Objective:To investigate the anti-tumor effect of the Histone Deacetylase 6 (HDAC6) inhibitor ACY-738 and its underlying mechanisms in Diffuse Large B-cell Lymphoma (DLBCL) .Methods:The expression of HDAC6 in various tumors and DLBCL was analyzed using bioinformatics. DLBCL cells were treated with different concentrations of ACY-738. Cell viability, DNA synthesis, and clone formation were assessed by CCK-8 assay, EdU assay, and soft agar assay, respectively. Intracellular reactive oxygen species (ROS) levels were detected by fluorescence microscopy. Morphological changes in cells were observed using transmission electron microscopy (TEM). Mitochondrial ROS levels and apoptosis were measured by flow cytometry. The expression levels of apoptosis-related and autophagy-related proteins were detected by Western blotting.Results:HDAC6 was highly expressed in DLBCL ( P<0.05). ACY-738 inhibited the proliferation, DNA synthesis, and colony formation of DLBCL cells in a dose-dependent manner ( P<0.05). Treatment with ACY-738 increased intracellular and mitochondrial ROS levels in DLBCL cells in a dose-dependent manner ( P<0.05). TEM revealed that after ACY-738 treatment, mitochondria in cells were swollen and ruptured, mitochondrial cristae were reduced or absent, autolysosomes appeared, and features characteristic of apoptosis were observed. Western blotting showed that after ACY-738 treatment, the expression of the anti-apoptotic protein BCL-2 was downregulated, while the expression of Cleaved-PARP, Cleaved caspase-3, and BAX was upregulated ( P<0.05). The expression of autophagy-related proteins Atg7, Atg3, LC3B, and P62 was downregulated, and the expression of acetylated P53 protein was upregulated ( P<0.05) . Conclusion:The HDAC6 inhibitor ACY-738 induces mitochondria-dependent apoptosis and autophagy in DLBCL cells by acetylating P53, thereby inhibiting DLBCL cell proliferation.

Objective:To investigate the distribution of iodine and other chemical elements in soil, grain and vegetables in different water iodine areas of Xi'an City, and to provide theoretical basis for prevention and treatment of iodine related diseases and water improvement measures.Methods:From September to November 2021, a stratified cluster sampling method was used to select three survey villages in Xi'an, namely Yehu Village, Xingbei Village, and Quanzhong Village, where the iodine level of residents' drinking water < 10, 10 - 100, and > 100 μg/L. Drinking water samples were collected from seven survey sites based on the source of domestic drinking water to determine the iodine level of the water. At the same time, soil samples of cultivated land, residents' grains (wheat, corn), and vegetables were collected from survey villages to determine the content of 14 elements including calcium, iron, magnesium, chromium, nickel, copper, zinc, cadmium, lead, arsenic, mercury, selenium, iodine, and fluoride.Results:The iodine level in the water of 7 survey sites in three survey villages was 5.80, 6.40, 25.51, 42.20, 53.90, 111.65, and 177.63 μg/L, respectively. A total of 70 samples of soil, 65 samples of wheat, 76 samples of corn, and 141 samples of vegetables were collected. Among them, the levels of various elements in vegetables and grains were lower than those in the soil. Only calcium and fluoride were higher in vegetables than in grains, while iron, chromium, copper, zinc, selenium, and iodine were lower in vegetables than in grains. According to the range of water iodine level, there were statistically significant differences in the content of calcium, iron, chromium, nickel, copper, zinc, mercury, iodine, and fluoride in soils from different water iodine regions ( Fcalcium, iron, chromium, nickel = 42.04, 13.55, 12.22, 11.20, Hcopper, zinc, mercury, iodine, fluoride = 14.27, 9.19, 14.72, 25.14, 16.50, P < 0.05). The comparison of magnesium, zinc, cadmium, arsenic, and selenium content in wheat showed statistically significant differences ( Fadmium, selenium = 6.34, 3.31, Hmagnesium, zinc, arsenic = 6.12, 11.55, 6.23, P < 0.05). The comparison of calcium, iron, magnesium, chromium, nickel, copper, zinc, cadmium, lead, arsenic, mercury, iodine, and fluoride content in corn showed statistically significant differences ( Fmagnesium, chromium, nickel, copper, zinc, iodine = 18.89, 13.76, 17.86, 24.17, 28.46, 15.96, Hcalcium, iron, cadmium, lead, arsenic, mercury, fluoride = 11.57, 40.53, 26.50, 33.05, 33.73, 36.01, 29.21, P < 0.05). The comparison of calcium, iron, magnesium, chromium, zinc, cadmium, lead, arsenic, mercury, and selenium content in vegetables showed statistically significant differences ( H = 23.93, 8.12, 10.03, 7.01, 16.09, 18.36, 23.07, 6.51, 27.67, 7.86, P < 0.05). Conclusions:There are significant differences in the distribution of 14 elements in soil, grain, and vegetables in different water iodine regions. In addition to drinking water, precise guidance should also be provided based on the iodine content in soil, grain, and vegetables in different water iodine areas.

