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.

ObjectiveTo explore the epidemic levels and epidemiological characteristics of influenza-like illness (ILI) in Hongkou District of Shanghai, to track the trends in virus mutations, so as to offer a scientific foundation for precisely predicting influenza epidemic trends, providing early alerts, and implementing prompt prevention and control measures. MethodsData on ILI and etiological surveillance from Hongkou District between 2015 and 2024 were collected and statistically analyzed. ResultsThe consultation percentage of ILI (ILI%) in Hongkou District from 2015 to 2024 was 0.58%, and the differences were statistically significant between different years (χ²=19 280.500, P<0.001), with winter and summer being the prevalence peaks. The highest proportion of ILI cases was observed in the 25‒<60 years age group, and the proportion of cases aged ≥60 years showed an increasing trend. The positive rate for influenza viruses was 17.60%, with seasonal influenzaA (H3N2) subtype (49.78%) and influenza A(H1N1) (30.03%) being the predominant strains,and the positive rate was different by years. There was a correlation between ILI% and the positive rate of influenza viruses (r=0.260, P<0.001). The median intensity of influenza activity in 2023‒2024 was 23.09, which was significantly higher than that in 2015‒2019 (H=37.052, P<0.001) and that in 2020‒2022 (H=40.436, P<0.001). ConclusionFrom 2015 to 2022, the ILI% in Hongkou District, Shanghai remained at a relatively low level, but it significantly increased in 2023‒2024, with peaks observed in winter and summer. The predominant influenza virus strains varied and alternated by years. The 2023‒2024 period witnessed an intensified influenza activity. It is necessary to continuously monitor the impact of other respiratory pathogens on influenza epidemic, so as to provide a scientific basis for early warning and prevention and control of influenza.

Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.
Humans ; Cholangiocarcinoma/drug therapy* ; Immunotherapy/methods* ; Bile Duct Neoplasms/drug therapy* ; Molecular Targeted Therapy/methods*

Objective Zinc finger protein 335 (Zfp335) plays a crucial role in the early development of thymic T cells and the differentiation of peripheral T cell subpopulations. The objective of this study is to investigate the role and underlying mechanisms of Zfp335 in the regulation of regulatory T cell (Treg) within tumor immunity. Methods The Zfp335 gene was specifically knocked out in Treg using tamoxifen (Zfp335^fl/fl FOXP3^creERT2), and the MC38 tumor model was established. On the 7th day after tumor inoculation, tumor size was observed and measured. Tumor size was monitored and recorded daily starting from day 7 post-inoculation. On day 12, tumors were harvested, and the proportions of CD4⁺ T cells, CD8⁺ T cells, and Treg were analyzed by flow cytometry. Additionally, the mitochondrial function of effector regulatory T cell (eTreg) was assessed. Results From day 10 post-tumor inoculation, tumor volume in the Zfp335^CKO group was significantly reduced compared to that of the wild-type (WT) group. Furthermore, the infiltration of CD4⁺ and CD8⁺ T cells, along with their respective effector cells, was significantly higher in the Zfp335^CKO group than in the WT group. The proportions of CD4⁺ and CD8⁺ T cells producing interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) were also significantly increased in the Zfp335^CKO group compared to that of the WT group. In addition, the percentage of CD8⁺ T cells secreting granzyme B (GzmB) was significantly higher in the Zfp335^CKO group than that in the WT group. In contrast, the proportion of Treg and inducible T cell co-stimulator (ICOS)⁺ Treg in the Zfp335^CKO group was significantly lower than that in the WT group. Finally, the expression level of Mitotracker Deep Red in eTreg from the Zfp335^CKO group was significantly reduced compared to that in the WT group. Conclusion During tumorigenesis, the specific deletion of Zfp335 impairs Treg activation, which is related to decreased mitochondrial function in eTreg. In Zfp335^CKO mice. Tumors exhibit increased infiltration of effector T cells, accompanied by elevated levels of cytotoxic cytokines, ultimately enhancing resistance to tumor progression.
Animals ; T-Lymphocytes, Regulatory/metabolism* ; Mice ; CD8-Positive T-Lymphocytes/immunology* ; Neoplasms/genetics* ; Cell Line, Tumor ; Mice, Inbred C57BL ; Mice, Knockout ; DNA-Binding Proteins/genetics* ; Female

