BACKGROUND:Spinal canal decompression using uniportal endoscopic surgery is a new minimally invasive surgery in the treatment of lumbar spinal stenosis.However,this technique needs a steep learning curve and high requirements for surgical equipment and instruments,which limits its clinical application.We previously use the spinal endoscopy as a monitoring endoscopy and combined with unilateral biportal endoscopy to propose a hybrid technique of spinal endoscopy to achieve coaxial endoscopic operation and hands-separate operation. OBJECTIVE:To compare the clinical outcome of hybrid technique and uniportal endoscopic surgery in treatment of lumbar spinal stenosis with bilateral lower limb pain symptoms. METHODS:Ninety patients diagnosed of lumbar spinal stenosis with bilateral symptoms were included and retrospectively analyzed at First People's Hospital,Shanghai Jiao Tong University from August 2020 to August 2022.44 cases were included in group A(hybrid technique group),while 46 cases were included in group B(uniportal endoscopic surgery).The nerve decompression was observed during the surgery.Operation time,hospital stay time,and expenses were recorded in both groups.The visual analog scale scores of lower back pain and both lower extremities pain,Oswestry disability index scores of quality of life and excellent and good rate of modified Macnab criteria were recorded and compared at preoperative,postoperative 3 days,and postoperative 3 and 6 months. RESULTS AND CONCLUSION:(1)The operation time of group A was significantly shorter than that of group B(P<0.05).(2)The lower back pain and lower extremity pain of the severe side at postoperative 3 days,and 3 and 6 months were significantly relieved in both groups(P<0.05).The visual analog scale score of lower extremity pain on the mild side was significantly decreased at postoperative 3 days,3 and 6 months than preoperative score in the group A(P<0.05).The visual analog scale score of lower extremity pain on the mild side was significantly decreased at postoperative 3 days than preoperative score in the group B(P<0.05).The visual analog scale scores of lower extremity pain on the mild side at postoperative 3 and 6 months did not show significant difference than preoperative score in the group B.The comparison between the two groups showed that there was no significant difference in the visual analog scale scores of postoperative lower back pain and lower extremity pain of the severe side(P>0.05).The visual analog scale scores of lower extremity pain on the mild side in the group A were significantly lower than those of group B at postoperative 3 and 6 months(P<0.05).(3)The Oswestry disability index scores of both groups at postoperative 3 day were significantly lower than preoperative score(P<0.05),and there was no significant difference between the two groups 3 days after operation.Oswestry disability index scores of group A at postoperative 3 and 6 months were significantly decreased than preoperative score(P<0.05).The Oswestry disability index scores of group B at postoperative 3 and 6 months did not show significant differences than preoperative score(P>0.05).The comparison between the two groups showed the Oswestry disability index scores of group A were significantly lower than group B at postoperative 3 and 6 months(P<0.05).(4)The results of modified Macnab showed that the excellent and good rate of group A was significantly higher than that of group B(95%,78%,P<0.05).(5)It is indicated that the hybrid technique is a new spinal endoscopy technique,which has the advantages of less trauma and faster recovery as a minimally invasive surgery.The clinical outcome of hybrid technique is superior to that of uniportal endoscopic surgery in the treatment of lumbar spinal stenosis with bilateral symptoms.Additionally,it also has the advantages of good operational flexibility and high decompression efficiency as an open surgery.

Acute-on-chronic liver failure （ACLF） is an acute and critical illness with a high short-term mortality rate， and current therapies mainly focus on elimination of causes， organ support， and prevention of complications. Although liver transplantation is the most effective treatment modality， its clinical application is limited， and traditional Chinese medicine has shown significant advantages and characteristics in the treatment of ACLF. In traditional Chinese medicine， ACLF is classified into the same category as diseases such as “jaundice”， and unlike traditional jaundice which is mostly characterized by excess and heat syndromes， the syndrome of ACLF has gradually transformed from Yang jaundice to Yin jaundice due to the changing disease spectrum of ACLF. With reference to the pathogenesis of ACLF in Western medicine and traditional Chinese medicine theories， this article discusses the essential pathogenesis of ACLF in traditional Chinese medicine， explores the evolution of ACLF syndromes， and reviews the research advances in the clinical efficacy and mechanisms of traditional Chinese medicine based on the three-factor differentiation-based treatment of damp-heat， blood stasis-heat， and spleen deficiency， as well as the safety of spleen-strengthening and Yang-warming drugs in the clinical treatment of ACLF， in order to provide ideas， methods， and evidence for the application of traditional Chinese medicine in ACLF.

Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

Objective To investigate the potential value of exosomes derived from rat ectoderm mesenchymal stem cells(EMSCs-exo)for repairing secondary spinal cord injury.Methods EMSCs-exo were obtained using ultracentrifugation from EMSCs isolated from rat nasal mucosa,identified by transmission electron microscope,nanoparticle tracking analysis(NTA),and Western blotting,and quantified using the BCA method.Neonatal rat microglia purified by differential attachment were induced with 100 μg/L lipopolysaccharide(LPS)and treated with 37.5 or 75 mg/L EMSCs-exo.PC12 cells were exposed to 400 μmol/L H2O2 and treated with EMSCs-exo at 37.5 or 75 mg/L.The protein and mRNA expressions of Arg1 and iNOS in the treated cells were determined with Western blotting and qRT-PCR,and the concentrations of IL-6,IL-10,and IGF-1 in the supernatants were measured with ELISA.The viability and apoptosis of PC12 cells were detected using CCK-8 assay and flow cytometry.Results The isolated rat EMSCs showed high expressions of nestin,CD44,CD105,and vimentin.The obtained EMSCs-exo had a typical cup-shaped structure under transmission electron microscope with an average particle size of 142 nm and positivity for CD63,CD81,and TSG101 but not vimentin.In LPS-treated microglia,EMSCs-exo treatment at 75 mg/L significantly increased Arg1 protein level and lowered iNOS protein expression(P<0.05).EMSCs-exo treatment at 75 mg/L,as compared with the lower concentration at 37.5 mg/L,more strongly increased Arg1 mRNA expression and IGF-1 and IL-10 production and decreased iNOS mRNA expression and IL-6 production in LPS-induced microglia,and more effectively promoted cell survival and decreased apoptosis rate of H2O2-induced PC12 cells(P<0.05).Conclusion EMSCs-exo at 75 mg/L can effectively reduce the proportion of M1 microglia and alleviate neuronal apoptosis under oxidative stress to promote neuronal survival,suggesting its potential in controlling secondary spinal cord injury.

Objective To investigate the potential value of exosomes derived from rat ectoderm mesenchymal stem cells(EMSCs-exo)for repairing secondary spinal cord injury.Methods EMSCs-exo were obtained using ultracentrifugation from EMSCs isolated from rat nasal mucosa,identified by transmission electron microscope,nanoparticle tracking analysis(NTA),and Western blotting,and quantified using the BCA method.Neonatal rat microglia purified by differential attachment were induced with 100 μg/L lipopolysaccharide(LPS)and treated with 37.5 or 75 mg/L EMSCs-exo.PC12 cells were exposed to 400 μmol/L H2O2 and treated with EMSCs-exo at 37.5 or 75 mg/L.The protein and mRNA expressions of Arg1 and iNOS in the treated cells were determined with Western blotting and qRT-PCR,and the concentrations of IL-6,IL-10,and IGF-1 in the supernatants were measured with ELISA.The viability and apoptosis of PC12 cells were detected using CCK-8 assay and flow cytometry.Results The isolated rat EMSCs showed high expressions of nestin,CD44,CD105,and vimentin.The obtained EMSCs-exo had a typical cup-shaped structure under transmission electron microscope with an average particle size of 142 nm and positivity for CD63,CD81,and TSG101 but not vimentin.In LPS-treated microglia,EMSCs-exo treatment at 75 mg/L significantly increased Arg1 protein level and lowered iNOS protein expression(P<0.05).EMSCs-exo treatment at 75 mg/L,as compared with the lower concentration at 37.5 mg/L,more strongly increased Arg1 mRNA expression and IGF-1 and IL-10 production and decreased iNOS mRNA expression and IL-6 production in LPS-induced microglia,and more effectively promoted cell survival and decreased apoptosis rate of H2O2-induced PC12 cells(P<0.05).Conclusion EMSCs-exo at 75 mg/L can effectively reduce the proportion of M1 microglia and alleviate neuronal apoptosis under oxidative stress to promote neuronal survival,suggesting its potential in controlling secondary spinal cord injury.