Objective To analyze the relationship between apolipoprotein E(APOE)genotype and cognitive impairment among individuals aged 40 and above in rural Xi'an and to explore the potential influence of education on this relationship.Methods All permanent residents aged 40 and above from two villages in Huyi District,Xi'an City,were selected as research subjects,employing a cross-sectional survey approach.The Mini-Mental State Examination(MMSE)was utilized to assess overall cognitive function,with MMSE scores below the threshold values(illiterate ≤17,primary school ≤20,junior high and above ≤24)considered as cognitive impairment.Fasting elbow venous blood was drawn in the morning,and the APOE genotype was determined.The population was divided into low-education(LE,≤9 years)and high-education(HE,＞9 years)groups based on educational level.Univariate and multivariate analyses were applied to explore the association between APOE genotype and cognitive impairment,as well as MMSE scores in both the total and stratified populations.Results Out of the 1 692 participants,there were 263 APOE ε4 allele carriers(E2/4,E3/4,E4/4)(15.3％),and 205 individuals met the criteria for cognitive impairment(12.1％).Multivariate Logistic regression and linear regression analyses revealed that in both the total population and the LE population,compared to APOE ε4 allele non-carriers(E2/2,E2/3,E3/3),APOE ε4 allele carriers exhibited a higher risk of cognitive impairments(total population:OR=1.509,95％CI:1.030-2.211,P=0.035;LE:OR=1.604,95％CI:1.080-2.381,P=0.019),and their MMSE scores were lower(total population:β=-0.053,95％CI:-0.983--0.162,P=0.006;LE:β=-0.052,95％CI:-1.052--0.124,P=0.013).However,in the HE population,there was no statistically significant difference in the prevalence of cognitive impairment(OR=1.883,95％CI:0.254-13.980,P=0.536)and MMSE scores(β=0.001,95％CI:-0.635-0.642,P=0.992)between APOE ε4 allele carriers and non-carriers.Conclusion The APOE ε4 allele was associated with an increased risk of cognitive impairment in individuals aged 40 and above in rural areas of Xi'an,while HE attainment may offer protective effects against cognitive impairment in APOE ε4 allele carriers.

