Objective:To describes the probability and rate of native liver survival (NLS) in biliary atresia (BA) patients after Kasai portoenterostomy (KPE)over various time periods and analyzes the perioperative factors associated with liver transplantation or death.Methods:A retrospective case-summary.BA patients administrated at the Department of Fetal and Neonatal Surgery in Hunan Children′s Hospital between January 2015 and December 2021.Probability and rate of NLS were calculated by life table.Cox proportional hazards regression model and Logistic model was applied to explore the perioperative factors related to post-Kasai liver transplantation/death.Results:The median age at Kasai surgery was 62 days.The rate of jaundice clearance (JC) was 64.5% within 3 months after Kasai, and 58.3% of the patients had cholangitis.The probability of NLS reached its lowest point in the first 1 year after Kasai (76.2%) and ranged from 93.2% to 98.0% in years 2-8 after Kasai.The rates of NLS in 2 years, 5 years and 8 years were 71.1%, 62.8% and 56.0%, respectively.Cytomegalovirus (CMV) infection before or on the day of Kasai without antiviral treatment can increase the risk of liver transplantation or death[ HR(95% CI): 1.628 (1.081-2.452), P=0.020].Preoperative gamma-glutamyl transferase increased the risk of liver transplantation/death within 1 year after Kasai[ OR(95% CI): 1.001 (1.000-1.001), P=0.021], and early cholangitis was a risk factor for liver transplantation/death within 5 years after Kasai[ OR(95% CI): 1.934 (1.004-3.726), P=0.048].JC within 3 months post-KPE was a protective factor of NLS. Conclusions:The first year after Kasai was the highest risk period for liver transplantation/death, which should be the focus of follow-up management.JC within 3 months after surgery is the protective factor for overall NLS, 1-year NLS and 5-year NLS.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective To investigate the occurrence of liver function abnormalities in patients with follicular lymphoma(FL)treated with the G-CDOP regimen in the real world.Methods Using the hospital information system,a retrospective collection of clinical data was conducted on inpatients diagnosed with FL and treated with at least four courses of the G-CDOP regimen in the Department of Hematology,the First Affiliated Hospital of Soochow University from September 2021 to August 2023.The analysis focused on the incidence,severity,and types of liver function abnormalities,as well as the timing of these occurrences in relation to medication use and other relevant clinical characteristics.Results The study encompassed a total of 55 patients with FL,out of which 30 patients encountered liver function abnormalities during the G-CDOP regimen treatment,yielding an incidence rate of 54.5%.There were 23 cases(41.8%)of grade 1,3 cases(5.5%)of grade 2,and 4 cases(7.3%)of grade 3 liver function abnormalities.Among them,12 cases(21.8%)were hepatocellular injury type,while the cholestasis type was observed in 4 cases(7.3%),and the mixed type was found in 14 cases(25.5%).Liver function abnormalities appeared in 21 patients(38.2%)during the first cycle of the G-CDOP regimen treatment,5 patients(9.1%)in the second cycle,and 1 patient(1.8%),2 patients(3.6%),and 1 patient(1.8%)in the third,fourth,and fifth cycles.Conclusion The G-CDOP regimen has the potential to impact liver function indicators in FL patients,but most are mild and reversible.However,there are also cases of severe liver injury that need to attract clinical attention.

Objective To explore the targeted regulatory relationship of miR-330-5p on OY-TES-1 in glioblastoma and the effect of miR-330-5p/OY-TES-1 axis on the migration ability of glioblastoma.Methods Bioinformatics analysis was performed to analyze the expression level of miR-330-5p in patients with glioblastoma and its influence on prognosis and survival of patients.The glioblastoma cells U251 were divided into miR-330-5p minics group,minics-NC group,and miR-330-5p+OY-TES-1 overexpression group(miR-330-5p minics+pcDNA3.1-OY-TES-1).The effect of miR-330-5p on the activity of OY-TES-1 3'UTR region was detected by double luciferase reporter gene experiment.The expression of OY-TES-1 mRNA was detected by qRT-PCR.The effect of miR-330-5p/OY-TES-1 axis on the migration ability of glioblastoma cells was detected by Transwell migration assay.Results The expression of miR-330-5p in glioblastoma tissue was significantly lower than those in non-tumor brain tissue and low-grade glioma tissue(P<0.05).The survival time of glioblastoma patients with high expression of miR-330-5p was significantly longer than that of patients with low expression of miR-330-5p(P<0.05).After overexpression of miR-330-5p,the activity of OY-TES-1 3'UTR region was decreased(P<0.05).Compared with minics-NC group,the expression levels of OY-TES-1 mRNA of U251 and U87MG cells in miR-330-5p minics group were significantly decreased(P<0.01).Compared with minics-NC group,the numbers of migrating cells in miR-330-5p minics group and miR-330-5p+OY-TES-1 overexpression group were significantly decreased(P<0.05).Compared with miR-330-5p minics group,the number of migrating cells in miR-330-5p+OY-TES-1 overexpression group was significantly increased(P<0.01).Conclusion MiR-330-5p targets OY-TES-1 to inhibit the migration of glioblastoma.

