Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

AIM: To investigate the effects of Conbercept on various optical coherence tomography(OCT)biomarkers in patients with retinal vein occlusion-related macular edema(RVO-ME), and to analyze the correlation of these biomarker changes with visual prognosis.METHODS: Retrospective study. A total of 57 patients(57 eyes)with RVO-ME, including 25 patients(25 eyes)with central retinal vein occlusion(CRVO)and 32 patients(32 eyes)with branch retinal vein occlusion(BRVO), were enrolled in this study. All the patients received intravitreal injection of conbercept once a month, three times in total. The preoperative and postoperative best-corrected visual acuity(BCVA), and changes in OCT biomarkers, including central macular thickness(CMT), the length of disorganization of the retinal inner layers(DRIL), the number of hyperreflective dots(HRD), the area of intraretinal fluid(IRF), the area of subretinal fluid(SRF), and the length of ellipsoid zone(EZ)disruption were compared. Furthermore, the relationship of these changes with BCVA was analyzed.RESULTS:Compared with the baseline, at 3 mo post-treatment, BCVA(LogMAR)was improved, CMT was decreased, the length of DRIL was shortened, the number of HRD was reduced, the area of IRF was decreased, the area of SRF was reduced, and the length of EZ disruption was shortened(all P<0.05). Spearman correlation analysis showed that there was no correlation between the changes in CMT, the length of DRIL, the number of HRD, the area of IRF, the area of SRF and the change in BCVA before and after treatment(P>0.05). However, the change in the length of EZ disruption was positively correlated with the change in BCVA(rs=0.34, P=0.011), and the R2 value of the fitting curve between the change in the length of EZ disruption and the change in BCVA was 0.113(P=0.011). When comparing the pre- and post-treatment changes in BCVA, the length of DRIL, the number of HRD, the area of IRF, the area of SRF, and the length of EZ disruption between patients in the CRVO group and BRVO group, no significant differences were observed(all P>0.05). In contrast, a significant difference was found in the change in CMT between the two groups(P=0.002).CONCLUSION:Conbercept effectively improves multiple OCT biomarkers in patients with RVO-ME. Repair of EZ disruption is a key driver of visual recovery, and its stability may serve as a novel indicator for personalized decision-making in anti-vascular endothelial growth factor therapy.

AIM To study the chemical constituents from Gymnema tingens Spreng.and their in vitro hypoglycemic activity.METHODS The 70％ethanol extract was isolated and purified by macroporous resin,silica gel,sephadex LH-20,and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical propeties and spectral data.The in vitro hypoglycemic activity was evaluated by glucose uptake test in L6 cells.RESULTS Seventeen compounds were isolated and identified as 7-desoxyneocynapanogenin A(1),glaucogenin(2),cynatratoside A(3),atratcynoside F(4),(+)-lyoniresinol(5),(+)-lyoniresinol 3-O-α-D-rhamnopyranoside-(1→6)-β-D-glucopyranoside(6),fernandoside(7),3,4-dimethoxy-phenyl-1-O-β-D-apiofuranosyl-(1→2)-β-D-glucopyranoside(8),khaephuoside A(9),khaephuoside B(10),3,4,5-trimethoxy-phenyl-O-β-D-glucopyranoside(11),liquiritigenin(12),7,3'-dihydroxy-flavanone-4'-O-β-D-glucopyranoside(13),pinoresinol(14),syringaldehyde(15),(+)-1-hydroxy-pinoresinol-1-β-D-glucopyranoside(16),β-amyrin(17).Compounds 2-5、7、9、10、12、17 could promote the glucose uptake in L6 cells.CONCLUSION Compound 1 is a new compound,and 2-9、11-13、15-17 are isolated from this plant for the first time.Compounds 2-5、7、9、10、12、17 have good hypoglycemic activity.

