ObjectiveThis paper aims to investigate the effects of Xixintang on aquaporin-4 （AQP4） polarity distribution， blood-brain barrier （BBB） function， and neuroinflammationin rats with Alzheimer's disease （AD）， thereby revealing the potential mechanism through which this formula protects the BBB by regulating AQP4 polarization. The aim is to provide a scientific basis for clinical treatment. MethodsSixty Sprague-Dawley （SD） rats were randomly divided into a normal group， a model group， a probiotic group， a donepezil group， and an Xixintang group. The model was established by intraperitoneal injection of D-galactose （D-Gal） combined with bilateral intracerebroventricular injection of amyloid-β_25-35 （Aβ_25-35）. The probiotic group （30.85 mg·kg^-1）， donepezil group （0.88 mg·kg^-1）， and Xixintang group （1.174 g·kg^-1） received daily gavage administration， while the normal and model groups received intragastric administration with an equal volume of normal saline for one month. Cognitive ability was assessed by using the Morris water maze. BBB permeability was detected via Evans blue extravasation. The contents of interleukin-6 （IL-6）， amyloid-β_1-42 （Aβ_1-42）， and tumor necrosis factor-α （TNF-α） in the hippocampal tissues were measured by enzyme-linked immunosorbent assay （ELISA）. The protein expressions of zonula occludens-1 （ZO-1）， occludin， tissue inhibitor of metalloproteinase-1 （TIMP-1）， matrix metalloproteinase-9 （MMP-9）， and AQP4 in the hippocampal tissues were detected by western blot. The expression and co-localization levels of Aβ_1-42， ionized calcium-binding adapter molecule 1 （IBA1）， and AQP4/platelet endothelial cell adhesion molecule 31 （CD31） in the hippocampal region were examined by immunofluorescence. ResultsCompared with the normal group， the model group exhibited a significant decline in cognitive ability （P<0.01） and a marked increase in Evans blue extravasation in the brain （P<0.01）. The expressions of ZO-1， occludin， and TIMP-1 were significantly decreased （P<0.01）， while the expressions of AQP4 and MMP-9 were significantly increased （P<0.01）. The co-localization level of AQP4/CD31 was significantly reduced （P<0.01）， and the expressions of Aβ_1-42， IL-6， TNF-α， and IBA1 were significantly elevated （P<0.01）. Compared with the model group， the Xixintang group showed significant improvement in cognitive ability （P<0.01） and a significant reduction in Evans blue extravasation in the brain （P<0.01）. The expressions of occludin， TIMP-1， and ZO-1 were significantly increased （P<0.05， P<0.01）， while the expressions of AQP4 and MMP-9 were significantly decreased （P<0.05）. The co-localization level of AQP4/CD31 was significantly enhanced （P<0.01）， and the expressions of Aβ_1-42， IL-6， TNF-α， and IBA1 were significantly reduced （P<0.05， P<0.01）. ConclusionXixintang may improve cognitive function and alleviate AD pathology in AD model rats by regulating AQP4 polarity distribution， thereby breaking the vicious cycle of "Aβ deposition-neuroinflammation-BBB damage" and restoring the homeostasis of the microenvironment in the brain.

