ObjectiveTo elucidate the expression patterns of CYHR1 in colorectal cancer （CRC） and its regulatory role in tumour cell proliferation and metastasis-related phenotypes. MethodsExpression differences of CYHR1 between colorectal cancer tissues and adjacent normal tissues were analyzed using data from The Cancer Genome Atlas （TCGA） database， and the association between CYHR1 expression and patient survival was evaluated. A CRC cell model with CYHR1 overexpression was established， and changes in the expression of related molecules were verified by quantitative real-time PCR （qRT-PCR）. Cell proliferation and metastatic potential were assessed using MTT assays， colony formation assays， and Transwell migration and invasion assays to evaluate the effects of CYHR1 and MALAT1 on CRC cell proliferation and migration/invasion， including combined intervention experiments. ResultsDatabase analysis revealed that CYHR1 is significantly overexpressed in CRC tissues， and that this overexpression is significantly associated with poorer overall survival. Compared with normal control cells， mRNA expression levels of CYHR1 were markedly elevated in CRC cell lines （HCT116， RKO， etc.） （P=0.002； P=0.006）. Functional experiments demonstrated that CYHR1 overexpression significantly promoted the proliferation （P＜0.001）， colony formation （P＜0.001）， migration （P=0.002） and invasive capacity （P=0.002） of HCT116 cells； whereas knockdown of either CYHR1 or MALAT1 inhibited CRC cell proliferation and reduced their migration （P=0.006） and invasive capacity （P=0.006）. In the context of CYHR1 overexpression， combined knockdown of MALAT1 partially reversed the promotional effect of CYHR1 on CRC cell proliferation， migration and invasion （P＜0.001； P=0.001）. Mechanistic studies further revealed that CYHR1 overexpression upregulates MALAT1 mRNA expression levels （P＜0.001）， whilst CYHR1 knockdown leads to downregulation of MALAT1 expression （P＜0.001）； MALAT1 knockdown likewise downregulates CYHR1 expression， suggesting a mutually reinforcing positive regulatory relationship between the two. Furthermore， CYHR1 can activate the IL-6/STAT3 signalling axis， whilst knockdown of IL-6 or STAT3 inhibited the upregulation of MALAT1 expression by CYHR1 （P=0.031； P=0.006）. ConclusionCYHR1 is abnormally overexpressed in colorectal cancer and is closely associated with poor prognosis. CYHR1 may promote the proliferation， migration， and invasion of colorectal cancer （CRC） cells by activating the IL-6/STAT3/MALAT1 axis.

Background and aim:Few studies have reported hepatitis B surface antigen(HBsAg)kinetics after nucleos(t)ide analog(NA)discontinuation in patients with noncirrhotic chronic hepatitis B(CHB).The study specifically investigated long-term HBsAg kinetics after NA discontinuation. Methods:Between January 2014 to January 2024,this study prospectively enrolled 106 outpatients with noncirrhotic CHB who met the discontinuation criteria after NA consolidation treatment.Demographic,clinical,and laboratory data were collected and analyzed after NA discontinuation. Results:Ninety-six patients who finished 5 years of follow-up were included.HBsAg remained unde-tectable in 29 patients with end of treatment(EOT)HBsAg negativity.Among 67 patients with EOT HBsAg positivity,HBsAg seroclearance occurred in 12(17.9％)patients with an estimated annual inci-dence of HBsAg seroclearance of 3.6％.Patients with EOT HBsAg levels of ≤1000 IU/mL had a higher HBsAg seroclearance rate than those with EOT HBsAg levels of＞1000 IU/mL(33.3％vs.5.4％).The pro-portion of patients with HBsAg ≤1000 IU/mL increased during follow-up.Logistic regression analysis indicated that the EOT HBsAg level was an independent factor for HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL.The optimal EOT HBsAg cutoff for both HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL was 359 IU/mL. Conclusions:Patients with EOT HBsAg negativity experienced no relapse and maintained HBsAg sero-clearance during 5 years of follow-up after NA discontinuation.A higher HBsAg seroclearance rate can be obtained in patients with EOT HBsAg levels of ≤1000 IU/mL during 5 years of follow-up after NA discontinuation.Close monitoring and proper NA retreatment are recommended to guarantee the safety of NA discontinuation.

Objective To investigate the relationship between plasma homocysteine (Hcy) and cognitive impairment so as to provide basis for dementia prevention.Methods Subjects at high risk for stroke were selected from the Screening and Prevention Program of Stroke (organized by the Ministry of Health,from August to December,2012) in Yanta area,Xi' an.Fasting blood was taken from cubital vein to measure Hcy.When Hcy＞ 15 μmol/L was defined as hyperhomocysteinmia,Hcy in the range of 16-30 μ mol/L was considered mild,≥31 μ mol/L as moderate-severe hyperhomocysteinemia.The cognitive function was evaluated by the Mini Mental State Examination (MMSE).MMSE grades under normal value were defined as cognitive impairment.Results 393 subjects were randomly recruited,including 173 men (44.0％) and 220 women (56.0％).Number of cases with cognitive impairment was 70 (17.8％ of the total subjects),with hyperhomocysteinmia was 220 (56.0％ of the total subjects).The prevalence of cognitive impairment did not show significant difference with hyperhomocysteinemia or normal Hcy group (16.8％ vs.19.1％,P ＞ 0.05),neither with mild and moderate-severe hyperhomocysteinemia group (17.0％ vs.16.3％,P＞0.05).Results from Spearman correlation analysis indicated that there was no correlation between MMSE grades and Hcy (rs=-0.01,P=0.85).Prevalence of cognitive impairment in the smoking group was higher than that in the non-smoking group(21.3％ vs.7.8％,P＜0.01),but higher in hypertension group than that in the normal blood pressure group (21.7％ vs.8.0％,P＜0.01).In the stroke group,prevalence of cognitive impairment was seen higher than that in the non-stroke group (25.3％ vs.15.4％,P＜0.05).Based on the results from Binary logistic regression,cognitive impairment appeared to be associated with the levels of education (OR=0.90,95％ CI:0.81-0.98,P=0.02),histories of hypertension (OR=1.02,95％CI:1.01-1.04,P=0.01) and stroke (OR=1.86,95％CI:1.04-3.33,P=0.04),but there was no correlation seen between Hcy and cognitive impairment (OR=0.90,95％ CI:0.51-1.58,P=0.71).Conclusion Plasma homocysteine did not seem a risk factor for cognitive impairment.