Objective To explore the feasibility and reference value of allogeneic lung transplantation and postoperative monitoring in miniature pigs for lung transplantation research. Methods Two miniature pigs (R1 and R2) underwent left lung allogeneic transplantation. Complement-dependent cytotoxicity tests and blood cross-matching were performed before surgery. The main operative times and partial pressure of arterial oxygen (PaO₂) after opening the pulmonary artery were recorded during surgery. Postoperatively, routine blood tests, biochemical blood indicators and inflammatory factors were detected, and pathological examinations of multiple organs were conducted. Results The complement-dependent cytotoxicity test showed that the survival rate of lymphocytes between donors and recipients was 42.5%-47.3%, and no agglutination reaction occurred in the cross-matching. The first warm ischemia times of D1 and D2 were 17 min and 10 min, respectively, and the cold ischemia times were 246 min and 216 min, respectively. Ultimately, R1 and R2 survived for 1.5 h and 104 h, respectively. Postoperatively, in R1, albumin (ALB) and globulin (GLB) decreased, and alanine aminotransferase increased; in R2, ALB, GLB and aspartate aminotransferase all increased. Urea nitrogen and serum creatinine increased in both recipients. Pathological results showed that in R1, the transplanted lung had partial consolidation with inflammatory cell infiltration, and multiple organs were congested and damaged. In R2, the transplanted lung had severe necrosis with fibrosis, and multiple organs had mild to moderate damage. The expression levels of interleukin-1β and interleukin-6 increased in the transplanted lungs. Conclusions The allogeneic lung transplantation model in miniature pigs may systematically evaluate immunological compatibility, intraoperative function and postoperative organ damage. The data obtained may provide technical references for subsequent lung transplantation research.

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.

Objective To explore the predictive value of serum levels of CXC chemokine ligand 4(CXCL4),CXC receptor 3 chemokine(CXCR3)for postoperative cerebral vasospasm(CVS)in patients with ruptured intracranial aneurysms.Methods The clinical data of 106 patients with intracranial aneurysms rupture who under went craniotomy and clipping surgery at the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture from October 2020 to December 2022 were collected.The incidence of CVS was observed.Serum CXCL4 and CXCR3 levels were compared at 1,3,7 days after surgery between patients without CVS and patients with CVS.Spearman correlation coefficient was used to analyze the relationship between serum CXCL4,CXCR3 levels and CVS degree.ROC curve was used to analyze the value of serum CXCL4 and CXCR3 levels in predicting postoperative CVS.Results Among 106 patients with ruptured intracranial aneurysms,a total of 38 cases(35.85%)developed CVS after surgery,and 68 cases(64.15%)did not develop CVS.There was no statistically obvious difference in preoperative serum levels of CXCL4 and CXCR3 between the CVS group and the non CVS group(t=0.104,0.141,all P>0.05).The serum levels of CXCL4 and CXCR3 in the non CVS group were lower than those before surgery 1,3,and 7 day after surgery,and the differences were statistically significant(q=14.867,17.525,24.384;16.274,20.251,34.237,all P<0.05).Compated with preoperative levels,the levels of serum CXCL4 and CXCR3 in the CVS group decreased on postoperative 1 and 7 days,and the differences were statistically significant(q=9.486,4.858;10.760,9.104,all P<0.05).Compared with the mild CVS group,the serum levels of CXCL4 and CXCR3 in the moderate and severe CVS groups were obviously increased(q=2.982,5.992;2.961,3.465),and the serum levels of CXCL4 and CXCR3 in the severe CVS group were higher than those in the moderate CVS group(q=3.564,4.036),and the differences were statistically significant(all P<0.05),respectively.Spearman results showed that serum levels of CXCL4 and CXCR3 were positively correlated with the severity of CVS(r=0.491,0.483,all P<0.05).The ROC curve results showed that the AUC of CXCL4 and CXCR3 combined in predicting postoperative CVS in patients with intracranial ruptured aneurysms was higher than that of CXCL4,CXCR3 alone,and the differences were statistically significant(Z=2.937,2.750,all P<0.05).Conclusion The serum levels of CXCL4 and CXCR3 in ruptured intracranial aneurysms patients with postoperative CVS are obviously elevated,and the combined detection of the two can effectively predict the occurrence of CVS.

AIM To study the chemical constituents from ethyl acetate fraction of Balanophora harlandii Hook.f.and their tyrosinase inhibitory activity.METHODS Separation and purification were performed using silica gel,MCI,ODS,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The monophenolase inhibitory activity was determined by the tyrosinase-catalyzed oxidation of L-tyrosine.RESULTS Twenty-four compounds were isolated and identified as sesamin(1),methyl caffeate(2),quercetin(3),5,7-dihydroxychromanone(4),methyl 3,4-dihydroxybenzoate(5),esculetin(6),kaempferol(7),naringenin(8),pyrogallic acid(9),pinosylvin(10),methyl propionate(11),caffeic acid(12),saccharinol(13),ferulic acid(14),trans-p-hydroxycinnamic acid(15),cinnamic acid(16),vanillic acid(17),vanillin(18),4-hydroxyacetophenone(19),4-hydroxybenzaldehyde(20),apigenin(21),(-)-isolariciresinol(22),(-)-secoisolariciresinol(23)and meso-2,3-di(3′,4′-methylenedioxybenzyl)butane-1,4-diol(24).The IC50 values of compounds 3,5,7,8,19,and 20 ranged from(0.246 5±0.028 3)to(1.278 2±0.021 3)mmol/L.CONCLUSION Compounds 1-9、11、15、17-21、24 are isolated from this plant for the first time,and 1,6,9,17-19,24 are first isolated from genus Balanophora.Compounds 3、5、7、8、19 and 20 have tyrosinase inhibitory activity.