OBJECTIVE: To investigate the clinical effect of transposition of gracilis muscle flap in repairing urethral perineal fistula after Miles operation. METHODS: The clinical data of 3 patients with urethral perineal fistula treated in the Second Affiliated Hospital of Zhejiang University from September 2023 to November 2024 were analyzed retrospectively. All patients were male, aged from 59 to 68 years (mean 63 years). All patients underwent Miles operation because of low rectal cancer. Urethral perineal fistula occurred after 2 months to 13 years of the operation. The underlying comorbidities included diabetes (2/3), preoperative chemoradiotherapy (1/3), and chemotherapy alone (1/3). The endourethral fistula was located in the apical and membranous part of the prostate, with a diameter of 1.5-2.0 cm and a mean of 1.7 cm. Suprapubic cystostomy was performed one month before operation. In all 3 cases, perineal inverted "Y" incision was taken under general anesthesia to expose urethral fistula, cut off necrotic tissue and suture urethral fistula. The gracilis muscle of the right thigh was taken and turned through the perineal subcutaneous tunnel. and 6 stitches were suture at the urethral fistula. RESULTS: The operations of all 3 patients were completed successfully. The follow-up period ranged from 2 months to 12 months, with an average of 8 months. There was no case of urinary incontinence after removal of catheter 3 weeks after operation. In two patients, urethrography was reviewed 1 month after surgery to show no fistula residue and urethral stenosis, and the fistula was removed. In one patient with a history of radiotherapy, urethrography was reviewed 1 month after surgery to show a small amount of contrast overflow around the urethra, and urethrography was reviewed again 3 months after surgery to show no contrast overflow around the urethra. All the 3 patients had no disturbance of movement of the right lower limb, and the pain of different degrees of thigh incision was acceptable and basically relieved half a month after operation. CONCLUSION Gracilis muscle flap is one of the effective methods for repairing urethral perineal fistula after Miles operation，which has a precise surgical result and few complications.
Humans ; Male ; Middle Aged ; Aged ; Gracilis Muscle/transplantation* ; Urinary Fistula/surgery* ; Retrospective Studies ; Surgical Flaps ; Perineum/surgery* ; Rectal Neoplasms/surgery* ; Postoperative Complications/surgery* ; Urethral Diseases/surgery* ; Urethra/surgery*

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

The objective of this study was to examine the effects of electroacupuncture on the expression of ATP-binding cassette transporter A1(ABCA1),ATP-binding cassette transporter G1(ABCG1),and class B type Ⅰ scavenger receptor(SR-B Ⅰ)genes and proteins in peritoneal macrophages of atherosclerotic rabbits.The study aimed to explore the mechanism underlying the treatment of atherosclerosis(AS)with electroacupuncture.Methods Twenty-six male New Zealand rabbits were randomly divided into the negative control group(n=7)and the modeling group(n=19)using a random number table method.The negative control group rabbits were fed a regular diet,while the modeling group was induced with a combination of high-fat feed and common carotid artery balloon injury surgery to create an AS model.After successful modeling,the rabbits in the modeling group were further divided into the model group,the electroacupuncture group,and the atorvastatin group,with 6 rabbits in each group.The rabbits in the electroacupuncture group received electroacupuncture at"'Neiguan'(PC6)","'Zusanli'(ST36)",and"'Guanyuan'(ST25)"acupoints,using a density wave,a current of 1 mA,and a frequency of 4 Hz/20 Hz,once a day.The needle was retained for 20 minutes each time,and a total of 4 courses of treatment were conducted,with 6 days per course.The rabbits in the atorvastatin group were administered atorvastatin calcium tablet suspension(1 mg/kg)orally once a day,for 6 days per course,with a total of 4 courses.After the interventions,HE staining was performed to observe the morphological changes in the common carotid artery tissue of the rabbits.Peritoneal macrophages were collected from the rabbits,and the mRNA expression levels of ABCA1,ABCG1,and SR-B Ⅰ were measured using real-time fluorescence PCR.The protein expression levels of ABCA1,ABCG1,and SR-B Ⅰ were detected using Western blotting.Results The negative control group exhibited smooth intima of common carotid artery in rabbits,while the model group displayed damaged intima of common carotid artery,thickened artery walls,and the formation of atherosclerotic plaques.The electroacupuncture group and atorvastatin group showed significant improvements in wall thickening and a reduction in plaque area.Compared with the negative control group,the mRNA and protein expressions of ABCA1,ABCG1,and SR-B Ⅰ in peritoneal macrophages of rabbits in the model group were reduced(P＜0.01).Compared with the model group,the electroacupuncture group and atorvastatin group exhibited increased mRNA and protein expressions of ABCA1,ABCG1,and SR-B Ⅰ in abdominal macrophages of rabbits(P＜0.01).Furthermore,the atorvastatin group demonstrated increased mRNA levels of ABCG1 and SR-B Ⅰ,as well as increased protein expressions of ABCA1,ABCG1,and SR-B Ⅰ in peritoneal macrophages of rabbits,in comparison to the electroacupuncture group(P＜0.01).Conclusion Electroacupuncture can enhance the expressions of ABCA1,ABCG1,and SR-B Ⅰ mRNA and protein in abdominal macrophages of AS rabbits,thereby promoting the process of cholesterol reverse transport.This may be one of the mechanisms underlying the effectiveness of acupuncture in the treatment of AS.