Objective:To summarize the clinical characteristics of patients with renal angiomyolipoma(RAML)combined with inferior vena cava(IVC)tumor thrombus,and to explore the feasibility of par-tial nephrectomy and thrombectomy in this series of patients.Methods:The clinical data of patients diagnosed with RAML combined with IVC tumor thrombus in the Department of Urology of the Peking University Third Hospital from April 2014 to March 2023 were retrospectively analyzed,and demographic and perioperative data of RAML patients with IVC tumor thrombus were recorded and collected from Elec-tronic Medical Record System,including age,gender,surgical methods,and follow-up time,etc.The clinical characteristics between classic angiomyolipoma(CAML)patients with IVC tumor thrombus and epithelioid angiomyolipoma(EAML)patients with IVC tumor thrombus were compared to determine the clinical characteristics of these patients.Results:A total of 11 patients were included in this study,in-cluding 7 patients with CAML with IVC tumor thrombus and 4 patients with EAML with IVC tumor thrombus.There were 9 females(9/11,81.8％)and 2 males(2/11,18.2％),with an average age of(44.0±17.1)years.9 patients(9/11,81.8％)experienced clinical symptoms,including local symp-toms including abdominal pain,hematuria,abdominal masses,and systemic symptoms including weight loss and fever;2 patients(2/11,18.2％)with RAML and IVC tumor thrombus did not show clinical symptoms,which were discovered by physical examination.Among the 11 patients,10 underwent radical nephrectomy with thrombectomy,of whom,3 underwent open surgery(3/10,30.0％),2 underwent laparoscopic surgery(2/10,20.0％),and 5 underwent robot-assisted laparoscopic surgery(5/10,50.0％).In addition,1 patient underwent open partial nephrectomy and thrombectomy.The patients with EAML combined with I VC tumor thrombus had a higher proportion of systemic clinical symptoms(100％vs.0％,P=0.003),more intraoperative bleeding[400(240,3 050)mL vs.50(50,300)mL,P=0.036],and a higher proportion of tumor necrosis(75％vs.0％,P=0.024)compared to the patients with CAML combined with I VC tumor thrombus.However,there was no statistically significant difference in operation time[(415.8±201.2)min vs.(226.0±87.3)min,P=0.053]between the two groups.Conclusion:Compared with the patients with CAML and IVC tumor thrombus,the patients with EAML and IVC tumor thrombus had a higher rate of systemic symptoms and tumor necrosis.In addi-tion,in the selected patients with CAML with IVC tumor thrombus,partial nephrectomy and tumor thrombectomy could be performed to better preserve renal function.

Objective:To investigate the effect of miR-199a on interstitial transdifferentiation (EMT) of human renal tubular epithelial cells stimulated by high glucose.Methods:Human renal tubular epithelial cells were cultured in vitro and divided into low glycemic group (LG), high osmotic group (HM) and high glycemic group (HG) according to different glucose concentrations. They were divided into miR-199a inhibition group (miR-199ai group), negative control group (miR-INC group) and liposome group (Mock group) according to whether they were transfected with miR-199a inhibitors (miR199ai). They were divided into si-hypoxia-inducible factor-1α (si-HIF-1α) group, miR-199ai group, miR-199ai+ si-HIF-1α group and negative control group (NC group) according to whether they converted to si-HIF-1α and miR-199ai. The expressions of miR-199a, HIF-1α, fibronectin (FN) and α-smooth muscle actin (α-SMA) in different groups of cells were detected by real-time quantitative fluorescent polymerase chain reaction (qRT-PCR) and Western blot. Dual luciferase target assay was used to verify the targeting relationship between miR-199a and HIF-1α gene.Results:The mRNA expression level of miR-199a in the HG group was significantly lower than that in the LG group and the HM group (all P<0.01), and the mRNA and protein expression levels of HIF-1α, FN and α-SMA in Hg group were significantly higher than those in LG group and HM group (all P<0.01). The mRNA and protein expression levels of HIF-1α, FN and α-SMA in the miR-199ai group were significantly higher than those in the miR-iNC group and the Mock group (all P<0.01). Target gene prediction by TargetScan and miRanda showed that miR-199a could target the 3′-untranslated region(3′-UTR) that binds HIF-1α. Dual luciferase reported results: Inhibition of miR-199a resulted in a significant increase in luciferase activity ( P<0.01), but there was no significant change in luciferase activity after 3 ′-UTR mutation of HIF-1α ( P>0.05). After transfection with si-HIF-1α, the mRNA and protein expression levels of HIF-1α, FN and α-SMA in si-HIF-1α group were significantly lower than those in NC group (all P<0.05). After transfection with miR-199ai, the mRNA and protein expression levels of HIF-1α, FN and α-SMA in miR-199ai group were significantly higher than those in NC group (all P<0.05). However, when co-transfected with si-HIF-1α and miR-199ai, the expression levels of mRNA and protein in miR-199AI group were significantly higher than those in NC group (all P<0.05). The mRNA and protein expression changes of HIF-1α, FN and α-SMA induced by transfection of si-HIF-1α or miR-199ai alone can be recovered. Conclusions:miR-199a can alleviate hyperglycemia-induced EMT in human renal tubular epithelial cells through targeted regulation of HIF-1α.

