’an virus isolate carried 86 SNPs, including 40 SNPs in the coding region as non-synonymous mutations and 73 SNPs as nucleotide mutations caused by APOBEC3 (APOBEC3). Of the 97 mpox virus gene sequences, 79 sequences were included in the molecular network (81.44%), and the threshold of the genetic distance accessed to the network was 0.35/10⁵. There were two large molecular transmission clusters and one scattered cluster in the molecular transmission network of the mpox virus, andthehMpxV/China/JS-HA01/2023 sequence was located in the large cluster. The 97 gene sequences formed 92 haplotypes, including three shared haplotypes Hap_4, Hap_6 and Hap_38, and an exclusive haplotype Hap_1 of hMpxV/China/JS-HA01/2023 generated from mutation of the exclusive haplotype Hap_43, while the exclusive haplotype Hap_43 was generated from mutation of the shared haplotype Hap_38. Conclusions The whole genome sequence of the mpox virus isolated from the first confirmed mpox case in Huai’an City has been successfully obtained, and the molecular evolutionary and molecular transmission network characteristics of the virus have been preliminarily understood.

Objective To observe the value of clinical and CT radiomics features for predicting microsatellite instability-high(MSI-H)status of gastric cancer.Methods Totally 150 gastric cancer patients including 30 cases of MSI-H positive and 120 cases of MSI-H negative were enrolled and divided into training set(n=105)or validation set(n=45)at the ratio of 7∶3.Based on abdominal vein phase enhanced CT images,lesions radiomics features were extracted and screened,and radiomics scores(Radscore)was calculated.Clinical data and Radscores were compared between MSI-H positive and negative patients in training set and validation set.Based on clinical factors and Radscores being significant different between MSI-H positive and negative ones,clinical model,CT radiomics model and clinical-CT radiomics combination model were constructed,and their predictive value for MSI-H status of gastric cancer were observed.Results Significant differences of tumor location and Radscore were found between MSI-H positive and negative patients in both training and validation sets(all P＜0.05).The area under the curve(AUC)of clinical model,CT radiomics model and combination model for evaluating MSI-H status of gastric cancer in training set was 0.760,0.799 and 0.864,respectively,of that in validation set was 0.735,0.812 and 0.849,respectively.AUC of clinical-CT radiomics combination model was greater than that of the other 2 single models(all P＜0.05).Conclusion Clinical-CT radiomics combination model based on tumor location and Radscore could effectively predict MSI-H status of gastric cancer.

Objective:To study the biological traits and mutations of the influenza A (H3N2) virus in order to produce a vaccine and offer references for controlling and preventing influenza epidemics.Methods:Four strains of the influenza A(H3N2) virus were chosen from the Huai′an surveillance network laboratory. Nucleic acid extraction, library building, and sequencing (CridION x5 MKI Nanopore) were used to produce the whole-genome sequences. Using homologous alignments of whole-genome sequences, phylogenetic tree construction, and amino acid variant screening, bioinformatics analysis was carried out.Results:The nucleotide identity between 8 gene segments ranged from 97.1% to 100.0%. The gene that differed the most from the reference sequences was HA (97.1%-99.9%), and the gene that differed the least was MP (98.6%-99.9%). The HA gene (3.06%) and MP gene (1.43%) were the regions with the greatest and lowest frequencies of nucleotide site change, respectively. The rates of nucleotide change varied significantly between the genes ( χ2=14.293, P=0.046). Four influenza A(H3N2) virus strains′ whole-genome phylogenies from each of the eight gene segments maintained a roughly consistent topological structure. One strain was linked to the 3C.2a1b.1b clade, which was lost at the 142NWT, 149NGT(HA1), and 436NLS(NA). Three strains were linked to the 3C.2a1b.2a.1a clade lineage. Amantadine and NA inhibitors were effective against all Huai′an strains. Conclusions:The antigenicity of one strain of Huai'an strain changed and its matching with the vaccine strain of that year was low. It is suggested that the genetic surveillance of H3N2 influenza virus should be continuously strengthened to provide scientific basis for influenza prevention and control and influenza vaccine screening.