Objective To investigate the expressions of H3.3G34W,p63 and SATB2 in giant cell tumor of bone(GCTB)and the effect and value of their combined application in the diagnosis of GCTB.Methods We collected the samples and medical records of 54 cases of GCTB and 83 cases of non-giant cell tumor of bone(14 cases of aneurysmal bone cyst,16 cases of chondroblastoma and 53 cases of non-ossifying fibroma)diagnosed between 2020 and 2022 in the Department of Pathology of Honghui Hospital Affiliated to Xi'an Jiaotong University.The expressions of H3.3G34W,p63 and SATB2 were detected by EliVision immunohistochemical method.X2 test was used to determine whether there are significant differences in the positive rates of H3.3G34W,p63 and SATB2 among all the groups.The combined diagnostic model including H3.3G34W,p63 and SATB2 was established by Logistic regression analysis,and the diagnostic value of the model was evaluated by ROC curve analysis.Results The positive rates of H3.3G34W,p63 and SATB2 in GCTB group were 81.5％,90.7％and 92.6％,respectively;the positive rates in NGCTB group were 2.4％,28.9％and 62.7％.Compared with NGCTB group,the age of GCTB group was significantly older[(41.222±14.849)vs.(16.566±9.439),P＜0.001],and the prevalence was higher in women than in men(51.9％vs.48.1％,P＜0.001).In addition,compared with the NGCTB group,the positive rates of H3.3G34W(81.5％vs.2.4％,P＜0.001),p63(90.7％vs.28.9％,P＜0.001)and SATB2(92.6％vs.62.7％,P＜0.001)were significantly higher in the GCTB group.Univariate regression analysis built a univariate prediction modeland ROC curve analysis showed that age(AUC=92.9％,P＜0.001),sex(AUC=64.5％,P=0.004),H3.3G34W positive rate(AUC=89.5％,P＜0.001),p63 positive rate(AUC=80.9％,P＜0.001)and SATB2 positive rate(AUC=65.0％,P=0.003)were independent predictors of diagnosis of giant cell tumor of bone.Multivariate regression analysis(Logistic)constructed a hybrid prediction model.ROC curve analysis suggested that the hybrid model showed better prediction value than the single factor model(AUC=98.4％,P＜0.001).Conclusion H3.3G34W,p63 and SATB2 are effective molecular markers for the diagnosis of GCTB,and their combined application can improve the prediction efficiency of the diagnosis of GCTB.