Objectives:To investigate the effect and mechanism of mitochondrial targeting peptide SS-31 on senescence and pyroptosis of nucleus pulposus(NP)cells induced by inflammation.Methods:NP cells were isolated and cultured in vitro from 6-week-old male SD rats,and were divided into control group,lipopolysaccharide(LPS)group,and LPS+SS-31 group;And the control group of cells received no treatment,LPS group of cells were treated with 100μg/mL LPS for 24h,and LPS+SS-31 group of cells were pre-treated with SS-31 30min before LPS intervention.The levels of cellular senescence and pyroptosis were assessed in each group using β-galactosidase(SA-β-Gal)staining and westem blot(WB)assay;Transmission electron mi-croscopy and oxygen consumption rate(OCR)assay were used to analyze the mitochondrial function of NP cells in each group;The expressions of phosphorylated nuclear factor-κB-p65(p-NF-κB-p65),cyclic GMP-AMP synthase(cGAS),and interferon stimulating gene(STING)in each group were detected by WB and im-munofluorescence;Hematoxylin-eosin(HE)staining,immunohistochemistry(IHC)staining and WB assay were performed to analyze the effects of in vivo injection of SS-31 on intervertebral disc degeneration,senescence,and pyroptosis.Results:The positive SA-β-Gal staining of NP cells,expression of senescence marker pro-teins(p53,p21),and pyroptosis-related molecules(NLRP3,Caspase-1 p20)were significantly lower in the LPS+SS-31 group compared with the LPS group(P＜0.05);Transmission electron microscopy(TEM)showed that the mitochondrial swelling of NP cells was round,the matrix was translucent,and the interstitial lumen of the mitochondrial cristae was dilated in the LPS group,while the mitochondrial swelling was subsided,and the morphology of mitochondria tended to be normalized in the LPS+SS-31 group.Meanwhile,the maximum respi-ration level of NP cells was significantly enhanced in the LPS+SS-31 group compared with the LPS group(P＜0.05).The results of WB and immunofluorescence showed that LPS significantly up-regulated the expression of p-NF-κB-p65,cGAS,and STING(P＜0.05),while SS-31 pretreatment significantly inhibited the expression of p-NF-κB-p65,cGAS and STING in NP cells induced by LPS(P＜0.05).Finally,in vivo experiments con-firmed that local injection of SS-31 reduced the senescence and pyroptosis of NP cells,and alleviated the degeneration of intervertebral disc induced by annulus fibropuncture.Conclusions:SS-31 alleviates inflamma-tion-induced senescence and pyroptosis of NP cells,which is related to the inhibition of NF-κB signaling pathway and cGAS/STING signaling pathway.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Bovine rotavirus(BRV)is an important pathogen causing diarrhea in calves.To understand the genomic charac-teristics and genetic variations in bovine rotavirus,and to further enrich data on the biological characteristics of rotavirus,we aimed to amplify 11 gene segments of the isolated and cultured G6P[1]bovine rotavirus BLL strain,perform whole genome se-quencing,and analyze the molecular characteristics.MEGA7.0 and DNAMAN software were used for homology and typing a-nalysis,and the whole genome phylogenetic tree was constructed to analyze genetic evolution relationships.The complete geno-type of the BLL strain was G6-P[1]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis of the VP7 and VP4 genes of the BLL strain showed that the VP7 gene had the highest homology with RVA/Cow-wt/HB01/China/2021,and the VP4 gene of the BLL strain was in the same branch as RVA/Human-tc/ISR/Ro8059/1995.From the sequence alignment of VP8*amino acids,the sialic acid domain of the BLL strain was found to be similar to that in other P[1]strains,but different from those in other types of strains,except for residue 189,which was the same as that in Ro8059 but different from that in other strains.The results suggested that the BLL strain might potentially infect humans.Therefore,continued monitoring and study of the biological characteristics of this strain are necessary to provide more information and evidence supporting further research on the cross-species transmission of group A rotavirus in China.

AIM To study the chemical constituents from Gymnema tingens Spreng.and their in vitro hypoglycemic activity.METHODS The 70％ethanol extract was isolated and purified by macroporous resin,silica gel,sephadex LH-20,and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical propeties and spectral data.The in vitro hypoglycemic activity was evaluated by glucose uptake test in L6 cells.RESULTS Seventeen compounds were isolated and identified as 7-desoxyneocynapanogenin A(1),glaucogenin(2),cynatratoside A(3),atratcynoside F(4),(+)-lyoniresinol(5),(+)-lyoniresinol 3-O-α-D-rhamnopyranoside-(1→6)-β-D-glucopyranoside(6),fernandoside(7),3,4-dimethoxy-phenyl-1-O-β-D-apiofuranosyl-(1→2)-β-D-glucopyranoside(8),khaephuoside A(9),khaephuoside B(10),3,4,5-trimethoxy-phenyl-O-β-D-glucopyranoside(11),liquiritigenin(12),7,3'-dihydroxy-flavanone-4'-O-β-D-glucopyranoside(13),pinoresinol(14),syringaldehyde(15),(+)-1-hydroxy-pinoresinol-1-β-D-glucopyranoside(16),β-amyrin(17).Compounds 2-5、7、9、10、12、17 could promote the glucose uptake in L6 cells.CONCLUSION Compound 1 is a new compound,and 2-9、11-13、15-17 are isolated from this plant for the first time.Compounds 2-5、7、9、10、12、17 have good hypoglycemic activity.

