This paper proposes a two-stage method integrating visual foundation models （VFM） and diffusion models. The segment anything model （SAM） as VFM is combined with the SegRefiner diffusion model to construct the SAM-SegRefiner framework for automated segmentation of edema， inflammation， and thrombus regions in histopathological images of hemorrhoidal tissue， providing a reproducible technical tool for the objective quantification of pathological morphology and its application in traditional Chinese medicine （TCM） syndrome research. Trained and validated on multi-center retrospective data， the SAM-SegRefiner model achieved an average pixel accuracy of 95.32% and a mean intersection over union （mIoU） of 66.81% on an independent test set， significantly outperfor-ming comparative models such as U-Net， MixU-Net， and SAM-Med2D， and also demonstrating robust cross-center generalization capability. Furthermore， by correlating the quantitatively segmented results from the model with the patients' TCM syndrome types， the potential associations between pathomorphological features and TCM syndrome differentiation have been explored. The analysis revealed no statistically significant differences in the degree of inflammatory infiltration and thrombus formation among different syndrome types， suggesting a complex relationship between local pathological changes and systemic syndrome manifestations.

Primary biliary cholangitis （PBC） is a cholestatic autoimmune liver disease characterized by the injury of small intrahepatic bile ducts， and at present， the pathogenesis of PBC remains unclear. Recent studies have shown that bile acid metabolism disorder and gut microbiota imbalance play a key role in the development and progression of PBC， and they form a complex and dynamic interaction network via the “gut-liver axis” and regulate core physiopathological processes such as immune response， metabolic homeostasis， and inflammatory response in a synergistic manner. This article systematically elaborates on the abnormal features of bile acid metabolism and gut microbiota in PBC， discusses their synergistic mechanisms in PBC， and then proposes a combined strategy of targeting bile acid receptors and modulating gut microbiota， in order to overcome the limitations of current treatment modalities and provide new insights and directions for the clinical management of PBC.

The amino-terminal pro-C-type natriuretic peptide(NT-proCNP)is a diagnostic inflam-matory marker clinically used for diagnosing bacterial infections.This study aims to establish a phage display library of single-chain variable fragment(scFv)antibodies against canine NT-proC-NP and to screen for scFvs with high binding affinity to NT-proCNP.Initially,NT-proCNP was prepared using prokaryotic expression system and was used to immunize New Zealand White rab-bits.Upon achieving the desired serum titer,total RNA was extracted from the splenocytes of rab-bits and reverse transcribed into cDNA.Using this cDNA as a template,degenerate primers were employed to amplify the genes of the rabbit antibody light chain variable region(VL)and heavy chain variable region(VH).The VL and VH regions were spliced together to form a complete scFv fragment via overlap extension PCR.The scFv was then ligated into the phagemid pComb3XSS and electroporated into competent E.coli TG1 cells to construct a rabbit-derived anti-NT-proCNP scFv immunological library.This library underwent four rounds of enrichment and screening to isolate specific single-chain antibodies.The selected antibody was subsequently ex-pressed in a soluble form within a prokaryotic system,and its immunological activity was evalua-ted.Using phage display technology,this study successfully identified a single-chain antibody scFv-1-CNP with strong antigen-binding activity and genetic sequence characteristics of scFvs,providing a research direction for further exploration of scFv applications in the detection of NT-proCNP.

Sinisan is a classical prescription developed and applied by ancient medical experts and it is first recorded in the Treatise on Cold Damage written by ZHANG Zhongjing in the Eastern Han Dynasty. Later physicians have modified this prescription based on this original one. The bibliometrics methods were used to analyze the key information and research trend of Sinisan. According to the inclusion and exclusion criteria， 69 pieces of effective data were extracted， involving 67 ancient traditional Chinese medicine （TCM） books. The results showed that the name， composition， and decocting methods of Sinisan in later generations were inherited from the original record in the Treatise on Cold Damage. The original plants of medicinal materials used in Sinisan are basically clear. We recommend Bupleuri Radix as the dried root of Bupleurem scorzonerifolium， Paeoniae Radix Alba as the dried root of Paeonia lactiflora， Aurantii Fructus as the dried fruit of Citrus aurantium， Glycyrrhizae Radix et Rhizoma as the dry root and rhizome of Glycyrrhiza uralensis. Raw materials of Bupleuri Radix and Paeoniae Radix Alba， Aurantii Fructus stir-fried with bran， and stir-fried Glycyrrhizae Radix et Rhizoma should be used for preparation of Sinisan. According to measurement system in the Han Dynasty， a bag of Sinisan is composed of 1.25 g Bupleuri Radix， 1.25 g Paeoniae Radix Alba， 1.25 g Aurantii Fructus， and 1.25 g Glycyrrhizae Radix et Rhizoma. The materials should be grounded into coarse powder and taken with a proper amount of rice soup， 3 times a day. Sinisan has the effects of regulating qi movement and harmonizing the liver and spleen. It can be used for treating reversal cold in limbs and cold damage. In modern clinical practice， Sinisan can be used to treat chronic gastritis， irritable bowel syndrome， and dyspepsia. The above research results provide scientific reference for the future research and development of Sinisan.