Objective:To investigate the distribution of iodine and other chemical elements in soil, grain and vegetables in different water iodine areas of Xi'an City, and to provide theoretical basis for prevention and treatment of iodine related diseases and water improvement measures.Methods:From September to November 2021, a stratified cluster sampling method was used to select three survey villages in Xi'an, namely Yehu Village, Xingbei Village, and Quanzhong Village, where the iodine level of residents' drinking water < 10, 10 - 100, and > 100 μg/L. Drinking water samples were collected from seven survey sites based on the source of domestic drinking water to determine the iodine level of the water. At the same time, soil samples of cultivated land, residents' grains (wheat, corn), and vegetables were collected from survey villages to determine the content of 14 elements including calcium, iron, magnesium, chromium, nickel, copper, zinc, cadmium, lead, arsenic, mercury, selenium, iodine, and fluoride.Results:The iodine level in the water of 7 survey sites in three survey villages was 5.80, 6.40, 25.51, 42.20, 53.90, 111.65, and 177.63 μg/L, respectively. A total of 70 samples of soil, 65 samples of wheat, 76 samples of corn, and 141 samples of vegetables were collected. Among them, the levels of various elements in vegetables and grains were lower than those in the soil. Only calcium and fluoride were higher in vegetables than in grains, while iron, chromium, copper, zinc, selenium, and iodine were lower in vegetables than in grains. According to the range of water iodine level, there were statistically significant differences in the content of calcium, iron, chromium, nickel, copper, zinc, mercury, iodine, and fluoride in soils from different water iodine regions ( Fcalcium, iron, chromium, nickel = 42.04, 13.55, 12.22, 11.20, Hcopper, zinc, mercury, iodine, fluoride = 14.27, 9.19, 14.72, 25.14, 16.50, P < 0.05). The comparison of magnesium, zinc, cadmium, arsenic, and selenium content in wheat showed statistically significant differences ( Fadmium, selenium = 6.34, 3.31, Hmagnesium, zinc, arsenic = 6.12, 11.55, 6.23, P < 0.05). The comparison of calcium, iron, magnesium, chromium, nickel, copper, zinc, cadmium, lead, arsenic, mercury, iodine, and fluoride content in corn showed statistically significant differences ( Fmagnesium, chromium, nickel, copper, zinc, iodine = 18.89, 13.76, 17.86, 24.17, 28.46, 15.96, Hcalcium, iron, cadmium, lead, arsenic, mercury, fluoride = 11.57, 40.53, 26.50, 33.05, 33.73, 36.01, 29.21, P < 0.05). The comparison of calcium, iron, magnesium, chromium, zinc, cadmium, lead, arsenic, mercury, and selenium content in vegetables showed statistically significant differences ( H = 23.93, 8.12, 10.03, 7.01, 16.09, 18.36, 23.07, 6.51, 27.67, 7.86, P < 0.05). Conclusions:There are significant differences in the distribution of 14 elements in soil, grain, and vegetables in different water iodine regions. In addition to drinking water, precise guidance should also be provided based on the iodine content in soil, grain, and vegetables in different water iodine areas.

Objective To analyze the relationship between apolipoprotein E(APOE)genotype and cognitive impairment among individuals aged 40 and above in rural Xi'an and to explore the potential influence of education on this relationship.Methods All permanent residents aged 40 and above from two villages in Huyi District,Xi'an City,were selected as research subjects,employing a cross-sectional survey approach.The Mini-Mental State Examination(MMSE)was utilized to assess overall cognitive function,with MMSE scores below the threshold values(illiterate ≤17,primary school ≤20,junior high and above ≤24)considered as cognitive impairment.Fasting elbow venous blood was drawn in the morning,and the APOE genotype was determined.The population was divided into low-education(LE,≤9 years)and high-education(HE,＞9 years)groups based on educational level.Univariate and multivariate analyses were applied to explore the association between APOE genotype and cognitive impairment,as well as MMSE scores in both the total and stratified populations.Results Out of the 1 692 participants,there were 263 APOE ε4 allele carriers(E2/4,E3/4,E4/4)(15.3％),and 205 individuals met the criteria for cognitive impairment(12.1％).Multivariate Logistic regression and linear regression analyses revealed that in both the total population and the LE population,compared to APOE ε4 allele non-carriers(E2/2,E2/3,E3/3),APOE ε4 allele carriers exhibited a higher risk of cognitive impairments(total population:OR=1.509,95％CI:1.030-2.211,P=0.035;LE:OR=1.604,95％CI:1.080-2.381,P=0.019),and their MMSE scores were lower(total population:β=-0.053,95％CI:-0.983--0.162,P=0.006;LE:β=-0.052,95％CI:-1.052--0.124,P=0.013).However,in the HE population,there was no statistically significant difference in the prevalence of cognitive impairment(OR=1.883,95％CI:0.254-13.980,P=0.536)and MMSE scores(β=0.001,95％CI:-0.635-0.642,P=0.992)between APOE ε4 allele carriers and non-carriers.Conclusion The APOE ε4 allele was associated with an increased risk of cognitive impairment in individuals aged 40 and above in rural areas of Xi'an,while HE attainment may offer protective effects against cognitive impairment in APOE ε4 allele carriers.

