ObjectiveTo explore effect of Xianlian Jiedu prescription on the recurrence of colorectal cancer （CRC） and investigate the related mechanisms. MethodsA postoperative recurrence model was established in 25 Balb/c mice by injecting CT26 cells subcutaneously into the armpit， followed by surgical removal of 99% of the subcutaneous tumor. The mice were randomly divided into model group， low-dose Xianlian Jiedu prescription （XLJDP-L） group （6.45 g·kg^-1·d^-1）， medium-dose Xianlian Jiedu prescription （XLJDP-M） group （12.9 g·kg^-1·d^-1）， high-dose Xianlian Jiedu prescription （XLJDP-H） group （25.8 g·kg^-1·d^-1）， and 5-fluorouracil （5-FU） group （1×10^-3 g·kg^-1·d^-1）. The mice were euthanized after 14 days of continuous intervention， and recurrent tumor tissue was harvested. Hematoxylin and eosin （HE） staining was used to observe pathological and morphological changes in the recurrent tumor tissue. Immunohistochemistry （IHC） was employed to assess the expression of proliferating cell nuclear antigen （Ki67）， vascular endothelial growth factor （VEGF）， and platelet-endothelial cell adhesion molecule （CD31） in recurrent tumor tissue. The Western blot was used to detect the protein expression levels of angiopoietin-2 （ANG-2）， VEGF， phosphorylated-protein kinase B （p-Akt）， protein kinase B （Akt）， phosphorylated-phosphatidylinositol 3-kinase （p-PI3K）， and phosphatidylinositol 3-kinase （PI3K） in recurrent tumor tissue. ResultsBefore treatment， there were no statistical differences in tumor volume， tumor weight， and body mass among the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group compared to the model group， indicating model stability. After treatment， compared with those in the model group， the tumor volume and tumor weight in the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group were significantly reduced （P<0.01）， showing dose dependency. Meanwhile， there were no significant differences in body weight among the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group compared to the model group. HE staining showed that compared with that in the model group， tumor tissue in the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group had loosely arranged cells， increased intercellular spaces， small and shriveled nuclei， light staining， fewer mitotic figures and atypical nuclei， and increased necrotic areas. IHC showed that compared with those of the model group， the positive rates of Ki67， VEGF， and CD31 in the recurrent tumor tissue of the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group were significantly reduced （P<0.01） in a dose-dependent manner. Western blot results showed that compared with those of the model group， the protein expression levels of ANG-2 and VEGF in the recurrent tumor tissue of the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group were significantly downregulated （P<0.05， P<0.01）， and the p-Akt/Akt and p-PI3K/PI3K ratios were significantly decreased in a dose-dependent manner （P<0.05， P<0.01）. ConclusionXianlian Jiedu prescription significantly inhibits the recurrence of CRC in mice after subcutaneous tumor surgery. The mechanism may involve regulating the PI3K/Akt pathway and downregulating key angiogenic proteins such as ANG-2， VEGF， and CD31.

