Objective To investigate the relationship between the expression of BRCA1,β-tubulin III (TUBB3) and their efficacies with platinum-based chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). Methods The expression levels of BRCA1 and TUBB3 were detected by immunohistochemistry. The relationship between BRCA1 and TUBB3 expressions and their efficacies were analyzed. Results The high expression rate of BRCA1 was 34.8%, and the efficacy of platinum-based chemotherapy in patients with BRCA1-lower expression is obviously better than that in patients with BRCA1-higher expression. There was a significant difference between these two groups (30.4%vs 67.4%, P=0.004). The effective rate of platinum-based chemotherapy in TUBB3-higher expression group and TUBB3-lower expression group were illustrated no significance (59.4% vs 50.0%, P=0.445). Conclusion Platinum-based chemotherapy is more suitable for the advanced NSCLC patients with lower expression of BRCA1. The expression level of BRCA1 could be used to predict the efficacy of platinum-based chemotherapy in advanced NSCLC patients.

Objective:To investigate the relationship between the activation level of Nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome and the change of cognitive functions in patients with acute ischemic stroke.Methods:A total of 88 patients with acute ischemic stroke in Department of Neurology from October 2018 to July 2020 were selected as case group and 100 healthy physical examinees were selected as control group.Peripheral blood of the case group and the control group was collected, and peripheral blood mononuclear cells (PBMCs) were isolated by centrifugation.Then the NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1 and interleukin-1β (IL-1β) expression were detected by Western blot.The cognitive function of patients with acute ischemic stroke was detected by Montreal Cognitive Assessment (MoCA). The differences in expression levels of NLRP3, ASC, Caspase-1 and IL-1β were compared between the case group and the control group.Pearson correlation analysis was used to analyze the correlation between expression levels of NLRP3, ASC, Caspase-1, IL-1β and MoCA score.Logistic multivariate regression was used to analyze the relationship between expression levels of NLRP3, ASC, caspase-1, IL-1β and the cognitive dysfunction.Results:(1)Western blot results showed that NLRP3, ASC, Caspase-1 and IL-1β expressions in PBMCs cells in the case group were higher than those in the control group (all P<0.05). (2)The expression level of NLRP3 in stroke patients with hypertension, hyperlipidemia, National Institutes of Health Stroke Scale (NIHSS) score ≥ 8 points was significantly higher than that in patients without hypertension, hyperlipidemia and NIHSS score<8 points ( P<0.05); (3)The incidence of cognitive dysfunction in the case group was 34.09% (30/88). The MoCA scores of the cognitive dysfunction group and the non-cognitive dysfunction group were 20 (24, 28) and 27 (26, 28) points respectively, and the difference between the groups was statistically significant ( P<0.05); (4)Pearson correlation analysis showed that NLRP3, ASC, caspase-1 and IL-1β expression in PBMCs cells were negatively correlated with MoCA scores ( r=-0.426, -0.396, -0.417, -0.320 respectively, all P<0.05). (5)Logistic regression analysis showed that hyperlipidemia, NIHSS scores, frontotemporal lobe infarction, and NLRP3 expression were the influencing factors for the occurrence of cognitive dysfunction (all P<0.05). Conclusion:Patients with acute ischemic stroke have high activated NLRP3 inflammasome, and its activation degree is closely related to the condition and the occurrence of cognitive dysfunction after stroke.Targeted inhibition or regulation of NLRP3 inflammasome activation may become a new idea of neuroprotection for acute ischemic stroke.

Objective To summarize the clinical,electrophysiological profile and prognosis in paraneoplastic syndrome with SRY-like high-mobility group superfamily of developmental transcription factors (SOX) 1 antibody.Methods The clinical profile,laboratory examination,electrophysiology,tumor,treatment and prognosis of three patients of paraneoplastic syndrome with SOX1 antibody in Tangdu Hospital,Air Force Military Medical University from 2016 to 2018 were retrospectively analyzed.Results Proximal lower limbs weakness was the first symptom in all the three patients,weakness normally spreading proximally to distally,involving feet and hands,finally reaching the oculobulbar region,and dry mouth was the most common autonomic dysfunction.Compound muscle action potential (CMAP) amplitude was low in all the patients,and the CMAP amplitude became even lower at low stimulating frequencies.An increase in CMAP amplitude with high-frequency stimulation was found in two patients during the follow-up.Lambert-Eaton myasthenic syndrome (LEMS) and motor axonal peripheral neuropathy were considered.Acetylcholine receptors antibody was positive in one case and voltage-gated calcium channel antibody was positive in another case.Two cases were found complicated with small cell lung carcinoma,one case with small cell carcinoma of the esophagus.After treatment of intravenous immunoglobulin,chemotherapy and pyridostigmine,the prognosis of the patients was different.Conclusions SOX1 antibody as an antibody in paraneoplastic syndrome,is most common in small cell lung cancer with LEMS,sometimes with axonal peripheral neuropathy.LEMS needs to be considered when patients manifest proximal limb weakness and dry mouth,and screening for tumors is needed.

