UNC-51-like kinase 1(ULK1)is an important factor involved in regulating the initiation of autophagy.ULK1 regu-lates inflammatory cytokines through autophagy and mitochondrial oxidative stress,and is involved in the pathological processes of var-ious diseases.ULK1 and its complexes are regulated by rapamycin(mTOR)and AMP-activated protein kinase(AMPK)to initiate au-tophagy,thereby exerting differential effects on a variety of inflammatory diseases.In inflammatory diseases,mitochondrial oxidative stress can induce ULK1 into the nucleus to accelerate apoptosis.Therefore,ULK1 plays different important roles in inflammatory dis-eases.For example,ULK1 initiates airway epithelial mitochondrial autophagy in asthma,participates in mitochondrial oxidative stress in acute liver failure,affects related inflammatory factors in atherosclerosis,and modulates beneficial effects of autophagy in diabetes.This article reviews the biological function of ULK1,its impact on inflammatory diseases and the research progress of targeted drugs.

Objective To evaluate the effectiveness of tumor cell Vimentin combined with endoscopic ultrasound-guided fine-needle biopsy(EUS-FNB)in diagnosing solid pancreatic tumors.Methods Clinical data from 110 patients who underwent EUS-FNB from October 2021 to December 2023 were retrospectively analyzed.Solid pancreatic tumors including but not limited to pancreatic cancer and pancreatic neuroendocrine tumors.The sensitivity,specificity,and accuracy of EUS-FNB were assessed by comparing its results with the final pathological diagnoses.Result Clear histopathological diagnoses were obtained in 106 cases,accounting for 96.37%.Among them,87 cases were definitively diagnosed as adenocarcinoma or pancreatic ductal adenocarcinoma.Immunohistochemical staining showed that Vimentin was expressed in the tumor cells.There was no statistically significant difference in positive rates among biopsies from different anatomical sites(P>0.05),but significant differences were observed in lesions of different diameters(P<0.05).Immunohistochemical staining suggested that Vimentin expression levels might be associated with the nature of the lesions.The overall diagnostic accuracy,sensitivity,and specificity of Vimentin combined with EUS-FNB for pancreatic masses were 86.09%,84.57%,and 100.00%,respectively.Specifically,for solid masses,the diagnostic accuracy,sensitivity,and specificity were 87.67%,86.55%,and 100.00%,respectively.For pancreatic cystic tumors,the diagnostic accuracy,sensitivity,and specificity were 65.42%,69.79%,and 100.00%,respectively.Conclusion The combination of tumor cell Vimentin and EUS-FNB demonstrates high diagnostic accuracy for solid pancreatic tumors,making it a valuable tool for clinical application.

We investigated whether FTY-720 might have an effect on bleomycin-induced pulmonary fibrosis through inhibiting TGF-β1 pathway, and up-regulating autophagy. The pulmonary fibrosis was induced by bleomycin. FTY-720 (1 mg/kg) drug was intraperitoneally injected into mice. Histological changes and inflammatory factors were observed, and EMT and autophagy protein markers were studied by immunohistochemistry and immunofluorescence. The effects of bleomycin on MLE-12 cells were detected by MTT assay and flow cytometry, and the related molecular mechanisms were studied by Western Blot. FTY-720 considerably attenuated bleomycin-induced disorganization of alveolar tissue, extracellular collagen deposition, and α-SMA and E-cadherin levels in mice. The levels of IL-1β, TNF-α, and IL-6 cytokines were attenuated in bronchoalveolar lavage fluid, as well as protein content and leukocyte count. COL1A1 and MMP9 protein expressions in lung tissue were significantly reduced. Additionally, FTY-720 treatment effectively inhibited the expressions of key proteins in TGF-β1/TAK1/P38MAPK pathway and regulated autophagy proteins. Similar results were additionally found in cellular assays with mouse alveolar epithelial cells. Our study provides proof for a new mechanism for FTY-720 to suppress pulmonary fibrosis. FTY-720 is also a target for treating pulmonary fibrosis.