OBJECTIVES: To investigate the effect of age-friendly social and family care environment on the long-term care (LTC) services for the disabled elderly people. METHODS: A questionnaire-based survey was conducted among disabled elderly people in three cities of Zhejiang province from June to August 2022, involving 311 subjects from Ningbo city (LTC service insurance pilot site, insured group) and 542 subjects from Hangzhou and Quzhou cities (uninsured group). The service provisions, including ensuring daily activities, preventive healthcare, and satisfying spiritual comfort, were compared among the groups. The family friendly care environment was evaluated with the Family Function Scale and assistance of daily activities, financial support and emotional comfort. The social friendly care environment was measured with the revised WHO recommended age-friendly city environmental framework, including accessibility guarantee environment, information dissemination environment, social participant environment, and life security environment. After controlling for covariates such as sociodemographic, elderly care status, and health risk characteristics, the impact of environment on the effectiveness of service provision of LTC insurance was explored by multiple logistic regression analysis. The mediating and moderating effects were tested to explore the role of age-friendly care environment. A fixed effects model was used to test the service provision effects of LTC insurance policy. RESULTS: Disabled elderly with LTC insurance had a higher proportion of their preventive health care and spiritual comfort needs met. Additionally, a multifactorial analysis found a significant positive association between LTC insurance and meeting the spiritual comfort needs. Compared with insured group (Ningbo city), disabled elderly people in Hangzhou urban area (OR=0.45, 95%CI:0.27-0.74, P<0.01) and Quzhou rural area (OR=0.21, 95%CI:0.12-0.37, P<0.01) were more likely to feel unsatisfied with spiritual comfort. The results of mediation analysis showed that the scores of accessibility guarantee environment (OR=1.22, 95%CI:1.02-1.45, P<0.05), information dissemination environment (OR=1.19, 95%CI:1.02-1.39, P<0.05), and social participation environment (OR=1.40, 95%CI:1.17-1.67, P<0.01) in a socially friendly care environment were positively correlated with the satisfaction rate of mental comfort services. The results of the moderation effect analysis indicated that a socially friendly care environment (OR=1.46, 95%CI:1.16-1.84, P<0.01) could compensate for the difference in effectiveness between insured (Ningbo) and uninsured (Hangzhou and Quzhou) areas of LTC insurance. A fixed effect model confirmed the policy chain of LTC insurance policy-social friendly care environment-mental health service satisfaction. CONCLUSIONS The implementation of LTC insurance has improved service accessibility, making disabled elderly people feel "seen and valued", and generating psychological and spiritual satisfaction. Accelerating the establishment and improvement of the LTC insurance system requires systematic design, especially emphasizing the supportive role of a socially friendly care environment, and promoting it in urban and rural areas according to the local conditions.
Humans ; Aged ; Persons with Disabilities ; Surveys and Questionnaires ; Long-Term Care ; Female ; Male ; China ; Social Environment ; Middle Aged ; Aged, 80 and over

China is a high-incidence region for gastric cancer globally. The disease is characterized by a high morbidity rate, low early diagnostic rate, and poor long-term outcomes, imposing a significant burden on both patients and society. Therefore, exploring the pathogenesis of gastric cancer, developing novel therapeutic strategies, and identifying new drug targets is of great importance. Telomerase expression is broadly associated with cancer cell targeting, and its up-regulation is one of the key factors driving the initiation and progression of gastric cancer. Additionally, telomerase is intricately involved in the regulation of autophagy and autophagy-associated cell death. While autophagy can induce chemoresistance, excessive autophagy may lead to cell death, which also constitutes one of the mechanisms of chemotherapy. Telomerase not only directly contributes to gastric cancer pathogenesis but also indirectly influences its development and treatment by modulating autophagy and autophagic cell death. Therefore, telomerase holds promise as a novel therapeutic target in gastric cancer.
Humans ; Stomach Neoplasms/genetics* ; Telomerase/genetics* ; Autophagy/physiology*

Booster vaccinations are highly recommended in combating the SARS-CoV-2 Omicron variant and its subvariants. However, the optimal booster vaccination strategies and related immune mechanisms with different prior vaccinations are under-revealed. In this study, we systematically evaluated the immune responses in mice and hamsters with different prime-boost regimens before their protective efficacies against Omicron were detected. We found that boosting with Ad5-nCoV, S_WT-2P or S_Omicron-6P induced significantly higher levels of neutralization activities against Omicron variants than CoronaVac and ZF2001 by eliciting stronger germinal center (GC) responses. Specifically, S_Omicron-6P induced even stronger antibody responses against Omicron variants in CoronaVac and Ad5-nCoV-primed animals than non-Omicron-specific vaccines but with limited differences as compared to Ad5-nCoV and S_WT-2P. In addition, boosting with a specific vaccine has the potential to remodel the existing immune profiles. These findings indicated that adenovirus-vectored vaccines and mRNA vaccines would be more effective than other types of vaccines as booster shots in combating Omicron infections. Moreover, the protective efficacies of the vaccines in booster vaccinations are highly related to GC reactions in secondary lymphatic organs. In summary, these findings provide timely important information on prime-boost regimens and future vaccine design.

