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BACKGROUND: Superficially invasive squamous cell carcinoma (SISCC) and high-grade squamous intraepithelial lesions (HSIL) involving the anal canal are rare, and their surgical management involves local excision. Endoscopic submucosal dissection (ESD) has recently emerged as a promising treatment. This study aimed to evaluate the feasibility and safety of ESD for SISCC and HSIL in the anal canal. METHODS: All patients diagnosed with SISCC or HSIL in the anal canal who underwent ESD between November 2018 and May 2023 were included. Patient age, sex, pathology, human immunodeficiency virus (HIV) status, human papillomavirus (HPV) status, T stage, en bloc rate, and R0 resection rate were analyzed. RESULTS: Ten patients, including two men and eight women, with a median age of 61 (51-68) years were enrolled. All patients were HIV-negative, but five (50%) were HPV-positive. Pathological examination showed tumor stage of two patients as T2, one as T0 of SISCC, and seven as Tis of HSIL. The median specimen and tumor sizes were 24 (6-65) mm and 18 (6-55) mm, respectively. The en bloc and R0 resection rates were 100% and 80%, respectively. No severe complications occurred and no recurrence was observed at the follow-up (median follow-up period, 9 (1-35) months). CONCLUSIONS: ESD is a reliable and minimally invasive procedure that enables more individualized treatment options for specific groups. As we were limited by the length of the observation period, the long-term performance of ESD for SISCC and HSIL involving the anal canal requires further investigation.

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OBJECTIVE: To evaluate the effects and safety of Tripterygium wilfordii polyglycoside (TWP) in the treatment of immunoglobulin A (IgA) nephropathy. SUBJECTS AND METHODS: A computer-assisted study search of Chinese Biomedical Database (CBM), Chinese Journal Full-text Database (CNKI), Wanfang Database, Chinese Scientific Journal Database (VIP), PubMed, Medline, EMBASE and Cochrane Library was performed, with the time range of retrieval set between the establishment of the database to December 31, 2019. Articles of randomized controlled trials on the treatment of IgA nephropathy by Tripterygium wilfordii polyglycoside were collected, and then screened according to the inclusion and exclusion criteria. Next, the quality of the papers was assessed, effective data were extracted, and a meta-analysis of the included studies was conducted using the Review Manager 5.3 software provided by the Cochrane Collaboration. RESULTS: Thirty randomized controlled trials (RCT) were included ultimately, and the meta-analysis showed that 1) Single (Sgl) TWP group was superior to angiotensin-converting enzyme inhibitor/angiotension receptor blocker (ACEI/ARB) group in terms of complete remission [odds ratio (OR) = 4.74, p-value < 0.00001], total remission (OR = 3.90, p-value < 0.0001), 24-hour proteinuria [mean difference (MD) = 1.18, p-value < 0.00001], and serum albumin (MD = - 8.23, p-value < 0.00001), and no significant difference in serum creatinine (MD = 2.09, p-value = 0.08) was found between Sgl TWP and control groups; TWP + ACEI/ARB group was superior in complete remission (OR = 2.57, p-value < 0.00001), total remission (OR = 4.36, p-value < 0.00001), serum albumin [standardized mean difference (SMD) = -0.68, p-value = 0.0005], 24-hour proteinuria (SMD = 1.24, p-value < 0.00001) and serum creatinine (SMD = 0.48, p-value = 0.006); 2) TWP group was superior to glucocorticoid group in complete remission (OR = 1.93, p-value < 0.0010), total remission (OR = 3.71, p-value < 0.00001), serum albumin (MD = -3.50, p-value = 0.002), 24-hour proteinuria (SMD = 0.93, p-value < 0.0001) and serum creatinine (SMD = 0.88, p-value = 0.006); 3) TWP group was better than mycophenolate mofetil (MMF) group in complete remission (OR = 2.05, p = 0.005), total remission (OR = 3.30, p-value = 0.002), 24-hour proteinuria (MD = 2.61, p-value < 0.0001), and serum albumin (MD = -6.43, p-value < 0.00001), but the differences in serum creatinine (MD = 1.28, p-value = 0.89) between TWP and control groups were not significant. Besides, TWP + ACEI/ARB group had a higher adverse reaction rate than the control group (OR = 2.21, p-value = 0.04), but there was no significant difference in the adverse reaction rate between other control and experimental groups (p-value > 0.05). CONCLUSIONS: The present evidence shows that Tripterygium wilfordii polyglycoside can effectively improve the remission rate, reduce proteinuria, and protect kidney function of IgA nephropathy patients, and also has good safety. However, limited by the quality of the included studies, the effects and safety of Tripterygium wilfordii polyglycoside in the treatment of IgA nephropathy need to be verified by more high-quality, large-scale, multi-center RCTs.

