On August 24 2024, Xiaoshan District Center for Disease Control and Prevention, Hangzhou City, received a report of two cases of varicella infection among staff in the intensive care unit (ICU) of a hospital in its jurisdiction. The center immediately organized personnel to conduct an epidemiological investigation of the cases and their close contacts. The index case was a patient admitted to the ICU who had large areas of red rash and pustules on the chest, back, and right axilla. This case was diagnosed with herpes zoster by a dermatology consultation within the hospital. The other nine secondary cases were all nursing staff in the ICU, who were clinically diagnosed with varicella between August 21 and September 1, with an attack rate of 14.06%. All secondary varicella cases had a history of contact with the herpes zoster case and no history of varicella infection. Their varicella vaccination history was unknown. Based on the results of the on-site epidemiological and sanitary investigations, it was determined that this was an outbreak of varicella in the hospital caused by a herpes zoster case. After the last case was diagnosed, no new cases were reported within the longest incubation period (21 days), and the outbreak was declared over on September 21. Close contact with the herpes zoster case was likely the main cause of the outbreak. This highlights the need for early identification and isolation of suspected herpes zoster cases in hospitals in the future, as well as enhanced protective measures to prevent nosocomial infections.

OBJECTIVES: To investigate the effect of orexin-A-mediated regulation of ionotropic glutamate receptors for promoting motor function recovery in rats with spinal cord injury (SCI). METHODS: Thirty-six newborn SD rats (aged 7-14 days) were randomized into 6 groups (n=6), including a normal control group, a sham-operated group, and 4 SCI groups with daily intrathecal injection of saline, DNQX, orexin-A, or orexin-A+DNQX for 3 consecutive days after PCI. Motor function of the rats were evaluated using blood-brain barrier (BBB) score and inclined plane test 1 day before and at 1, 3, and 7 days after SCI. For patch-clamp experiment, spinal cord slices from newborn rats in the control, sham-operated, SCI, and SCI+orexin groups were prepared, and ventral horn neurons were acutely isolated to determine the reversal potential and dynamic indicators of glutamate receptor-mediated currents under glutamate perfusion. RESULTS: At 3 and 7 days after SCI, the orexin-A-treated rats showed significantly higher BBB scores and grip tilt angles than those with other interventions. Compared with those treated with DNQX alone, the rats receiving the combined treatment with orexin and DNQX had significantly higher BBB scores and grip tilt angles on day 7 after PCI. In the patch-clamp experiment, the ventral horn neurons from SCI rat models exhibited obviously higher reversal potential and greater rise slope of glutamate current with shorter decay time than those from sham-operated and orexin-treated rats. CONCLUSIONS Orexin-A promotes motor function recovery in rats after SCI possibly by improving the function of the ionotropic glutamate receptors.
Animals ; Spinal Cord Injuries/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Receptors, Ionotropic Glutamate/metabolism* ; Recovery of Function/drug effects* ; Orexins/pharmacology* ; Male ; Female ; Animals, Newborn ; Neuropeptides/pharmacology* ; Intracellular Signaling Peptides and Proteins/pharmacology*

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

Objective·To investigate the effect of cancer-testis antigen family member CT57 on proliferation,migration and invasion of the human liver cancer cells and tumorigenesis in nude mice,and the possible mechanism.Methods·Bioinformatics methods were used to analyze the differential expression of CT57 in several cancer tissues and normal tissues,and its effect on the prognosis of liver cancer patients.Lentiviral vectors were used to establish liver cancer cell lines with stable knockdown and overexpression of CT57,which were confirmed by Western blotting.CCK-8 cell proliferation assay,soft agar colony formation assay and cell cycle experiment were used to detect the effect of CT57 on the proliferation and colony formation ability of liver cancer cells.Wound healing and Transwell assays were used to detect the effect of CT57 on the migration and invasion of liver cancer cells,and the expression of epithelial-mesenchymal transition(EMT)markers was detected by quantitative real-time PCR(qRT-PCR).To explore the effect of CT57 on liver cancer cells in vivo,CT57 knockdown liver cancer cells(experimental group)and control liver cancer cells(control group)were used to conduct subcutaneous tumor formation experiments in nude mice.Results·Bioinformatics analysis of multiple tumors and corresponding normal tissues in The Cancer Genome Atlas Program(TCGA)database showed that CT57 was highly expressed in most tumor tissues,including liver cancer,and the expression level of CT57 was significantly correlated with the prognosis of liver cancer patients.Cell proliferation assay,soft agar colony formation assay,and cell cycle experiment showed that knockdown of CT57 inhibited the proliferation and colony formation of liver cancer cells and led to cell cycle arrest.In wound healing and Transwell assays,knockdown of CT57 inhibited the invasion and migration of liver cancer cells,while overexpression of CT57 promoted it.The results of qRT-PCR indicated that overexpression of CT57 resulted in downregulation of epithelial cell markers ECAD(E-cadherin)and OCLN(occludin),and upregulation of mesenchymal cell markers VIM(vimentin),TWIST1(twist family bHLH transcription factor 1),and MMP2(matrix metallopeptidase 2).In the in vivo experiments,knockdown of CT57 significantly reduced the tumor formation rate of liver cancer cells,tumor volume,and tumor weight in nude mice.Conclusion·Knockdown of CT57 leads to cell cycle arrest,thereby inhibiting the proliferation of liver cancer cell and subcutaneous tumorigenesis in nude mice;CT57 promotes the invasion,migration and EMT of liver cancer cells.

