Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

Objective To explore the feasibility of magnetic compression technique (MCR) in the treatment of severe single mid-ureteral stricture in a rabbit model. Methods After 10 female New Zealand rabbits were selected, the distal end of the right ureter was ligated with silk thread. Two weeks after the operation, when the right ureter was dilated, the mid-ureter was ligated again with silk thread to create a severe single mid-ureteral stricture animal model. Longitudinal incisions were made at the upper and lower ends of the ligation site, and cylindrical NdFeB magnets with central holes (sub-magnets and main magnets) were placed to anastomose and recanalize the mid-ureteral stricture. The magnets were adjusted to the appropriate position to automatically align and attract each other. The longitudinal incision sites of the ureter were sutured with 6-0 Prolene thread, and the abdominal cavity was closed layer by layer. The operation time was recorded. X-ray films were taken every two days to confirm the position of the magnets and record the time of magnet detachment. Three weeks after the operation, the anastomotic specimens were obtained, and the formation of the anastomosis was evaluated with gross observation and histological staining. Results Two weeks after ligation, all experimental rabbits showed obvious dilation of the right ureter. The mid-ureteral ligation and placement of the male and female magnets were successfully completed in all 10 experimental rabbits, with an operation time of (24.00±5.15)minutes. The male and female magnets attracted each other well. X-ray examination showed that the magnets detached and entered the distal ureter (14.0±1.9) days after magnetic compression. The recanalization of the severe single mid-ureteral stricture was successfully achieved. The gross specimens and histological examination of the anastomosis showed that the anastomosis remained patent and the mucosal healing was good. All experimental rabbits survived well after the operation without serious complications. Conclusion MCT provides a new idea and novel method for the treatment of mid-ureteral stricture. This study confirmed the feasibility of this technique in treating severe single mid-ureteral stricture in a rabbit model. The operation is relatively simple and has potential for clinical application.

Objective To investigate and elucidate the effect of trigonelline(TRG)on the ARPE-19 ferroptosis sig-naling pathway under hypoxia conditions.Methods ARPE-19 cells were routinely cultured and intervened with different concentrations of TRG.According to the optimal concentration(40 mg·L-1)of TRG determined for ARPE-19 interven-tion,the cells were divided into an NC group(routinely cultured for 24 h),a CoCl2 group(treated with 150 mmol·L-1 CoCl2 for 24 h),a Fer-1 group(treated at first with 1 μmol·L-1 Fer-1 for 12 h and then with 150 mumol·L-1 CoCl2 for 12 h),and a TRG group(treated at first with 40 mg·L-1 TRG for 24 h and then with 150 mmol·L-1 CoCl2 for 24 h).The levels of glutathione(GSH),malondialdehyde(MDA)and Fe2+ions in each group of cells were evaluated by detectionkits.The levels of reactive oxygen species(ROS)in each group of cells were detected by flow cytometry.Western blot was used to analyze the expression levels of hypoxia-induced factor-1α(HIF-1α),vascular endothelial growth factor(VEGF),glutathione peroxidase 4(GPX4)and acyl-CoA synthetase long-chain family member 4(ACSL4)in each group of cells.The expression levels of VEGF and ACSL4 proteins in each group of cells were measured by immunofluorescence staining.Results The ROS levels in TRG and Fer-1 groups were significantly lower than those in the CoCl2 group(t=27.91,31.61;both P＜0.01).The change trend of MDA and Fe2+levels was the same with that of ROS levels in each group.Com-pared with those in the CoCl2 group,the GSH levels were increased significantly(t=15.95,12.76;both P＜0.01)and the relative expression levels of HIF-1α and VEGF proteins were decreased significantly in Fer-1 and TRG groups(all P＜0.01).The CoCl2 group had higher ACSL4 levels and lower GPX4 levels than the NC group(t=31.05,13.18;both P＜0.01).Fer-1 and TRG groups had lower ACSL4 expression levels and higher GPX4 expression levels than the CoCl2 group(all P＜0.01).The results of immunofluorescence staining showed that the expression levels of VEGF and ACSL4 proteins in the CoCl2 group were higher than those in the NC group.The expression levels of VEGF and ACSL4 proteins in Fer-1 and TRG groups were lower than those in the CoCl2 group.Conclusion TRG protects ARPE-19 cells from hypoxia-induced oxidative stress damage by inhibiting ferroptosis.

