Acral melanoma(AM)is a distinct and aggressive subtype of melanoma characterized by high metastatic potential and poor prognosis.The pathogenesis and therapeutic strategies for advanced AM differ significantly from those of other melanoma subtypes,yet AM has received relatively less attention.AM exhibits high heterogeneity and a low tumor mutation burden.Mutations in braf,nras,and the tert promoter occur at much lower frequencies in AM than in cutaneous melanoma,limiting the effectiveness of treatments such as recombinant B-Raf proto oncogene serine/threonine protein kinase(BRAF)inhibitors.Additionally,reduced tumor immunogenicity due to low tumor-infiltrating lymphocyte levels contributes to the limited efficacy of immune checkpoint inhibitors,including anti-programmed death-1 and anti-cytotoxic T-lymphocyte-associated protein 4 therapies.Recent discoveries of novel therapeutic targets,such as receptor tyrosine kinases and cyclin-dependent kinases,along with emerging immune checkpoints,including V-domain immunoglobulin suppressor of T cell activation,adenosine A2A receptor,T cell immunoglobulin and ITIM domain,and T cell immunoglobulin and mucin-domain containing-3,offer new prospects for improving AM patient outcomes.Many AM treatments remain in the experimental stage,with research focusing on small-molecule targeted therapies,immune checkpoint inhibitors,and tumor microenvironment modulation.Combination strategies incorporating next-genera-tion cell therapies,oncolytic virus therapies,and therapeutic vaccines are also gaining prominence.Notably,clinical trials of personalized mRNA cancer vaccines have been promising,while antibody-drug conjugate and radionuclide-conjugated therapies present additional opportunities for enhancing AM prognosis.This article summarizes the cellular immune characteristics,mutation profiles,and tumor microenvironment of AM,as well as the current therapeutic strategies and advancements in the hope of expanding clinical benefits for AM patients.

Objective:Investigate key genes influencing vascular calcification through bioinformatics analysis and experimental validation.Methods:Three vascular calcification datasets (GSE159832, GSE229679 and GSE37558) were obtained from the Gene Expression Omnibus database. Subsequently, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and conventional gene set enrichment analysis (GSEA) were performed on the common differential expressed genes(DEGs). For in vitro validation, a vascular smooth muscle cell calcification model was established by stimulating mouse primary vascular smooth muscle cells with high phosphate and calcium chloride (Pi+CaCl 2). Cells were divided into a control group and a Pi+CaCl 2 group. To investigate the role of TK1, cells were transfected with TK1-targeting siRNA (siTK1) or control siRNA (siControl) prior to Pi+CaCl 2 stimulation, creating siControl+Pi+CaCl 2 and siTK1+Pi+CaCl 2 groups. The association between key DEGs and vascular calcification was assessed at the protein and mRNA levels using Western blot and quantitative real-time PCR, respectively. Changes in the phosphorylation of the downstream effector, AKT (p-AKT/AKT), were also measured. Results:A total of 2275, 449, and 381 DEGs were identified from the three vascular calcification datasets (GSE159832, GSE229679, and GSE37558), respectively. Two common DEGs-phosphoserine aminotransferase 1 and thymidine kinase 1 (TK1)-were identified across all datasets. GO enrichment analysis revealed that TK1 was significantly enriched in pathways related to ribosome biogenesis, assembly, and rRNA processing and maturation. GSEA-KEGG analysis indicated significant enrichment in the PI3K-AKT signaling pathway, pathways in cancer, neurodegenerative diseases, cytoskeleton, and smooth muscle contraction. Conventional GSEA of TK1 further confirmed significant enrichment in pathways including dynein, epithelial tight junctions, axon guidance, and vascular smooth muscle contraction pathways. At the experimental level, both protein and mRNA expression of TK1, along with the p-AKT/AKT ratio, were significantly lower in the Pi+CaCl 2 group compared to the control group (all P<0.05). Furthermore, compared to the siControl+Pi+CaCl 2 group, the siTK1+Pi+CaCl 2 group exhibited decreased expression of differentiation markers, increased expression of calcification markers, and a further reduced p-AKT/AKT ratio (all P<0.05). Conclusion:Integrated bioinformatics and cellular validation demonstrate a correlation between TK1 expression and vascular calcification, suggesting a potential protective role for TK1 in this pathological process.