ObjectiveThis study aims to investigate whether Xixintang could ameliorate cognitive dysfunction in an Alzheimer's disease （AD） rat model induced by D-galactose and β-amyloid （Aβ_25-35）， by means of repairing the colonic mucosal barrier， regulating the Toll-like receptor 4 （TLR4）/nuclear factor-κB p65 （NF-κB p65） signaling pathway， and intervening in the pathological process mediated by the gut-brain axis. MethodsSixty specific pathogen-free （SPF） male Sprague-Dawley （SD） rats were randomly divided to five groups （n=12）： A control group， a model group， a donepezil group， an Xixintang group， and a probiotic group. Except for those in the control group， rats in all other groups received daily intraperitoneal injections of D-galactose for six consecutive weeks. Subsequently， aggregated Aβ_25-35 was injected stereotactically into the bilateral ventricles to establish the AD model. During the intervention periods， the rats in all groups were administered their respective drugs and normal saline by gavage. The Morris water maze test was used to assess the capacity for spatial learning and memory. Hematoxylin-eosin （HE） staining was employed to observe the histopathological changes in the colon tissues. Immunofluorescence was used to detect Aβ_1-41 deposition in the hippocampal region and Mucin 2 （MUC2） expression in the colonic mucosa. Western blot was performed to measure the protein expression levels of FFAR2，TLR4， NF-κB p65， occludin （OCLN）， zonula occludens-1 （ZO-1）， and MUC2 in the colonic tissues. Enzyme-linked immunosorbent assay （ELISA） was used to determine the contents of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， serum amyloid A （SAA）， and Aβ_1-42 in the hippocampal region from the colonic tissues. The lipopolysaccharide （LPS） concentrations in colon tissues of rats were measured by using a dynamic chromogenic limulus assay. ResultsCompared with those in the control group， the rats in the model group exhibited a significantly prolonged escape latency and a markedly shorter duration in the target quadrant （P<0.01）. The integrity of the colonic mucosal structure was compromised， with disordered gland arrangement and a reduced number of goblet cells. The Aβ_1-42 deposition in the hippocampal region was significantly increased （P<0.01）. The protein expression levels of TLR4 and NF-κB p65 in colonic tissues were significantly upregulated （P<0.01）， while those of occludin and ZO-1 were downregulated （P<0.01）. The contents of inflammatory factors such as IL-6， TNF-α， and SAA were significantly elevated （P<0.01）， and the LPS level in the serum was markedly increased （P<0.01）. In comparison to those in the model group， the rats in the Xixintang group showed a significantly shortened escape latency and a prolonged duration in the target quadrant （P<0.01）. The colonic mucosal structure was ameliorated， with neat gland arrangement and an increased number of goblet cells. The Aβ_1-42 deposition in the hippocampal region was reduced （P<0.01）. The protein expressions of TLR4 and NF-κB p65 in the colon tissues were decreased （P<0.05，P<0.01）， while the protein levels of occludin and ZO-1 were increased （P<0.01）. The contents of IL-6， TNF-α， and serum amyloid A （SAA） were decreased （P<0.01）， and the LPS level was reduced （P<0.01）. ConclusionXixintang can significantly ameliorate cognitive dysfunction of AD model rats， by means of restoring the colonic mucosal barrier structure， reducing cerebral Aβ deposition， and suppressing peripheral and central inflammatory response. Its mechanism of action may be closely associated with the suppression of the TLR4/NF-κB signaling pathway activation， reduction of endotoxin levels， and regulation of the gut-brain axis.

ObjectiveThis study aims to investigate whether Xixintang could ameliorate cognitive dysfunction in an Alzheimer's disease （AD） rat model induced by D-galactose and β-amyloid （Aβ_25-35）， by means of repairing the colonic mucosal barrier， regulating the Toll-like receptor 4 （TLR4）/nuclear factor-κB p65 （NF-κB p65） signaling pathway， and intervening in the pathological process mediated by the gut-brain axis. MethodsSixty specific pathogen-free （SPF） male Sprague-Dawley （SD） rats were randomly divided to five groups （n=12）： A control group， a model group， a donepezil group， an Xixintang group， and a probiotic group. Except for those in the control group， rats in all other groups received daily intraperitoneal injections of D-galactose for six consecutive weeks. Subsequently， aggregated Aβ_25-35 was injected stereotactically into the bilateral ventricles to establish the AD model. During the intervention periods， the rats in all groups were administered their respective drugs and normal saline by gavage. The Morris water maze test was used to assess the capacity for spatial learning and memory. Hematoxylin-eosin （HE） staining was employed to observe the histopathological changes in the colon tissues. Immunofluorescence was used to detect Aβ_1-41 deposition in the hippocampal region and Mucin 2 （MUC2） expression in the colonic mucosa. Western blot was performed to measure the protein expression levels of FFAR2，TLR4， NF-κB p65， occludin （OCLN）， zonula occludens-1 （ZO-1）， and MUC2 in the colonic tissues. Enzyme-linked immunosorbent assay （ELISA） was used to determine the contents of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， serum amyloid A （SAA）， and Aβ_1-42 in the hippocampal region from the colonic tissues. The lipopolysaccharide （LPS） concentrations in colon tissues of rats were measured by using a dynamic chromogenic limulus assay. ResultsCompared with those in the control group， the rats in