Objective Low-density lipoprotein cholesterol(LDL-C)is causally associated with atherosclerotic cardiovascular disease(ASCVD).Proprotein convertase subtilisin/kexin type 9(PCSK9)increases the degradation of low-density lipoprotein receptor(LDL-R),thereby promoting lipid accumulation.This study investigated the mechanism of microRNA(miRNA)-125a-5p in regulating PCSK9 transcriptional expression and lipid accumulation through histone deacetylase sirtuin 6(SIRT6)-mediated histone acetylation.Methods RAW264.7 macrophages exposed to oxidized low-density lipoprotein(ox-LDL)were used to establish a macrophage lipid accumulation model.The cells were divided into eight groups:control group(Group A),ox-LDL group(Group B),SIRT6 agonist group(Group C),si-SIRT6 group(Group D),miR-125a-5p mimic group(Group E),miR-125a-5p mimic negative control group(Group F),miR-125a-5p inhibitor group(Group G),and miR-125a-5p inhibitor negative control group(Group H).Oil red O staining was used to verify lipid ac-cumulation in macrophages.Real-time fluorescent quantitative polymerase chain reaction(PCR)was employed to detect the gene expression levels of miR-125a-5p,SIRT6 and PCSK9.Western blotting was used to detect the protein expression levels of SIRT6,histone 3 lysine 9 acetylation(H3K9ac),histone 3(H3),and PCSK9.An LDL-C kit was used to measure cellular LDL-C con-tent.Results Compared with Group A,Group B exhibited increased relative gene expression of miR-125a-5p,decreased relative SIRT6 gene and its protein expression,increased H3K9ac/H3 rati-o,increased relative gene and protein expression of PCSK9,and elevated LDL-C levels,with statis-tically significant differences(P＜0.01).In Group B,a positive correlation was observed between H3K9ac and PCSK9 protein expression(r=0.935 0,P＜0.01),as well as between PCSK9 and LDL-C(r=0.981 3,P＜0.01).Compared with Group B,Group C showed no significant change in miR-125a-5p expression(P＞0.05),but increased relative SIRT6 gene and its protein expres-sion,decreased H3K9ac/H3 ratio,decreased relative gene and protein expression of PCSK9,and reduced LDL-C levels(P＜0.01).In contrast,Group D,compared with Group B,had no signifi-cant change in miR-125a-5p gene expression(P＞0.05),but decreased relative gene and protein expression of SIRT6,increased H3K9ac/H3 ratio,increased relative PCSK9 gene and its protein expression,and elevated LDL-C levels(P＜0.05 or P＜0.01).Group E,compared with Group B,showed increased relative gene expression of miR-125a-5p,decreased relative SIRT6 gene and its protein expression,increased H3K9ac/H3,increased relative PCSK9 gene and its protein ex-pression,and elevated LDL-C levels(P＜0.01).Group G,compared with Group B,had de-creased relative gene expression of miR-125a-5p,increased relative gene and protein expression of SIRT6,decreased H3K9ac/H3 ratio,decreased relative PCSK9 gene and protein expression,and reduced LDL-C levels(P＜0.01).No significant changes were observed in miR-125a-5p,SIRT6,H3K9ac/H3 ratio,PCSK9,or LDL-C levels in Groups F and H compared with Group B(P＞0.05).Conclusion Epigenetics is an important regulatory mechanism in the development of ather-osclerosis(AS).Elevated LDL-C is a significant risk factor for AS,and increased PCSK9 expres-sion exacerbates lipid accumulation.Imbalance in histone acetylation is a novel mechanism involved in PCSK9-mediated lipid accumulation,potentially serving as an early detection marker for lipid me-tabolism disorders.SIRT6 acts as a protective factor by reversibly regulating PCSK9 transcriptional expression,reducing lipid accumulation,and delaying AS progression.MiR-125a-5p,as an up-stream regulatory gene of SIRT6,targets and inhibits SIRT6 transcription,thereby modulating his-tone acetylation,and may serve as a new target for early screening and prevention of dyslipidemia.