Acral melanoma(AM)is a distinct and aggressive subtype of melanoma characterized by high metastatic potential and poor prognosis.The pathogenesis and therapeutic strategies for advanced AM differ significantly from those of other melanoma subtypes,yet AM has received relatively less attention.AM exhibits high heterogeneity and a low tumor mutation burden.Mutations in braf,nras,and the tert promoter occur at much lower frequencies in AM than in cutaneous melanoma,limiting the effectiveness of treatments such as recombinant B-Raf proto oncogene serine/threonine protein kinase(BRAF)inhibitors.Additionally,reduced tumor immunogenicity due to low tumor-infiltrating lymphocyte levels contributes to the limited efficacy of immune checkpoint inhibitors,including anti-programmed death-1 and anti-cytotoxic T-lymphocyte-associated protein 4 therapies.Recent discoveries of novel therapeutic targets,such as receptor tyrosine kinases and cyclin-dependent kinases,along with emerging immune checkpoints,including V-domain immunoglobulin suppressor of T cell activation,adenosine A2A receptor,T cell immunoglobulin and ITIM domain,and T cell immunoglobulin and mucin-domain containing-3,offer new prospects for improving AM patient outcomes.Many AM treatments remain in the experimental stage,with research focusing on small-molecule targeted therapies,immune checkpoint inhibitors,and tumor microenvironment modulation.Combination strategies incorporating next-genera-tion cell therapies,oncolytic virus therapies,and therapeutic vaccines are also gaining prominence.Notably,clinical trials of personalized mRNA cancer vaccines have been promising,while antibody-drug conjugate and radionuclide-conjugated therapies present additional opportunities for enhancing AM prognosis.This article summarizes the cellular immune characteristics,mutation profiles,and tumor microenvironment of AM,as well as the current therapeutic strategies and advancements in the hope of expanding clinical benefits for AM patients.

Objective:Investigate key genes influencing vascular calcification through bioinformatics analysis and experimental validation.Methods:Three vascular calcification datasets (GSE159832, GSE229679 and GSE37558) were obtained from the Gene Expression Omnibus database. Subsequently, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and conventional gene set enrichment analysis (GSEA) were performed on the common differential expressed genes(DEGs). For in vitro validation, a vascular smooth muscle cell calcification model was established by stimulating mouse primary vascular smooth muscle cells with high phosphate and calcium chloride (Pi+CaCl 2). Cells were divided into a control group and a Pi+CaCl 2 group. To investigate the role of TK1, cells were transfected with TK1-targeting siRNA (siTK1) or control siRNA (siControl) prior to Pi+CaCl 2 stimulation, creating siControl+Pi+CaCl 2 and siTK1+Pi+CaCl 2 groups. The association between key DEGs and vascular calcification was assessed at the protein and mRNA levels using Western blot and quantitative real-time PCR, respectively. Changes in the phosphorylation of the downstream effector, AKT (p-AKT/AKT), were also measured. Results:A total of 2275, 449, and 381 DEGs were identified from the three vascular calcification datasets (GSE159832, GSE229679, and GSE37558), respectively. Two common DEGs-phosphoserine aminotransferase 1 and thymidine kinase 1 (TK1)-were identified across all datasets. GO enrichment analysis revealed that TK1 was significantly enriched in pathways related to ribosome biogenesis, assembly, and rRNA processing and maturation. GSEA-KEGG analysis indicated significant enrichment in the PI3K-AKT signaling pathway, pathways in cancer, neurodegenerative diseases, cytoskeleton, and smooth muscle contraction. Conventional GSEA of TK1 further confirmed significant enrichment in pathways including dynein, epithelial tight junctions, axon guidance, and vascular smooth muscle contraction pathways. At the experimental level, both protein and mRNA expression of TK1, along with the p-AKT/AKT ratio, were significantly lower in the Pi+CaCl 2 group compared to the control group (all P<0.05). Furthermore, compared to the siControl+Pi+CaCl 2 group, the siTK1+Pi+CaCl 2 group exhibited decreased expression of differentiation markers, increased expression of calcification markers, and a further reduced p-AKT/AKT ratio (all P<0.05). Conclusion:Integrated bioinformatics and cellular validation demonstrate a correlation between TK1 expression and vascular calcification, suggesting a potential protective role for TK1 in this pathological process.

