BACKGROUND:Nobiletin has been found to improve lipopolysaccharide-induced abnormal activation of microglia,excessive release of inflammatory factors and redox imbalance.However,the specific mechanism is not fully understood. OBJECTIVE:To investigate the molecular mechanism by which nobiletin can inhibit lipopolysaccharide-induced inflammation in BV2 microglia. METHODS:Passage 3 BV2 microglia were divided into three groups:control group was cultured for 24 hours(without any treatment).Lipopolysaccharide group was treated with 10 μg/mL lipopolysaccharide for 24 hours.Lipopolysaccharide+nobiletin group was treated with 20 μmol/L nobiletin for 6 hours and then 10 μg/mL lipopolysaccharide for 24 hours.After the processing,cell proliferation was detected by CCK-8 assay.The level of intracellular reactive oxygen species was detected by fluorescent probe.The mRNA expression levels of nuclear factor κB p65,tumor necrosis factor α,and interleukin-1β were detected by qRT-PCR.The protein expression levels of nuclear factor κB p65,p-nuclear factor κB p65,tumor necrosis factor α,and interleukin-1β were detected by western blot assay. RESULTS AND CONCLUSION:(1)Compared with the control group,the proliferation activity of lipopolysaccharide group was decreased(P<0.001).Compared with the lipopolysaccharide group,the cell proliferation activity of lipopolysaccharide+nobiletin group was increased(P<0.001).(2)Compared with the control group,the level of intracellular reactive oxygen species was increased in the lipopolysaccharide group(P<0.001).Compared with the lipopolysaccharide group,the level of intracellular reactive oxygen species was decreased in the lipopolysaccharide+nobiletin group(P<0.01).(3)Compared with the control group,the mRNA expression levels of tumor necrosis factor α and interleukin-1β were increased in the lipopolysaccharide group(P<0.001,P<0.01).Compared with the lipopolysaccharide group,mRNA expression levels of tumor necrosis factor α and interleukin-1β were decreased in the lipopolysaccharide+nobiletin group(P<0.01,P<0.05).(4)Compared with the control group,the protein expression levels of p-nuclear factor κB p65,tumor necrosis factor α,and interleukin-1β in were increased the lipopolysaccharide group(P<0.001).Compared with the lipopolysaccharide group,the expression of p-nuclear factor κB p65,tumor necrosis factor α,and interleukin-1β was decreased in the lipopolysaccharide+nobiletin group(P<0.001).(5)These findings suggest that nobiletin attenuates lipopolysaccharide-induced inflammatory response in BV2 microglia by suppressing nuclear factor-κB signaling pathway.

Urolithiasis represents a prevalent clinical challenge marked by high recurrence rates and morbidity，with existing preventive strategies struggling to effectively curb its epidemic trajectory，thereby posing a significant threat to public health. The etiology of this condition is intricate，involving a complex network of interactions spanning classical supersaturation-crystallization theory，Randall’s plaque theory，and multifactorial elements such as cellular injury，inflammatory responses，metabolic derangements，the gut-kidney axis，immune dysregulation，and genetic predisposition. However，the critical mechanisms initiating stone formation and the early pathophysiological processes remain incompletely elucidated，constituting the core impasse in current preventive strategies. This review systematically synthesizes classical theories and cutting-edge advancements in urolithiasis etiology research，emphasizing the urgent need to integrate emerging technologies，including high-dimensional omics，advanced imaging modalities，and artificial intelligence，to dissect pivotal pathological nodes in early stone formation. Such interdisciplinary efforts are essential to overcome cognitive bottlenecks and ultimately achieve personalized，precision-based prevention strategies.

