Objective:To investigate the epidemiological dynamics and spatiotemporal diffusion trend of brucellosis in China from 2010 to 2024.Methods:Data on reported human brucellosis cases in mainland China from January 1, 2010, to December 31, 2024, were collected via the"China Information System for Disease Control and Prevention", including detailed information on the date of onset, gender, age, occupation, and residential address of the cases. The Joinpoint regression and spatial interpolation techniques were used to investigate the spatiotemporal dynamics and population distribution characteristics of human brucellosis in pastoral/semi-pastoral areas and other regions, as well as urban and rural areas, and explore the epidemic trends of the disease.Results:From 2010 to 2024, pastoral/semi-pastoral regions reported 252 094 brucellosis cases, with a mean annual incidence rate of 36.57±7.28 per 100 000. In contrast, other regions cumulatively recorded 519 748 cases during the same period, demonstrating a significantly lower mean annual incidence rate of 2.54±0.74 per 100 000. The incidence rate of human brucellosis in pastoral/semi-pastoral regions exhibited a declining-rebounding-declining trend. Specifically, the incidence rate decreased significantly from 2010 to 2017 (APC=-7.20; P<0.001) and increased notably from 2017 to 2021 (APC=18.00; P=0.015) with a decline again from 2021 to 2024 (APC=-7.53; P=0.027). In other regions, the incidence rate showed a fluctuating upward trend. Specifically, the incidence rate increased significantly from 2010 to 2015 (APC=20.37; P<0.001) and decreased notably from 2015 to 2018 (APC=-21.78; P<0.001), followed by an increase again from 2018 to 2024, a significant upward trend in incidence rate from 2018 to 2021 (APC=26.73; P<0.001) and a non-significant decline from 2021 to 2024 (APC=-0.99; P=0.735), resulting in the maintenance of a relatively high incidence level. Rural areas demonstrated significantly higher brucellosis incidence rates than urban settings (all P<0.001). Brucellosis exhibited a diffusion trend from the northern epidemic areas of China to neighboring regions, along with sporadic diffusion in southern regions between 2010 and 2024. The age structure of patients in pastoral/semi-pastoral areas differed significantly from that in other regions. Specifically, in pastoral/semi-pastoral areas, the incidence rate was higher among the 35-49 age groups, while in other regions, the incidence rate was higher among those aged 55-64. Conclusion:There are notable disparities in the incidence of human brucellosis between pastoral/semi-pastoral areas and other regions in China. Human brucellosis exhibits a diffusion trend from the northern epidemic areas of China to neighboring regions, along with sporadic diffusion in southern regions.

Objective To analyze trend changes of disease burden of hypertensive nephropathy (HTN) between 2012 and 2023 in Chongqing, and to provide the suggestion for HTN prevention and treatment. Methods Death cases of HTN from Chongqing death registration data between 2012 and 2023 were analyzed to calculate indicators such as mortality, age standardization mortality rate (ASMR), rate of years of life lost (YLL) and Average years of life lost. The mortality of HTN between male and female, urban and rural were compared by Chi-square test. The trend change was explained by average annual percent of change (AAPC). Results The mortality and standardized mortality of HTN in Chongqing decreased from 5.44/100 000 and 3.13/100 000 in 2012 to 2.76/100 000 and 1.07/100,000 in 2023 respectively. The average annual percent change (AAPC) was -5.41% and -8.35% respectively, and the differences in the change trends were statistically significant (P<0.01). The mortality and standardized mortality of HTN in males and females decreased with AAPC of 5.50%, 8.07%, 5.27% and 8.69% respectively, and the differences in the change trends were all statistically significant (all P< 0.05). From 2012 to 2014, 2019 and 2021, the mortality rate of HTN in rural areas was higher than that in urban areas (all P < 0.05). The mortality and standardized mortality of HTN in rural areas decreased with AAPC of 6.58% and 9.46% respectively, and the differences in the change trends were all statistically significant (all P<0.05). The rate of YLL and standardized YLL of HTN in Chongqing decreased from 96.02/100 000 and 60.42/100 000 in 2012 to 44.98/100 000 and 21.49/100 000 in 2023 respectively. The AAPC was -5.83% and -7.80% respectively, and the differences in the change trends were statistically significant (both P < 0.05). AYLL of HTN were 17.88 years in 2012, and it was 17.08 years in 2023. There were no statistically significant differences in the changes (both P > 0.05). The standardized AYLL of HTN in rural areas increased at an average annual rate of 1.14%, and the difference was statistically significant (P < 0.05). Conclusion The mortality and YLL rate of HNT in Chongqing was lower than it in China. Moreover, its trend was decreased. It should be strengthened early screening and healthy management of HNT.