AIM:To investigate the potential mechanism of licorice on liver injury induced by Se-men Strychni based on network pharmacology,mo-lecular docking combined with animal experiments,providing an effective strategy for prevention and treatment of liver injury induced by Semen Strych-ni.METHODS:Firstly,the active ingredients of Se-men Strychni and licorice were obtained through the ETCM,TCMSP database and analysis platform,CTD database and literature supplementation.Then,the potential toxic ingredients of Semen Strychni were further screened based on the Swis-sADME platform,and the targets corresponding to the active ingredients were predicted through the SwissTargetPrediction platform.By using the Gene-Cards and OMIM databases to collect DILI-related targets,the potential targets for licorice to alleviate liver injury caused by Semen Strychni were ob-tained.By constructing the active ingredient-target network,the core ingredients of licorice in alleviat-ing liver injury caused by Semen Strychni were screened.The key targets obtained were used to construct and analyze the protein-protein interac-tion networks(PPI)through the STRING database and Cytoscape 3.9.0 software.The potential targets were subjected to GO and KEGG pathway enrich-ment analysis with the aid of the DAVID database,and constructed a network of active ingredient-tar-get-pathway.Molecular docking study was ap-proved for the core targets and the active ingredi-ents by using Schrodinger 2023-1 software,and the visualization operation was conducted through Py-mol.Finally,the regulatory effect of licorice on the key pathway of liver injury caused by Semen Strych-ni was validated by establishing a rat model of liver injury induced by Semen Strychni.RESULTS:After screening,6 potential toxic components of Semen Strychni and 104 corresponding targets,89 active components of licorice and 347 corresponding tar-gets,and 3 200 DILI targets were obtained.A total of 23 intersection targets were obtained through Venn analysis.By constructing the active ingredi-ent-target network,it was found that the main core ingredients were 7-methoxy-2-methyl isofla-vone,medicarpin,shinpterocarpin,quercetin,for-mononetin and isoliquiritigenin.The PPI network indicated that the core targets were protein kinase B1(AKT1),epidermal growth factor receptor(EG-FR),human epidermal growth factor receptor 2(ERBB2),glycogen synthase kinase 3 beta(GSK3B),kinase insert domain receptor(KDR)and Janus ki-nase 2(JAK2).A total of 39 relevant pathways were enriched in KEGG(P＜0.01),among which the phos-phatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)(PI3K-AKT)signaling pathway,which has been confirmed and ranks first in enrichment,and was closely related to liver injury.Molecular docking re-sults showed that the core components have good binding ability with the core targets.In vivo animal experiments demonstrated that,compared to the model group,licorice significantly reduced the liver index(P＜0.01),serum levels of alkaline phospha-tase(ALP),alanine aminotransferase(ALT),aspar-tate aminotransferase(AST),indirect bilirubin(IBIL),and total bilirubin(TBIL)in rats with liver in-jury,while increasing total protein(TP)levels(P＜0.05 or P＜0.01).Additionally,licorice alleviated con-gestion in the central veins and hepatic sinusoids,improved the alignment of hepatocytes,and re-duced inflammatory cell infiltration.Furthermore,licorice significantly decreased the levels of malo-ndialdehyde(MDA),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)in the liver tissue of injured rats,while elevating the levels of superoxide dismutase(SOD)and glutathi-one peroxidase(GSH-Px)(P＜0.01).It also markedly downregulated the phosphorylation levels of PI3K and AKT(P＜0.01).CONCLUSION:Licorice has multi-component and multi-target properties in the treat-ment of liver injury induced by Semen Strychni,which may play a hepatoprotective role by inhibit-ing the activation of PI3K-AKT signaling pathway.