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PURPOSE: Chemoradiotherapy is regarded as a standard scheme for inoperable and unresectable esophageal cancers. Our aims were to explore the prognostic factors relevant to esophageal squamous cell carcinoma (ESCC) following intensity-modulated radiation therapy (IMRT) plus chemotherapy. MATERIAL AND METHODS: Totally 495 ESCC patients undergoing IMRT combined with chemotherapy in our hospital between 2011 and 2020 were retrospectively analyzed. Potential clinical prognosis-related factors were assessed by uni- and multivariate analyses. RESULTS: The median overall survival (OS) and progression-free survival (PFS) of the ESCC patients were 2.25 and 1.24years, respectively. Uni- and multivariate analyses demonstrated the relevant independent prognostic factors of OS and PFS were gender, T stage, N stage, clinical stage, and tumor location (P<0.05), but not chemotherapy or radiotherapy dose. We further compared the 5-year OS rates among different T stages, N stages, clinical stages, genders, and tumor locations. The survival rate at the higher clinical stage was significantly lower (P<0.001). The 5-year OS in the upper thorax of the tumor was 46.0% and exceeded other tumor locations (P<0.05). The 5-year OS was 56.1% among females and 33.3% among males (P=0.001). CONCLUSIONS: For ESCC patients receiving IMRT combined with chemotherapy, their long-term curative effects are influenced by T stages, N stages, clinical stages, genders, and tumor locations. ESCC patients who are females, or have upper thoracic tumor, or are at early clinical stage own better prognosis.

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OBJECTIVE: The aim of this study was to investigate the influences of the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway on preeclampsia rats as well as the proliferation and apoptosis of trophoblasts. MATERIALS AND METHODS: A proper number of conceived rats were applied to prepare the preeclampsia model (group P). Meanwhile, others were enrolled as control group (group C). The differences in placental structure between the two groups were compared via hematoxylin-eosin (HE) staining. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were compared between the two groups as well. In addition, T25 cell lines were divided into three groups, including Control group, hypoxia/reoxygenation (H/R) group and H/R + Staurosporine group (an activator of the ERK1/2 signaling pathway). The protein expression of phosphorylated (p)-ERK1/2 in the aforementioned model groups and cells was detected through Western blotting. Cell apoptosis rate was determined by a flow cytometer. Moreover, methyl thiazolyl tetrazolium was utilized to measure the proliferative capacity of trophoblasts in the three groups. Transwell chamber assay was adopted to count the transmembrane cells. RESULTS: The cells in group P were arranged disorderly. Group P had remarkably lower SOD activity but higher MDA content than group C (p<0.05). The protein expression levels of ERK1/2 and p-ERK1/2 in the placenta of group C were evidently higher than those of group P (p<0.05). Besides, the protein expression levels of ERK1/2 and p-ERK1/2 were markedly up-regulated in Control group when compared with H/R + Staurosporine group, with the lowest in H/R group (p<0.05). The proliferative capacity of cells was gradually enhanced in the three groups with the increase of culture time. Cell proliferation was the strongest in Control group, followed by H/R + Staurosporine group and H/R group (p<0.05). The apoptosis and death rates of cells were the highest in H/R group, followed by H/R + Staurosporine group and Control group (p<0.05). However, the number of transmembrane cells was the largest in Control group, followed by H/R + Staurosporine group and H/R group (p<0.05). CONCLUSIONS: The ERK1/2 signaling pathway is associated with preeclampsia in rats, whose activation can enhance cell proliferation and weaken cell apoptosis.