Objective:To investigate the epidemiological dynamics and spatiotemporal diffusion trend of brucellosis in China from 2010 to 2024.Methods:Data on reported human brucellosis cases in mainland China from January 1, 2010, to December 31, 2024, were collected via the"China Information System for Disease Control and Prevention", including detailed information on the date of onset, gender, age, occupation, and residential address of the cases. The Joinpoint regression and spatial interpolation techniques were used to investigate the spatiotemporal dynamics and population distribution characteristics of human brucellosis in pastoral/semi-pastoral areas and other regions, as well as urban and rural areas, and explore the epidemic trends of the disease.Results:From 2010 to 2024, pastoral/semi-pastoral regions reported 252 094 brucellosis cases, with a mean annual incidence rate of 36.57±7.28 per 100 000. In contrast, other regions cumulatively recorded 519 748 cases during the same period, demonstrating a significantly lower mean annual incidence rate of 2.54±0.74 per 100 000. The incidence rate of human brucellosis in pastoral/semi-pastoral regions exhibited a declining-rebounding-declining trend. Specifically, the incidence rate decreased significantly from 2010 to 2017 (APC=-7.20; P<0.001) and increased notably from 2017 to 2021 (APC=18.00; P=0.015) with a decline again from 2021 to 2024 (APC=-7.53; P=0.027). In other regions, the incidence rate showed a fluctuating upward trend. Specifically, the incidence rate increased significantly from 2010 to 2015 (APC=20.37; P<0.001) and decreased notably from 2015 to 2018 (APC=-21.78; P<0.001), followed by an increase again from 2018 to 2024, a significant upward trend in incidence rate from 2018 to 2021 (APC=26.73; P<0.001) and a non-significant decline from 2021 to 2024 (APC=-0.99; P=0.735), resulting in the maintenance of a relatively high incidence level. Rural areas demonstrated significantly higher brucellosis incidence rates than urban settings (all P<0.001). Brucellosis exhibited a diffusion trend from the northern epidemic areas of China to neighboring regions, along with sporadic diffusion in southern regions between 2010 and 2024. The age structure of patients in pastoral/semi-pastoral areas differed significantly from that in other regions. Specifically, in pastoral/semi-pastoral areas, the incidence rate was higher among the 35-49 age groups, while in other regions, the incidence rate was higher among those aged 55-64. Conclusion:There are notable disparities in the incidence of human brucellosis between pastoral/semi-pastoral areas and other regions in China. Human brucellosis exhibits a diffusion trend from the northern epidemic areas of China to neighboring regions, along with sporadic diffusion in southern regions.

Hereditary hemochromatosis is a rare autosomal genetic disorder that can cause multi-organ dysfunction in the liver,pancreas,spleen,heart and pituitary gland,with diverse clinical manifestations,make the diagnosis difficult.In recent years,with the deepening of clinical understanding and the development of genetic diagnosis tools,the diagnostic rate of this disease has increased significantly.In this paper,we report a case of hereditary hemochromatosis type 3 involving multiple organs and complicated by severe heart failure,aiming to improve the clinicians'understanding of this disease and reduce the leakage and misdiagnosis.

