Objective To explore the mechanism by which cancer-associated fibroblasts(CAFs)regulate CD13-high expression neutrophil-like myeloid-derived suppressor cell(CD13hi-nMDSC)migration in pancreatic ductal adenocarcinoma(PDAC),so as to provide potential molecular targets and experimental evidences for immunotherapy in patients.Methods CAFs were isolated and purified from pancreatic cancer tissues of 5 PDAC patients.The phenotype and purity of CAFs were identified by immunofluorescence and flow cytometry.The expression of related factors in CAF was detected by quantitative polymerase chain reaction(qPCR)and enzyme-linked immunosorbent assay(ELISA).CAF conditioned medium and myeloid-derived suppressor cell(MDSC)migration system were constructed by Transwell to observe the migration of MDSCs and to study the specific mechanisms by which the aforementioned cytokines participate in regulating the migration of MDSCs.Results The isolated primary CAFs expressed activation biomarkers fibroblast activation protein(FAP)and α-smooth muscle actin(α-SMA),while the human foreskin fibroblasts(HFFs)of control cells did not express FAP and α-SMA.qPCR results showed that the mRNA expression levels of interleukin 6(IL-6),monocyte chemotactic protein 1(MCP-1),and stromal cell-derived factor 1(SDF-1)in CAFs were higher than those in HFFs(all P＜0.01).The contents of IL-6,MCP-1,and SDF-1 in the CAF culture supernatant were significantly higher than those in the HFF culture supernatant(all P＜0.01),and the secretion content increased with the prolongation of culture time.Compared with HFF conditioned medium and regular medium(RPMI 1640),CAF conditioned medium could recruit more total MDSCs and CD13hi-nMDSCs(all P＜0.01).The addition of SDF-1 recombinant protein alone in the culture system could induce the migration of total MDSCs and CD13hi-nMDSCs,and the addition of SDF-1 neutralizing antibodies or C-X-C motif chemokine receptor 4(CXCR4)blocking antibodies could significantly reduce the migration of CD13hi-nMDSCs induced by CAF conditioned medium(all P＜0.01).Although MCP-1 alone could also induce the migration of total MDSCs and CD13hi-nMDSCs,the number of CD13hi-nMDSCs migrating was significantly less than that of the SDF-1 experimental group.The IL-6 recombinant protein did not induce the migration of total MDSCs or CD13hi-nMDSCs.Conclusion CAFs can mediate the migration of total MDSCs and CD13hi-nMDSCs in PDAC through SDF-1/CXCR4 pathway.

Objective:To investigate the clinical and genetic variation characteristics of a child with autosomal dominant lateral temporal lobe epilepsy caused by de novo variation of the MICAL1 gene. Methods:Clinical data of the patient with autosomal dominant lateral temporal lobe epilepsy caused by MICAL1 gene variation diagnosed in Children′s Hospital of Soochow University in August 2019 were collected. The whole exome sequencing was performed on the core members of the family, and the characteristics of gene variations were analyzed. Results:The proband, a 10 years and 5 months old boy, was admitted to the hospital because of "intermittent convulsions for 7 years". The clinical manifestations included focal or generalized tonic-clonic seizures and hearing aura, with normal language and intellectual development. No abnormalities were found in the T 1 and fluid attenuated inversion recovery sequences of the cranial 3.0 T magnetic resonance imaging and 3D thin-slice magnetic resonance imaging.Long-range video electroencephalogram showed the distribution of spinous and slow spinous waves in the left frontal and temporal areas. The results of whole exome gene sequencing in the core family members showed heterozygous de novo missense variation in the MICAL1 gene of the proband (NM_022765): c.763G>T(exon6)(p.Val255Leu) that had not been reported. According to American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines (2015), the mutation was considered potentially pathogenic. The application of antiepileptic drugs was effective in controlling epileptic seizures. Conclusions:Auditory symptoms are main clinical manifestations for the child with autosomal dominant lateral temporal lobe epilepsy. Antiepileptic drugs can effectively control epileptic seizures of the child, and the MICAL1 gene c.763G>T (p.Val255Leu) mutation is the genetic cause of the proband.

Non-small cell lung cancer (NSCLC), a leading cause of cancer-related deaths worldwide, remains a significant clinical challenge despite advances in immune checkpoint inhibitors therapy, with drug resistance persisting as a major obstacle. Palmitoylation, a critical post-translational modification (PTM) primarily catalyzed by palmitoyltransferases of the zinc finger DHHC-type (ZDHHC), has recently demonstrated important implications in NSCLC. This review aims to elucidate the mechanisms and clinical potential of ZDHHC-mediated protein palmitoylation in NSCLC progression and immune escape.
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Humans ; Lipoylation ; Lung Neoplasms/pathology* ; Acyltransferases/genetics* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Animals

