Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective To investigate the curative effect of traditional Chinese medicine fumigation com-bined with meibomain gland massage in the middle-aged and elderly patients with meibomain gland dysfunc-tion(MGD)dry eye syndrome.Methods Ninety patients with MGD visiting in the ophthalmology depart-ment of this hospital from November 1,2021 to October 31,2023 were selected as the study subjects and di-vided into the routine group,control group and observation group according to the random number table meth-od,30 cases in each group.The routine group used 0.3％Sodium Hyaluronate Eye Drops and simple mei-bomain gland massage.The control group was given the simple vapor fumigation combined with meibomain gland massage on the basis of the routine group.The observation group was given the Chinese medicine fumi-gation and washing combined with meibomain gland massage on the basis of the control group.The changes of OSDI score,tear secretion test(SIt),breakup time of tear film(BUT)and fluorescein eye surface staining be-fore treatment and in 1,4 weeks after treatment were compared among the three groups.Results The OSDI score,eyelid margin morphology score and scores of SIt,BUT and FL had the interaction in different groups and treatment time(P＜0.01),moreover the main effect was remarkable.Compared with before treatment,the OSDI score,eyelid margin morphology score and FL score in 1,4 weeks after treatment in the three groups were decreased,moreover the observation group was the lowest,while the SIt level and BUT were increased,moreover the observation group was the highest,and the differences were statistically significant(P＜0.05).Compared with the routine group,the effective rate in the control group and observation group was higher(83.33％vs.96.67％vs.76.67％),moreover the observation group was higher than the control group,and the differences were statistically significant(P＜0.05).Conclusion The traditional Chinese medicine fumiga-tion combined with meibomian gland massage could significantly improve the ocular symptoms and improve-ment of tear secretion level in the patients with MGD dry eye.

Objective To investigate the mobilization effect of low-does granulocyte-colony stimulation factors(G-CSF) on allogenic peripheral stem cell transplantation (PBSCT) and the best acquisition time for haemopoietic stem cell. Methods G-CSF was administered subcutaneously at 5μg·kg~(-1)·d~(-1)to 108healthy donors. The mobilization effects were assayed by mononuclear cell count,flow cytometry and colonyforming units analysis.Results Onfourth day,fifty day and sixth day, the ratio of CD_(34)~+ were (0.71 ±0.08)%, (1.09±0.09) %, (0.57±0.08) %, respectively. The CFU-GM yield were (93.33±44.51)/10~5MNC, (124.61±57.85)/ 10~5MNC, (80.25±49.24)/10~5MNC, respectively. The number of CD_(34)~+ were (3.33±1.36)×10~6/kg, (4.14±1.67) ×10~6/kg, (2.79±1.47)×l0~6/kg, respectively. The ratio and number of CD_(34)~+ cell of PBSC collections of fifth day was higher than that of the fourth day (P <0.05). And the fourth day was higher than that of the sixth day(P < 0.05). Twice day (fourth day and fifth day) collection can obtain enough CD_(34)~+ cell for PBSCT. There were no significant adverse effects. Conclusion Low-does G-CSF takes good effects on the mobilization of PBSC. And it was better to collect stem cell on fourth day and fifth day rather than on fifth day and sixth day after mobilization.

Objective To construct and apply a cell line screening Mycobacterium tuberculosis (Mtb)-specific tetramers of CD4+α/β T cell receptor(TCR). Methods The β chains of HLA class Ⅱ (DR) were amplified from tuberculosis patients by PCR. The pMT-HLA-DRB expression vectors that carries the HLA-DR 13 chain and pMT-HLA-DRA-P expression vectors which carries the genes of HLA-DR α chain loaded with Mtb antigen were transfected into S2 cells with the method of calcium phosphate transfection. The expressed Mtb peptide/HLA-DR complexes were primarily identified by the method of cell immunohistochemistry. The cell lines expressing Mtb peptide/HLA-DR complexes were used to screen tetramers of CD4+ TCR by flow cytometry. Results S2 cell lines expressing Mtb peptide/HLA-DR complexes on the cell surface were obtained, two kinds of Mtb specific tetramers of CD4+α/β TCR were screened. Conclusion S2 cell lines expressing Mtb peptide/HLA-DR complexes on the cell surface provide the solid basis of the further research on the TCR tetramers and are helpful for exploring new diagnostic study methods about tuberculosis and developing new vaccines.