Colorectal cancer is one of the most common malignant tumors of the digestive system.Oxali-platin(OXA)-based combination chemotherapy is the most commonly used strategy for treating patients with advanced-stage disease in clinical practice.However,the development of resistance greatly limits the effectiveness of chemotherapy and is a major cause of treatment failure.Due to the unknown mecha-nisms of resistance,there is an urgent need for a high-throughput,highly specific sequencing method to explore the causes of oxaliplatin resistance.Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9 (CRISPR/Cas9) is a rapidly advancing high-throughput technology that can be employed for screening resistance genes.However,its role in identifying genes involved in oxaliplatin resistance in colorectal cancer remains unclear.We constructed an sgRNA library containing 5256 small-guide RNAs (sgRNAs) targeting 910 human epigenetic-related genes,using lentivirus packaging.By de-termining the viral infection conditions through protein immunoblotting and flow cytometry,we maintained the multiplicity of infection (MOI) below 30％ to ensure that each cell is infected with only one sgRNA,thereby knocking out one gene.Colorectal cancer cells HCT116 and SW620 were infected with lentivirus carrying library,and single clones were obtained and expanded through a positive selection strategy.By the positive selection strategy,we identified 21 genes that regulate the sensitivity of colorectal cancer cells to oxaliplatin.By knocking out of candidate genes,we observed that deletion of TDRKH,ALKBH3,UNKL,TTF2,TNKS,AURKA,RBM12,ELAVL2,DKC1,LSM5,NOL8 and PRPF3 significantly in-creased the half-maximal inhibitory concentration (IC50) of oxaliplatin in colorectal cancer cells (P<0.05) .Among them,high expression of the ALKBH3,AURKA,and RBM12 genes was significantly cor-related with clinical prognosis (overall survival:P=0.043,P<0.0001,P=0.045;recurrence-free sur-vival:P=0.004,P=0.0019,P=0.0064) .Our study demonstrates that the CRISPR/Cas9 library is a high-throughput method for screening tumor sensitivity genes,providing target references for further ex-ploring the mechanism of colorectal cancer sensitivity to oxaliplatin.

Colorectal cancer is one of the most common malignant tumors of the digestive system.Oxali-platin(OXA)-based combination chemotherapy is the most commonly used strategy for treating patients with advanced-stage disease in clinical practice.However,the development of resistance greatly limits the effectiveness of chemotherapy and is a major cause of treatment failure.Due to the unknown mecha-nisms of resistance,there is an urgent need for a high-throughput,highly specific sequencing method to explore the causes of oxaliplatin resistance.Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9 (CRISPR/Cas9) is a rapidly advancing high-throughput technology that can be employed for screening resistance genes.However,its role in identifying genes involved in oxaliplatin resistance in colorectal cancer remains unclear.We constructed an sgRNA library containing 5256 small-guide RNAs (sgRNAs) targeting 910 human epigenetic-related genes,using lentivirus packaging.By de-termining the viral infection conditions through protein immunoblotting and flow cytometry,we maintained the multiplicity of infection (MOI) below 30％ to ensure that each cell is infected with only one sgRNA,thereby knocking out one gene.Colorectal cancer cells HCT116 and SW620 were infected with lentivirus carrying library,and single clones were obtained and expanded through a positive selection strategy.By the positive selection strategy,we identified 21 genes that regulate the sensitivity of colorectal cancer cells to oxaliplatin.By knocking out of candidate genes,we observed that deletion of TDRKH,ALKBH3,UNKL,TTF2,TNKS,AURKA,RBM12,ELAVL2,DKC1,LSM5,NOL8 and PRPF3 significantly in-creased the half-maximal inhibitory concentration (IC50) of oxaliplatin in colorectal cancer cells (P<0.05) .Among them,high expression of the ALKBH3,AURKA,and RBM12 genes was significantly cor-related with clinical prognosis (overall survival:P=0.043,P<0.0001,P=0.045;recurrence-free sur-vival:P=0.004,P=0.0019,P=0.0064) .Our study demonstrates that the CRISPR/Cas9 library is a high-throughput method for screening tumor sensitivity genes,providing target references for further ex-ploring the mechanism of colorectal cancer sensitivity to oxaliplatin.

Literature research on ancient books of traditional Chinese medicine （TCM） is an important carrier for inheriting the academic achievements and thoughts of TCM， and a key step for continuing the Chinese civilization and realizing the great rejuvenation of the Chinese nation. Based on this， the paper puts forward the purpose of sorting out TCM ancient books：to explore the treasure of traditional culture， reveal its significance， carry forward its spirit， learn from its experiences， so as to make a contribution to the development of TCM. And this paper expounds several major problems in the literature research， that is， paying attention to the phenomenon of "stubborn bass"， avoiding the trend of "latecomers turning inferior"， attaching importance to the hidden trouble of "making comments on behalf of the ancients". Then， this paper discusses the methodology of carrying out accurate research and revealing the true nature and true value of scholarship with the idea of confucian orthodoxy， the rules of not forgetting the original intention and the scientific method. Taking the materia medica archaeology as an example， the author shared the practical exploration of how to crack the historical code with scientific and technological means， so as to provide useful reference for the literature research on TCM ancient books.