Urolithiasis represents a prevalent clinical challenge marked by high recurrence rates and morbidity，with existing preventive strategies struggling to effectively curb its epidemic trajectory，thereby posing a significant threat to public health. The etiology of this condition is intricate，involving a complex network of interactions spanning classical supersaturation-crystallization theory，Randall’s plaque theory，and multifactorial elements such as cellular injury，inflammatory responses，metabolic derangements，the gut-kidney axis，immune dysregulation，and genetic predisposition. However，the critical mechanisms initiating stone formation and the early pathophysiological processes remain incompletely elucidated，constituting the core impasse in current preventive strategies. This review systematically synthesizes classical theories and cutting-edge advancements in urolithiasis etiology research，emphasizing the urgent need to integrate emerging technologies，including high-dimensional omics，advanced imaging modalities，and artificial intelligence，to dissect pivotal pathological nodes in early stone formation. Such interdisciplinary efforts are essential to overcome cognitive bottlenecks and ultimately achieve personalized，precision-based prevention strategies.

Objective To explore the clinical effect and safety of carrellizumab combined with albumin-bound paclitaxel on the treatment of patients with locally advanced esophageal cancer.Methods Ninety-eight patients with locally advanced esophageal cancer were randomly divided into the study group and the reference group,with 49 cases in each group.The reference group was treated with albumin-bound paclitaxel,while the study group was treated with camrelizumab+albumin-bound paclitaxel.After treatment,the overall efficacy was evaluated,and the disease control rate was calculated.Serum tumor markers[high mobility group protein B1(HMGB1),squamous cell carcinoma associated antigen(SCCA)],PD-1 and PD-L1 levels were detected by enzyme-linked immunosorbent assay(ELISA)before and after treatment.Immunohistochemistry was used to detect the microvascular density(MVD)and the expression levels of PD-1 and PD-L1 in esophageal carcinoma tissue.The percentages of CD3+,CD4+and CD8+cells were detected by flow cytometry.Patients were followed up and adverse reactions and survival were recorded.Results The disease control rate was higher in the study group than that of the control group(P＜0.05).There were no significant differences in all indexes between the groups before treatment(P＞0.05).After treatment,HMGB1 level,SCCA level,MVD,serum PD-1 level and tumor tissue high expression rate of PD-1 were all decreased in the two groups,while serum PD-L1 level,PD-L1 high expression rate and percentages of CD3+,CD4+and CD8+cells were all increased(P＜0.05).Except there was no significant difference in MVD between groups,the other indexes were significantly changed in the study group compared with the control group(P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).The progression-free survival rate was higher in the study group than that of the control group(P＜0.05).Conclusion Carrellizumab combined with albumin-bound paclitaxel in the treatment of locally advanced esophageal cancer can help control lesion progression and inhibit angiogenesis,with good safety.

Identifying the compound formulae-related xenobiotics in bio-samples is full of challenges.Conventional strategies always exhibit the insufficiencies in overall coverage,analytical efficiency,and degree of automation,and the results highly rely on the personal knowledge and experience.The goal of this work was to establish a software-aided approach,by integrating ultra-high performance liquid chromatography/ion-mobility quadrupole time-of-flight mass spectrometry(UHPLC/IM-QTOF-MS)and in-house high-definition MS2 library,to enhance the identification of prototypes and metabolites of the compound formulae in vivo,taking Sishen formula(SSF)as a template.Seven different MS2 acquisition methods were compared,which demonstrated the potency of a hybrid scan approach(namely high-definition data-independent/data-dependent acquisition(HDDIDDA))in the identification precision,MS1 coverage,and MS2 spectra quality.The HDDIDDA data for 55 reference compounds,four component drugs,and SSF,together with the rat bio-samples(e.g.,plasma,urine,feces,liver,and kidney),were acquired.Based on the UNIFI? platform(Waters),the efficient data processing workflows were estab-lished by combining mass defect filtering(MDF)-induced classification,diagnostic product ions(DPIs),and neutral loss filtering(NLF)-dominated structural confirmation.The high-definition MS2 spectral li-braries,dubbed in vitro-SSF and in vivo-SSF,were elaborated,enabling the efficient and automatic identification of SSF-associated xenobiotics in diverse rat bio-samples.Consequently,118 prototypes and 206 metabolites of SSF were identified,with the identification rate reaching 80.51％and 79.61％,respectively.The metabolic pathways mainly involved the oxidation,reduction,hydrolysis,sulfation,methylation,demethylation,acetylation,glucuronidation,and the combined reactions.Conclusively,the proposed strategy can drive the identification of compound formulae-related xenobiotics in vivo in an intelligent manner.