Objective:To investigate the anti-tumor effect of the Histone Deacetylase 6 (HDAC6) inhibitor ACY-738 and its underlying mechanisms in Diffuse Large B-cell Lymphoma (DLBCL) .Methods:The expression of HDAC6 in various tumors and DLBCL was analyzed using bioinformatics. DLBCL cells were treated with different concentrations of ACY-738. Cell viability, DNA synthesis, and clone formation were assessed by CCK-8 assay, EdU assay, and soft agar assay, respectively. Intracellular reactive oxygen species (ROS) levels were detected by fluorescence microscopy. Morphological changes in cells were observed using transmission electron microscopy (TEM). Mitochondrial ROS levels and apoptosis were measured by flow cytometry. The expression levels of apoptosis-related and autophagy-related proteins were detected by Western blotting.Results:HDAC6 was highly expressed in DLBCL ( P<0.05). ACY-738 inhibited the proliferation, DNA synthesis, and colony formation of DLBCL cells in a dose-dependent manner ( P<0.05). Treatment with ACY-738 increased intracellular and mitochondrial ROS levels in DLBCL cells in a dose-dependent manner ( P<0.05). TEM revealed that after ACY-738 treatment, mitochondria in cells were swollen and ruptured, mitochondrial cristae were reduced or absent, autolysosomes appeared, and features characteristic of apoptosis were observed. Western blotting showed that after ACY-738 treatment, the expression of the anti-apoptotic protein BCL-2 was downregulated, while the expression of Cleaved-PARP, Cleaved caspase-3, and BAX was upregulated ( P<0.05). The expression of autophagy-related proteins Atg7, Atg3, LC3B, and P62 was downregulated, and the expression of acetylated P53 protein was upregulated ( P<0.05) . Conclusion:The HDAC6 inhibitor ACY-738 induces mitochondria-dependent apoptosis and autophagy in DLBCL cells by acetylating P53, thereby inhibiting DLBCL cell proliferation.

Objective To preliminarily investigate the anti-tumor effects of phytosphingosine(PHS)and the involvement of inducing apoptosis of leukemia cells.Methods Cellular model of leukemia was established in leukemia cell lines K562 and SUP-B15.CCK-8 assay and EdU assay were used to measure the viability and DNA synthesis of K562 and SUP-B15 cells.RNA-seq was carried out to verify the differentially expressed genes(DEGs)after PHS treatment.Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were applied to analyze the involved functions and signaling pathways.Comparative Toxicogenomics Database(CTD)and Discovery Studio software were employed to predict the underlying targets of PHS and molecular docking.Cell apoptosis was detected by flow cytometry,mitochondrial membrane potential was evaluated by JC-1 probe,and protein expression of key molecules was validated by Western blotting.Results PHS inhibited the proliferation of K562 and SUP-B15 cells in a time-and dose-dependent manner.The half-maximal inhibitory concentration(IC50)of K562 cells was 17.67 and 12.52 pmol/L for 24 and 48 h,respectively,and the IC50 value of SUP-B15 cells was 17.58 and 14.86 μmol/L for 24 and 48 h,respectively.PHS treatment at a dose of 20 μmol/L for 48 h resulted in significant inhibition of DNA synthesis.GO enrichment analysis of the K562 cells showed that PHS might be involved in positive regulation of apoptotic process,plasma membrane and its integral components,and protein kinase binding and activity.Reverse predictive analysis showed that BCL-2 protein was the most likely target of PHS.PHS significantly increased the apoptotic rate of leukemia cells(P＜0.05)in a dose-dependent manner,reduced the mitochondrial membrane potential,and down-regulated BCL-2 level(P＜0.05)and up-regulated the levels of Cleaved caspase-3 and Cleaved caspase-9(P＜0.05).Conclusion PHS may inhibit the proliferation of leukemia cells by inducing mitochondria-dependent apoptosis,possibly through PHS and BCL-2 interaction.