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OBJECTIVE: To investigate the application value of the technique of fracture body surface localization film combined with CT volume rendering in the selection of minimally invasive incision for internal fixation of rib fractures. PATIENTS AND METHODS: Clinical data of 55 cases of patients who underwent internal fixation for rib fracture in our hospital from June 2019 to April 2020 were selected. The differences in the accuracy of preset incision, incision length, operation time, intraoperative blood loss, postoperative wound drainage, and postoperative pain score between the group with fracture body surface localization film combined with CT volume rendering (n=32) and the group with traditional localization method (n=23). RESULTS: Compared with traditional localization method, fracture body surface localization film combined with CT volume rendering could improve the accuracy of surgical incision, reduce the operation time, incision length, intraoperative blood loss, postoperative wound drainage, and postoperative pain score (p<0.05). CONCLUSIONS: The application of fracture body surface localization film combined with CT volume rendering has obvious effects on the accurate selection of incision of rib fracture internal fixation, and it is an effective method that is worthy of promotion.

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OBJECTIVE: To evaluate the comparative safety of biological treatment in patients with axial spondyloarthritis (axSpA) enrolled in randomized controlled trials (RCTs) with placebo. MATERIALS AND METHODS: Studies were systematically retrieved from the Web of Science, PubMed, Cochrane Library, and Embase databases. The last search was performed on 8 June 2020. The primary outcome measures were adverse events (AEs), serious AEs, infection, serious infection, and discontinuation due to AEs. This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: A total of twenty-two trials, including 2599 participants treated with biologics and 1547 participants treated with placebo, met the inclusion criteria. There was a significantly higher risk of infection, AEs, and discontinuation due to AEs in the biologics groups compared to the placebo groups [risk ratio (RR) = 1.38, 95% confidence interval (95% CI) = 1.22-1.57, p < 0.01; RR = 1.17, 95% CI = 1.10-1.25, p < 0.01; and RR = 1.72, 95% CI = 1.03-2.87, p = 0.04, respectively], and low heterogeneity was found among the included studies (I2 = 0%, p = 0. 49; I2 = 29%, p = 0.10; and I2 = 0%, p = 0.79, respectively). The risk of serious infection and serious AEs was not significantly different between axSpA patients treated with biologics and those treated with placebo [RR = 1.62, 95% CI = 0.54-4.90, p = 0.39 and RR = 1.17, 95% CI = 0.79-1.73, p = 0.44]. Low heterogeneity was found among the included studies (I2 = 0%, p = 0.94 and I2 = 0%, p = 0.69). The subgroup analyses based on tumour necrosis factor inhibitors and interleukin antagonists did not yield significant differences. CONCLUSIONS: This meta-analysis is the first comprehensive assessment of the safety of various biological agents in axSpA patients. The use of biological agents in axSpA is generally safe and tolerable.

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OBJECTIVE: To observe the intervention effect of circular ribonucleic acid (circRNA) 010567 on myocardial infarction (MI)-induced myocardial fibrosis (MF) in rats, and to explore whether its mechanism of action is related to the regulation on the transforming growth factor-ß1 (TGF-ß1) signaling pathway. MATERIALS AND METHODS: The rat model of acute MI was established using ligation of the left anterior descending coronary artery. Model rats were randomly divided into circRNA 010567 siRNA group and Model group, with sham operation group as Control group. The effects of circRNA 010567 on the cardiac function, MF, myocardial apoptosis, mRNA, and protein expression levels of TGF-ß1 and Smad3 in heart tissues of MI rats were detected using the small animal ultrasound system, Masson staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, reverse transcription-polymerase chain reaction (RT-PCR), and Western blotting, respectively. RESULTS: Compared with Control group, Model group had significantly decreased cardiac function, significantly lower left ventricular ejection fraction (LVEF), and left ventricular fractional shortening (LVFS), markedly increased left ventricular end-diastolic diameter (LVDd), and left ventricular end-systolic diameter (LVDs), severe MF, as well as a significantly higher apoptosis rate of myocardial cells, and evidently increased mRNA and protein levels of TGF-ß1 and Smad3 in heart tissues. Compared with Model group, circRNA 010567 siRNA group had evidently improved cardiac function, significantly higher LVEF and LVFS, markedly decreased LVDd and LVDs, alleviated MF, a significantly lower apoptosis rate of myocardial cells, and evidently decreased mRNA and protein levels of TGF-ß1 and Smad3 in heart tissues. CONCLUSIONS: CircRNA 010567 siRNA can improve the cardiac function, alleviate the MF, and inhibit the myocardial apoptosis, thereby further suppressing MI-induced MF, whose mechanism may be related to the inhibition on the TGF-ß1 signaling pathway.