A phytochemical investigation of the whole plant of Parasenecio rubescens(S.Moore)Y.L.Chen yielded 14 previ-ously undescribed,highly oxidized bisabolane-type sesquiterpenoids,named pararunines L-Y,along with one known oplopane-type sesquiterpenoid.The structural elucidation of these compounds was accomplished through comprehensive spectroscopic analysis,in-cluding nuclear magnetic resonance(NMR)and high-resolution electrospray ionization mass spectrometry(HR-ESI-MS)techniques.Motivated by traditional uses and previous studies on this genus,all isolated compounds were subjected to in vitro cytotoxicity assays against four human cancer cell lines(MCF-7,Hela,HCT116,and HT-29).Considering that the reported chemical constituents of nu-merous other species within this genus primarily consist of eremophilane-type sesquiterpenoids,our findings not only expand the struc-tural diversity of bisabolane-type sesquiterpenoids but also contribute valuable scientific evidence to the chemotaxonomy of this genus.

AIM:To explore the roles and associations of hepatocyte nuclear factor 4 alpha(HNF4A)and mu-protocadherin(MUCDHL)in the kidney of diabetic mice.METHODS:(1)A cohort of six 12-week-old db/m mice and six db/db mice were selected and maintained on a standard diet until 16 weeks.The protein levels of fibronectin(FN),collagen type III(Col-III),E-cadherin,α-smooth muscle actin(α-SMA),HNF4A,Snail and MUCDHL in renal tissues were scrutinized using Western blot.Immunohistochemical staining was conducted to observe the distribution and expres-sion of FN,HNF4A and MUCDHL.(2)Mouse renal tubular epithelial cells(mRTEC)were cultured in vitro and catego-rized into groups:normal glucose(NG)group,high glucose(HG)group,overexpression control groups(NG+vector and HG+vector),overexpression groups(NG+OE-MUCDHL,HG+OE-MUCDHL,NG+OE-HNF4A and HG+OE-HNF4A),knockdown control groups(NG+control and HG+control),and knockdown groups(NG+si-MUCDHL,HG+si-MUCDHL,NG+si-HNF4A and HG+si-HNF4A).The relevant protein levels were also detected by Western blot.RESULTS:(1)In db/db group,elevated body weight,blood glucose and urine albumin-to-creatinine ratio(UACR)indicated significant re-nal injury.Compared with db/m group,the mice in db/db group exhibited increased expression of FN,Col-III,α-SMA and Snail,and decreased expression of E-cadherin,HNF4A and MUCDHL.MUCDHL was predominantly expressed in the apical membrane of renal tubular epithelial cells,FN in the tubular mesenchyme,and HNF4A in the plasma and nu-cleus of renal tubular cells.(2)In HG group,there was an up-regulation in the expression of fibrosis-related proteins and a down-regulation in the expression of E-cadherin,HNF4A and MUCDHL compared with NG group.Overexpression of MUCDHL led to a decrease in the expression of FN,Col-III,α-SMA and Snail proteins,an increase in the expression of E-cadherin and MUCDHL proteins,and unaltered expression of HNF4A.Knockdown of MUCDHL resulted in a reversal of the aforementioned effects,with HNF4A expression remaining unaltered.Overexpression of HNF4A led to an increased ex-pression of MUCDHL,and the expression changes of the remaining indicators were consistent with the overexpression of MUCDHL.Knockdown of HNF4A reversed the aforementioned effects.MUCDHL may represent a downstream target gene of HNF4A.CONCLUSION:The diminished expression of HNF4A and MUCDHL in the renal tubules of diabetic mice implies their involvement in the progression of renal fibrosis in diabetic kidney disease(DKD).HNF4A may potentially impede the progression of renal fibrosis in DKD by up-regulating the expression of MUCDHL.