Objective:To investigate the clinical features and treatment strategies of ischemic stroke during pregnancy and puerperium.Methods:This study retrospectively analyzed the clinical data of six women diagnosed with ischemic stroke during pregnancy and puerperium by cranial CT or MRI at the Second Affiliated Hospital of Shandong First Medical University from January 2013 to December 2021. Descriptive data analysis was performed.Results:There were 31 082 deliveries at the hospital in this period. The incidence of ischemic stroke during pregnancy and puerperium was 0.019% (6/31 082) during the study period. Among the six patients, three occurred in early pregnancy, one in late pregnancy, and two in the puerperium. The most common symptoms included headache, nausea, vomiting, blurred vision, convulsions, and limb movement disorders. All six patients received conservative treatment. Two term neonates were born vaginally, and one preterm infant was delivered by cesarean section. None of the three babies had any significant malformations or abnormalities in growth and development. Two pregnancies were terminated, and one received a medical abortion due to a missed abortion after embryo arrest.Conclusions:Symptoms of ischemic stroke during pregnancy and puerperium are atypical. The treatment should be individualized based on a comprehensive assessment of the etiology, severity, and maternal and fetal conditions. Maternal and fetal conditions and gestational weeks should be considered in obstetric management.

Objective:To investigate the effect of long non-coding RNA HOTAIR (LncRNA HOTAIR) on the proliferation, apoptosis and drug resistance of Wilms tumor cells and its molecular mechanism.Methods:Collected nephroblastoma tissues and normal tumor side tissues in 32 children with renal syblastoma surgical treatment at Zhengzhou University Children′s Hospital from 2015 to 2019. Real-time quantitative reverse transcription polymerase chain reaction, (qRT-PCR)was used to detect the expression of HOTAIR in Wilms tumor tissues and adjacent tissues. Small interfering RNA technology was used to delete the expression of HOTAIR in Wilms tumor cell SK-NEP-1. Cell counting kit-8 (CCK-8)was used to detect cell proliferation after transfection. Flow cytometry and terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) staining to detect the apoptosis. Western blot was used to detect the expression of Wnt/β-catenin signaling pathway related proteins.CCK-8 was used to detect the proliferation inhibition of cells treated with different concentrations of cisplatin after transfection.Results:Compared with adjacent tissues, HOTAIR was highly expressed in Wilms tumor tissues ( P<0.05). The expression levels of Wnt, β-catenin, Cyclin D1, c-myc in the control group were (0.89±0.08), (0.94±0.10), (0.72±0.06), (1.10±0.11), and (1.06±0.11), (0.92±0.08), (0.66±0.07), (1.25±0.11) of the si-RNA group, while (0.54±0.05), (0.41±0.05), (0.25±0.03), (0.56±0.06) of the si-HOTAIR group. The expression levels of these protein were significantly down-regulated in the si-HOTAIR group when compared with the control group and the si-RNA group ( P<0.05). The absorbance (A) values of SK-NEP-1 cells in the si-HOTAIR group at 24, 48 and 72 hours after transfection were (0.31±0.02), (0.37±0.04), (0.69±0.07), significantly lower than (0.49±0.05), (0.78±0.08), (1.22±0.14) in the control group and (0.57±0.06), (0.68±0.07), (0.94±0.09) in the si-RNA group ( P<0.05). The apoptosis rate in the si-HOTAIR group was (13.81±1.25)%, significantly higher than (6.54±0.72)% in the control group and (4.35±0.40)% in the si-RNA group ( P<0.05). The cell positive rate of TUNEL cells in the si-HOTAIR group was (35.14±3.50)%, significantly higher than (20.16±2.18)% in the control group and (21.09±2.35)% in the si-RNA group ( P<0.05). The median inhibitory concentration (IC 50) of the si-HOTAIR group was (62.48±5.97) μmol/L, significantly lower than (88.27±9.05) μmol/L of the control group and (92.50±9.11) μmol/L of the si-RNA group ( P<0.05). Conclusions:Suppression of LncRNA HOTAIR can inhibit the proliferation of Wilms tumor cells, promote cell apoptosis, decrease cell resistance to cisplatin. The mechanism may be related to the inhibition of Wnt/β-catenin signaling pathway activation.