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Neopterin is primarily synthesized and released by activated macrophages/monocytes upon stimulation with interferon-γ and is considered as a marker for macrophage activation. This study aimed to analyze the serum levels of neopterin in patients with dermatomyositis (DM) in association with clinical manifestations, laboratory data and patient prognosis. One hundred and eighty-two consecutive DM patients and 30 healthy controls were retrospectively enrolled into the study. Serum levels of neopterin were significantly increased in DM patients compared to healthy controls (P < 0·001). High serum neopterin levels were associated with anti-melanoma differentiation-associated gene (MDA5) antibody, rapidly progressive interstitial lung disease (RP-ILD) and characteristic DM cutaneous involvement. Longitudinal assessment of serum samples revealed that the serum neopterin levels were closely correlated with disease severity (ß = 30·24, P < 0·001). In addition, a significant increase in serum neopterin concentration of non-survivors was observed when compared to that of survivors (P < 0·001). Receiver operator characteristic curves showed that serum neopterin could distinguish non-survivors and survivors at an optimal cut-off level of 22·1 nmol/l with a sensitivity and specificity of 0·804 and 0·625, respectively (P < 0·001). Kaplan-Meier survival curves revealed that DM patients with serum neopterin > 22·1 nmol/l had a significantly higher mortality compared to the patient group with serum neopterin < 22·1 nmol/l (log-rank P < 0·001). Multivariate regression analysis identified high serum neopterin concentration to be an independent risk factor for poor prognosis in DM (adjusted hazard ratio = 4·619, 95% confidence interval = 2·092-10·195, P < 0·001). In conclusion, increased serum levels of neopterin were significantly associated with RP-ILD and reduced survival in DM patients, suggesting it as a promising biomarker in disease evaluation of DM.

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OBJECTIVE: To elucidate whether circHIPK3 could inhibit proliferation and induce apoptosis of cardiomyocytes via binding to miRNA-124-3p, thus aggravating myocardial ischemia/reperfusion (IR) injury. MATERIALS AND METHODS: CircHIPK3 expression in HCM cells simulated with myocardial I/R was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Influences of circHIPK3 on myocardial injury marker levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in the in vitro model of myocardial I/R were evaluated using the relative commercial kits. The regulatory effects of circHIPK3 on proliferative ability and apoptosis of simulated HCM cells were examined by Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. Dual-Luciferase reporter gene assay was conducted to verify the binding of circHIPK3 to miRNA-124-3p. Finally, the roles of the circHIPK3/miRNA-124-3p axis in regulating apoptotic gene expressions and cardiomyocyte repair after myocardial I/R were explored. RESULTS: CircHIPK3 was highly expressed in HCM cells with simulated myocardial I/R relative to those with normoxic treatment. The overexpression of circHIPK3 in simulated HCM cells decreased levels of LDH, SOD and GSH-PX, whereas increased the MDA level. Inhibited proliferation and accelerated apoptosis were observed in simulated HCM cells overexpressing circHIPK3. Western blot analyses illustrated that circHIPK3 overexpression upregulated pro-apoptotic Bax, and downregulated anti-apoptotic Bcl-2. Subsequently, we confirmed the binding between circHIPK3 and miRNA-124-3p. Rescue experiments demonstrated that circHIPK3 overexpression reversed the protective effects of miRNA-124-3p on myocardial I/R and cardiomyocyte apoptosis. CONCLUSIONS: CircHIPK3 inhibits proliferative ability and induces apoptosis of cardiomyocytes after myocardial I/R injury by binding to miRNA-124-3p, which may serve as a potential therapeutic target for I/R.