Objective To investigate the antigen presentation characteristics of dendritic cells(DC)and B cells in cardiac grafts.Methods The heart of BALB/c mice was transplanted into the abdominal cavity of C57BL/6J mice.CD45+cells in the heart graft were extracted and sorted by flow cytometry at postoperative 5 d,and single cell RNA sequencing was performed.Taking DC and B cell subsets in cardiac grafts as the main study cells,the changing trend,antigen presenting ability and intercellular communication with T cells after heart transplantation were analyzed by bioinformatics analysis and flow cytometry.Gene ontology(GO)function enrichment difference analysis was adopted to prove the specific function and the reliability annotation of cell subsets.Results Germinal center-like B cell(GC-L B)was the B cell subset with the largest increase in quantity during the acute rejection phase,accounting for 87％.Classical DC(cDC)2 was the only DC subset with a significant increase in quantity during acute rejection of heart transplantation,accounting for 44％of DC subset,and it occupied the highest communication intensity with T cells after heart transplantation.Mononucleated DC(moDC)and memory B cell(MBC)were the main transmitters of T cell input signals in non-transplanted hearts,whereas transformed into cDC2 and GC-L B during the acute rejection phase.Among them,MBC and GC-L B were the main sources of T cell input signals in non-transplanted hearts and heart grafts.Conclusions Compared with DC,B cells occupy a higher number and weight in the intercellular communication with T cells in non-transplanted hearts and heart grafts,prompting that the antigen presenting activity of B cells is more active and stronger than DC in the early stage of acute rejection of heart transplantation.

ObjectiveTo investigate the clinical efficacy of Niaoxue No.1 Prescription in treating Henoch-Schönlein purpura （HSP） nephritis with blood heat and stasis syndrome and its effect on urine erythrocyte， urine protein， blood neutrophils， and blood routine-derived indicators. MethodA multicenter， randomized controlled trial （RCT） was conducted involving 108 HSP nephritis patients from three hospitals. The patients were randomly divided into a control group （54 cases） and a treatment group （54 cases）. The treatment group received Niaoxue No.1 prescription once daily， while the control group was treated with captopril and ferulic acid tablets. Both groups underwent a 4-week course of treatment. The urine erythrocyte， urine microalbumin （mAlb）， urine sediment red blood cell count， traditional Chinese medicine （TCM） syndrome score， 24-hour urine protein， blood neutrophil count， neutrophil to lymphocyte ratio （NLR）， platelet to lymphocyte ratio （PLR）， lymphocyte to monocyte ratio （LMR）， D-dimer， and immunoglobulin A were detected. The recurrence rate of HSP nephritis was followed up for 6 months. ResultThe total effective rates were 88.9% （48/54） in the treatment group and 70.4% （38/54） in the control group， and the treatment group was superior to the control group （χ²=5.708， P<0.05）. Compared with the results before treatment， after 14 days of treatment， the TCM syndrome total score， urine erythrocyte， urine mAlb， and 24-hour urine protein in both groups significantly decreased （P<0.05，P<0.01）， and the improvement was more significant in the treatment group than the control group （P<0.05）. After 28 days of treatment， compared with the results before treatment， the TCM syndrome total score， urine erythrocyte， urine mAlb， urine sediment red blood cell count， D-dimer， and 24-hour urine protein in both groups significantly decreased （P<0.05，P<0.01）， with the treatment group showing a more significant reduction in urine mAlb than the control group （P<0.05）. On the 14^th and 28^th days of treatment， the neutrophil percentage and NLR were lower in the treatment group than in the control group （P<0.05）， while there was no statistically significant difference in PLR and LMR. The recurrence rate of nephritis in both groups showed no statistically significant difference after a 6-month follow-up. ConclusionNiaoxue No.1 Prescription in the treatment of HSP nephritis with blood heat and stasis syndrome can significantly improve clinical symptoms， shorten the course of the disease， and reduce urine erythrocyte， urine mAlb， 24-hour urine protein， blood neutrophils， and NLR， thereby effectively alleviating the inflammatory state and reducing kidney damage in children with HSP nephritis.