BACKGROUND:Ankylosing spondylitis is a chronic inflammatory disease with chronic rheumatic immunity.Soft tissue ossification and fusion and spinal stiffness can cause biomechanical changes. OBJECTIVE:To reconstruct the lumbar-sacral intervertebral disc in ankylosing spondylitis patients with lumbar kyphosis by finite element analysis,and to study the range of motion of each segment of T11-S1 and the biomechanical characteristics of annulus fibrosus and nucleus pulposus. METHODS:The imaging data were obtained from an ankylosing spondylitis patient with lumbar kyphosis.The original CT image data of continuously scanned spine were imported into Mimics 21.0 in DICOM format,and T11-S1 was reconstructed respectively.The established model was imported into 3-Matic software in the format of"Stl"to reconstruct the intervertebral disc,and the fibrous intervertebral disc model was obtained.The improved model was further imported into Hypermesh software,and the vertebra,nucleus pulposus,annulus fibrosus and ligament were mesh-divided.After the material properties were given,the model was imported into ABAQUS software to observe the range of motion of each vertebral body in seven different working conditions of T11-S1,and analyze the biomechanical characteristics of each segment of annulus fibrosus and nucleus pulposus. RESULTS AND CONCLUSION:(1)The range of motion of L1 vertebrae was higher than that of other vertebrae under six different working conditions:extension,forward flexion,rotation(left and right),and lateral flexion(left and right).The maximum range of motion was 2.18° during L1 vertebral flexion,and the minimum range of motion was 0.12° during L5 vertebral extension.(2)The annular fiber flexion at L2-L3 segments was greater than the extension(P<0.05),and the annular fiber flexion at L3-L4 and L4-L5 segments was less than the extension(P<0.05).The left rotation of L1-L2 annular fibers was greater than the right rotation(P<0.05).The left flexion of the annulus was greater than the right flexion in L1-L2,L2-L3,L3-L4,L4-L5 and L5-S1 segments(P<0.05).(3)The nucleus pulposus stresses of T11-L12,L1-L2,L2-L3,L3-L4 and L4-L5 segments in forward flexion were greater than in extension(P<0.05).The left rotation of T12-L1 and L3-L4 segments was smaller than the right rotation(P<0.05),and that of T11-T12,L1-L2,and L2-L3 segments was larger than the right rotation(P<0.05).The left flexion was larger than the right flexion in the T11-S1 segment.(4)It is concluded that in ankylosing spondylitis patients with lumbar kyphosis,the minimum range of motion of the vertebral body is located at the L5 vertebral body in extension.To prevent fractures,it is recommended to avoid exercise in the extension position.During the onset of lumbar kyphosis in patients with ankylosing spondylitis,the maximum stress of the annulus fibrosus and nucleus pulposus is located in the L1-L2 segment,which is fixed and will not alter with the change of body position.The late surgical treatment and correction of deformity should focus on releasing the pressure of the annulus fibrosus and nucleus pulposus in this segment to avoid the rupture of the annulus fibrosus and the injury of the nucleus pulposus.

BACKGROUND:Ankylosing spondylitis is a progressive inflammation of spinal stiffness deformity caused by tissue ossification and fibrosis.The posture of ankylosing spondylitis patients is abnormal and their activities are limited that minor injuries can lead to thoracolumbar fractures.Traditional medical image observation limits doctors'preoperative decision planning and postoperative disease prevention for ankylosing spondylitis treatment. OBJECTIVE:Based on the spinal model of ankylosing spondylitis patients before and after posterior spinal cancellous ossification osteotomy("Y"osteotomy for short),to explore the biomechanical changes of"Y"osteotomy and fixation in the treatment of ankylosing spondylitis. METHODS:Based on the preoperative and postoperative CT images of an ankylosing spondylitis patient who went to the Second Affiliated Hospital of Inner Mongolia Medical University,a three-dimensional spine model(T11-S1)before and after"Y"osteotomy(L3 osteotomy)was reconstructed in Mimics 19.0 software.A 7.5 Nm torque was applied to the top of T11 vertebral body to simulate the movement of the spine under six conditions:flexion,extension,left bending,right bending,left rotation and right rotation.Finally,the range of motion of each vertebral body,the stress of each intervertebral disc,and the stress of the screw rod system were simulated. RESULTS AND CONCLUSION:(1)After"Y"type osteotomy and posterior fixation,the range of motion of all vertebrae in the spine decreased,and the loss rate of upper vertebrae was large(L1:77.95%).(2)The maximum stress of the spinal intervertebral disc before operation occurred at the L1-L2 segment(0.55 MPa),and the maximum stress of the spinal intervertebral disc after operation occurred at the T11-T12 segment(0.50 MPa),and the stress of intervertebral disc below T12 was far less than that before operation.(3)The maximum stress of the screw rod system(166.67 MPa)occurred in the upper and middle segments of the rod body and the root of the pedicle screw.(4)In conclusion,the"Y"type posterior fixation operation enhances the stability of the spine and reduces the range of motion of the spine.The vertebral body decompression of the fixed segment is great and the stress-shielding phenomenon of the lower vertebral body is significant.The stiffness of the rod body and the stress concentration area of the pedicle screw should be strengthened to avoid the fracture of the rod caused by stress fatigue.