OBJECTIVES: This study aimed to explore the therapeutic effect and mechanism of ginsenoside Rb3 on experimental periodontitis and bone resorption in rats. METHODS: Male SD rats were randomly divided into a control group, a ligation group, an Rb3 group, and a doxycycline (Dox) group for in vivo experiments. A periodontitis model was established by ligating the maxillary second molar, and samples were collected after 3 weeks of drug treatment. Micro-CT assessment of alveolar bone resorption was performed, and hematoxylin-eosin (HE) staining was used to observe pathological changes in periodontal and visceral tissues. Tartrate resistant acid phosphatase (TRAP) staining was applied to detect the formation of osteoclasts in periodontal tissues, and enzyme-linked immunosorbent assay (ELISA) was adopted to detect the serum levels of interleukin (IL)-6, IL-8, immunoglobulin (Ig)M, and IgG. Quantitative polymerase chain reaction (qPCR) was employed to detect the expression of factors related to gingival inflammation and osteoclast formation. Immunofluorescence staining was used to detect phospho-extracellular signal-regulated kinase (p-ERK) expression. In vitro experiments were conducted by pretreating RAW264.7 cells with drugs and adding lipopolysaccharides (LPS) stimulation from Porphyromonas gingivalis (P. gingivalis). IL-1β and IL-6 mRNA expression was detected by qPCR, and Western blot was used to detect the effect of Rb3 on the mitogen-activated protein kinases (MAPKs) signaling pathway. RESULTS: Compared with the control group, the ligation group showed significant periodontitis and bone resorption. Compared with the ligation group, the Rb3 group showed a decrease in alveolar bone resorption and osteoclast formation; p-ERK/ERK ratio, IL-1β, IL-6, and nuclear factor of activated T cells (NFATc1) mRNA levels and downstream gene expression in periodontal tissues; serum IL-6, IL-8, IgG, and IgM levels. Rb3 reduced IL-8 and IL-1β mRNA expression levels and p-ERK/ERK and p-p38 MAPK/p38 MAPK ratios in RAW264.7 cells induced by P. gingivalis LPS stimulation. CONCLUSIONS Rb3 inhibits inflammation and bone resorption in experimental periodontitis in rats. Compared with Dox, Rb3 has better effects in inhibiting pro-inflammatory factors and osteoclast gene expression and may exert anti-inflammatory effects by activating the MAPK signaling pathway.
Animals ; Ginsenosides/therapeutic use* ; Rats, Sprague-Dawley ; Male ; Periodontitis/pathology* ; Rats ; Osteoclasts/drug effects* ; Interleukin-1beta/metabolism* ; Interleukin-6/blood* ; Mice ; Alveolar Bone Loss ; Interleukin-8/blood* ; Immunoglobulin G/blood* ; RAW 264.7 Cells ; Transcription Factors

Biosensors have become powerful tools for real-time monitoring of specific small molecules and precise control of gene expression in biological systems. High-throughput sensors for 1, 4-butanediamine biosynthesis can greatly improve the screening efficiency of high-yielding 1, 4-butanediamine strains. However, the strategies for adapting the characteristics of biosensors are still rarely studied, which limits the applicability of 1, 4-butanediamine biosensors. In this paper, we propose the development of a 1, 4-butanediamine biosensor based on the transcriptional regulator PuuR, whose homologous operator puuO is installed in the constitutive promoter P_gapA of Escherichia coli to control the expression of the downstream superfolder green fluorescent protein (sfGFP) as the reporter protein. Finally, the biosensor showed a stable linear relationship between the GFP/OD₆₀₀ value and the concentration of 1, 4-butanediamine when the concentration of 1, 4-butanediamine was 0-50 mmol/L. The promoters with different strengths in the E. coli genome were used to modify the 1, 4-butanediamine biosensor, and the functional properties of the PuuR-based 1, 4-butanediamine biosensor were explored and improved, which laid the groundwork for high-throughput screening of engineered strains highly producing 1, 4-butanediamine.
Biosensing Techniques/methods* ; Escherichia coli/metabolism* ; Promoter Regions, Genetic/genetics* ; Green Fluorescent Proteins/metabolism* ; Transcription Factors/genetics* ; Escherichia coli Proteins/genetics* ; Diamines/metabolism* ; Gene Expression Regulation, Bacterial