[Purpose]To analyze the incidence,mortality and disease burden of malignant tumors in the cancer registration areas of Hebei Province in 2020.[Methods]The incidence and mortality data of cancer in 2020 were collected from the cancer registries of Hebei Province,and the quality of data was evaluated.The crude incidence(mortality)rate,age-specific incidence(mortality)rates and age-standardized incidence(mortality)rates by Chinese standard population(ASIRC/ASMRC)and world standard population(ASIRW/ASMRW)were calculated and analyzed.The disability-ad-justed life years(DALY)were calculated and analyzed according to the Excel disease burden cal-culation template recommended by the World Health Organization(WHO).[Results]In 2020,the crude incidence rate,ASIRC,ASIRW of malignant tumors in the cancer registration areas of Hebei Province were 229.36/105,147.06/105 and 143.74/105,respectively.The incidence rate in men was higher than that in women.The incidence rates in urban and rural areas were 230.26/105 and 228.84/105,and the age-standardized incidence rates reached a peak in the age group of 80～84 years old.The crude mortality rate,ASMRC,ASMRW were 146.38/105,85.33/105 and 84.79/105,respectively.The mortality rate in men was higher than that in women.The age-standardized mor-tality rate rose with age,reaching a peak in the age group of 85+years old,and the crude mortality rates in urban and rural areas were 143.82/105 and 147.84/105,respectively.The DALY of ma-lignant tumors in the cancer registration areas of Hebei Province were 345 030 person-years,reaching a maximum in the age group of 45～59 years old,with a DALY rate of 15.00/103,and the highest in the age group of 70～79 years old.Lung cancer had the heaviest disease burden,with DALY of 83 684 person-years,accounting for 24.25％of all malignant tumors,followed by stomach,liver,female breast,and colorectal cancers.The DALY in urban and rural areas were 122 062 and 222 993 person-years,respectively,and the trends in DALY rates were basically stable.[Conclusion]The disease burden of malignant tumors in Hebei Province is relatively heavy,cancer prevention and control should be further strengthened and focused on urban men and the elderly to reduce disease burden of malignant tumors in the future.

Objective To observe the effects of Huosha Oral Liquid on irritable bowel syndrome with diarrhea(IBS-D)rats with cold and dampness syndrome based on Notch1/Hes-1/Math-1 signaling pathway;To elucidate its mechanism of repair of intestinal mucosal barrier.Methods An IBS-D cold and dampness syndrome rat model was established by using restraint stress combined with bitter-cold cathartic method and cold and dampness environmental method.After modeling,the rats were randomly divided into model group,Western medicine group and Huosha Oral Liquid low-,medium-and high-dosage groups,with 6 rats in each group.An additional 6 rats were set as the normal group.The Western medicine group was given mebeverine(13.5 mg/kg)by gavage,while the Huosha Oral Liquid low-,medium-and high-dosage groups were given Huosha Oral Liquid(3.15,6.3,12.6 g/kg)by gavage,the normal group and model group were given distilled water by gavage,for 4 weeks.The general status of rats were ovserved,the body mass,loose stool rate,fecal water rate and abdominal withdrawal reflex(AWR)score were measured,the morphalogy of colon tissue were observed by HE staining,the mRNA expression of Occludin,ZO-1,Notch1,Hes-1 and Math-1 in colon tissue were detected by RT-PCR,the protein expression of Notch1 was detected by Western blot.Results Compared with the normal group,the model group had a reduced body mass(P<0.05)and increased loose stool rate,fecal water rate and AWR score(P<0.05),inflammatory cell infiltration was observed in colon tissue and the expressions of Occludin,ZO-1,Math-1 mRNA decreased(P<0.05),the expressions of Notch1,Hes-1 mRNA increased(P<0.05),and the expression of Notch1 protein increased(P<0.05).Compared with the model group,the body mass of rats in Western medicine group and Huosha Oral Liquid low-,medium-and high-dosage groups increased(P<0.05),loose stool rate,fecal water rate and AWR scores decreased(P<0.05),a small amount of neutrophils was visible in the colon tissue,the expressions of Occludin,ZO-1,Math-1 mRNA in colon tissue increased in Huosha Oral Liquid medium-and high-dosage groups(P<0.05)and the expressions of Notch1 and Hes-1 mRNA decreased(P<0.05),the expression of Notch1 protein decreased in Western medicine group and Huosha Oral Liquid groups(P<0.05).Conclusion Huosha Oral Liquid may regulate the expressions of tight junction proteins by inhibiting excessive activation of the Notch/Hes-1/Math-1 signaling pathway,thereby protecting the intestinal mucosal barrier function,improving diarrhea symptoms in IBS-D rats with cold and dampness syndrome,and reducing visceral sensitivity and colonic tissue inflammation.