During the growth period, mouth breathing caused by upper airway obstruction can adversely affect normal development of children's maxillofacial region, manifesting various types of growth patterns and facial appearance. Therefore, to further understand the influence of different obstructive parts of upper airway on maxillofacial growth patterns, this knowledge would be helpful for clinicians in guiding the normal development of children's maxillofacial region. This review describes the common causes of oral breathing, and analyzes the maxillofacial development characteristics of children with different upper airway stenosis anatomical planes and various age stages. In order to provide a reference frame basis for the intervention timing, program formulation and the maintenance of the post-operative efficacy of children with oral breathing.
Humans ; Maxillofacial Development ; Child ; Mouth Breathing/physiopathology* ; Airway Obstruction

Objective To explore the correlation of neutrophil/lymphocyte ratio(NLR),monocyte/high density lipoprotein cholesterol ratio(MHR)and mild cognitive impairment(MCI)in patients with type 2 diabetes mellitus(T2DM).Methods 159 T2DM patients hospitalized in the Department of Endocrinology,Affiliated Hospital of Xuzhou Medical University from February 2023 to April 2023 were selected.The subjects were divided into normal cognitive function(Con,n=72)group and MCI group(n=87)based on score of Montreal cognitive assessment scale(MoCA).NLR and MHR were calculated and compared between the two groups.Spearman correlation analysis was used to analyze the correlation between NLR,MHR and MoCA score.Logistic regression analysis of the factors influencing the association between T2DM with MCI.Receiver operator characteristic(ROC)curve was used to evaluate the predictive value of NLR and MHR for DM complicated with MCI.Results Compared with Con group,MCI group showed a significant increase in hemoglobin A1c(HbA1c),fasting plasma glucose,NLR,MHR,neutrophil count,monocyte count,serum creatinine,cystatin C,while high density lipoprotein cholesterol lymphocytes,visual space and executive function,naming,attention,language ability,abstract thinking,delayed memory,orientation and MoCA score decreased(P＜0.05).Spearman correlation analysis showed that there was a negative correlation between MHR,NLR and MoCA score,visuospatial and executive function,delayed recall and attention.Logistic regression analysis showed that NLR,MHR,HbA1c were all risk factors for MCI in T2DM.ROC curve analysis showed that the area under the curve of NLR combined with MHR for diagnosing T2DM with MCI was 0.872,with corresponding sensitivity of 81.6%and specificity of 87.5%.Conclusions NLR and MHR are closely related to MCI in T2DM patients.The combination of NLR and MHR have certain efficacy in prediction T2DM with MCI.

Inflammatory bowel disease (IBD) is a chronic and nonspecific disease affected by both genetic and environmental factors. Ecological and social environmental factors, including air pollutants, heavy metals, industrial pollutants and organic pollutants, diet, and lifestyle, influence the occurrence and development of IBD and regulate IBD gene expression through epigenetics and gut microbiota. This article summarizes the role of environmental factors in IBD and explores the ways in which they influence the regulation of gene expression.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disorder with unclear etiology. Existing studies indicate that diet plays an important role in both the pathogenesis and prognosis of IBD. This review summarizes clinical evidence regarding the association between diet and the development of IBD, analyze the current nutritional status of the IBD population at the prognosis level and underlying mechanisms of dietary interventions in disease management, and explores the application of precision nutrition in personalized care. The review ultimately aims to provide guidance for developing more precise and personalized dietary management strategies for IBD patients.