Objective:To investigate the clinical and genetic variation characteristics of a child with autosomal dominant lateral temporal lobe epilepsy caused by de novo variation of the MICAL1 gene. Methods:Clinical data of the patient with autosomal dominant lateral temporal lobe epilepsy caused by MICAL1 gene variation diagnosed in Children′s Hospital of Soochow University in August 2019 were collected. The whole exome sequencing was performed on the core members of the family, and the characteristics of gene variations were analyzed. Results:The proband, a 10 years and 5 months old boy, was admitted to the hospital because of "intermittent convulsions for 7 years". The clinical manifestations included focal or generalized tonic-clonic seizures and hearing aura, with normal language and intellectual development. No abnormalities were found in the T 1 and fluid attenuated inversion recovery sequences of the cranial 3.0 T magnetic resonance imaging and 3D thin-slice magnetic resonance imaging.Long-range video electroencephalogram showed the distribution of spinous and slow spinous waves in the left frontal and temporal areas. The results of whole exome gene sequencing in the core family members showed heterozygous de novo missense variation in the MICAL1 gene of the proband (NM_022765): c.763G>T(exon6)(p.Val255Leu) that had not been reported. According to American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines (2015), the mutation was considered potentially pathogenic. The application of antiepileptic drugs was effective in controlling epileptic seizures. Conclusions:Auditory symptoms are main clinical manifestations for the child with autosomal dominant lateral temporal lobe epilepsy. Antiepileptic drugs can effectively control epileptic seizures of the child, and the MICAL1 gene c.763G>T (p.Val255Leu) mutation is the genetic cause of the proband.

Objective To explore the perioperative safety of video-assisted thoracic surgery (VATS) in Day Care Unit and the risk factors for delayed discharge under centralized management model. Methods The patients with VATS managed by the Day Care Unit of the Drum Tower Hospital Affiliated to Nanjing University Medical School in 2021 were retrospectively collected. The patients’ postoperative data and risk factors for delayed discharge were analyzed. Results A total of 383 patients were enrolled, including 179 males and 204 females with an average age of 46.09±14.82 years. Eleven (2.87%) patients developed grade 3-4 postoperative complications during the hospitalization. Eighteen (4.70%) patients visited unscheduled outpatient clinic within 7 days, and 6 (1.57%) patients were re-hospitalized within 30 days after discharge. The remaining patients had no significant adverse events during the 30-day follow-up. The average length of hospital stay was 2.27±0.35 d. The length of hospital stay was over 48 h in 48 (12.53%) patients. The independent risk factor for delayed discharge was lobectomy or combined resection (OR=3.015, 95%CI 1.174-7.745, P=0.022). Conclusion VATS can be safely conducted under the centralized management in Day Care Unit. The risk factor for delayed discharge is the extent of surgical resection.

Respiratory syncytial virus (RSV) is an enveloped, negative-sense, single-stranded RNA virus of the Orthopneumovirus  genus of the Pneumoviridae family in the order Mononegavirales. RSV can cause acute upper and lower respiratory tract infections, sometimes with extrapulmonary complications. The disease burden of RSV infection is enormous, mainly affecting infants and older adults aged 75 years or above. Currently, treatment options for RSV are largely supportive. Prevention strategies remain a critical focus, with efforts centered on vaccine development and the use of prophylactic monoclonal antibodies. To date, three RSV vaccines have been approved for active immunization among individuals aged 60 years and above. For children who are not eligible for these vaccines, passive immunization is recommended. A newly approved prophylactic monoclonal antibody, Nirsevimab, which offers enhanced neutralizing activity and an extended half-life, provides exceptional protection for high-risk infants and young children. This review provides a comprehensive and detailed exploration of RSV's virology, immunology, pathogenesis, epidemiology, clinical manifestations, treatment options, and prevention strategies.
Humans ; Respiratory Syncytial Virus Infections/prevention & control* ; Respiratory Syncytial Viruses/pathogenicity* ; Respiratory Syncytial Virus, Human/pathogenicity* ; Antiviral Agents/therapeutic use*

Lipid Droplets/metabolism* ; Bacteria ; Lipid Metabolism

BACKGROUND: The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis. METHODS: In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis. RESULTS: A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP. CONCLUSIONS Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.
Humans ; Bronchoalveolar Lavage Fluid ; Prospective Studies ; Alveolitis, Extrinsic Allergic/diagnosis* ; Fibrosis ; Carbohydrates

BACKGROUND: After major liver resection, the volume status of patients is still undetermined. However, few concerns have been raised about postoperative fluid management. We aimed to compare gut function recovery and short-term prognosis of the patients after laparoscopic liver resection (LLR) with or without inferior vena cava (IVC) respiratory variability-directed fluid therapy in the anesthesia intensive care unit (AICU). METHODS: This randomized controlled clinical trial enrolled 70 patients undergoing LLR. The IVC respiratory variability was used to optimize fluid management of the intervention group in AICU, while the standard practice of fluid management was used for the control group. The primary outcome was the time to flatus after surgery. The secondary outcomes included other indicators of gut function recovery after surgery, postoperative length of hospital stay (LOS), liver and kidney function, the severity of oxidative stress, and the incidence of severe complications associated with hepatectomy. RESULTS: Compared with patients receiving standard fluid management, patients in the intervention group had a shorter time to anal exhaust after surgery (1.5 ± 0.6 days vs. 2.0 ± 0.8 days) and lower C-reactive protein activity (21.4 [95% confidence interval (CI): 11.9-36.7] mg/L vs. 44.8 [95%CI: 26.9-63.1] mg/L) 24 h after surgery. There were no significant differences in the time to defecation, serum concentrations of D -lactic acid, malondialdehyde, renal function, and frequency of severe postoperative complications as well as the LOS between the groups. CONCLUSION: Postoperative IVC respiratory variability-directed fluid therapy in AICU was facilitated in bowel movement but elicited a negligible beneficial effect on the short-term prognosis of patients undergoing LLR. TRIAL REGISTRATION ChiCTR-INR-17013093.
Humans ; Hepatectomy ; Vena Cava, Inferior/surgery* ; Liver ; Laparoscopy ; Fluid Therapy