[Purpose]To analyze the prevalence characteristics and disease burden of lung cancer in Hebei cancer registration areas from 2012 to 2020.[Methods]Lung cancer data were collected from the Hebei Provincial Cancer Registry from 2012 to 2020.The crude incidence/mortality rates,age-standardized incidence/mortality rates by Chinese standard population(ASIRC/ASMRC)and by world standard population(ASIRW/ASMRW)were calculated.The Joinpoint model was used to calculate the annual percentage change(APC)and average annual percentage change(AAPC).Years of life lost(YLL)and years lived with disability(YLD)and the disability-adjusted life years(DALY)were calculated.[Results]From 2012 to 2020,the ASIRW of lung cancer in Hebei can-cer registration areas was 33.13/105,44.56/105 for men and 22.54/105 for women,respectively;the incidence rates of urban and rural areas were 29.05/105 and 33.52/105,respectively.The incidence rates increased with ages,reaching a peak in the age group of 80～84 years old.There was a de-creasing trend in the ASIRW of lung cancer(AAPC=-3.99％,P＜0.05).From 2012 to 2020,the ASMRW of lung cancer was 25.80/105,36.56/105 for men and 15.96/105 for women,respectively;the mortality rates of urban and rural areas were 25.14/105 and 26.12/105,respectively.The mor-tality rates increase with ages,reaching a peak in the age group of 85 and above years old.There was a decreasing trend in the mortality of lung cancer(AAPC=-4.65％,P＜0.001)from 2012 to 2020.The DALY of lung cancer in Hebei Province from 2012 to 2020 was 484 194 person-years,with male accounting for 66.77％,female accounted for 33.23％,the DALY rate of lung cancer was 3.31‰,of which 35.57％in urban areas and 64.43％in rural areas.[Conclusion]Lung can-cer incidence and mortality rate in Hebei cancer registration areas from 2012 to 2020 showed a decreasing trend.The disease burden is gradually increasing with age in middle-aged and el-derly population.

Objective:With the aggravation of population aging, the burden of malignant tumors in the elderly population is becoming more and more heavy. This study aims to analyze the incidence and mortality of malignant tumors in the elderly population in Hebei Province in the past decade.Methods:The incidence and mortality data of malignant tumors in people aged ≥60 years old in 38 cancer registration areas in Hebei Province from 2011 to 2020 were collected, and the incidence and mortality were analyzed by gender, urban and rural areas, and age groups. The age standardized rates were calculated using the 2000 Chinese population census and Segi′s world population. The trend of incidence and mortality was analyzed using the Joinpoint model and the average annual percent change (AAPC).Results:From 2011 to 2020, 216 200 new cases of malignant tumors were reported in the elderly population in the cancer registration areas of Hebei Province, and 170 700 deaths were reported. The peak ages of incident cases number for males and females were 65-69 years old and 60-64 years old, respectively. The crude incidence rate of malignant tumors in the elderly was 905.42/10 5, and the crude mortality rate was 714.96/10 5. In general, the incidence and mortality in rural areas were higher than those in urban areas, and the incidence and mortality in males were higher than those in females. The peak ages of incidence and mortality were 80-84 years old and 85+ years old, respectively. From 2011 to 2020, lung cancer, gastric cancer, esophageal cancer, female breast cancer, and colorectal cancer were the main malignant tumors of incidence rate in the elderly population in Hebei Province, and lung cancer, gastric cancer, liver cancer, esophageal cancer, and colorectal cancer were the main malignant tumors in the mortality rate. From 2011 to 2020, the incidence and mortality of malignant tumors in the elderly population in Hebei Province showed a decreasing trend, and AAPC for the age-standardized incidence and mortality were -4.69% and -5.53%, respectively. The rank of incidence and mortality rate of each cancer had changed, but the top two were still lung cancer and stomach cancer. Conclusions:The incidence and mortality of cancer in the elderly population in Hebei province have decreased, but the burden is still heavy. Lung cancer and stomach cancer are still the focus of prevention and treatment in the elderly population in Hebei province.