Objective:To explore the risk factors of spontaneous rupture of hepatocellular carcinoma (HCC), and to analyze the prognosis of transcatheter arterial embolization (TAE) in the treatment of spontaneous rupture of HCC.Methods:From January 2008 to December 2018, at Tianjin Third Central Hospital, 126 patients diagnosed with spontaneous rupture of HCC (spontaneous rupture group) and in the same period 252 patients diagnosed as HCC without rupture (non-spontaneous rupture group) were retrospectively selected. Independent sample t test, Mann-Whitney U test and chi-square test were used to compare the general data, laboratory test results and imaging results between spontaneous rupture group and non-spontaneous rupture group. Multivariate logistic regression was used to analyze the independent risk factors of spontaneous rupture of HCC. Kaplan-Meier method and log-rank test were used for survival analysis of 92 patients treated with TAE and 31 patients treated with conservative treatment in patients with spontaneous rupture of HCC, and multivariate Cox proportional hazard regression was used to analyze the independent prognostic factors of patients treated with TAE. Results:The proportions of tumor maximum diameter ≥5 cm, tumors mainly located in segment Ⅱ, Ⅲ, Ⅳ and Ⅵ of the liver, tumors protruding height from the surface of liver ≥1 cm, liver cirrhosis and portal vein thrombosis (PVT) in spontaneous rupture group were all higher than those in non-spontaneous rupture group (46.8%, 59/126 vs. 35.7%, 90/252; 61.1%, 77/126 vs. 46.0%, 116/252; 73.0%, 92/126 vs. 18.7%, 47/252; 81.7%, 103/126 vs. 69.0%, 174/252; 20.6%, 26/126 vs. 11.5%, 29/252), and the level of fibrinogen is lower than that in non-spontaneous rupture group ((3.07 ±1.38) g/L vs. (3.92±1.13) g/L), and the differences were statistically significant ( χ2=4.343, 7.644, 106.780, 6.918 and 5.628, t=-3.276, all P<0.05). The results of multivariate logistic regression analysis showed that the location of tumors in segment Ⅱ, Ⅲ, Ⅳ, Ⅵ of the liver, the height of tumors protruding from the surface of liver ≥1 cm, liver cirrhosis and the fibrinogen was lower than the lower limit of the reference value were independent risk factors of spontaneous rupture of HCC (odds ratio ( OR)=1.354, 5.726, 1.152, 1.892; 95% confidence interval ( CI) 1.062 to 2.008, 1.049 to 19.575, 1.016 to 1.895, 1.267 to 3.346; all P<0.05). Among 92 patients with spontaneous rupture of HCC treated with TAE, the TAE technical success rate and clinical success rate were 100.0% (92/92) and 93.5% (86/92), respectively. Thirty-one patients received conservative treatment. The median survival time of the patients treated with TAE was 243 d (38 d, 377 d), which was about 10 times that of the patients who accepted conservative treatment (23 d (9 d, 51 d)). The 1-month, 3-month, 6-month, 1-year and 3-year survival rates of the patients treated with TAE were 72.8%, 50.8%, 46.0%, 31.1% and 13.6%, respectively, and those of patients who accepted conservative treatment were 25.8%, 17.2%, 11.5%, 5.7% and 0, respectively; and the differences in survival rates between the two groups were statistically significant ( χ2=34.606, P<0.01). Log-rank test analysis showed that initial hemoglobin <60 g/L, C grade of liver function, total bilirubin (TBil)≥50 μmol/L, complicated with portal vein tumor thrombus, hepatic lobe embolism during TAE, and tumor maximum diameter ≥10 cm were all correlated with poor survival rates of patients with spontaneous rupture of HCC after TAE ( χ2=3.752, 4.146, 22.318, 4.087, 5.685 and 7.893, all P<0.05). The results of multivariate Cox proportional hazard regression analysis showed that TBil ≥ 50 μmol/L, hepatic lobe embolism during TAE, and tumor maximum diameter ≥10 cm were independent factors of poor prognosis of spontaneous rupture of HCC treated with TAE ( OR=25.873, 8.415, 18.620; 95% CI 4.916 to 126.005, 1.136 to 27.319, 2.754 to 84.368; all P<0.05). Conclusions:In HCC patients with tumors located in segments Ⅱ, Ⅲ, Ⅳ and Ⅵ of the liver, the height of tumors protruding from the surface of liver ≥1 cm, liver cirrhosis or the fibrinogen is lower than the lower limit of the reference value, close attention should be paid to the risk of spontaneous tumor rupture. TAE is an effective treatment for acute spontaneous rupture of HCC, and the prognosis of patients treated with TAE is better than that of patients receiving conservative treatment. However, patients with TBil ≥50 μmol/L, hepatic lobe embolism during TAE and tumor maximum diameter ≥10 cm have a poor prognosis after TAE treatment.