the model group exhibited a significantly prolonged escape latency and a markedly shorter duration in the target quadrant （P<0.01）. The integrity of the colonic mucosal structure was compromised， with disordered gland arrangement and a reduced number of goblet cells. The Aβ_1-42 deposition in the hippocampal region was significantly increased （P<0.01）. The protein expression levels of TLR4 and NF-κB p65 in colonic tissues were significantly upregulated （P<0.01）， while those of occludin and ZO-1 were downregulated （P<0.01）. The contents of inflammatory factors such as IL-6， TNF-α， and SAA were significantly elevated （P<0.01）， and the LPS level in the serum was markedly increased （P<0.01）. In comparison to those in the model group， the rats in the Xixintang group showed a significantly shortened escape latency and a prolonged duration in the target quadrant （P<0.01）. The colonic mucosal structure was ameliorated， with neat gland arrangement and an increased number of goblet cells. The Aβ_1-42 deposition in the hippocampal region was reduced （P<0.01）. The protein expressions of TLR4 and NF-κB p65 in the colon tissues were decreased （P<0.05，P<0.01）， while the protein levels of occludin and ZO-1 were increased （P<0.01）. The contents of IL-6， TNF-α， and serum amyloid A （SAA） were decreased （P<0.01）， and the LPS level was reduced （P<0.01）. ConclusionXixintang can significantly ameliorate cognitive dysfunction of AD model rats， by means of restoring the colonic mucosal barrier structure， reducing cerebral Aβ deposition， and suppressing peripheral and central inflammatory response. Its mechanism of action may be closely associated with the suppression of the TLR4/NF-κB signaling pathway activation， reduction of endotoxin levels， and regulation of the gut-brain axis.

Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors, including non-small cell lung cancer (NSCLC). However, its detailed molecular mechanism has not been adequately demonstrated. In this research, it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft (PDX) model. Mechanistically, employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis (MST), microRNA-145-5p (miR-145-5p) was pinpointed as a critical target through which elemene exerts its anti-tumor effects. Interestingly, elemene serves as a binding stabilizer for miR-145-5p, demonstrating a strong binding affinity (dissociation constant (K _D) = 0.39 ± 0.17 μg/mL) and preventing its degradation both in vitro and in vivo, while not interfering with the synthesis of the primary microRNA transcripts (pri-miRNAs) and precursor miRNAs (pre-miRNAs). The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA, subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3 (MAP3K3)/nuclear factor kappaB (NF-κB) pathway. Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors,including non-small cell lung cancer(NSCLC).However,its detailed molecular mechanism has not been adequately demonstrated.In this research,it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft(PDX)model.Mechanistically,employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis(MST),microRNA-145-5p(miR-145-5p)was pinpointed as a critical target through which elemene exerts its anti-tumor effects.Inter-estingly,elemene serves as a binding stabilizer for miR-145-5p,demonstrating a strong binding affinity(dissociation constant(KD)=0.39±0.17 μg/mL)and preventing its degradation both in vitro and in vivo,while not interfering with the synthesis of the primary microRNA transcripts(pri-miRNAs)and precursor miRNAs(pre-miRNAs).The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA,subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated pro-tein kinase kinase kinase 3(MAP3K3)/nuclear factor kappaB(NF-κB)pathway.Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

Objective To explore the functional improvement effect of acupuncture and moxibustion therapy of traditional Chinese medicine(mainly acupuncture on the three yang meridians of the hand,moxibustion on the governor vessel,and moxibustion through drugs)on cervical spondylosis of wind cold blocking collateral type.Methods 120 patients with wind cold obstruction type cervical spondylosis admitted to our hospital from July 2021 to July 2023 were randomly divided into two groups,with 60 cases in each group,using a random number table method.The control group was treated with conventional cervical traction,while the observation group was treated with traditional Chinese medicine acupuncture and moxibustion on the basis of the control group(mainly acupuncture at the hand Sanyang meridian+moxibustion at the governor's meridian+moxibustion through drugs).Compare the TCM syndrome scores,NDI,HO-1,LpPLA2,clinical efficacy,adverse reactions,hospitalization costs,and duration between two groups.Results After 4 weeks of treatment,the effective rate of disease in the observation group with wind cold obstructing cervical spondylosis(96.67%)was higher than that in the control group(83.33%),while the traditional Chinese medicine syndrome score,NDI score,HO-1,LpPLA2 in the observation group were lower than those in the control group(P<0.05).No adverse reactions were observed in both groups.Conclusion Traditional Chinese medicine acupuncture and moxibustion therapy(mainly acupuncture of the three yang meridians of the hand,governor vessel moxibustion,and herbal penetration moxibustion)has significant clinical effect in the application of cervical spondylosis of wind cold blocking collateral type,which can effectively improve clinical symptoms and biochemical indicators,promote the rehabilitation of cervical function,and has high safety.