AIM:To investigate the involvement of HIF-1α/VEGF regulation in its anti-angiogenesis effects using adjuvant-induced arthritis(AIA)rats.METHODS:AIA rats were orally treated by QLY ex-tract for 24 days.After sacrifice,the joints were subjected to histological examination,while the blood was used in ELISA or biochemical tests.In ad-dition,HUVEC cells were treated by QLY in vitro.MTT,wound-healing and tube-formation experi-ments were then performed.Expression of some relevant proteins in cells were investigated.RE-SULTS:Compared to the healthy controls,obvious synovial invasion and angiogenesis occurred in AIA rats.Blood levels of HIF-1α,VEGF,PDGF,and TGF-β1 were increased,while the ratio of MDA/SOD was decreased a lot.After QLY treatment,all these ab-normalities were attenuated.In vitro experiments,QLY showed notable potentials in inhibiting prolifer-ation,migration and tube-constructing abilities of HUVEC cells.Furthermore,it suppressed the ex-pression of p-MEK/MEK and p-ERK/ERK.CONCLU-SION:QLY can reduce the pathological functions of vascular endothelial cells by inhibiting HIF-1α/VEGF,and it consequently eased AIA-related abnor-mal angiogenesis in AIA rats'joints.

AIM To study the chemical constituents from salt-processed Litchi Semen and their antioxidant activities.METHODS The 85％ethanol extract from salt-processed Litchi Semen was isolated and purified by silica gel,Sephadex LH-20,MCI,ODS and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.DPPH and ABTS+free radical scavenging method were used to evaluate their antioxidant activities.RESULTS Fifteen compounds were isolated and identified as dehydrocostuslactone(1),ananosmoside A(2),funingensin A(3),(2S)-pinocembrin-7-O-(6-O-α-L-rhamnopyranosyl-β-D-glucopyranoside)(4),liquiritienin(5),quercetin(6),rutin(7),isorhamnetin-3-O-β-rutinoside(8),procyanidin A2(9),procyanidin A1(10),ethyl protocatechuate(11),5-hydroxymethylfurfural(12),di(2-ethyl-hexyl)phthalate(13),nicotinamide(14),(10E,15Z)-9,12,13-trihydroxyoctadeca-10,15-dienoic acid(15).Compounds 6-7,9-10 exhibited scavenging activities against DPPH radicals with IC50 values of(12.929±1.232),(14.104±0.946),(10.417±1.736),(6.944±0.030)μmol/L,respectively.Compounds 6-10 exhibited scavenging activities against ABTS+radicals with IC50 values of(21.952±0.577),(25.683±0.625),(22.970±1.336),(20.210±1.435),(18.725±0.324)μmol/L,respectively.CONCLUSION Compounds 1,5,14-15 are isolated from Litchi genus for the first time.Compounds 6-7,9-10 have strong in vitro antioxidant activities.

AIM To prepare fisetin-loaded nanostructured lipid carriers,and to evaluate their in vivo pharmacokinetics.METHODS Ethanol injection method was applied to preparing the nanostructured lipid carriers.With monostearin-phospholipid ratio,monostearin-triacetin ratio and D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)concentration as influencing factors,encapsulation efficiency as an evaluation index,the formulation was optimized by Box-Behnken response surface method.The crystal form was analyzed by X-ray powder diffraction,after which the morphology was observed by transmission electron microscopy,infrared spectroscopy analysis was performed,the drug relaese was investigated by dialysis bag method,and the stability was determined.Eighteen rats were randomly assigned into 3 groups and given intragastric administration of the 0.5％CMC-Na suspensions of fisetin and its phospholipid complex,nanostructured lipid carriers(150 mg/kg),respectively,after which blood collection was made at0.25,0.5,1,1.5,2,3,4,6,8,12 h,UPLC-MS/MS was adopted in the plasma concentration determination of fisetin,and main pharmacokinetic parameters were calculated.RESULTS The optimal formulation was determined to be 1.56∶1 for monostearin-phospholipid ratio,3.05∶1 for monostearin-triacetin ratio,and 0.2 mg/mL for TPGS concentration.The nearly round fisetin-loaded nanostructured lipid carriers demonstrated the average encapsulation efficiency,drug loading,particle size and Zeta potential of(86.14±1.28)％,(8.96±0.26)％,(212.35±9.04)nm and-(31.13±1.16)mV,respectively.Raw medicine existed in the nanostructured lipid carriers in an amorphous state,preparation process did not affect the hydrogen bonding between raw medicine and phospholipids.The nanostructured lipid carriers displayed the accumulative release rate of 46.12％within 3 h in simulated gastric juice,and that of about 50％within 18 h in simulated intestinal fluid,whose freeze-dried powder exhibited good stability after being placed for 6 months.Compared with raw medicine and phospholipids complex,the nanostructured lipid carriers displayed prolonged tmax,t1/2(P＜0.01)and increased Cmax,AUC0-t,AUC0-∞(P＜0.01),whose relative bioavailability was enhanced to 7.07 times.CONCLUSION Nanostructured lipid carriers can improve the oral bioavailability of fisetin.