Objective:To evaluate the effectiveness of Z-plasty combined with auricular cartilage grafting in the correction of cryptotia.Methods:A retrospective analysis was conducted on the clinical data of cryptotia patients who underwent Z-plasty combined with auricular cartilage grafting at the Department of Ear Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, from January 2020 to December 2023. The surgery consisted of five steps: design of the Z-plasty flap, harvesting of auricular cartilage from the conchal cavity, dissection and reshaping of the auricular cartilage, transplantation of auricular cartilage, and skin coverage with flap transfer. Early and late complications were recorded according to postoperative follow-up, and the external ear morphology was evaluated by both plastic surgeons and the patients’ guardians using a Likert 4-point scale (the higher the score, the better the auricular morphology). Normally distributed data were presented as Mean±SD.Results:A total of 32 patients were included in the study, comprising 23 males and 9 females, aged 5 to 14 years, with an average age of 7.3 years. Two children were lost to follow-up, and 30 completed long-term follow-up, with follow-up periods ranging from 6 to 24 months, averaging 9.3 months. Early complications included hematoma in 2 cases [6.3%(2/32)] and flap vascular compromise in 1 case[3.1%(1/32)]. Late complications primarily involved hypertrophic scars in 2 cases[6.7%(2/30)], with no recurrence of deformity. After the operation, the cranioauricular sulcus on the upper pole of the auricle were significantly deepened, and the patients could wear masks and glasses. The average score for the external ear morphology was 3.5±0.5 by plastic surgeons and 3.5±0.5 by patients.Conclusion:Z-plasty combined with auricular cartilage grafting provides satisfactory result in the correction of cryptotia, with few postoperative complications and high patient satisfaction, making it suitable for the treatment of cryptotia.

Objective:To evaluate the effectiveness of Z-plasty combined with auricular cartilage grafting in the correction of cryptotia.Methods:A retrospective analysis was conducted on the clinical data of cryptotia patients who underwent Z-plasty combined with auricular cartilage grafting at the Department of Ear Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, from January 2020 to December 2023. The surgery consisted of five steps: design of the Z-plasty flap, harvesting of auricular cartilage from the conchal cavity, dissection and reshaping of the auricular cartilage, transplantation of auricular cartilage, and skin coverage with flap transfer. Early and late complications were recorded according to postoperative follow-up, and the external ear morphology was evaluated by both plastic surgeons and the patients’ guardians using a Likert 4-point scale (the higher the score, the better the auricular morphology). Normally distributed data were presented as Mean±SD.Results:A total of 32 patients were included in the study, comprising 23 males and 9 females, aged 5 to 14 years, with an average age of 7.3 years. Two children were lost to follow-up, and 30 completed long-term follow-up, with follow-up periods ranging from 6 to 24 months, averaging 9.3 months. Early complications included hematoma in 2 cases [6.3%(2/32)] and flap vascular compromise in 1 case[3.1%(1/32)]. Late complications primarily involved hypertrophic scars in 2 cases[6.7%(2/30)], with no recurrence of deformity. After the operation, the cranioauricular sulcus on the upper pole of the auricle were significantly deepened, and the patients could wear masks and glasses. The average score for the external ear morphology was 3.5±0.5 by plastic surgeons and 3.5±0.5 by patients.Conclusion:Z-plasty combined with auricular cartilage grafting provides satisfactory result in the correction of cryptotia, with few postoperative complications and high patient satisfaction, making it suitable for the treatment of cryptotia.

ObjectiveTo discover and analyze single or several correlative key amino acid sites that influence the host tropism during the influenza A virus （IAV） infection based on complete internal protein gene segments of IAV strains， and to provide evidence for the study of human host-adaptive mutations of IAV. MethodsThe full-length nucleotide sequences of 43 671 IAV strains containing 6 complete internal gene segments were downloaded from the GISAID EpiFlu^TM database， and 698 human-tropic （HU） and 1 266 avian-tropic （AV） representative strains were included. The consensus coding sequences of the representative strains from the amphitropic category were compared by R script， and the differential amino acid sites and their polymorphisms were then obtained. The multi-site combination analysis of differential sites was conducted with R script. ResultsA total of 49 and 57 conserved differential sites were obtained from the consensus sequence comparison between AV and H1N1 （subtype from HU）， and comparison between AV and H3N2 （another subtype from HU）， separately. 79 and 65 multi-site combinations were found between HU and AV strains through 3 and 4 sites combination analysis， respectively， and a total of 11 conserved sites were involved： site 271 and 684 in PB2； site 336， 486， 581 and 621 in PB1； site 204 and 356 in PA； site 33， 305 and 357 in NP. No eligible differential sites were found in M1 and NS1. ConclusionSeveral conserved amino acid differential sites， between HU and AV strains of IAV， are found in PB2， PB1， PA and NP proteins. Instead of working as single units， these sites may have interactions， forming specific amino acid combinations that determine the host tropism of IAV collectively.

