Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective:To detect and analyze the α-galactosidase A ( GLA) gene mutations in Fabry disease patients and their family members, observe the clinical phenotype of the patients, and assess the therapeutic effect of agalsidase alpha. Methods:It was a case series analysis. A total of 5 Fabry disease patients was diagnosed at the First Affiliated Hospital of Sun Yat-sen University from March 2022 to April 2023, and the clinical data and blood samples of the patients and their family members were collected. Genetic testing was performed using whole exome sequencing. GLA activity and substrate concentration were measured using the liquid chromatography-tandem mass spectrometry. Patients' clinical manifestations, family history, and auxiliary examination results were collected, and the therapeutic efficacy of agalsidase alpha and disease progression were followed up.Results:A total of 5 GLA gene mutations were identified by gene sequencing, including 1 novel mutation. Among them, 4 mutations were missense mutation, and the other one was nonsense mutation. Common clinical manifestations included edema (4/5) and reduced sweating (4/5). Renal pathology biopsy of 4 patients showed varying degrees of kidney damage, one of which was combined with IgA nephropathy. Auxiliary examinations revealed ocular involvement in 4 patients, cardiac involvement in 4 patients, and hearing impairment in 2 patients. All 5 patients received agalsidase alpha treatment, with 4 male patients receiving (16.8±5.9) times administrations of agalsidase alpha, and their globotriaosylsphingosine (Lyso-GL-3) levels decreased by 45.6%±15.5% from baseline. Conclusions:One novel GLA gene mutation is detected, which enriches the human gene mutation database. Fabry disease can be accompanied by kidney disease such as IgA nephropathy. When patients present with unexplained proteinuria combined with extrarenal manifestations such as reduced sweating, Fabry disease should be considered. Agalsidase alpha treatment can reduce Lyso-GL-3 concentration, and improve clinical symptoms.

Objective:To analyze the effect of problem-based learning (PBL) combined with case-based learning (CBL) and clinical pathway (CP) teaching methods in standardized residency training in department of hepatobiliary surgery.Methods:A total of 64 residents who received the standardized residency training in the Department of Hepatobiliary Surgery in Shaanxi Provincial People's Hospital from July 2018 to July 2019 were selected and divided into the observation group and the control group. The control group used PBL + CBL teaching methods, while the observation group adopted PBL + CBL + CP teaching methods. The after-department examination scores and the teaching cognition scores of the two groups were compared. SPSS 15.0 was used for t-test and Chi-square test. Results:The after-department examination scores of the two groups were compared. Compared with the control group, the examination scores of professional theories, case analysis and operation skills in the observation group were significantly higher, and the difference was statistically significant ( t = 6.98, 7.85, 7.01, P < 0.05). In terms of recognition of teaching, the observation group was significantly higher than the control group, and the difference was statistically significant ( t = 9.14, P < 0.05). Conclusion:The PBL + CBL + CP teaching is conducive to the comprehensive and systematic mastery of knowledge and the rapid establishment of scientific clinical thinking. It has a strong scientific and systematic nature and is worthy of promotion.

Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N⁶-methyladenosine (m⁶A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m⁶A methylation. We then indicate that SRSF7 is a novel m⁶A regulator, which specifically facilitates the m⁶A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m⁶A methyltransferase. The two m⁶A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m⁶A and validates the presence and functional importance of temporal- and spatial-specific regulation of m⁶A mediated by RNA-binding proteins (RBPs).
Humans ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glioblastoma/genetics* ; Methyltransferases/metabolism* ; RNA Splicing Factors/metabolism* ; RNA, Messenger/genetics* ; RNA-Binding Proteins/metabolism* ; Serine-Arginine Splicing Factors/metabolism* ; RNA Methylation/genetics*

Isochrysis galbana is considered an ideal bait for functional foods and nutraceuticals of humans because of its high fucoxanthin(Fx)content.However,multi-omics analysis of the regula-tory networks for Fx biosynthesis in I.galbana has not been reported.In this study,we report a high-quality genome assembly of I.galbana LG007,which has a genome size of 92.73 Mb,with a contig N50 of 6.99 Mb and 14,900 protein-coding genes.Phylogenetic analysis confirmed the monophyly of Haptophyta,with I.galbana sister to Emiliania huxleyi and Chrysochromulina tobinii.Evolutionary analysis revealed an estimated divergence time between I.galbana and E.huxleyi of～133 million years ago.Gene family analysis indicated that lipid metabolism-related genes exhibited significant expansion,including IgPLMT,IgOAR1,and IgDEGS1.Metabolome analysis showed that the content of carotenoids in I.galbana cultured under green light for 7 days was higher than that under white light,and β-carotene was the main carotenoid,accounting for 79.09％of the total carotenoids.Comprehensive multi-omics analysis revealed that the content of β-carotene,antheraxanthin,zeaxanthin,and Fx was increased by green light induction,which was significantly correlated with the expression of IgMYB98,IgZDS,IgPDS,IgLHCX2,IgZEP,IgLCYb,and IgNSY.These findings contribute to the understanding of Fx biosynthesis and its regulation,pro-viding a valuable reference for food and pharmaceutical applications.