Objective:To analyze the distribution characteristics of UGT1A1 mutant genes (including enhancers, promoters, and exons 1-5) and further explore the correlation between UGT1A1 genotype and clinical phenotypes in patients with inherited hyperunconjugated bilirubinemia.Methods:Patients diagnosed with hereditary hyperunconjugated bilirubinemia at Nanjing Second Hospital from June 2015 to December 2022 were retrospectively analyzed. The UGT1A1 gene was examined using Sanger sequencing in all patients. Complete blood count, liver function, and abdominal imaging examinations were performed. Comparison of categorical variable data using χ2 testor Fisher percision tests. Comparison of continaous veriable data with normal distribution using t-test. Results:112 cases (male:female ratio 81:31, aged 9-70 years) had inherited hyperunconjugated bilirubinemia, with a total of 14 mutation sites identified, of which seven were confirmed mutations, and the frequency ranged from high to low: (TA)n accounted for 50%, c.211G>A (p.G71R) accounted for 49.10%, 1456T>G (p.Y486D) accounted for 16.96%, c.686C>A (p.R229W) accounted for 12.5%, 1091C>T (p.P364L) accounted for 8.04%, and c- 3279T>G accounted for 0.982%. Simultaneously, all patients had one to four mutations, of which only one mutation was the most common (55.36%), followed by two mutations (37.5%), and rare three and four mutations (5.36% and 1.78%). There was no statistical significance in total bilirubin (TBil) levels among the four groups ( F=0.652, P=0.583). One mutation was most common in (TA)n and c.211G>A (p.G71R), among which TA6/TA7 ( n=10) and TA7/TA7 ( n=14) mutations were statistically significant in TBil ( t=2.143, P=0.043). The c.211G>A (p.G71R) heterozygous ( n=9) and isolated ( n=15) mutation had no statistical significance in TBil ( t=0.382, P=0.706). The GS group accounted for 75%, the intermediate group accounted for 16.9%, and the CNS-Ⅱ group accounted for 8%. TBil was statistically significant among the three groups ( F=270.992, P<0.001). There was no statistically significant difference ( χ2=3.317, P=0.19) between mutation 1 (44 cases, 14 cases, and 4 cases, respectively) and mutations ≥ 2 (40 cases, 5 cases, and 5 cases, respectively) in the GS group, intermediate group, and CNS-II group. Conclusion:The number of UGT1A1 gene mutation sites may have no synergistic effect on TBil levels in patients with inherited hyperunconjugated bilirubinemia. TA7/TA7 mutations are not uncommon, and TBil levels are relatively high.

ObjectiveTo investigate the impact of acute respiratory infections in children under 12 years old in Pudong New Area， Shanghai from 2019 to 2023. MethodsAcute respiratory infection samples of children under 12 years old from three sentinel hospitals in Pudong New Area， Shanghai from 2019 to 2023 were collected， and 42 respiratory infection pathogens， including influenza virus， adenovirus， parainfluenza virus， respiratory syncytial virus， human enterovirus/rhinovirus， human pulmonary virus， human bokavirus， coronavirus （229E， HKU1， NL63 and OC43）， and novel coronavirus， were detected with microfluidic chips. The situation of acute respiratory infections among outpatient and inpatient children in this area was analyzed for the before the implementation of non pharmacological intervention measures （2019.12‒2020.1）， during the period of non pharmacological intervention measures （2020.2‒2022.12）， and after non pharmacological intervention measures （2023.1‒2023.6）. ResultsFrom 2019 to 2023， a total of 1 770 samples were collected， and 445 pathogens were detected， with a detection rate of 25.14% （445/1 770）. The main pathogens detected during the study period were influenza virus： 8.70% （154/1 770）， respiratory syncytial virus： 4.41% （78/1 770）， human enterovirus/rhinovirus： 2.66% （47/1 770）， human adenovirus： 2.49% （44/1 770）， and parainfluenza virus： 2.20% （39/1 770）. Before the implementation of non pharmacological intervention measures， outpatients were primarily infected with influenza， parainfluenza virus， and respiratory syncytial virus， with detection rates of 8.09%， 4.49%， and 4.04%， respectively； inpatients were mainly infected with influenza， respiratory syncytial virus， and parainfluenza virus， with detection rates of 4.49%， 3.82%， and 3.15%， respectively. During the period of non pharmacological intervention measures， influenza， rhinovirus and respiratory syncytial virus were the main viruses detected in the samples of outpatient children， with detection rates of 4.04%， 3.60%， and 2.47%， respectively； inpatient samples mainly detected respiratory syncytial virus， rhinovirus， and influenza virus， with detection rates of 3.60%， 2.02%， and 1.80%， respectively. After non pharmacological intervention measures， influenza， rhinovirus and respiratory syncytial virus were the main pathogens detected in the outpatients， with detection rates of 9.89%， 2.92% and 2.02%， respectively； influenza， respiratory syncytial virus， and rhinovirus were the main pathogens detected in inpatient children， with detection rates of 6.29%， 1.57%， and 1.35%， respectively. ConclusionThe prevalence of pathogens related to acute respiratory infections in children is influenced by non pharmacological preventive measures.