Objective:To understand the burden of cancer disease in Hebei Province in recent years and to analyze the change trend of cancer in Hebei Province from 2011 to 2020.Methods:The incidence and death data of cancer were collected from 38 cancer registries in Hebei Province during 2011-2020. The incidence (mortality) rate, standardized incidence (mortality) rate and composition ratio of each region, sex, and age were calculated respectively, and the incidence and death of major cancers in our province were summarized. The age-standardized morbidity (mortality) rates of China and the world population were calculated using the 2000 China standard population composition and Segi's world population composition respectively. Trend analysis of morbidity and mortality was performed and average annual percentage change (AAPC) was calculated.Results:In 2020, the crude cancer incidence rate and the age-standardized morbidity rate of China was 229.36/100 000 and 147.06/100 000, respectively. An estimated 171 600 new cases were reported in the province. The crude cancer mortality rate and the age-standardized mortality rates of China was 146.38/100 000 and 85.33/100 000. The estimated number of deaths in the province is 108 900. In the cancer registration areas of Hebei Province, 84% of all cancer patients occurred in people 50 years of age and older. From 2011 to 2020, the incidence and mortality of cancer in Hebei Province showed a decreasing trend. The AAPC was -4.2% ( P＜0.001), which decreased from 206.61/100 000 in 2011 to 143.74/100 000 in 2020. The world standard mortality rate of cancer was 147.69/100 000 in 2011, and decreased to 84.79/100 000 in 2020. The AAPC was -5.7% ( P＜0.001). The world-standard incidence and mortality of lung cancer, esophageal cancer, gastric cancer, liver cancer and colorectal cancer decreased from 2011 to 2020. The AAPCs of the world-standard incidence were -4.0%, -12.3%, -9.4%, -6.0% and -1.6%, respectively. The AAPCs of the world-standard mortality were -4.9%, -11.3%, -8.5%, -5.7% and -3.3%, which were statistically significant. The incidence of thyroid cancer increased rapidly, the AAPC of which was 9.7% ( P＜0.001). The rates of female breast cancer and male prostate cancer in Hebei Province were stable. Conclusions:The world-standard incidence and mortality of cancer in Hebei Provincial cancer registries areas show a downward trend from 2011 to 2020. However, the cancer incidence and mortality in Hebei Province are still at high levels. It's necessary to strengthen cancer prevention and control in Hebei Province, improve the awareness of cancer prevention and control in the whole society, and promote the concept of tertiary cancer prevention to reduce the cancer burden in Hebei Province.