Objective:To investigate the impact of a reduced portacaval shunt on hepatic myelopathy (HM) in patients with cirrhosis after a transjugular intrahepatic portosystemic shunt (TIPS).Methods:Patients who developed HM after receiving TIPS at the First Affiliated Hospital of Xi'an Jiaotong University from January 2013 to June 2018 were retrospectively analyzed. HM severity was quantified by clinical spasticity index (CSI) and Fugl-Meyer Assessment (FMA) of the lower extremity. Clinical manifestations were combined with grades Ⅰ-Ⅳ. HM patients were divided into drug treatment (group A) and flow restriction group (group B) according to different treatment methods. The changes in CSI and FMA of the lower extremity after treatment were statistically analyzed in the two groups. P<0.05 was considered a statistically significant difference. Results:A total of 421 cases of cirrhosis who underwent TIPS were enrolled. Among them, 30 developed HM, with 22 in group A and 8 in group B. The incidence of HM after TIPS surgery was about 7.13%. After treatment, CSI was gradually increased and FMA of lower extremity was gradually decreased in group A, while vice-versa in group B. CSI in the two groups were differed significantly at 6, 12, 18, and 24 months after treatment ( P<0.05), while the difference in FMA of the lower extremity was statistically significant at 12, 18, and 24 months after treatment ( P<0.05). CSI was decreased and FMA of lower extremity was increased after treatment in patients with group A HM grade I. CSI, and FMA of lower extremity changes were statistically significant ( P<0.05) when compared with patients with HM grades Ⅱ-Ⅳ. The incidence of hepatic encephalopathy was significantly lower in group B than that in group A ( P=0.034), but there was no statistically significant difference between the two groups in the incidence of gastrointestinal bleeding, ascites, infection, MELD score and mortality. Conclusion:A reduced portacaval shunt can improve HM in patients with liver cirrhosis after TIPS, and drug therapy alone is effective for patients with early HM grade I.

Objective To compare the effects of different stent configurations on shunt failure,hepatic encephalopathy,and hepatic myelopathy after transjugular intrahepatic portosystemic shunt (TIPS).Methods From March 2014 to June 2015,the clinical data of 73 hospitalized,patients who met the inclusion and exclusion criteria,and underwent TIPS for upper gastrointestinal hemorrhage caused by cirrhotic portal hypertension were retrospectively analyzed.According to the stent configuration during operation,patients were divided into simple coated stent group (hepatic vein,portal vein and hepatic parenchyma coated stent,23 cases),simulated Viatorr stent group (hepatic vein and hepatic parenchyma coated stent plus portal vein bare stent,27 cases) and combined stent group (hepatic vein and portal vein hare stent plus hepatic parenchyma coated stent,23 cases).Patients were followed up for one year,the incidences of shunt failure,hepatic encephalopathy and hepatic myelopathy within one year after TIPS of three groups were compared.Chi-square test,Fisher exact probability method and variance analysis were performed for comparison among groups.Cox regression analysis was used for difference analysis in imbalance of variables and incidence of outcome events among the three groups.Results The portal vein pressure gradient of simple coated stent group,simulated Viatorr stent group and combined stent group decreased from (22.15±4.52),(23.01±5.48) and (21.13±4.49) mmHg (1 mmHg=0.133 kPa) to (9.15±2.94),(11.20±3.27) and (8.75+4.06) mmHg after operation,respectively.Before and after operation,the differences in portal venous pressure gradient were statistically significant of three groups (t=10.488,7.188 and 7.850,all P＜0.05).The shunt failure rates of simple coated stent group,simulated Viatorr stent group and combined stent group were 13.0％ (3/23),18.5％ (5/27) and 30.4％ (7/23),respectively.The results of Cox regression analysis indicated that there was no statistically significant difference in shunt failure rates among different stent configurations after TIPS (P=0.339).The incidences of hepatic encephalopathy of simple coated stent group,simulated Viatorr stent group and combined stent group postoperative were 69.6％ (16/23),33.3％ (9/27) and 30.4％ (7/23),respectively,the difference was not statistically significant among the three groups (P＞ 0.05).The results of Cox regression analysis showed that the relative ratio values (95％ confidence interval) of incidence of postoperative hepatic encephalopathy of simple coated stent group compared with simulated Viatorr stent group and combined stent group were 2.901 (1.279 to 6.584) and 2.735 (1.123 to 6.658),and the differences were statistically significant (both P＜0.05).The incidences of hepatic myelopathy of simple coated stent group,simulated Viatorr stent group and combined stent group were 8.7％ (2/23),3.7％ (1/27) and 4.3％ (1/23),respectively,and there was no statistically significant difference in the incidence of hepatic myelopathy among three groups after operation (P＞0.05).During one-year follow-up,among 73 patients,two patients died,one in simple coated stent group and the other in combined stent group.The one-year survival rate after TIPS was 97.3％.Conclusions One year after operation,the incidences of shunt failure are similar between simple coated stent group,simulated Viatorr stent group and combined stent group.One year after operation,the incidence of hepatic encephalopathy is similar between simulated Viatorr stent group and combined stent group which are both lower than that of simple coated stent.The incidence of hepatic myelopathy is low,and its association with TIPS remains to be further investigated.

Objective To find out the cognition understanding of iodine deficiency disorders(IDD) of target population in Xi’an City, and evaluate the effectiveness of a health education project on prevention and control of IDD. Methods By using the random number table, three towns in each project county were selected. Obeying the requirements of the education program for IDD control, the health education activities were implemented during 2007 - 2011. Before and after intervention, questionnaire was used to investigate the intervention effect. The primary school grade 5 students and women of childbearing age were included in the survey of IDD knowledge. Hierarchical random sampling method was used to select pupils and childbearing women. Results After health education, the rate of knowledge on IDD increased from 66.97%(13 321/19 890) to 93.49%(18 610/19 905,χ2 = 4 413.07, P < 0.05) among pupils, and 62.27%(6 193/9 945) to 93.96%(9 361/ 9 963, χ2= 2 924.18, P<0.05) among childbearing women. And the awareness had reached the national standard. But the survey results showed that: the rate of IDD related knowledge in rural areas was lower than that in town areas. The awareness rates of IDD in precaution, main hazards, identification of iodized salt were 46.50%(239/514), 55.25%(284/514) and 50.97%(262/514) among pupils in rural areas and 61.44%(376/612), 65.69%(402/612) and 70.59%(432/612) among pupils in town areas, and the awareness rates of pupils in rural areas were lower than those of pupils in town areas. Thirty-six point ninety-three per cent(226/612) of the pupils in towns and 35.60%(183/514) of the pupils in rural areas told this information to their parents. The awareness rates of IDD in precaution, main hazards, IDD prevention day were 49.25%(197/400), 50.75%(203/400) and 36.50%(146/400) among women in rural areas and 75.44%(298/395), 80.25%(317/395) and 57.97%(229/395) among women in town areas, and the rates of women in rural areas were lower than those of women in town areas. The rate of consciously purchasing of qualified iodized salt was 51.75%(207/400) and the consumption rate of iodized salt was 36.75%(147/400) among women in rural areas, which were 73.42%(290/395) and 43.80%(173/395) among women in town areas, and the rates in rural areas were lower than those in town areas. Conclusions Before health education of IDD, the rate of IDD related knowledge in Xi’an City is poor, rural areas are lower than town areas. Health education project is effective in promoting the understanding and grasp of IDD knowledge.