The amino-terminal pro-C-type natriuretic peptide(NT-proCNP)is a diagnostic inflam-matory marker clinically used for diagnosing bacterial infections.This study aims to establish a phage display library of single-chain variable fragment(scFv)antibodies against canine NT-proC-NP and to screen for scFvs with high binding affinity to NT-proCNP.Initially,NT-proCNP was prepared using prokaryotic expression system and was used to immunize New Zealand White rab-bits.Upon achieving the desired serum titer,total RNA was extracted from the splenocytes of rab-bits and reverse transcribed into cDNA.Using this cDNA as a template,degenerate primers were employed to amplify the genes of the rabbit antibody light chain variable region(VL)and heavy chain variable region(VH).The VL and VH regions were spliced together to form a complete scFv fragment via overlap extension PCR.The scFv was then ligated into the phagemid pComb3XSS and electroporated into competent E.coli TG1 cells to construct a rabbit-derived anti-NT-proCNP scFv immunological library.This library underwent four rounds of enrichment and screening to isolate specific single-chain antibodies.The selected antibody was subsequently ex-pressed in a soluble form within a prokaryotic system,and its immunological activity was evalua-ted.Using phage display technology,this study successfully identified a single-chain antibody scFv-1-CNP with strong antigen-binding activity and genetic sequence characteristics of scFvs,providing a research direction for further exploration of scFv applications in the detection of NT-proCNP.

Objective : To investigate the efficacy of standardized allergen subcutaneous immunotherapy (SCIT) in children with asthma sensitized to single dust mite allergens versus multiple allergens and to assess the safety of SCIT. Methods : 62 children with confirmed allergic asthma who received standardized allergen SCIT were retro⁃ spectively analyzed and divided into the monosensitized group (dust mite results≥ + + + ) and the polysensitized group (dust mite results ≥ + + + combined with other positive allergens) according to the results of skin pricktest , we observed the changes of pulmonary function , medication score and visual analog scale (VAS) scores , children asthma control test (C - ACT) scores , asthma control questionnaire (ACQ) scores before and after treatment in both groupsand compared the efficacy of the two groups. The incidence of local and systemic adverse effects was recorded during treatment in all children to assess the safety of SCIT. Results : Standardized allergen SCIT treatmentimproved lung function parameters , medication scores and VAS scores , C ⁃ACT scores , ACQ scores in both the monosensitized and polysensitized groups , with statistically significant differences before and after treatment (P < 0. 05) . In comparison between the two groups , lung function parameters [forced expiratory flow at 50% vital capacity(FEF50% ) , maximum midexpiratory flow(MMEF)] , medication scores , C ⁃ACT scores and ACQ scores improved significantly in the monosensitized group compared with the polysensitized group after treatment ( P <0. 001) . 62 patients received a total of 2 606 injections during the treatment of SCIT , 6 children had a total of 10 local adverse reactions and 3 children had 3 mild to moderate systemic adverse reactions , with an incidence of 0. 38% for local adverse reactions and 0. 12% for systemic adverse reactions. Conclusion The children with asthma in both the monosensitized group and polysensitized group achieved significant and safe clinical outcomes under standardized allergen SCIT. The children in the monosensitized group had more obvious clinical effects than the polysensitized group under standardized allergen SCIT.