Objective:To observe the effects of electroacupuncture(EA)on sleep electroencephalogram(EEG)and event-related potential(ERP)in patients with somatoform disorders(SFD). Methods:Seventy-five SFD patients were recruited as an EA group to receive EA at Shenting(GV24)and Baihui(GV20)once daily,30 min each time,with 6 straight days as a treatment course,and 4 courses were conducted at 1-day intervals.Before treatment,patients underwent a survey using a physical symptom checklist on their primary symptoms.Before and after treatment,their sleep EEG was monitored using Quisi,and the ERP mismatch negativity(MMN)and P300 were detected.The Quisi sleep EEG and ERP were also examined among 40 normal volunteers as the normal group data. Results:During the trial,13 cases were removed from the EA group due to incomplete data,and 62 cases were finally included for statistical analyses.Of the 62 SFD patients,the main disturbing symptoms were cognitive impairments,sleep disorders,respiratory symptoms,digestive symptoms,five-sense organ problems,and cardiovascular symptoms in order.Before treatment,the EA group had increased MMN and P300 latencies and decreased amplitudes compared with the normal control group(P<0.01 or P<0.05);according to Quisi,the EA group also had reduced total sleep time(TST),shorter rapid eye movement sleep(REM)latency(RL)and REM time(RT),smaller number of REM period(NRP),extended sleep latency(SL),longer awaking time(AT),lower sleep efficiency(SE),larger percent of non-rapid eye movement sleep(NREM)stage 1(S1)and smaller percent of NREM stage 2(S2),and the percent of slow wave sleep(SWS),i.e.NREM stage 3(S3)plus stage 4(S4),also went down,all presenting significant differences between groups(P<0.01 or P<0.05).After 4 courses of treatment,the MMN and P300 latencies were reduced,and their amplitudes became larger in the EA group compared with the baseline(P<0.05);they had insignificant differences compared with the normal control group(P>0.05).Quisi showed that the TST and RL increased,and the SL and AT decreased in the EA group,and the predominant change in sleep architecture was reduced S1 percent,increased S2,and improved SE,all showing significant intra-group differences(P<0.01 or P<0.05);however,the intra-group difference in the NRP was statistically insignificant(P>0.05).Except the TST,RT,S1 percent,and SWS,there was no statistical significance in comparing the other Quisi parameters(including RL,NRP,SL,AT,SE,and S2 percent)between the two groups(P>0.05). Conclusion:SFD patients have a variety of clinical symptoms,and most of them show abnormal sleep EEG and ERP;EA can correct abnormal sleep EEG parameters and the MMN and P300 of ERP in SFD patients.

Objective To construct a domain knowledge graph of dementia care,so as to provide the foundation and guarantee for the next intelligent application based on the knowledge graph.Methods A top-down approach was adopted to construct a domain knowledge graph of dementia care.Firstly,the ontology concept is constructed from the top level,namely the schema layer of knowledge graph.Then,instances are filled,and knowledge extraction is carried out from the existing data sources,and the extracted entities and relationships are filled into the pattern layer ontology database to complete the data layer construction of the knowledge graph.Finally,the"entity relationship entity"triplet data was input into the Neo4j graph database for storage.Results In this study,the personalized care plan set of 1 012 dementia cases was used as the corpus to construct a domain knowledge graph of dementia care.The knowledge graph takes people with dementia as the core,and unfolds,one by one,around basic characteristics,care problems,and care plans in a standardized"entity-relationship-entity"triplet format,forming a large knowledge network,which contains a total of 1 522 specific dementia care knowledge entities and 8 kinds of inter-entity relationships.Conclusion The domain knowledge graph of dementia care constructed in this study clearly and intuitively shows the global pedigree and logical path of knowledge,which provides an efficient and intelligent basic guarantee for the browsing,retrieval and application of dementia care knowledge,so as to realize personalized and intelligent management of people with dementia,break through the bottleneck of lack of professionals,improve the health outcomes of people with dementia,promote the implementation of inclusive pension services,and promote healthy aging.