Objective To evaluate the correlation between the changes of vascular density in deep and shallow layers,retinal hyperreflexia and the therapeutic response of diabetic macular edema(DME).Methods Retrospectively selected DME patients(45 cases and 59 eyes)who visited the Department of Ophthalmology from April 2020 to November 2023 as the experimental group.Compare the change of deep and superficial blood vessel density and retinal hyperreflective points before and after treatment of the patients.The correlation between each index and poor response to anti-vascular endothelial growth factor(VEGF)treatment with DME was analyzed using the Pearson test.The value of baseline deep retinal capillary plexus(DCP),central macular retinal thickness(CMT),number of high-reflective foci(HRF)in the retina,and blood flow density(FD300-VD)in diagnosing poor response to anti-VEGF therapy in DME was analyzed using the subject operating characteristic curve(ROC).Results Compared with pre-treatment,patients'superficial retinal capillary plexus(SCP),DCP,FD300-VD,and deep-superficial flow ratio(DSFR)increased and CMT thickness significantly decreased after treatment(P<0.05).Pearson's correlation test showed that the outcome of patients with poor response to anti-VEGF therapy was negatively correlated with baseline SCP-VD,DCP-VD,DSFR,and FD300-VD(r=-0.458,-0.433,-0.604,and-0.452,P<0.05)and positively correlated with CMT(r=0.427,P<0.05).The results of multifactorial logistic regression analysis showed that a rise in SCP,DCP,FD300-VD,and DSFR,and a decrease in CMT were corre-lates affecting the response to anti-VEGF therapy in DME(OR=0.285,0.272,0.291,0.268,2.821,P<0.05).The results of ROC curve analysis showed that the AUCs of baseline DCP,CMT,HRF quantity,and FD300-VD were 0.918,0.934,0.947,and 0.927,respectively,which were of good value in diagnosing poor response to anti-VEGF therapy in DME.Conclusion Morphologic indicators such as changes in the density of deep and superfi-cial blood vessels and retinal hyperreflective spots have good application value in assessing the response to DME treatment and can assist in clinical treatment.

BACKGROUND: The choice of unicompartmental knee arthroplasty (UKA) vs . total knee arthroplasty (TKA) in the surgical treatment of knee osteoarthritis (KOA) remains controversial. This study aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the clinical results of UKA and TKA for treating unicompartmental KOA. METHODS: PubMed, Embase, and the Cochrane Library were systematically searched for articles published up to January 2, 2023. The literature was rigorously screened to include only RCTs comparing UKA and TKA for unicompartmental KOA. A systematic review and meta-analysis were performed to calculate the mean difference (MD), relative risk (RR), and 95% confidence interval (CI) according to the Cochrane standards. RESULTS: Thirteen publications involving 683 UKAs and 683 TKAs were analyzed. Except for one study with a follow-up period of 15 years, all outcome measures reported were within 5 years of follow-up. Meta-analysis showed better knee recovery (MD: 1.23; 95% CI: 1.01-1.45; P  <0.001), greater knee function (MD: 1.78; 95% CI: 0.34-3.22; P  = 0.020), less pain (MD: 0.75; 95% CI: 0.43-1.06; P  <0.001), and better health status (MD: 3.75; 95% CI: 0.81-6.69; P  = 0.010) after UKA than TKA. However, considering the minimal clinically important difference values for these variables, the findings were not clinically relevant. Moreover, UKA patients had fewer complications (RR: 0.59; 95% CI: 0.45-0.78; P  <0.001) and shorter hospital stays (MD: -0.89; 95% CI: -1.57 to -0.22; P  = 0.009) than did TKA patients. There were no statistically significant differences in terms of postoperative range of movement, revision, failure, operation time, and patient satisfaction. CONCLUSIONS In terms of clinical efficacy, there was no obvious advantage of UKA over TKA in the surgical treatment of knee OA when considering the minimal clinically important difference. The main advantage of UKA over TKA is that it leads to fewer complications and a shorter length of hospital stay. It is ideal to perform prospective studies with longer follow-up periods to fully evaluate the long-term efficacy and safety of the two procedures in the future.
Humans ; Arthroplasty, Replacement, Knee/methods* ; Osteoarthritis, Knee/surgery* ; Randomized Controlled Trials as Topic ; Treatment Outcome

Objective To investigate the occurrence of liver function abnormalities in patients with follicular lymphoma(FL)treated with the G-CDOP regimen in the real world.Methods Using the hospital information system,a retrospective collection of clinical data was conducted on inpatients diagnosed with FL and treated with at least four courses of the G-CDOP regimen in the Department of Hematology,the First Affiliated Hospital of Soochow University from September 2021 to August 2023.The analysis focused on the incidence,severity,and types of liver function abnormalities,as well as the timing of these occurrences in relation to medication use and other relevant clinical characteristics.Results The study encompassed a total of 55 patients with FL,out of which 30 patients encountered liver function abnormalities during the G-CDOP regimen treatment,yielding an incidence rate of 54.5%.There were 23 cases(41.8%)of grade 1,3 cases(5.5%)of grade 2,and 4 cases(7.3%)of grade 3 liver function abnormalities.Among them,12 cases(21.8%)were hepatocellular injury type,while the cholestasis type was observed in 4 cases(7.3%),and the mixed type was found in 14 cases(25.5%).Liver function abnormalities appeared in 21 patients(38.2%)during the first cycle of the G-CDOP regimen treatment,5 patients(9.1%)in the second cycle,and 1 patient(1.8%),2 patients(3.6%),and 1 patient(1.8%)in the third,fourth,and fifth cycles.Conclusion The G-CDOP regimen has the potential to impact liver function indicators in FL patients,but most are mild and reversible.However,there are also cases of severe liver injury that need to attract clinical attention.

Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.