OBJECTIVE: To explore the correlation of mitochondrial DNA (mtDNA) variants and coronary heart disease (CHD) in a Chinese pedigree and the possible molecular mechanisms. METHODS: A Chinese pedigree featuring matrilineal inheritance of CHD who visited Hangzhou First People's Hospital in May 2022 was selected as the study subject. Clinical data of the proband and her affected relatives was collected. By sequencing the mtDNA of the proband and her pedigree members, candidate variants were identified through comparison with wild type mitochondrial genes. Conservative analysis among various species was conducted, and bioinformatics software was used to predict the impact of variants on the secondary structure of tRNA. Real-time PCR was carried out to determine the copy number of mtDNA, and a transmitochondrial cell line was established for analyzing the mitochondrial functions, including membrane potential and ATP level. RESULTS: This pedigree had contained thirty-two members from four generations. Among ten maternal members, four had CHD, which yielded a penetrance rate of 40%. Sequence analysis of proband and her matrilineal relatives revealed the presence of a novel m.4420A>T variant and a m.10463T>C variant, both of which were highly conserved among various species. Structurally, the m.4420A>T variant had occurred at position 22 in the D-arm of tRNAMet, which disrupted the 13T-22A base-pairing, while the m.10463T>C variant was located at position 67 in the acceptor arm of tRNAArg, a position critical for steady-state level of the tRNA. Functional analysis revealed that patients with the m.4420A>T and m.10463T>C variants exhibited much fewer copy number of mtDNA and lower mitochondrial membrane potential (MMP) and ATP contents (P < 0.05), which were decreased by approximately 50.47%, 39.6% and 47.4%, respectively. CONCLUSION Mitochondrial tRNAMet 4420A>T and tRNAArg 10463T>C variants may underlay the maternally transmitted CHD in this pedigree, which had shown variation in mtDNA homogeneity, age of onset, clinical phenotype and other differences, suggesting that nuclear genes, environmental factors and mitochondrial genetic background have certain influence on the pathogenesis of CHD.
Humans ; Female ; Mutation ; Pedigree ; RNA, Transfer, Met ; East Asian People ; RNA, Transfer, Arg ; DNA, Mitochondrial/genetics* ; Coronary Disease/genetics* ; Adenosine Triphosphate

Background By analyzing the publication of scientific and technological papers of the provincial centers for disease control and prevention (CDCs) in China, we can understand their scientific research strength, dominant disciplines, research hotspots, and talent development, which is conducive for further optimizing the scientific research construction of the disease control system. Objective To conduct a bibliometric analysis and draw a visual map of the Chinese Science Citation Database (CSCD) sourced papers published by 31 provincial CDCs in China from 2011 to 2020, to understand the scientific research status of China's provincial CDC system in the past ten years. Methods In April 2021, China National Knowledge Infrastructure was used to retrieve CSCD sourced papers published by 31 provincial CDCs (excluding Taiwan Province, Hong Kong and Macau Special Administrative Regions) in China as the primary unit from 2011 to 2020, and finally 5231 CSCD papers were included. Bibliometric analysis indicators include number of CSCD papers published and financial support rate, proportion of CSCD papers to total Chinese papers, distribution of CSCD papers published in high-volume journals, and number of papers for a specific CDC that their first authors affiliated with. Citespace 5.8.R1 software was used to draw author's cooperation network map, keyword co-occurrence map, keyword clustering information table, and keyword emergence map. Results The number of CSCD papers published every year showed a stationary trend, and the total funding rate was 61%, showing an year-by-year upward trend (increased from 49.3% in 2011 to 68.7% in 2020). Jiangsu Province, Fujian Province, and Beijing CDCs ranked the top three in the total number of CSCD papers contributed by a specific CDC. The Chinese Journal of Epidemiology, Chinese Journal of Public Health, Chinese Journal of Zoonoses, Chinese Journal of Preventive Medicine, and Chinese Journal of Endemic Diseases were the top five high-volume journals. The top three authors of CSCD papers (counted as co-authors) were Xu Bianli of Henan Provincial Center for Disease Control and Prevention (110 papers), Yan Yansheng of Fujian Provincial Center for Disease Control and Prevention (72 papers), and Wang Quanyi of Beijing Center for Disease Prevention and Control (71 papers), and they studied the epidemiology of parasitic diseases and infectious diseases, the prevention and treatment of natural epidemic diseases and AIDS, and the epidemiology of infectious diseases, respectively. The keyword co-occurrence map showed that AIDS, zoonotic diseases, hand-foot-mouth disease, etc. (frequency ≥90) were the key research directions of provincial CDCs in the past ten years. The keyword clustering categories were closely related, although there were subtle differences, the topics focused on virus and chronic disease research. The keyword emergence results suggested that the frontiers of research had gradually shifted from infectious diseases such as enterovirus, hantavirus, and Zika virus to food-borne diseases and chronic non-communicable diseases such as tumors and senile diseases over time. Conclusion The number of papers issued by the provincial CDCs in China in the past ten years has shown an overall steady and rising trend. The leading themes of researchers and institutions are infectious diseases, parasitic diseases, etc., while food-borne diseases and elderly diseases are the hot frontiers.