BACKGROUND: Chronic noise exposure is one environmental hazard that is associated with genetic susceptibility factors that increase Alzheimer's disease (AD) pathogenesis. However, the comprehensive understanding of the link between chronic noise stress and AD is limited. Herein, we investigated the effects of chronic noise exposure on AD-like changes in senescence-accelerated mouse prone 8 (SAMP8). METHODS: A total of 30 male SAMP8 mice were randomly divided into the noise-exposed group, the control group, and aging group (positive controls), and mice in the exposure group were exposed to 98 dB SPL white noise for 30 consecutive days. Transcriptome analysis and AD-like neuropathology of hippocampus were examined by RNA sequencing and immunoblotting. Enzyme-linked immunosorbent assay and real-time PCR were used to further determine the differential gene expression and explore the underlying mechanisms of chronic noise exposure in relation to AD at the genome level. RESULTS: Chronic noise exposure led to amyloid beta accumulation and increased the hyperphosphorylation of tau at the Ser202 and Ser404 sites in young SAMP8 mice; similar observations were noted in aging SAMP8 mice. We identified 21 protein-coding transcripts that were differentially expressed: 6 were downregulated and 15 were upregulated after chronic noise exposure; 8 genes were related to AD. qPCR results indicated that the expression of Arc, Egr1, Egr2, Fos, Nauk1, and Per2 were significantly high in the noise exposure group. These outcomes mirrored the results of the RNA sequencing data. CONCLUSIONS These findings further revealed that chronic noise exposure exacerbated aging-like impairment in the hippocampus of the SAMP8 mice and that the protein-coding transcripts discovered in the study may be key candidate regulators involved in environment-gene interactions.

Objective:To investigate the clinical efficacy of percutaneous endoscopic lumbar discectomy (PELD) with the aid of neurophysiological monitoring under general anesthesia.Methods:From August 2016 to October 2019, 58 patients underwent PELD under general anesthesia were selected in our hospital; 30 were via transformational approach and 28 were via interlaminar approach. The whole operative procedures were performed under continuous monitoring of spontaneous electromyography (SEMG), and the peak value, waveform and motor unit of SEMG at the surgical side were observed. The clinical outcomes were evaluated by visual analogue scale (VAS) and Oswestry disability index (ODI).Results:PELD was successfully performed in all 58 patients. Abnormal SEMG reactions were recorded in 8 patients (13.8%), manifested as clustered or frequent high amplitude action potentials; 5 patients (16.7%, 5/30) were via transformational approach and 3 (10.7%, 3/28) were via interlaminar approach. Two patients relapsed at 3 and 6 weeks after surgery, respectively; one was treated with PELD again and the other one was treated with lumbar fusion and instrument fixation. The pain at the lumbago and leg was alleviated obviously after surgery in the 56 patients; the VAS scores were 7.43±1.32, 2.55±0.87 and 1.59±0.87 before surgery, and 3 d and 3 months after surgery, respectively, with significant differences ( P<0.05); the mean ODI before surgery and 3 months after surgery were 67.36±7.13 and 12.39±5.48, respectively, with significant difference ( P <0.05). Conclusion:PELD with the aid of neurophysiological monitoring under general anesthesia is safe and reliable, which can achieve good clinical efficacy.