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OBJECTIVE: The aim of this study was to investigate the effects of butylphthalide on oxidative stress and inflammatory response in rats with myocardial infarction through the protein kinase B/nuclear factor E2-related factor 2 (Akt/Nrf2) signaling pathway. MATERIALS AND METHODS: A total of 36 Sprague-Dawley rats were randomly divided into three groups, including sham group (n=12), model group (n=12) and butylphthalide group (n=12). In the sham group, the heart was exposed, and normal saline was intraperitoneally injected after the operation. In the model group, acute myocardial infarction (AMI) model was established, and normal saline was intraperitoneally injected after the operation. In the butylphthalide group, AMI model was established, and butylphthalide was intraperitoneally injected after the operation. After intervention for 4 weeks, the rats were killed, and the samples were collected. The morphology of heart tissues was observed via hematoxylin-eosin (HE) staining. The expression of nicotinamide adenine dinucleotide phosphate oxidase-1 (NOX-1) was detected via immunohistochemistry. The protein expressions of phosphorylated Akt (p-Akt) and p-Nrf2 were detected via Western blotting. Moreover, the content of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) was detected via enzyme-linked immunosorbent assay (ELISA). The messenger ribonucleic acid (mRNA) expression levels of IL-1ß, TNF-α and NOX-1 were detected via quantitative Polymerase Chain reaction (qPCR). Furthermore, the apoptosis rate of the cells was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. RESULTS: The morphology of heart tissues was significantly damaged in the model group and butylphthalide group compared with the sham group. However, it was significantly improved in the butylphthalide group when compared with the model group. The expression level of NOX-1 increased markedly in the model group and butylphthalide group compared with the sham group (p<0.05). However, it was remarkably reduced in the butylphthalide group compared with the model group (p<0.05). Meanwhile, the protein expression levels of p-Akt and p-Nrf2 were significantly higher in the model group and butylphthalide group than those of the sham group (p<0.05). However, the protein expression levels of p-Akt and p-Nrf2 in the butylphthalide group were remarkably lower than the model group (p<0.05). The mRNA expression levels of IL-1ß, TNF-α and NOX-1 were markedly higher in the model group and butylphthalide group than those of the sham group (p<0.05). However, they remarkably declined in the butylphthalide group compared with the model group (p<0.05). In addition, the content of IL-1ß and TNF-α increased in the model group and butylphthalide group when compared with the sham group (p<0.05). The content of IL-1ß and TNF-α in the butylphthalide group was significantly lower than the model group (p<0.05). Furthermore, the apoptosis rate was significantly higher in the model group and butylphthalide group than the sham group (p<0.05), which was significantly lower in the butylphthalide group than the model group (p<0.05). CONCLUSIONS: Butylphthalide inhibits inflammatory and oxidative stress responses after AMI by regulating the Akt/Nrf2 signaling pathway, thereby inhibiting myocardial apoptosis and benefiting the morphological repair of myocardial tissues.

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BACKGROUND: Postoperative complications have a great impact on the postoperative course and oncological outcomes following major cancer surgery. Among them, infective complications play an important role. The aim of this study was to evaluate whether postoperative infective complications influence long-term survival after liver resection for hepatocellular carcinoma (HCC). METHODS: Patients who underwent resection with curative intent for HCC between July 2003 and June 2016 were identified from a multicentre database (8 institutions) and analysed retrospectively. Independent risk factors for postoperative infective complications were identified. After excluding patients who died 90 days or less after surgery, overall survival (OS) and recurrence-free survival (RFS) were compared between patients with and without postoperative infective complications within 30 days after resection. RESULTS: Among 2442 patients identified, 332 (13·6 per cent) had postoperative infective complications. Age over 60 years, diabetes mellitus, obesity, cirrhosis, intraoperative blood transfusion, duration of surgery exceeding 180 min and major hepatectomy were identified as independent risk factors for postoperative infective complications. Univariable analysis revealed that median OS and RFS were poorer among patients with postoperative infective complications than among patients without (54·3 versus 86·8 months, and 22·6 versus 43·2 months, respectively; both P < 0·001). After adjustment for other prognostic factors, multivariable Cox regression analyses identified postoperative infective complications as independently associated with decreased OS (hazard ratio (HR) 1·20, 95 per cent c.i. 1·02 to 1·41; P = 0·027) and RFS (HR 1·19, 1·03 to 1·37; P = 0·021). CONCLUSION: Postoperative infective complications decreased long-term OS and RFS in patients treated with liver resection for HCC.