ObjectiveTo explore the biological foundation of colorectal adenoma in damp-heat accumulation syndrome and the possible anti-tumor mechanism of Shenbai Jiedu prescription. MethodEight patients with colorectal adenoma in damp-heat accumulation syndrome， 11 patients with non-damp-heat accumulation syndrome， and 10 patients with colorectal cancer recruited by Jiangsu Provincial Hospital of Traditional Chinese Medicine from February 2019 to December 2020 meeting the inclusion criteria were clinically obtained， and the tissue of the three groups of patients was subjected to transcriptome sequencing to screen for the differentially expressed genes between the syndrome and the diseases. The intersection of the differentially expressed genes between the syndrome and the disease was taken for further screening of the differentially expressed genes sequentially increasing or sequentially decreasing in patients with non-damp-heat accumulation syndrome， damp-heat accumulation syndrome， and colorectal cancer， and functional enrichment analysis and signaling pathway enrichment analysis were carried out. Real-time polymerase chain reaction （Real-time PCR） was used to detect the effect of Shenbai Jiedu prescription on the expression of the above key differential genes. ResultBy comparing the damp-heat accumulation syndrome and non-damp-heat accumulation syndrome， a total of 384 differentially expressed genes were screened， of which 203 were up-regulated genes， and 181 were down-regulated genes. By comparing the colorectal adenoma of colorectal cancer and damp-heat accumulation syndrome， a total of 2 965 differentially expressed genes were screened， of which 2 460 were up-regulated genes， and 505 were down-regulated genes. The intersection of differentially expressed genes of the two groups was taken， and a total of 58 differentially expressed genes with the same changes were screened. The gene ontology functions were mainly enriched in UDP-galactose： β-N-acetylglucosamine beta-1，3-galactosyltransferase activity， N-acetyllactosaminide beta-1，3-N-acetylglucosaminyltransferase activity， and poly-N-acetyllactosamine biosynthetic process. Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathways were mainly enriched in glycosphingolipid biosynthesis-globo and isoglobo series， glycosphingolipid biosynthesis-lacto and neolacto series， and IL-17 signaling pathway. Shenbai Jiedu prescription significantly inhibited the expression of key genes involved in the enrichment， such as FOSB and B3GALT5， in a dose-dependent manner （P<0.05）. ConclusionGlycolipid metabolism may be the biological foundation of colorectal adenoma in damp-heat accumulation syndrome， and Shenbai Jiedu prescription may inhibit colorectal adenoma carcinogenesis by down-regulating the expression of FOSB and B3GALT5.

ObjectiveTo observe the effects of Shenbai Jiedu prescription on fecal metabolomics and intestinal flora diversity distribution in patients with colorectal adenoma and explore its potential targets. MethodA total of 21 patients diagnosed with colorectal adenoma were enrolled in this study. Following a four-week administration of Shenbai Jiedu prescription， their clinical symptoms were observed， and fecal samples of patients before and after treatment were collected. Untargeted metabolomics and metagenomic analysis based on liquid chromatography-mass spectrometry （LC-MS） were employed to investigate the possible metabolic pathway of Shenbai Jiedu prescription and its influence on the distribution of intestinal flora in patients. ResultThe total scores of traditional Chinese medicine （TCM） syndromes of patients after drug administration decreased significantly （P<0.01）. The results of untargeted metabolomics showed that the distribution of metabolites exhibited aggregation before and after drug administration， and a total of 106 differential metabolites were screened out （P<0.05）. The Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis revealed that arginine-proline metabolism， ferroptosis， glycine， and serine and threonine metabolism were significantly enriched metabolic pathways （P<0.05）. Notably， L-4-hydroxyglutamate semialdehyde， glutathione， isopentenyl pyrophosphate， creatinine， 4-acetamido-2-aminobutanoic acid， and guanidoacetic acid were found to be involved in these aforementioned metabolic pathways. Furthermore， the association between these metabolites and different intestinal flora was analyzed， and the results showed that Shenbai Jiedu prescription could interfere with metabolic pathways such as amino acid and ferroptosis in patients with colorectal adenoma by regulating intestinal flora such as Lachnoclostridium， Eggerthella， and Dialister （P<0.05）. ConclusionShenbai Jiedu prescription may improve the clinical symptoms of patients by increasing the abundance of intestinal beneficial bacteria， reducing the abundance of harmful bacteria， and regulating metabolic pathways such as amino acid and ferroptosis in patients with colorectal adenoma. This study may provide some research ideas and directions for Shenbai Jiedu prescription to interfere with colorectal adenoma recurrence and carcinogenesis.