To investigate the therapeutic effect and mechanism of Qingfei oral liquid in idiopathic pulmonary fibrosis. Seventy-two male SD rats were divided into control group, model group, pirofenidone group and Qingfei group with 18 animals in each group. The idiopathic pulmonary fibrosis was induced in last three groups by intratracheal injection of bleomycin; pirofenidone group was given oral administration of pirofenidone b.i.d for 21 d, and Qingfei group was given Qingfei oral liquid 3.6 mL/kg q.d for Lung tissues were obtained for HE staining, Masson staining and transforming growth factor (TGF)-β immunohistochemical staining. Superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) were detected in tissue homogenates. The BATMAN-TCM database was used to retrieve the chemical components and their corresponding targets of Qingfei oral solution by network pharmacology method, and then the component-target-disease network diagram was constructed. Finally, the pathway enrichment analysis was carried out to explore the molecular mechanism of Qingfei oral liquid against idiopathic fibrosis. Histopathology results showed that Qingfei oral liquid had a similar relieving effect on pulmonary fibrosis as the positive drug pirfenidone; TGF-β secretion had a significant reduction in lung tissues of Qingfei group; and Qingfei oral liquid had better regulatory effect on SOD, MDA and GSH than pirfenidone. The results of component-target-disease network and pathway enrichment analysis showed that the related molecular pathways were concentrated in inflammation, extracellular matrix and cytokines. Qingfei oral liquid has a good therapeutic effect on idiopathic pulmonary fibrosis in rats via regulation of inflammation, extracellular matrix and cytokines.
Animals ; Bleomycin/pharmacology* ; Cytokines ; Drugs, Chinese Herbal ; Glutathione ; Idiopathic Pulmonary Fibrosis/drug therapy* ; Inflammation ; Lung/pathology* ; Male ; Network Pharmacology ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase/metabolism* ; Transforming Growth Factor beta/pharmacology*

Objective:In order to discuss the ovulation induction effect and clinical significance of human menopausal gonadotropin (hMG) and follicle-stimulating hormone (FSH) on progestin primed ovarian stimulation (PPOS) protocol in patients with diminished ovarian reserve during in vitro fertilization (IVF) cycle. Methods:Using retrospective cohort study method, the patients with diminished ovarian reserve who received PPOS in IVF assisted reproduction in the Reproductive Medicine Center of the First Affiliated Hospital of Fujian Medical University from November 2018 to June 2020 were included, 110 cycles met requirements and were divided into FSH group (63 cycles) and hMG group (47 cycles) according to the different gonadotropin (Gn) used. General information and the outcome of IVF between the two groups were compared.Results:The total number of retrieved oocytes, M Ⅱ oocytes, fertilized oocytes, cleaved oocytes, day 3 (D3) embryos, all freezing embryo, two pronucleus (2PN) fertilization rate, the blastocyst formation rate, day 5 (D5) blastocyst rate and the utilization rate of oocytes, the biochemical pregnancy rate and the miscarriage rate had no statistical differences (all P>0.05). The rate of D3 high-quality embryos, the clinical pregnancy rate and the embryo implantation rate of FSH group were higher than those of hMG group [64.2% (111/173) vs. 50.0% (48/96), P=0.024; 45.8% (22/48) vs. 21.2% (7/33), P=0.023; 36.5% (27/74) vs. 16.7% (8/48), P=0.018] with statistical significances. Conclusion:For patients with diminished ovarian reserve, the rate of D3 high-quality embryos, the clinical pregnancy rate and the embryo implantation rate of FSH group are higher.

Objective:In order to discuss the ovulation induction effect and clinical significance of human menopausal gonadotropin (hMG) and follicle-stimulating hormone (FSH) on progestin primed ovarian stimulation (PPOS) protocol in patients with diminished ovarian reserve during in vitro fertilization (IVF) cycle. Methods:Using retrospective cohort study method, the patients with diminished ovarian reserve who received PPOS in IVF assisted reproduction in the Reproductive Medicine Center of the First Affiliated Hospital of Fujian Medical University from November 2018 to June 2020 were included, 110 cycles met requirements and were divided into FSH group (63 cycles) and hMG group (47 cycles) according to the different gonadotropin (Gn) used. General information and the outcome of IVF between the two groups were compared.Results:The total number of retrieved oocytes, M Ⅱ oocytes, fertilized oocytes, cleaved oocytes, day 3 (D3) embryos, all freezing embryo, two pronucleus (2PN) fertilization rate, the blastocyst formation rate, day 5 (D5) blastocyst rate and the utilization rate of oocytes, the biochemical pregnancy rate and the miscarriage rate had no statistical differences (all P>0.05). The rate of D3 high-quality embryos, the clinical pregnancy rate and the embryo implantation rate of FSH group were higher than those of hMG group [64.2% (111/173) vs. 50.0% (48/96), P=0.024; 45.8% (22/48) vs. 21.2% (7/33), P=0.023; 36.5% (27/74) vs. 16.7% (8/48), P=0.018] with statistical significances. Conclusion:For patients with diminished ovarian reserve, the rate of D3 high-quality embryos, the clinical pregnancy rate and the embryo implantation rate of FSH group are higher.