Objective To investigate and compare the epidemiological characteristics of common respiratory viruses among influenza-like illness(ILI)and severe acute respiratory infection(SARI)cases in Huzhou,Zhejiang Province before and after the COVID-19 pandemic,so as to provide a basis for formulating and adjusting the prevention and control strategies for viral respiratory infectious diseases.Methods ILI and SARI cases at two influenza surveillance sentinel hospitals in Huzhou and had throat swab samples collected during Nov 2017 to Feb 2020(pre-COVID-19 pandemic period)and Dec 2022 to Apr 2024(post-COVID-19 mitigation phase)were selected as the participants.Seven common viral respiratory pathogens were tested,including influenza A virus(H1N1 and H3N2 subtypes),influenza B virus(Victoria lineage,FluB),respiratory syncytial virus(RSV),rhinovirus(HRV),adenovirus(ADV),and severe acute respiratory syndrome coronavirus-2(SARS-CoV-2).The positive rates of respiratory pathogens before and after the COVID-19 pandemic were compared across different age groups and different time.Results A total of 7 948 ILI samples and 2 294 SARI samples were included.The overall positive rate of ILI samples increased from 33.6%to 47.1%,primarily due to the increase in influenza and COVID-19 infections;the overall positive rate of SARI samples decreased from 31.4%to 24.8%,mainly due to the reduction in HRV and ADV infections.During the post-COVID-19 mitigation phase,SARS-CoV-2(22.1%),H3N2(12.7%),and FluB(6.0%)were the primary pathogens in ILI samples,while RSV(7.1%),H3N2(5.3%),and HRV(4.5%)dominated in SARI samples.During the post-COVID-19 mitigation phase,the influenza virus circulation period was shortened.Before the COVID-19 pandemic,RSV was mainly detected in autumn and winter,while during the post-COVID-19 mitigation phase,out-of-season RSV epidemics were observed in spring and summer.Co-infection rate in ILI cases increased significantly in the post-COVID-19 mitigation phase,predominantly consisting of co-infections of COVID-19 and influenza A virus,while co-infection rate in SARI cases showed a decline.Conclusion We found important epidemiological changes in respiratory viruses in Huzhou during the post-COVID-19 mitigation phase compared to pre-COVID-19 period,including increased positive rates of influenza and COVID-19,and disruptions to the seasonal patterns of influenza and RSV.The prevention and control strategies should be adjusted in a timely manner based on the monitoring data.

Hemorrhagic shock is a common clinical emergency that can aggravate cell injury after resuscitation. Astrocytes are crucial for the survival of neurons because they regulate the surrounding ionic microenvironment of neurons. Although hemorrhagic shock and resuscitation (HSR) injury can impair cognition, it remains unclear how this insult directly affects astrocytes. In this study, we established an HSR model by bleeding and re-transfusion in mice. The social interaction test and new object recognition test were applied to evaluate post-operative cognitive changes, and the results suggest that mice experience cognitive impairment following exposure to HSR. In the HSR group, the power spectral density of β and γ oscillations decreased, and the coupling of the θ oscillation phase and γ oscillation amplitude was abnormal, which indicated abnormal neuronal oscillation and cognitive impairment after HSR exposure. In brief, cognitive impairment in mice is strongly correlated with Ca²⁺ signal strength in lateral septum astrocytes following HSR.
Animals ; Astrocytes/metabolism* ; Shock, Hemorrhagic/metabolism* ; Resuscitation/adverse effects* ; Male ; Mice ; Calcium Signaling/physiology* ; Mice, Inbred C57BL ; Septal Nuclei/metabolism* ; Cognitive Dysfunction/etiology* ; Disease Models, Animal ; Cognition Disorders/etiology*