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OBJECTIVE: The aim of this study was to investigate the expression levels of toll-like receptor 9 (TLR9) and interleukin-23 (IL-23) in renal tissue and serum of patients with lupus nephritis (LN), and to explore their clinical correlation. PATIENTS AND METHODS: LN patients and healthy controls were enrolled in the experimental group and the control group, respectively. Blood samples, serum, and peripheral blood mononuclear cells (PBMCs) were collected. Renal lesion tissues and adjacent normal tissues of LN patients were harvested from a renal tissue biopsy. Serum level of IL-23 was detected by enzyme-linked immunosorbent assay (ELISA). Expression of IL-23 in PBMCs was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively. Meanwhile, TLR9 expression in renal tissues was accessed by immunohistochemistry staining. Subsequently, 24-h protein urine, renal tubular pathological activity index, erythrocyte sedimentation rate (ESR), serum complement C3 level, and blood albumin level of LN patients were recorded. Also, the correlation between TLR9 expression and these pathological indexes was measured by correlation analysis. RESULTS: Serum level of IL-23 in LN patients was significantly higher than that of healthy controls. Similarly, the mRNA and protein expressions of IL-23 in PBMCs of LN patients were markedly higher than those of healthy controls. IL-23 expression was positively correlated with renal tubular pathological activity index of LN patients. Meanwhile, TLR9 was highly expressed in renal tissues of LN patients. Furthermore, TLR9 expression was positively correlated with 24-h protein urine, renal tubular pathological activity index and ESR, whereas negatively correlated with serum complement C3 level and blood albumin level of LN patients. CONCLUSIONS: IL-23 is highly expressed in the serum of LN patients, and its expression is closely related to the occurrence of LN. Also, the expression of TLR9 is up-regulated in the tubulointerstitium of LN patients, which is correlated with relevant clinical indexes.

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Background: The safety and efficacy of sublingual immunotherapy (SLIT) have been confirmed by many studies. However, in China, the research on efficacy and safety in young and older children with allergic rhinitis (AR) is still rare. Objective: The aim of this retrospective study is to evaluate the efficacy and safety of SLIT with Dermatophagoides farinae drops in pre-school and school-age children with AR. Methods: A total of 282 subjects aged 2-13 years with AR received a two-year course of sublingual immunotherapy along with pharmacotherapy. According to the age, patients were defined as the pre-school group (2-6 years old, n = 116) and school-age group (7-13 years old, n = 166). Total nasal rhinitis symptom scores (TNSS), visual analogue score (VAS) and total medication scores (TMS) were evaluated at four time points: baseline, after SLIT for half a year, one year and two years. The adverse events (AEs) were evaluated at each visit. Results: After two-year SLIT, the four rhinitis symptom scores, TNSS, VAS and TMS scores were significantly lower than baseline (all P < 0.05). The comparison of efficacy between one and two-year duration showed no significant difference in global clinical outcomes (all P > 0.05). In addition, there were no significant differences between the pre-school and school-age group in TNSS (all P > 0.05), VAS (all P > 0.05) and TMS scores (P > 0.05) after SLIT for half a year, one year and two years. No severe systemic AEs were reported. Conclusion: SLIT with D. farinae drops is clinically effective and safe in pre-school and school-age patients with house dust mites (HDMs)-induced AR (AU)

