Objective To assess mid- and long-term outcomes of ascending aortic wrapping (AAW) in adult patients undergoing aortic valve replacement (AVR). Methods We retrospectively analyzed clinical data of adult patients who underwent AVR and AAW in Fuwai Hospital from January 2010 to August 2019. Ascending aorta diameter (AAD) was measured by echocardiography or CT scan preoperatively and postoperatively. Results A total of 33 patients were enrolled, including 23 males and 10 females aged 22-73 (51.06±12.61) years. There was no perioperative death. The mean preoperative, postoperative and follow-up AAD of the patients were (46.06±3.54) mm, (34.55±5.17) mm, and (37.12±5.64) mm, respectively. The differences in the AAD between pre-operation and post-operation, and between pre-operation and the last follow-up were both statistically significant (P<0.05). The median follow-up time was 38.20 (18.80-140.30) months. The median increase rate of diameter was 0.63 (−0.11, 1.36) mm per year after the surgery. The increase rate was >5 mm per year in 1 patient, and >3 mm in another one. Conclusion The mid- and long-term outcomes of AAW in adult patients undergoing AVR are satisfactory and encouraging.

To explore the role of the "Clinical Practice Guidelines" column and others in the Medical Joumnal of Peking Union Medical College Hospital (Med J PUMCH) in promoting diseiplinary development.

Objective:To investigate the application value of intraoperative electrocochleography（ECochG） monitoring technique and insertion techniques in cochlear implant（CI） and analyze its relationship with postoperative residual hearing（RH） preservation. Methods:Thirty-one patients（35 ears） who received CI in our hospital from June 2022 to July 2024 were enrolled. The Advanced Bionics Active Insertion Monitoring（AIM） system was used for real-time ECochG monitoring during surgery. Intraoperative cochlear microphonics （CM） waveform changes were recorded and analyzed in relation to postoperative RH preservation. Results:①ECochG recordings were successfully obtained in 34 of 35 ears （97.1%）. ②According to Harris classification, there were 7 ears（20.6%） of Type A（rising）, 7 ears（20.6%） of Type C（declining）, 8 ears（23.5%） of Type CC（fluctuating）, and 12 ears（35.3%） of Type D（no response）. ③The total CM amplitude decrease was significantly moderately correlated with postoperative low-mid frequency hearing loss（r=0.67, P=0.017）. The total CM amplitude decrease was significantly moderately correlated with postoperative low frequency hearing loss（r=0.65, P=0.023）. ④For the mean amplitude variation, the Amax was 30.70 μV, the Amin was 8.64 μV, and the Aend was 18.27 μV. ⑤Sixteen cases completed postoperative follow-up, with an average low-mid frequency（125-1 000 Hz） residual hearing loss of 15.25 dB HL and a RH preservation rate of 87.5%. Conclusion:Intraoperative ECochG monitoring can effectively predict postoperative residual hearing changes, effectively guide surgical manipulation, and improve residual hearing preservation rate.
Humans ; Cochlear Implantation/methods* ; Audiometry, Evoked Response ; Cochlear Implants ; Male ; Female ; Adult ; Middle Aged ; Monitoring, Intraoperative ; Adolescent ; Young Adult ; Minimally Invasive Surgical Procedures ; Child ; Aged ; Postoperative Period

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.

Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB⁺ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg ^-/- Rag2 ^-/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.

OBJECTIVES: To investigate the effects of dihydroartemisinin (DHA) combined with doxorubicin (DOX) on proliferation and apoptosis of triple-negative breast cancer cells and explore the underlying molecular mechanism. METHODS: MDA-MB-231 cells were treated with 50, 100 or 150 μmol/L DHA, 0.5 μmol/L DOX, or with 50 μmol/L DHA combined with 0.5 μmol/L DOX. The changes in proliferation and survival of the treated cells were examined with MTT assay and colony-forming assay, and cell apoptosis was analyzed with flow cytometry. Western blotting was performed to detect the changes in protein expression levels of PCNA, cleaved PARP, Bcl-2, Bax, STAT3, p-STAT3, HIF-1α and survivin. RESULTS: The IC₅₀ of DHA was 131.37±29.87 μmol/L in MDA-MB-231 cells. The cells with the combined treatment with DHA and DOX showed significant suppression of cell proliferation. Treatment with DHA alone induced apoptosis of MDA-MB-231 cells in a dose-dependent manner, but the combined treatment produced a much stronger apoptosis-inducing effect than both DHA and DOX alone. DHA at 150 μmol/L significantly inhibited clone formation of MDA-MB-231 cells, markedly reduced cellular expression levels of PCNA, p-STAT3, HIF-1α and survivin proteins, and obviously increased the expression level of cleaved PARP protein and the Bax/Bcl-2 ratio, and the combined treatment further reduced the expression level of p-STAT3 protein and increased the Bax/Bcl-2 ratio. CONCLUSIONS DHA combined with DOX produces significantly enhanced effects for inhibiting cell proliferation and inducing apoptosis in MDA-MB-231 cells possibly as result of DHA-mediated negative regulation of the STAT3/HIF-1α pathway.
Humans ; STAT3 Transcription Factor/metabolism* ; Apoptosis/drug effects* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Doxorubicin/pharmacology* ; Triple Negative Breast Neoplasms/metabolism* ; Cell Line, Tumor ; Artemisinins/pharmacology* ; Female ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects* ; Survivin