Objective:Based on ear cartilage of congenital microtia, we tried to find the different metabolites and variational metabolic pathways on molecular level by gas chromatography time-of-flight mass spectrometry (GC-TOFMS).Methods:Patients with microtia were collected from June 2017 to January 2018. During operation, the ear cartilage tissue was collected and labeled, and the case group was residual ear cartilage tissue of the patients with microtia, with 18 cases. The control group was normal ear cartilage tissue, total 18 cases. After the sample pretreatment, based on the technique of GC-TOFMS and the software of XploreMET, the differential metabolites in the residual ear cartilage of microtia were analyzed by orthogonal partial least square discriminant analysis (OPLS-DA) and its variable importance projection (VIP) and U test statistical method. Compared with the metabolite database, the metabolic pathway enrichment analysis (MPEA) was used to screen the most related metabolic pathways. Results:According to the multidimensional statistical analysis, it is different in the metabolites of ear cartilage between the two groups. According to the verification of single dimensional statistical analysis, 14 specific biomarkers were identified, and their P value was less than 0.05. According to the metabolic pathway enrichment analysis (MPEA), 3 metabolic pathways had statistically significant difference, including arginine metabolism, taurine and the taurine metabolism, pantothenate and CoA metabolism, beta-alanine metabolism, glycerophospholipid metabolism, P <0.05. Conclusions:Arginine, taurine, L-cysteine and pantothenic acid may have an association with microtia, which proved that it is feasible to study the pathogenesis of microtia by metabonomics.

Objective:To investigate the microenvironment associated with tumorimmunity in regenerated lymph nodes treated with VEGF-C, which involves the lymphangiogenesis, chemokine as well as alteration of cell populations.Methods:A total of 10 nude mice were randomized to 2 groups. 5 mice in group A were treated with autologous lymph nodes fragmentary transplantation together with VEGF-C, 5 mice without any intervention in group B were served as control group. 4 weeks after surgeries, MDA-MB-231-Luc-GFP cells (5×10 6 cells/mouse, 100 μl of 40% matrigel solution) were injected subcutaneously in the thoracic flunk of nude mice in group A, the same number cells were implanted into the second mammary fat pad in group B as well. 4 weeks post inoculation, the tumor draining lymph nodes (TDLNs) in both groups were harvested, and the microenvironment was assessed by hematoxylin-eosin (HE) staining and multispectral immunofluorescence staining for LYVE-1, chemokine CCL21, programmed death ligand-1(PD-L1) and F4/80. Results:The specific markers were analyzed based on positive cell percentage between group A and group B. The LYVE-1 and F4/80 expression in the group A was significantly higher than that in group B[LYVE-1: group A 21.44 0(34.675)% vs group B 2.964 (4.160)%, P<0.001; F4/80: group A 5.396 (7.205)% vs group B 3.573 (2.670)%, P=0.020)], and there were no significant differences in the expression of CCL21 and PD-L1 between these two groups [CCL21: group A 21.470((29.145)% vs group B 16.430((29.145)%( P=0.166); PD-L1: group A10.000 (14.430)%vs group B 4.070 (26.740)%, P=0.091]. Additionally, the double positive expression of LYVE-1/CCL21 and LYVE-1/F4/80 had still statistically significant differences[LYVE-1/CCL21: group A 8.637 (13.150)% vs group B 1.571 (1.680)%, P<0.001; LYVE-1/F4/80: group A 6.181 (9.050)% vs group B 1.454 (0.830)%, P<0.001], whereas, the two groups did not differ from each other in the double positive expression of LYVE-1/PD-L1 [group A 3.617 (4.195)% vs group B 2.363 (3.900)%, P=0.266]. Conclusions:The renewed lymph nodes treated with VEGF-C demonstrate some more immune suppressive conditions such as lymphatic endothelial cells hyperplasia, myeloid-derived suppressor cells infiltration, enhanced expression of CCL21 and PD-L1.