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The rat orthotopic liver transplantation model with extremely short anhepatic phase was established to study its protective effect on the recipients and graft. One hundred fifty adult male Wistar rats were randomly divided into three groups: group A (n = 30), using magnetic rings for the suprahepatic vena cava reconstruction; group B (n = 30), using 7/0 Prolene sutures for suprahepatic vena cava running anastomosis as control; and a sham-operated group (n = 30) as a blank control group. The changes in liver enzyme, serum creatinine, endotoxin, and cytokine levels and histopathology were recorded. The serum creatinine, potassium, alanine transaminase, and alkaline phosphatase levels at different points in time in group A were lower than those in group B (P < .05). The level of portal vein blood endotoxin in group A was significantly lower than that in group B at each point (P < .01). At the same time, all the cytokines in group B were higher than those in group A, and the two groups were higher than those in the sham operation group. The mean levels of tumor necrosis factor-α (TNF-α), interferon-γ, (IFN-γ), and interleukin-1ß (IL-1ß) at 3 hours were higher than at 6 hours in group A. IL-10 and tissue inhibitor of metalloproteinase-1 (TIMP-1) were all higher at 3 hours in groups A and B. Levels of monocyte chemotactic protein-1, L-selectin, and TIMP-1 in group A and IL-10, monocyte chemotactic protein-1, L-selectin, and TIMP-1 in group B were higher in blood than in the liver. Levels of TNF-α, IFN-γ, IL-1, IL-10, and intracellular adhesion molecule-1 in group A and TNF-α, IFN-γ IL-1ß, and intracellular adhesion molecule-1 in group B were higher in the liver than in blood. We conclude that the extremely short anhepatic phase has protective effects on recipients and grafts in rat liver transplantation because it is related to alleviating ischemia-reperfusion injury and reducing the endotoxin release.

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BACKGROUND: The safety and efficacy of sublingual immunotherapy (SLIT) have been confirmed by many studies. However, in China, the research on efficacy and safety in young and older children with allergic rhinitis (AR) is still rare. OBJECTIVE: The aim of this retrospective study is to evaluate the efficacy and safety of SLIT with Dermatophagoides farinae drops in pre-school and school-age children with AR. METHODS: A total of 282 subjects aged 2-13 years with AR received a two-year course of sublingual immunotherapy along with pharmacotherapy. According to the age, patients were defined as the pre-school group (2-6 years old, n=116) and school-age group (7-13 years old, n=166). Total nasal rhinitis symptom scores (TNSS), visual analogue score (VAS) and total medication scores (TMS) were evaluated at four time points: baseline, after SLIT for half a year, one year and two years. The adverse events (AEs) were evaluated at each visit. RESULTS: After two-year SLIT, the four rhinitis symptom scores, TNSS, VAS and TMS scores were significantly lower than baseline (all P<0.05). The comparison of efficacy between one and two-year duration showed no significant difference in global clinical outcomes (all P>0.05). In addition, there were no significant differences between the pre-school and school-age group in TNSS (all P>0.05), VAS (all P>0.05) and TMS scores (P>0.05) after SLIT for half a year, one year and two years. No severe systemic AEs were reported. CONCLUSION: SLIT with D. farinae drops is clinically effective and safe in pre-school and school-age patients with house dust mites (HDMs)-induced AR.

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OBJECTIVE: To investigate the anti-tumor effect and potential mechanism of dopamine combined with 5-FU in colon cancer. MATERIALS AND METHODS: Babl/c F1 generation male mice (N = 60) were inoculated with mouse C26 colon cancer cells below the pit to construct colon cancer model. Tumor-bearing mice were then divided into 4 groups (N = 8 each): model control group, dopamine group, 5-FU group and dopamine combined with 5-FU group. Dopamine (100 mg/kg/d) was intraperitoneally injected into mice. The tumor-suppressing rate was calculated. Serum VEGF concentration was gained. Tumor tissues were subjected to HE staining. KLF2 expression was determined by immunohistochemical (IHC) staining. In vitro cultured C26 cells which treated with dopamine and cell apoptosis were analyzed by flow cytometry. RESULTS: Compared with model control group, all treatment groups showed significantly decreased tumor weight and volume (p < 0.01), increased tumor necrosis (p < 0.05), reduced serum VEGF concentration (p < 0.05), and enhanced KLF2 expression in microvessels (p < 0.05). Combined treatment in terms of dopamine combined with 5-FU had the most pronounced effect compared with both dopamine and 5-FU treatment groups individually. Dopamine single t 5-FU and 5-FU groups showed a similar proportion of viable C26 cells (p > 0.05). CONCLUSIONS: Dopamine exerts anti-tumor effects by modulating tumor vascular homeostasis through the KLF2 signaling pathway, and potentiates the treatment efficacy of anti-tumor drug 5-FU. Our study discovered clinical significance concerning the novelty of therapeutic strategy against colon cancer.