Objective:To investigate the effect of long non-coding RNA HOTAIR (LncRNA HOTAIR) on the proliferation, apoptosis and drug resistance of Wilms tumor cells and its molecular mechanism.Methods:Collected nephroblastoma tissues and normal tumor side tissues in 32 children with renal syblastoma surgical treatment at Zhengzhou University Children′s Hospital from 2015 to 2019. Real-time quantitative reverse transcription polymerase chain reaction, (qRT-PCR)was used to detect the expression of HOTAIR in Wilms tumor tissues and adjacent tissues. Small interfering RNA technology was used to delete the expression of HOTAIR in Wilms tumor cell SK-NEP-1. Cell counting kit-8 (CCK-8)was used to detect cell proliferation after transfection. Flow cytometry and terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) staining to detect the apoptosis. Western blot was used to detect the expression of Wnt/β-catenin signaling pathway related proteins.CCK-8 was used to detect the proliferation inhibition of cells treated with different concentrations of cisplatin after transfection.Results:Compared with adjacent tissues, HOTAIR was highly expressed in Wilms tumor tissues ( P<0.05). The expression levels of Wnt, β-catenin, Cyclin D1, c-myc in the control group were (0.89±0.08), (0.94±0.10), (0.72±0.06), (1.10±0.11), and (1.06±0.11), (0.92±0.08), (0.66±0.07), (1.25±0.11) of the si-RNA group, while (0.54±0.05), (0.41±0.05), (0.25±0.03), (0.56±0.06) of the si-HOTAIR group. The expression levels of these protein were significantly down-regulated in the si-HOTAIR group when compared with the control group and the si-RNA group ( P<0.05). The absorbance (A) values of SK-NEP-1 cells in the si-HOTAIR group at 24, 48 and 72 hours after transfection were (0.31±0.02), (0.37±0.04), (0.69±0.07), significantly lower than (0.49±0.05), (0.78±0.08), (1.22±0.14) in the control group and (0.57±0.06), (0.68±0.07), (0.94±0.09) in the si-RNA group ( P<0.05). The apoptosis rate in the si-HOTAIR group was (13.81±1.25)%, significantly higher than (6.54±0.72)% in the control group and (4.35±0.40)% in the si-RNA group ( P<0.05). The cell positive rate of TUNEL cells in the si-HOTAIR group was (35.14±3.50)%, significantly higher than (20.16±2.18)% in the control group and (21.09±2.35)% in the si-RNA group ( P<0.05). The median inhibitory concentration (IC 50) of the si-HOTAIR group was (62.48±5.97) μmol/L, significantly lower than (88.27±9.05) μmol/L of the control group and (92.50±9.11) μmol/L of the si-RNA group ( P<0.05). Conclusions:Suppression of LncRNA HOTAIR can inhibit the proliferation of Wilms tumor cells, promote cell apoptosis, decrease cell resistance to cisplatin. The mechanism may be related to the inhibition of Wnt/β-catenin signaling pathway activation.

Objective:To evaluate the efficacy of preoperative neoadjuvant chemoradiotherapy for low and locally advanced rectal cancer.Methods:Clinical data of 46 patients with low rectal tumors located within 6 cm from the edge of anal admitted to our hospital between February 2014 and December 2018 were retrospectively analyzed. SIB-IMRT technique was adopted for preoperative radiotherapy. Rectal tumors and positive lymph nodes were irradiated with a dose of 58.75 Gy in 25 fractions (2.35 Gy/fraction), and pelvic lymphatic drainage area was given with 50 Gy in 25 fractions (2.0 Gy/fraction). Oral administration of capecitabine was delivered for concurrent chemotherapy. Radical surgery for rectal cancer was performed at 6 to 12 weeks after the end of chemoradiotherapy. The overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), local recurrence-free survival (LRFS) and metastasis-free survival (MFS) were calculated by using Kaplan- Meier method. Univariate analysis was conducted by log-rank test, and multivariate analysis was performed by Cox’s regression model. Results:After a median follow-up of 47 months, local recurrence occurred in 3 patients and distant metastasis in 6 patients. The ypCR rate was 26%(12/46), the sphincter-preservation rate was 74%(34/46), the R 0 resection rate was 100%(44/44), the overall tumor response TN down staging rate was 87%(40/46), and the postoperative complication rate was 13%(6/46). The 3-year OS, DFS, and PFS were 93%, 91% and 87%, respectively. In univariate analysis, ypN staging was an important factor affecting OS, DFS, PFS, LRFS and MFS (all P<0.05). In multivariate analysis, ypN staging was significantly correlated with DFS, PFS, LRFS and MFS (all P<0.05). Conclusions:Preoperative SIB-IMRT 58.75 Gy in 25 fractions combined with capecitabine chemotherapy is a safe and efficacious treatment for patients with low and locally advanced rectal cancer, which improves the ypCR rate and quality of life, and yields tolerable adverse reactions. Nevertheless, the long-term survival benefits remain to be validated.