Objective:Based on ear cartilage of congenital microtia, we tried to find the different metabolites and variational metabolic pathways on molecular level by gas chromatography time-of-flight mass spectrometry (GC-TOFMS).Methods:Patients with microtia were collected from June 2017 to January 2018. During operation, the ear cartilage tissue was collected and labeled, and the case group was residual ear cartilage tissue of the patients with microtia, with 18 cases. The control group was normal ear cartilage tissue, total 18 cases. After the sample pretreatment, based on the technique of GC-TOFMS and the software of XploreMET, the differential metabolites in the residual ear cartilage of microtia were analyzed by orthogonal partial least square discriminant analysis (OPLS-DA) and its variable importance projection (VIP) and U test statistical method. Compared with the metabolite database, the metabolic pathway enrichment analysis (MPEA) was used to screen the most related metabolic pathways. Results:According to the multidimensional statistical analysis, it is different in the metabolites of ear cartilage between the two groups. According to the verification of single dimensional statistical analysis, 14 specific biomarkers were identified, and their P value was less than 0.05. According to the metabolic pathway enrichment analysis (MPEA), 3 metabolic pathways had statistically significant difference, including arginine metabolism, taurine and the taurine metabolism, pantothenate and CoA metabolism, beta-alanine metabolism, glycerophospholipid metabolism, P <0.05. Conclusions:Arginine, taurine, L-cysteine and pantothenic acid may have an association with microtia, which proved that it is feasible to study the pathogenesis of microtia by metabonomics.

Objective:To investigate the microenvironment associated with tumorimmunity in regenerated lymph nodes treated with VEGF-C, which involves the lymphangiogenesis, chemokine as well as alteration of cell populations.Methods:A total of 10 nude mice were randomized to 2 groups. 5 mice in group A were treated with autologous lymph nodes fragmentary transplantation together with VEGF-C, 5 mice without any intervention in group B were served as control group. 4 weeks after surgeries, MDA-MB-231-Luc-GFP cells (5×10 6 cells/mouse, 100 μl of 40% matrigel solution) were injected subcutaneously in the thoracic flunk of nude mice in group A, the same number cells were implanted into the second mammary fat pad in group B as well. 4 weeks post inoculation, the tumor draining lymph nodes (TDLNs) in both groups were harvested, and the microenvironment was assessed by hematoxylin-eosin (HE) staining and multispectral immunofluorescence staining for LYVE-1, chemokine CCL21, programmed death ligand-1(PD-L1) and F4/80. Results:The specific markers were analyzed based on positive cell percentage between group A and group B. The LYVE-1 and F4/80 expression in the group A was significantly higher than that in group B[LYVE-1: group A 21.44 0(34.675)% vs group B 2.964 (4.160)%, P<0.001; F4/80: group A 5.396 (7.205)% vs group B 3.573 (2.670)%, P=0.020)], and there were no significant differences in the expression of CCL21 and PD-L1 between these two groups [CCL21: group A 21.470((29.145)% vs group B 16.430((29.145)%( P=0.166); PD-L1: group A10.000 (14.430)%vs group B 4.070 (26.740)%, P=0.091]. Additionally, the double positive expression of LYVE-1/CCL21 and LYVE-1/F4/80 had still statistically significant differences[LYVE-1/CCL21: group A 8.637 (13.150)% vs group B 1.571 (1.680)%, P<0.001; LYVE-1/F4/80: group A 6.181 (9.050)% vs group B 1.454 (0.830)%, P<0.001], whereas, the two groups did not differ from each other in the double positive expression of LYVE-1/PD-L1 [group A 3.617 (4.195)% vs group B 2.363 (3.900)%, P=0.266]. Conclusions:The renewed lymph nodes treated with VEGF-C demonstrate some more immune suppressive conditions such as lymphatic endothelial cells hyperplasia, myeloid-derived suppressor cells infiltration, enhanced expression of CCL21 and PD-L1.

Objective: Autologous lymph nodes fragmentary transplantation combined with vascular endothelial growth factor-C (VEGF-C) on athymic nude mice to explore the association between regeneration of lymphatic vessel and tumor cell migration. Methods: A total of 45 nude mice were randomly divided into 3 groups: Group A, simple autologous lymph nodes fragmentary transplantation, n=15; Group B, autologous lymph nodes fragmentary transplantation together with VEGF-C, n=15; Group C, without any intervention, n=15. At 1 month, 2 months and 6months after surgeries, the axillary lymph nodes of 5 mice in each group were dynamically examined by in vivo indocyanine green (ICG) fluorescence imaging respectively. The regenerated lymph nodes and relevant skin were evaluated using hematoxylin-eosin (H&E) staining and the skin was quantitatively analyzed via immunofluorescence staining for lymphatic vessel endothelial hyaluronan receptor 1(LYVE-1) as well. Results: One month after surgery, the right regenerated axillary lymph nodes in group B (5/5) were visible by in vivo ICG fluorescence imaging, whereas the same signals were not detected in group A (0/5). The results were the same at 2 and 6 months after surgery. HE staining showed that the cortical, paracortical, and medullary regions of the right axillary lymph nodes of the experimental group B were clear, and the lymphatic vessel structure was present, accompanied by lymphocyte infiltration. Immunofluorescence staining of the right upper limb showed that the expression of LYVE-1 in the lymphatic endothelium of the B group was significantly higher than that in group A (P<0.001) and the control group (both P<0.001). Conclusions Due to the promising consequence of regenerated lymph nodes, the procedure of autologous lymph nodes fragmentary transplantation combined with VEGF-C in athymic nude mice provides a reliable animal model for the next stage research.