Objective:To evaluate modified extended trochanteric osteotomy (ETO) applied in the revision of Vancouver B2/B3 periprosthetic femoral fractures (PFF).Methods:A retrospective study was conducted to analyze the 35 patients with Vancouver B2/B3 PFF who had been treated at Joint Disease Department Ⅱ, Zhengzhou Orthopedic Hospital from January 2012 to November 2020. There were 10 males and 15 females with an age of (74.3±7.8) years. The time from their primary replacement to revision was (120.3±28.6) months. By the Vancouver classification, 26 cases were type B2 and 9 ones type B3. The modified ETO was used in the revision surgery for all patients. The clinical efficacy was evaluated using Harris hip score, imaging evaluation was performed using the Beals and Tower criteria at the last follow-up, and complications were recorded.Results:The operation time for this cohort was (148±32) min and intraoperative bleeding (800±150) mL. All patients were followed up for (45.2±15.3) months. The Harris score increased significantly from preoperative (21.3±11.2) points to (86.2±5.2) points at the last follow-up ( P < 0.001). By the Beals and Tower evaluation, 9 cases were rated as excellent, 24 cases as good, and 2 as poor. All the fractures and sites of trochanteric osteotomy got healed after (4.4±2.8) months except for 1 case of nonunion. Prosthesis subsidence occurred in 3 cases, in 2 of which the subsidence stopped 6 months later and in only 1 of which revision was needed due to the subsidence. Upward block displacement of the greater trochanteric fracture occurred in 2 cases, but did not exceed 1 cm. One case of postoperative dislocation responded to manual reduction. Conclusion:In the revision of Vancouver B2/B3 PFF, the modified ETO can improve fracture healing, and reduce postoperative dislocations and complications, leading to satisfactory clinical efficacy.

Objective To explore the value of the combination of serum hemoglobin A1c(HbA1c),Alarin and Ficolin-3 in predicting adverse pregnancy outcomes in patients with gestational diabetes mellitus(GDM).Methods From March 2021 to March 2023,129 GDM patients who underwent prenatal examination and hospital delivery in Yantai Yeda Hospital were collected as the GDM group,while 133 pregnant women with normal glucose tolerance test results were regarded as the control group.Fully automated glycated hemoglobin analyzer was applied to detect serum HbA1c level.Enzyme linked immunosorbent assay(ELISA)was applied to detect serum Alarin and Ficolin-3 levels.Pearson method was used to analyze the correlation between serum HbA1c,Alarin,Ficolin-3 levels and 2 hour postprandial glucose(2 h PG),fasting blood glucose(FBG)and homeostasis model assessment method for insulin resistance(HOMA-IR)in GDM patients.Logistic regression was applied to analyze the relationship between HbA1c,Alarin,Ficolin-3 levels and adverse pregnancy outcomes in GDM patients.Receiver operating characteristic(ROC)curve was plotted to analyze the value of serum HbA1c,Alarin and Ficolin-3 levels in predicting adverse pregnancy outcomes in GDM patients.Results The 2 h PG,FBG,HOMA-IR,and serum HbA1c,Alarin,and Ficolin-3 levels were significantly higher in the GDM group than those in the control group(P＜0.05).The serum levels of HbA1c,Alarin and Ficolin-3 were positively correlated with 2 h PG,FBG and HOMA-IR in GDM patients(P＜0.05).The serum HbA1c,Alarin and Ficolin-3 levels were greatly higher in GDM patients with poor blood glucose control than those in GDM patients with good blood glucose control(P＜0.05).The above levels of three indicators in GDM patients with adverse pregnancy outcomes were significantly higher than those in GDM patients without adverse pregnancy outcomes(P＜0.05).Elevated levels of HbA1c,Alarin and Ficolin-3 were independent risk factors for adverse pregnancy outcomes in GDM patients(P＜0.05).The area under the curves of HbA1c,Alarin and Ficolin-3 alone and in combination were 0.840,0.865,0.815 and 0.979,respectively in predicting adverse pregnancy outcomes in GDM patients.Conclusion The serum HbA1c,Alarin and Ficolin-3 levels are abnormally elevated in GDM patients,and the combined detection of the three can improve the value in predicting adverse pregnancy outcomes.

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.