Background The COVID-19 pandemic hints at the importance of modernizing disease control system. To understand the scientific research strength of our country's disease control system in recent years is conducive to formulating more targeted policies or measures to promote the modernization of the disease control system. Objective To understand the scientific research strength and research hotspots of China's provincial-level centers for disease control and prevention (CDCs) from 2011 to 2020, and provide evidence for the development of scientific research work, discipline construction, and talent team construction in CDCs in the future. Methods The Science Citation Index Expanded (SCIE) and Social Science Citation Index (SSCI) of the Web of Science Core Collection were used to retrieve SCI-indexed English papers published by 31 provincial CDCs (excluding Taiwan Province, Hong Kong and Macau Special Administrative Regions) in our country from 2011 to 2020, and to screen literature with provincial CDCs as the first affiliation for bibliometric analysis and visual analysis. Bibliometric analysis included the SCI-indexed publications of different provincial CDCs (as co-affiliation and the first affiliation), the number of SCI-indexed papers published by provincial CDCs (as the first affiliation) and funding rates by years, the high-frequency authors of SCI-indexed papers published by provincial CDCs (as the first affiliation) and their distribution, and the characteristics of the journals. Visual analysis software Citespace 5.8.R1 was used to draw keyword co-occurrence maps, cluster information tables, and emergence maps to provide information on research hotspots and their evolution. Results From 2011 to 2020, the number of SCI-indexed papers from 31 provincial CDCs was 8420 (including co-affiliation), of which 2060 papers listed provincial CDCs as the first affiliation. The provincial CDCs of Zhejiang, Jiangsu, Shanghai, Beijing, Shandong, and Guangdong were the leading six institutes in terms of the total number of SCI-indexed papers contributed as co-affiliation or the first affiliation. There was a large gap in the total number of SCI-indexed papers among the provincial CDCs. The highest total number of SCI-indexed papers contributed by provincial CDCs as the first affiliation was Zhejiang CDC (448 papers), while the lowest number was Xinjiang CDC (only 1 paper). From 2011 to 2020, the total number of SCI-indexed papers contributed by the 31 provincial CDCs as the first affiliation showed an overall increasing trend. Except for 2011, which was 63.1%, the funding rates in other years exceeded 70%. In terms of high-frequency authors, 13 first authors published ≥10 SCI-indexed papers: Zhang Yingxiu from Shandong CDC had the highest number of SCI-indexed papers (47), followed by Hu Yu from Zhejiang CDC. Zhejiang, Jiangsu, Beijing, Guangdong, Shanghai, and Shandong still ranked the top six of ≥4 first authored-SCI papers. In terms of journal characteristics, the top 20 journals with the highest number of SCI papers published a total of 862 papers, accounting for 41.8% (862/2060), and PLOS ONE ranked the first (188 papers). The research hotspots were mainly concentrated in the fields of infection, child health, and epidemiology. The main keywords of the first three cluster categories were related to the research fields of adolescent overweight and obesity, HIV, and vaccine immunity. The results of keyword emergence showed that research hotspots shifted from overweight, obesity, and body mass index to antibodies, vaccines/vaccination, and cohorts. Conclusion The past ten years have witnessed increasing numbers of SCI-indexed papers published by provincial CDCs in our country and a stubbornly high funding rate. However, the gap among the provincial CDCs is still large seeing that economically developed eastern provincial CDCs published more SCI-indexed papers. Research hotspots have gradually shifted from overweight, obesity, and body mass index to antibodies, vaccines/vaccination, and cohorts.

Objective: To analyze the relationship between body fat distribution and bone mineral content (BMC) in adolescents and gender differences among Chinese adolescents, and to provide a scientific basis for the prevention and treatment of bone metabolic diseases. Methods: A total of 1 575 adolescents aged 12-18 years old were selected from Yinchuan by cluster random sampling. Body composition and bone mineral content were measured by bioelectrical impedance analysis(BIA). Multiple linear regression analysis was used to explore the relationship between body fat distribution and BMC after adjusting for confounding factors. Results: Except for LTFR, the levels of FM, AFM, TFM, TrTFR and TrLFR in boys were lower than those in girls( t =-13.52， -15.18 ，-12.47，-12.25，-7.96， P <0.05); After adjusting for age, sex and weight, FM, AFM, TFM, TrTFR and TrLFR were all negatively correlated with BMC level( P <0.05). For each increase of 1 standard deviation in TFM, BMC level decreased by 0.53 standard deviation(95% CI=-0.57--0.49, P<0.01]. LTFR had a linear negative correlation with BMC level in boys( B=0.07, P <0.01), no similar correlation was found in girls( B=0.01, P =0.74). There was a linear negative correlation between TrLFR and BMC level in girls( B=-0.06, P =0.03), but the correlation was of no significance in boys( B=-0.01, P =0.55). Conclusion Sex difference in body fat distribution in Chinese adolescents is observed. Body fat distribution is closely related to bone minerals content in adolescents.