[Purpose]To analyze the incidence,mortality and disease burden of malignant tumors in the cancer registration areas of Hebei Province in 2020.[Methods]The incidence and mortality data of cancer in 2020 were collected from the cancer registries of Hebei Province,and the quality of data was evaluated.The crude incidence(mortality)rate,age-specific incidence(mortality)rates and age-standardized incidence(mortality)rates by Chinese standard population(ASIRC/ASMRC)and world standard population(ASIRW/ASMRW)were calculated and analyzed.The disability-ad-justed life years(DALY)were calculated and analyzed according to the Excel disease burden cal-culation template recommended by the World Health Organization(WHO).[Results]In 2020,the crude incidence rate,ASIRC,ASIRW of malignant tumors in the cancer registration areas of Hebei Province were 229.36/105,147.06/105 and 143.74/105,respectively.The incidence rate in men was higher than that in women.The incidence rates in urban and rural areas were 230.26/105 and 228.84/105,and the age-standardized incidence rates reached a peak in the age group of 80～84 years old.The crude mortality rate,ASMRC,ASMRW were 146.38/105,85.33/105 and 84.79/105,respectively.The mortality rate in men was higher than that in women.The age-standardized mor-tality rate rose with age,reaching a peak in the age group of 85+years old,and the crude mortality rates in urban and rural areas were 143.82/105 and 147.84/105,respectively.The DALY of ma-lignant tumors in the cancer registration areas of Hebei Province were 345 030 person-years,reaching a maximum in the age group of 45～59 years old,with a DALY rate of 15.00/103,and the highest in the age group of 70～79 years old.Lung cancer had the heaviest disease burden,with DALY of 83 684 person-years,accounting for 24.25％of all malignant tumors,followed by stomach,liver,female breast,and colorectal cancers.The DALY in urban and rural areas were 122 062 and 222 993 person-years,respectively,and the trends in DALY rates were basically stable.[Conclusion]The disease burden of malignant tumors in Hebei Province is relatively heavy,cancer prevention and control should be further strengthened and focused on urban men and the elderly to reduce disease burden of malignant tumors in the future.

Objective To observe the effects of Huosha Oral Liquid on irritable bowel syndrome with diarrhea(IBS-D)rats with cold and dampness syndrome based on Notch1/Hes-1/Math-1 signaling pathway;To elucidate its mechanism of repair of intestinal mucosal barrier.Methods An IBS-D cold and dampness syndrome rat model was established by using restraint stress combined with bitter-cold cathartic method and cold and dampness environmental method.After modeling,the rats were randomly divided into model group,Western medicine group and Huosha Oral Liquid low-,medium-and high-dosage groups,with 6 rats in each group.An additional 6 rats were set as the normal group.The Western medicine group was given mebeverine(13.5 mg/kg)by gavage,while the Huosha Oral Liquid low-,medium-and high-dosage groups were given Huosha Oral Liquid(3.15,6.3,12.6 g/kg)by gavage,the normal group and model group were given distilled water by gavage,for 4 weeks.The general status of rats were ovserved,the body mass,loose stool rate,fecal water rate and abdominal withdrawal reflex(AWR)score were measured,the morphalogy of colon tissue were observed by HE staining,the mRNA expression of Occludin,ZO-1,Notch1,Hes-1 and Math-1 in colon tissue were detected by RT-PCR,the protein expression of Notch1 was detected by Western blot.Results Compared with the normal group,the model group had a reduced body mass(P<0.05)and increased loose stool rate,fecal water rate and AWR score(P<0.05),inflammatory cell infiltration was observed in colon tissue and the expressions of Occludin,ZO-1,Math-1 mRNA decreased(P<0.05),the expressions of Notch1,Hes-1 mRNA increased(P<0.05),and the expression of Notch1 protein increased(P<0.05).Compared with the model group,the body mass of rats in Western medicine group and Huosha Oral Liquid low-,medium-and high-dosage groups increased(P<0.05),loose stool rate,fecal water rate and AWR scores decreased(P<0.05),a small amount of neutrophils was visible in the colon tissue,the expressions of Occludin,ZO-1,Math-1 mRNA in colon tissue increased in Huosha Oral Liquid medium-and high-dosage groups(P<0.05)and the expressions of Notch1 and Hes-1 mRNA decreased(P<0.05),the expression of Notch1 protein decreased in Western medicine group and Huosha Oral Liquid groups(P<0.05).Conclusion Huosha Oral Liquid may regulate the expressions of tight junction proteins by inhibiting excessive activation of the Notch/Hes-1/Math-1 signaling pathway,thereby protecting the intestinal mucosal barrier function,improving diarrhea symptoms in IBS-D rats with cold and dampness syndrome,and reducing visceral sensitivity and colonic tissue inflammation.