Objective: To investigate the effect of repairing the skin and soft tissue defects of foot with the anterior tibial artery perforator flap. Methods: Nine patients received the operation using the anterior tibial artery periosteal perforator flap to repair distal foot lesion with skin and soft tissue defects.There were six males and three females.All cases were the distal foot defects of skin and soft tissue with tendon and bone exposure, including traffic accident injury in 5 cases, crush injury in 3 cases, other causes of injury in 1 case. The defects ranged from 5 cm×3 cm to 9 cm×6 cm. The flaps ranged from 7 cm×5 cm—11 cm×8 cm. The donor sites were repaired with direct suture or full-thickness skin grafts. Results: All the flaps were survived, without vascular crisis, congestion and blisters. 1 case had partial necrosis of flap margin, which was cured after dressing. All cases were followed up for 6 months to 34 months(mean 18 months). The appearance and function recovery of flaps were satisfactory. Conclusions It is an ideal flap donor site for repairing soft tissue defects of the distal foot with the anterior tibial artery perforator flap, which has the advantages of simple operation, less trauma, high skin flap survival rate and good appearance.

Objective To analyze the efficacy and complications of interventional treatment in hepatic hemangiomas with poor blood supply,and to explore the mode of treatment.Methods From May 2013 to October 2016,at Tianjin Third Central Hospital,82 patients with hepatic hemangiomas with poor blood supply were enrolled and divided into intervention group,puncture group and combination group.Conventional hepatic artery intubation was performed in intervention group,using a microcatheter to superselect to hemangioma and injecting pingyangmycin-lipiodol emulsion into the tumor of hemangioma.Patients of puncture group underwent the ultrasound-guided percutaneous liver puncture,and the pingyangmycin-lipiodol emulsion was injected into the tumor.The patients of combination group first received intervention treatment,and the pingyangmycin-lipiodol emulsion were injected again into the tumor area lacking of iodized oil deposition through percutaneous transhepatic puncture.After treatment,the complications and clinical efficacy of patients in three groups were evaluated and the reasons of patients lost to follow-up were analyzed.The analysis of variance,Chi-square test and Fisher's exact test were performed for statistical analysis.For patients lost to follow up,intention-to-treat (ITT) analysis and per protocol (PP) analysis were used.Results Among 82 patients with hepatic hemangiomas with poor blood supply,there were 27 in intervention group,24 in puncture group and 31 in combination group.Seven patients developed serious complications such as liver failure.At three months after the treatment,the overall efficacy of combination group (20.9％,9/31) was higher than that of intervention group (7.4％,2/27) and puncture group (4.2 ％,1/24),and the differences were statistically significant (x2 =6.296,P =0.014;x2 =5.622,P =0.031).At six months after the treatment,the overall efficacy of combination group (ITT analysis 70.3 ％,26/37;PP analysis 71.0 ％,22/31) was still higher than that of intervention group (40.9％,9/22) and puncture group (7/18),and the differences were statistically significant (ITT analysis x2 =4.929 and 4.969,PP analysis x2 =4.789 and 4.851;all P＜0.05).At twelve months after the treatment,a total of 41 patients of three group were lost.Among them,the patients with ineffective treatment by clinical effect evaluation accounted for 63.4％ (26/41),which was higher than those with significantly effective treatment (12.2 ％,5/41) and those with effective treatment (24.4 ％,10/41),and the differences were statistically significant (x2=22.873 and 12.676,both P＜0.01).Conclusions The efficacy of the interventional treatment alone for hepatic hemangiomas with poor blood supply is poor and the complications should be considered when selecting the appropriate treatment methods.