Objective:To explore the efficacy and mechanism of Danggui Shaoyaosan on rats of nonalcoholic fatty liver disease （NAFLD）. Method:Sixrty SPF SD male rats were randomly divided into normal group， model group，essentiale （0.144 g·kg^-1） and low， middle and high-dose of Danggui Shaoyaosan groups （2.44， 4.88， 9.76 g·kg^-1）. High fat diet were fed to bulid the NAFLD model， and each treatment group was given corresponding drugs at the same time. After 8 weeks， the serum and liver tissue were collected to detect the contents or activities of total cholesterol （TC）， triglyceride （TG）， alanine aminotransferase （ALT）， aspartic acid aminotransferase （AST）， tumor necrosis factor-α （TNF-α） and interleukin-10 （IL-10） in serum， the contents of TC， TG and free fatty acid （FFA） in liver tissue， Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to observe the gene and protein expressions of Toll-like receptor 4 （TLR4）， myeloid different factory 88 （MyD88） and c-Jun n-terminal kinase （JNK） and the protein expression of phosphorylation JNK（p-JNK） in liver tissue. Hematoxylin-eosin （HE） staining and Oil red staining to observe the pathological morphological changes of liver. Result:Compared with control group， the contents or activities of TC， TG， ALT， AST and TNF-α in serum， the contents of TC， TG and FFA in liver and the gene and protein expressions of TLR4， MyD88， JNK， and the protein expression of p-JNK in liver tissue of model group were distinctly increased （P<0.01）， the content of IL-10 was significantly decreased （P<0.01）. Compared with model group， the contents or activities of TC， TG， ALT， AST and TNF-α in serum， the contents of TC， TG and FFA in liver and the mRNA and protein expressions of TLR4， MyD88 and JNK， and the protein expression of p-JNK in liver tissue of Danggui Shaoyaosan groups were significantly reduced （P<0.05，P<0.01）， the content of IL-10 in serum of Danggui Shaoyaosan groups was distinctly increased（P<0.05，P<0.01）， HE staining and Oil red staining show that the degree of liver steatosis was alleviated obviously by Danggui Shaoyaosan. Conclusion:Danggui Shaoyaosan has a better treatment on NAFLD by inhibiting TLR4/MyD88/JNK pathway and alleviating the inflammation response.

Objective:To observe Plantaginis Semen's mechanism in treating diarrhea by observing the effect on inflammatory factors in serum and mRNA and protein expressions of aquaporin4 (AQP4) in colon tissue of diarrhea rats. Method:Senne Folium was orally administered to duplicate diarrhea rats. Sixty male SD rats were randomly divided into normal group, model group, hydrochlorothiazide group (9 mg·kg^-1), and low, middle, and high-dose Plantaginis Semen groups (0.95, 1.9, 3.8 g·kg^-1). Senne Folium (20 mL·kg^-1) was intragastrically administered in 5 groups in the morning, except for normal group that was orally given the same dose of distilled water. In the afternoon, each treatment group was orally given the corresponding drugs, while normal group and model group were orally given the same dose of distilled water. The loose stool rate, average degree of loose stool, and diarrhea index were compared according to fecal traits and stool times after 14 days of treatment. The serum and colon tissue were collected to detect the contents of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) in serum. Hematoxylin-eosin (HE) staining was used to observe the pathological morphological changes of colon tissue, and quantiative Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the mRNA and protein expressions of AQP4 in colon tissue. Result:In the model group, the loose stool rate, average degree of loose stool, and diarrhea index were significantly increased (P<0.01), apoptosis and necrosis were observed in the epidermal cells of colonic mucosa, telangiectasia and congestion in lamina propria were obvious, and a few neutrophils were infiltrated, and the contents of TNF-α, IL-6 and CRP in serum increased (P<0.05, P<0.01), the mRNA and protein expressions of AQP4 significantly decreased (P<0.01). Compared with the model group, the loose stool rate, average degree of loose stool, and diarrhea index were significantly decreased in low, middle, and high-dose Plantaginis Semen groups (P<0.01), the apoptosis and necrosis of epidermal cells, telangiectasia and hyperemia and neutrophil infiltration in colonic mucosa were obviously improved, and the contents of TNF-α and CRP in serum significantly decreased (P<0.05, P<0.01), the mRNA and protein expressions of AQP4 increased （P<0.05, P<0.01）. Conclusion:Plantaginis Semen has a better antidiarrheal effect, and its mechanism may be related to inhibition of inflammatory reaction, repair of pathological damage of colonic mucosa, up-regulation of AQP4 expression and promotion of water and fluid metabolism.