[Purpose]To analyze the prevalence characteristics and disease burden of lung cancer in Hebei cancer registration areas from 2012 to 2020.[Methods]Lung cancer data were collected from the Hebei Provincial Cancer Registry from 2012 to 2020.The crude incidence/mortality rates,age-standardized incidence/mortality rates by Chinese standard population(ASIRC/ASMRC)and by world standard population(ASIRW/ASMRW)were calculated.The Joinpoint model was used to calculate the annual percentage change(APC)and average annual percentage change(AAPC).Years of life lost(YLL)and years lived with disability(YLD)and the disability-adjusted life years(DALY)were calculated.[Results]From 2012 to 2020,the ASIRW of lung cancer in Hebei can-cer registration areas was 33.13/105,44.56/105 for men and 22.54/105 for women,respectively;the incidence rates of urban and rural areas were 29.05/105 and 33.52/105,respectively.The incidence rates increased with ages,reaching a peak in the age group of 80～84 years old.There was a de-creasing trend in the ASIRW of lung cancer(AAPC=-3.99％,P＜0.05).From 2012 to 2020,the ASMRW of lung cancer was 25.80/105,36.56/105 for men and 15.96/105 for women,respectively;the mortality rates of urban and rural areas were 25.14/105 and 26.12/105,respectively.The mor-tality rates increase with ages,reaching a peak in the age group of 85 and above years old.There was a decreasing trend in the mortality of lung cancer(AAPC=-4.65％,P＜0.001)from 2012 to 2020.The DALY of lung cancer in Hebei Province from 2012 to 2020 was 484 194 person-years,with male accounting for 66.77％,female accounted for 33.23％,the DALY rate of lung cancer was 3.31‰,of which 35.57％in urban areas and 64.43％in rural areas.[Conclusion]Lung can-cer incidence and mortality rate in Hebei cancer registration areas from 2012 to 2020 showed a decreasing trend.The disease burden is gradually increasing with age in middle-aged and el-derly population.

Objective:With the aggravation of population aging, the burden of malignant tumors in the elderly population is becoming more and more heavy. This study aims to analyze the incidence and mortality of malignant tumors in the elderly population in Hebei Province in the past decade.Methods:The incidence and mortality data of malignant tumors in people aged ≥60 years old in 38 cancer registration areas in Hebei Province from 2011 to 2020 were collected, and the incidence and mortality were analyzed by gender, urban and rural areas, and age groups. The age standardized rates were calculated using the 2000 Chinese population census and Segi′s world population. The trend of incidence and mortality was analyzed using the Joinpoint model and the average annual percent change (AAPC).Results:From 2011 to 2020, 216 200 new cases of malignant tumors were reported in the elderly population in the cancer registration areas of Hebei Province, and 170 700 deaths were reported. The peak ages of incident cases number for males and females were 65-69 years old and 60-64 years old, respectively. The crude incidence rate of malignant tumors in the elderly was 905.42/10 5, and the crude mortality rate was 714.96/10 5. In general, the incidence and mortality in rural areas were higher than those in urban areas, and the incidence and mortality in males were higher than those in females. The peak ages of incidence and mortality were 80-84 years old and 85+ years old, respectively. From 2011 to 2020, lung cancer, gastric cancer, esophageal cancer, female breast cancer, and colorectal cancer were the main malignant tumors of incidence rate in the elderly population in Hebei Province, and lung cancer, gastric cancer, liver cancer, esophageal cancer, and colorectal cancer were the main malignant tumors in the mortality rate. From 2011 to 2020, the incidence and mortality of malignant tumors in the elderly population in Hebei Province showed a decreasing trend, and AAPC for the age-standardized incidence and mortality were -4.69% and -5.53%, respectively. The rank of incidence and mortality rate of each cancer had changed, but the top two were still lung cancer and stomach cancer. Conclusions:The incidence and mortality of cancer in the elderly population in Hebei province have decreased, but the burden is still heavy. Lung cancer and stomach cancer are still the focus of prevention and treatment in the elderly population in Hebei province.