Metastasis accounts for 90% of breast cancer deaths, where the lethality could be attributed to the poor drug accumulation at the metastatic loci. The tolerance to chemotherapy induced by breast cancer stem cells (BCSCs) and their particular redox microenvironment further aggravate the therapeutic dilemma. To be specific, therapy-resistant BCSCs can differentiate into heterogeneous tumor cells constantly, and simultaneously dynamic maintenance of redox homeostasis promote tumor cells to retro-differentiate into stem-like state in response to cytotoxic chemotherapy. Herein, we develop a specifically-designed biomimic platform employing neutrophil membrane as shell to inherit a neutrophil-like tumor-targeting capability, and anchored chemotherapeutic and BCSCs-differentiating reagents with nitroimidazole (NI) to yield two hypoxia-responsive prodrugs, which could be encapsulated into a polymeric nitroimidazole core. The platform can actively target the lung metastasis sites of triple negative breast cancer (TNBC), and release the escorted drugs upon being triggered by the hypoxia microenvironment. During the responsiveness, the differentiating agent could promote transferring BCSCs into non-BCSCs, and simultaneously the nitroimidazole moieties conjugated on the polymer and prodrugs could modulate the tumor microenvironment by depleting nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) and amplifying intracellular oxidative stress to prevent tumor cells retro-differentiation into BCSCs. In combination, the BCSCs differentiation and tumor microenvironment modulation synergistically could enhance the chemotherapeutic cytotoxicity, and remarkably suppress tumor growth and lung metastasis. Hopefully, this work can provide a new insight in to comprehensively treat TNBC and lung metastasis using a versatile platform.

The regulation of spermatogonial proliferation and apoptosis is of great significance for maintaining spermatogenesis. The single-cell RNA sequencing (scRNA-seq) analysis of the testis was performed to identify genes upregulated in spermatogonia. Using scRNA-seq analysis, we identified the spermatogonia upregulated gene origin recognition complex subunit 6 (Orc6), which is involved in DNA replication and cell cycle regulation; its protein expression in the human and mouse testis was detected by western blot and immunofluorescence. To explore the potential function of Orc6 in spermatogonia, the C18-4 cell line was transfected with control or Orc6 siRNA. Subsequently, 5-ethynyl-2-deoxyuridine (EdU) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, flow cytometry, and western blot were used to evaluate its effects on proliferation and apoptosis. It was revealed that ORC6 could promote proliferation and inhibit apoptosis of C18-4 cells. Bulk RNA sequencing and bioinformatics analysis indicated that Orc6 was involved in the activation of wingless/integrated (Wnt)/ β-catenin signaling. Western blot revealed that the expression of β-catenin protein and its phosphorylation (Ser675) were significantly decreased when silencing the expression of ORC6. Our findings indicated that Orc6 was upregulated in spermatogonia, whereby it regulated proliferation and apoptosis by activating Wnt/β-catenin signaling.

Objective:To construct 2019 novel coronavirus (2019-nCoV) 614D and 614G pseudovirus by HIV lentivirus packaging system and explore their biological specificity.Methods:The recombinant expression plasmids pCDNA3.1-614D and pCDNA3.1-614G were transiently cotransfected with psPAX2 and pLenti CMV Puro LUC into 293T cells respectively. After 72 hours, the supernatant was collected and ultracentrifuged with 20% sucrose cushion. The titer, morphology, protein expression and neutralizing activity of pseudovirus were determined.Results:S protein specific fluorescence was detected by indirect immunofluorescence test, Western blot analysis showed S protein was expressed, and the spike of pseudovirus was observed under transmission electron microscope. The titers of pseudovirus 614D and 614G were 1.12×10 4 and 2.52×10 4 TCID 50/ml, respectively. The pseudovirus 614D and 614G could be neutralized by S rabbit polyclonal antibody, indicating that the pseudovirus has high specificity. Conclusions:In this study, 2019-nCoV 614D and 614G pseudovirus was successfully constructed, which laid the foundation for the establishment of in vitro neutralizing antibody detection platform based on pseudovirus.