OBJECTIVES: To investigate the mechanism by which chitosan (CS) hydrogel loaded with human umbilical cord mesenchymal stem cell (HUVECs)-derived exosomes (hUCMSC-exos) (Exos@CS-Gel) improves diabetic wound healing. METHODS: hUCMSC-exos were extracted and Exos@CS-Gel was prepared. The effect of Exos@CS-Gel on proliferation and migration of HUVECs were evaluated using scratch wound assay and CCK-8 assay. Diabetic rat models with full-thickness skin wounds established by streptozotocin induction were randomized divided into 4 groups for treatment with Exos@CS-Gel (100 µg hUCMSC-exos dissolved in 100 µL 24% CS hydrogel), hUCMSC-exos (100 µg hUCMSC-exos dissolved in 100 µL PBS), CS hydrogel (100 µL 24% CS hydrogel), or PBS (control group). Wound healing and the therapeutic mechanisms were assessed using immunohistochemistry, HE staining, immunofluorescence, and qRT-PCR. RESULTS: In cultured HUVECs, Exos@CS-Gel treatment significantly promoted cell proliferation and migration. In the rat models of chronic diabetic wounds, the wound healing rate in Exos@CS-Gel group reached 92.7% on day 14, significantly higher than those in hUCMSC-exos group (9.12%), CS hydrogel group (16.28%), and control group (25.98%). Microvessel density and the expression levels of vascular endothelial growth factor and transforming growth factor β-1 were significantly increased in the Exos@CS-Gel group. CONCLUSIONS Exos@CS-Gel promotes survival capacity of hUCMSC-exos in vitro and accelerates diabetic wound healing in rats by promoting angiogenesis and cell proliferation.
Animals ; Wound Healing ; Humans ; Chitosan ; Exosomes ; Mesenchymal Stem Cells/cytology* ; Diabetes Mellitus, Experimental ; Rats ; Umbilical Cord/cytology* ; Hydrogels ; Human Umbilical Vein Endothelial Cells ; Cell Proliferation ; Rats, Sprague-Dawley ; Male

Diabetic osteoporosis(DOP)is a serious complication of diabetes mellitus(DM),with bone loss and microstructure destruction.The onset of DOP is insidious,and early symptoms are not obvious.As the condition progresses,the disability and mortality rates increase in DM patients.The advanced glycation end products receptor(AGEs-RAGE)axis can mediate different signaling pathways involved in regulating osteoblasts.This article reviews the mechanism of AGEs-RAGE axis mediated p38 mitogen activated protein kinase signaling pathway in regulation of osteoblasts in DOP.

Objective:To investigate the impact of exogenous hypoxia-inducible factor 1α(HIF-1α)on glucose metabolism-related proteins and neurological function in the hippocampal CA1 region of rats with cerebral ischemia.Methods:Adult male SD rats were randomly assigned to four groups: sham operation group(Sham group), cerebral ischemia reperfusion group(CIR group), recombinant adenovirus empty vector intervention group(Ad group), and recombinant adenovirus HIF-1α gene intervention group(AdHIF-1α group), each consisting of 12 rats.A rat model of cerebral ischemia-reperfusion injury was induced using the modified suture method, and neurological deficits were assessed using the Longa method.In line with previous protocols, exogenous Ad and AdHIF-1α were introduced into the lateral ventricle of rats in the Ad and AdHIF-1α groups, respectively.After 28 days of observation, the animals were euthanized.Hippocampal tissue was collected for analysis, including Hematoxylin-eosin(HE)staining, terminal transferase labeling in situ(TUNEL)staining, and Nissl staining to evaluate pathological changes and neuronal survival in the hippocampal CA1 region.Western blot was performed to assess the expression levels of HIF-1α, glucose transporter 1(GLUT1), glucose transporter 3(GLUT3), and 6-phosphofructose-2-kinase/fructose-2, 6-bisphosphatase 3(PFKFB3)proteins in the hippocampal tissue.Results:Following 28 days of recombinant adenovirus HIF-1α gene therapy, rats in the AdHIF-1α group exhibited reduced neurological deficits compared to the CIR group( P<0.05).Histopathological analysis of nerve cells in the CA1 region of the hippocampus showed significant improvement, with an increase in the number of surviving nerve cells and a decrease in apoptotic cells( P<0.01).Western blot results indicated an upregulation of HIF-1α expression in the hippocampus of the CIR group compared to the Sham group, along with increased levels of glucose metabolism-related proteins(GLUT1, GLUT3, and PFKFB3)(all P<0.05).Furthermore, elevating HIF-1α expression through AdHIF-1α led to a further increase in the expression of glucose transporters(GLUT1, GLUT3, and PFKFB3)in the AdHIF-1α group, demonstrating statistically significant differences compared to the CIR group(all P<0.05).Notably, there were no statistically significant variances in the aforementioned parameters between the Ad group and the CIR group(all P>0.05). Conclusions:The AdHIF-1α gene has the potential to enhance neurological function, promote nerve cell survival, and decrease nerve cell apoptosis.This effect is likely achieved by increasing HIF-1α expression in the hippocampus, subsequently up-regulating GLUT1, GLUT3 and PFKFB3 expression, and ultimately improving glucose metabolism supply.Overall, this gene shows promise in protecting the brain.

Ureteral stenosis and bladder contracture after radiotherapy for cervical cancer are challenging issues in urology. Ileal ureteroplasty combined with ileal bladder augmentation is a potential method to improve hydronephrosis and voiding function of patients, however, the surgical procedure is complex, with high surgical risks and numerous intraoperative and postoperative complications, which have hindered the widespread application of this surgical technique. This article introduces our hospital's experience through a typical surgical case. During the surgery, ileal substitution for bilateral ureters was performed in combination with ileal " N-shaped" augmentation. Two weeks after the surgery, the single-J stent was removed, and the urinary catheter was removed three weeks after the surgery. The patient achieved voluntary urination control with smooth voiding. Follow-up examinations at 3 months and 18 months postoperatively showed no hydronephrosis in the bilateral ureters, normal renal function, and a significantly expanded bladder capacity.