Objective To study the clinical efficacy and safety of detachable titanium clip combined with rubber band intracavity dual traction assistance in endoscopic treatment of gastric submucosal tumors(SMT).Methods 52 patients who underwent endoscopic submucosal excavation(ESE)or endoscopic full thickness resection(EFR)for gastric SMT from January 2022 to July 2024 were selected.27 patients using the detachable titanium clip combined with rubber band intracavity dual traction assistance ESE or EFR were selected as experimental group,and 25 patients using the traditional ESE or EFR were selected as control group.Operation time,hospital stay,hospital cost,one time complete excavation rate and complication rates were compared between the two groups.Results The operation time and hospital stay in the experimental group were significantly shorter than those in the control group,and the hospital cost was also significantly lower,with all differences being statistically significant(P<0.05).The comparison of surgical complication rates between the two groups showed a statistically significant difference(P<0.05),with the experimental group having significantly lower total complication rates than that in the control group.However,there was no statistically significant difference(P>0.05)in the rate of one-time complete excavation between the two groups.Conclusion The detachable titanium clip combined with rubber band intracavitary dual-traction-assisted endoscopic treatment for gastric SMT significantly shortens the operation time and hospital stay,reduces hospital costs and surgical complications.It is a simple,effective auxiliary device that worthy for clinical application.

OBJECTIVE To observe the effect of acupuncture combined with a modified Zhengan Xifeng Decoction on the early clinical symptoms and oxidative stress status of patients with hypertensive intracerebral hemorrhage(HICH)of liver-kidney yin defi-ciency syndrome.METHODS A total of 60 patients with hypertensive intracerebral hemorrhage(liver-kidney yin deficiency syn-drome)who successfully received 24-hour acute-phase treatment at the Department of Neurosurgery,Acupuncture and Rehabilitation Department,and wards of Kunshan Hospital Affiliated to Nanjing University of Chinese Medicine(Kunshan Traditional Chinese Medi-cine Hospital)from July 2021 to January 2023 were recruited.A randomization table generated by SPSS 22.0 software was used to di-vide the patients into a control group and an observation group,with 30 patients in each group.The control group received symptomatic treatment,conventional rehabilitation training,and modified Zhengan Xifeng Decoction,while the observation group received additional acupuncture treatment on the basis of the control group.The treatment course was 1 month for both groups.Clinical effective rate,TCM syndrome scores,motor and neurological function scores[Activity of Daily Living(ADL)scale,National Institutes of Health Stroke Scale(NIHSS),Modified Ashworth Scale(MAS),Simplified Fugl-Meyer Assessment(FMA)scale],improvement in hematoma lesions,Fraction anisotropy(FA)ratio(rFA),and serum levels of antioxidant stress response factors Kelch-like ECH-associated protein 1(Keap1)and nuclear factor-E2-related factor 2(Nrf2)were observed before and after treatment in both groups.RESULTS After treat-ment,the clinical effective rate in the observation group was significantly higher than that in the control group(P<0.05);the TCM syn-drome scores in both groups decreased significantly(P<0.05),with the observation group showing better results than the control group(P<0.05);the ADL and FMA scores in both groups reduced significantly(P<0.05,P<0.01),while the NIHSS and Ashworth Scale scores increased significantly(P<0.05,P<0.01),with the observation group showing better improvement than the control group(P<0.05);serum Keap1 levels decreased significantly in both groups(P<0.01),while Nrf2 levels enhanced significantly(P<0.05,P<0.01),with the observation group showing better improvement than the control group(P<0.05);imaging studies showed that after treat-ment,the residual hematoma volume decreased significantly in both groups(P<0.05,P<0.01),and the rFA value increased signifi-cantly(P<0.05,P<0.01),with the observation group showing better results than the control group(P<0.01).CONCLUSION On the basis of standard treatment for the acute phase,acupuncture combined with Zhengan Xifeng Decoction can significantly improve the early clinical symptoms of HICH patients with liver-kidney yin deficiency,reduce oxidative stress levels,and promote the recovery of nerve and motor functions.