Objective:To understand the etiological characteristics of the patients with fever of unknown origin in Guizhou province through the isolation and identification of Leptospira interrogans and provide evidence for the control, prevention and treatment of human leptospirosis. Methods:Blood and urine samples were collected from patients with fever symptoms in Qiandongnan, an epidemic area, in Guizhou. The suspected Leptospira strains were primarily identified using pathogenic Leptospira specific G1/G2-PCR, and subsequently identified by using Leptospira serogroups specific PCR. The Leptospira strains were then genotyped with multiple locus sequence typing. MLST data based cluster analysis on the isolates and Leptospira reference strains of common serogroups were analyzed by using software NTsys 2.10e. Results:Three suspected strains of Leptospira were isolated from human blood samples, the isolation rate was 8.６%, which were designated as strain 17BX002, 17BX003 and 17AJX008. Strain 17BX002 was further identified as serogroup grippotyphosa by using Leptospira serogroup specific PCR, while the other two strains were negative (excluded as iterohaemorrhagiae, sejroe, canicola, autumnalis, grippotyphosa and hebdomadis). MLST genotyping showed that strain 17BX002 was typed as ST106, most closely clustered with Leptospira grippotyphosa, while strain 17BX003 and 17AJX008 were typed as ST96, the same as serogroup badaviae. Conclusion:There are leptospirosis cases in epidemic area of Guizhou in high incidence season, grippotyphosa and bataviae are the newly discovered serogroups of Leptospira in Guizhou.

Objective To assess the efficacy and side effects of intravesical instillation of BCG after transurethral resection of the bladder tumor (TURBT) in non-muscle invasive bladder cancer (NMIBC) patients.Methods The clinical data of patients treated with BCG 120 mg per course induced perfusion or more after TURBT from December 2013 to October 2016 in 18 hospitals of northeast China region,were analyzed retrospectively.The first part,data of 106 patients with moderate,high-risk NMIBC were collected.A total of 83 patients were male,while the other 23 patients were female.The average age was 66.7 years old.The clinical staging were T1 in 86(81.1％) cases,Ta in 20(18.9％) cases and carcinoma in situ in 6 (5.7％) patients.Intravesical instillation of BCG was executed after transurethral resection of the bladder tumor.The incidence rate of recurrence and progression during more than 6 months' follow-up time were observed.Multivariate analyses were done by using logistic analysis and Cox proportional hazards regression model with Kaplan-Meier method.The second part,treatment compliance of 276 patients with bladder cancer,including moderate/high-risk NMIBC in 263 cases,moderate/high-risk NMIBC followed with renal pelvis/ureteral carcinoma in 8 cases were and moderate/high-risk NMIBC with renal pelvis/ureteral carcinoma in 5 cases who treated with BCG after the surgeries,were observed.Patients consisted of 211 males and 65 females with average age of 68.3 years.Results With a median follow-up of 12 months,9 (8.5％) patients experienced tumor recurrence and 2 (1.9％) patients were found progression in the first part.The one-year cancer free recurrence rate of the patients was 91.5％.Statistically significant prognostic factors for recurrence identified by multivariable analyses were prior recurrence of the tumors (OR =3.214,95％CI0.804-12.845,P =0.099).In the second port,an incidence rate of adverse effects was 64.1％ (177/276).The Ⅲ/Ⅳ degree complications were occurred in 11 patients and satisfactory outcomes achieved with active treatment.A total of 36 patients withdrawal with the major causes were recurrence and progression of bladder tumor in 12 cases (4.4 ％),9 cases (3.3 ％) with economic reasons and 11 cases (4.0％) with serious complications.Conclusions NMIBC patients treated with intravesical BCG therapy have approving cancer free recurrence rates and acceptable adverse effects.Prior recurrence may be prognostic factor of recurrence after intravesical BCG therapy.