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Multilocus genome-wide association studies (GWAS) have become the state-of-the-art procedure to identify quantitative trait nucleotides (QTNs) associated with complex traits. However, implementation of multilocus model in GWAS is still difficult. In this study, we integrated least angle regression with empirical Bayes to perform multilocus GWAS under polygenic background control. We used an algorithm of model transformation that whitened the covariance matrix of the polygenic matrix K and environmental noise. Markers on one chromosome were included simultaneously in a multilocus model and least angle regression was used to select the most potentially associated single-nucleotide polymorphisms (SNPs), whereas the markers on the other chromosomes were used to calculate kinship matrix as polygenic background control. The selected SNPs in multilocus model were further detected for their association with the trait by empirical Bayes and likelihood ratio test. We herein refer to this method as the pLARmEB (polygenic-background-control-based least angle regression plus empirical Bayes). Results from simulation studies showed that pLARmEB was more powerful in QTN detection and more accurate in QTN effect estimation, had less false positive rate and required less computing time than Bayesian hierarchical generalized linear model, efficient mixed model association (EMMA) and least angle regression plus empirical Bayes. pLARmEB, multilocus random-SNP-effect mixed linear model and fast multilocus random-SNP-effect EMMA methods had almost equal power of QTN detection in simulation experiments. However, only pLARmEB identified 48 previously reported genes for 7 flowering time-related traits in Arabidopsis thaliana.

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OBJECTIVES: Polymorphisms of IKAROS family zinc finger 1 (IKZF1) have been found to be associated with systemic lupus erythematosus (SLE) by genome-wide association studies (GWAS). The aim of the current study was to investigate the association between IKZF1 functional variants and lupus nephritis (LN) in a northern Han Chinese population and analyse their relationship with clinical and pathological phenotypes in LN. METHOD: The association between IKZF1 functional variants and LN was analysed for the lead variant rs1456896 with both GWAS and expression quantitative trait loci (eQTL) top hits in 500 LN patients and 500 healthy controls. Replication was conducted in an independent cohort comprising 798 LN patients and 704 healthy controls. Using the ENCODE (Encyclopedia of DNA Elements) databases, functional annotations and differential gene expression data were evaluated. RESULTS: A significant association between the single nuclear polymorphism (SNP) rs1456896 and susceptibility to LN was observed in the two different cohorts (p = 9.32 × 10-3 and p = 3.00 × 10-2) and reinforced in combination (p = 1.36 × 10-3). In silico analysis indicates that rs1456896 is a regulatory variant and lower mRNA expressions of IKZF1 were observed in both peripheral blood mononuclear cells (PBMCs) and renal biopsies from SLE patients compared to normal controls. Although patients with the protective genotype AA of rs1456896 seemed to have more pronounced clinical manifestations and a lower ratio of histological classes III and IV, no significant associations between rs1456896 genotypes and sub-phenotypes of LN were detected. CONCLUSIONS: Our results suggest that the rs1456896 A allele is associated with protective susceptibility to LN. However, this association did not seem to be implicated in the disease and histopathological severity of LN in the current population.

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OBJECTIVE: Breast cancer is one of the most aggressive and pervasive cancers identified in females. Dexmedetomidine (Dex) is an efficient anesthetic used in surgery. Our study aimed to explore the role of Dex in the malignancy of breast cancer cells in vitro and in vivo. Further, we investigate the molecular mechanism involved in the function of Dex on breast cancer cells. MATERIALS AND METHODS: The methyl thiazolyl tetrazolium (MTT) assay was applied to detect cell proliferation. The migration and invasion capacity of MDA-MB-231 cells was tested by wound healing assay and transwell assay. Western blot analysis was performed to quantify the protein expression levels of α2-adrenoceptor and ERK. RESULTS: The proliferation, migration and invasion ability of MDA-MB-231 cells was gradually increased after treatment of Dex in a dose-dependent manner in vitro. In addition, Dex could significantly elevate the volume and weight of xenotransplant tumor in vivo. Furthermore, Dex up-regulated the protein level of a2-adrenoceptor and consistently enhanced the phosphorylation of ERK without changing the total level of it. Similarity, over-expression of a2-adrenoceptor via its agonist Clonidine could mimic the function of Dex on breast cancer. CONCLUSIONS: These data suggest that Dex could promote the proliferation, migration and invasion of breast cancer cells through the activation of α2B-adrenoceptor /ERK signaling.

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