Blood-brain barrier (BBB) damage after ischemia significantly influences stroke outcome. Compound LFHP-1c was previously discovered with neuroprotective role in stroke model, but its mechanism of action on protection of BBB disruption after stroke remains unknown. Here, we show that LFHP-1c, as a direct PGAM5 inhibitor, prevented BBB disruption after transient middle cerebral artery occlusion (tMCAO) in rats. Mechanistically, LFHP-1c binding with endothelial PGAM5 not only inhibited the PGAM5 phosphatase activity, but also reduced the interaction of PGAM5 with NRF2, which facilitated nuclear translocation of NRF2 to prevent BBB disruption from ischemia. Furthermore, LFHP-1c administration by targeting PGAM5 shows a trend toward reduced infarct volume, brain edema and neurological deficits in nonhuman primate

Ischemic stroke is the second leading cause of death worldwide with limited medications and neuroinflammation was recognized as a critical player in the progression of stroke, but how to control the overactive neuroinflammation is still a long-standing challenge. Here, we designed a novel SIRT6 activator MDL-811 which remarkably inhibited inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and primary mouse microglia, which were abolished by silencing SIRT6. RNA-seq screening identified the forkhead box C1 (

Objective The aim of this study was to explore the serum 25-(OH) Vitamin D and its correlation with liver function in children who have suffered from non-alcoholic fatty liver disease (NAFLD),and to explore the necessity of vitamin D treatment of NAFLD in children.Methods Forty children with NAFLD diagnosed by imaging were selected from the outpatient of pediatric digestive department of Shengjing Hospital of China Medical University,selected as observation group from July 2017 to August 2019,and 37 healthy children were selected as control group.The clinical data were collected and serum 25-(OH) Vitamin D were detected at the same time.Results There was no significant difference in 25-(OH) Vitamin D among children with NAFLD at different ages and gender (P ＞ 0.05).The level of 25-(OH) Vitamin D in children with NAFLD [(21.30 ±8.77) μg/L]was significantly lower than that in the control group [(28.53 ± 10.18) μg/L] (t =3.343,P ＜ 0.01).The incidence of vitamin D deficiency (＜ 20 μg/L) and insufficiency (＜30 μg/L)in children with NAFLD (35/40 =87.50％) was significantly higher than that in the control group (22/37 =59.46％) (x2 =10.035,P ＜ 0.05).Serum 25-(OH) Vitamin D was negatively correlated with fasting insulin (r =-0.464,P ＜ 0.01) and homeostasis model assessment of insulin resistance (r =-0.444,P ＜0.01),but not correlated with BMI,transaminase level (ALT,AST),uric acid and blood lipid (TG,TC,HDL-C,LDL-C,sd-LDL,Apo-A1,Apo-B).Vitamin D deficiency was the risk factor of NAFLD (OR =1.088,P ＜ 0.01).Conclusion Vitamin D deficiency is common in pediatric NAFLD,which may be a risk factor of NAFLD.The mechanism may be that vitamin D deficiency aggravates insulin resistance and further aggravates liver damage in children with NAFLD.

Chromosomal region maintenance 1 (CRM1) is associated with an adverse prognosis in glioma. We previously reported that CRM1 inhibition suppressed glioma cell proliferation both in vitro and in vivo. In this study, we investigated the role of CRM1 in the migration and invasion of glioma cells. S109, a novel reversible selective inhibitor of CRM1, was used to treat Human glioma U87 and U251 cells. Cell migration and invasion were evaluated by wound-healing and transwell invasion assays. The results showed that S109 significantly inhibited the migration and invasion of U87 and U251 cells. However, mutation of Cys528 in CRM1 abolished the inhibitory activity of S109 in glioma cells. Furthermore, we found that S109 treatment decreased the expression level and activity of MMP2 and reduced the level of phosphorylated STAT3 but not total STAT3. Therefore, the inhibition of migration and invasion induced by S109 may be associated with the downregulation of MMP2 activity and expression, and inactivation of the STAT3 signaling pathway. These results support our previous conclusion that inhibition of CRM1 is an attractive strategy for the treatment of glioma.