Objective To explore the effect of a mobile health intervention model based on self-determination theory on subthreshold depression in breast cancer patients.Methods By convenience sampling method,74 patients with breast cancer subthreshold depression who received chemotherapy in the breast department of a tertiary hospital in Guangxi from July 2021 to August 2022 were selected as the research subjects.According to the order of admission time,the patients admitted from February 2022 to August 2022 were taken as an experimental group,and the patients admitted from July 2021 to January 2022 were taken as a control group,with 37 cases in each group.On the basis of routine nursing,the experimental group implemented a mobile health intervention model based on self-determination theory.The control group received routine nursing,with every 21 days for 1 cycle and a total of 4 cycles of intervention.Before and after the intervention,the Centre for Epidemiological Studies Depression Scale(CES-D),Hamilton Rating Scale for Depression(HAMD-17),Basic Psychological Needs Satisfaction Scale(BPNS)and Functional Assessment of Cancer Therapy-Breast(FACT-B)were used to evaluate the intervention effect.Results 34 patients in the experimental group and 36 patients in the control group completed the study.After intervention,the CES-D score and HAMD-17 score of the 2 groups were lower than those before intervention(P＜0.05);the CES-D score and HAMD-17 score of the experimental group were lower than those of the control group,and the difference was statistically significant(t=7.748,P＜0.001;t=8.150,P＜0.001).The BPNS scores of the 2 groups were higher than those before the intervention,and the BPNS score of the experimental group was significantly higher than that of the control group(t=-6.534,P＜0.001).The scores of FACT-B in the 2 groups were higher than those before the intervention,and the scores of FACT-B in the experimental group were significantly higher than those in the control group(t=-4.579,P＜0.001).Conclusion The mobile health intervention model based on self-determination theory can improve the subthreshold depression,self-determination and quality of life of breast cancer patients.

Objective:To conduct a scoping review of the application of mobile health applications (MHA) in the care of patients with colorectal cancer, summarizing the development process, the functions achieved, as well as the evaluation metrics, to provide references for MHA practice and related research.Methods:Following the scoping review framework, a comprehensive search was conducted across both domestic and international databases, including the China Biomedical Literature Database, Wanfang Database, China National Knowledge Infrastructure (CNKI), VIP Database, Cochrane Library, PubMed, Embase, CINAHL, Web of Science, and Scopus. The search period was from the database inception to February, 2024.Results:A total of 16 studies were included. The development of MHA involved multiple methods including literature reviews, qualitative interviews, consultations with multidisciplinary teams, and guidance from theoretical models. The functions of MHA include health education, peer support, guided feedback, monitoring, and reminder features. Evaluation metrics for MHA comprise usability, adherence, and effectiveness.Conclusions:MHA has demonstrated positive effects in enhancing patients' knowledge and alleviating symptoms such as fatigue and vomiting in colorectal cancer patients. However, it is still in its early stages, and further high-quality studies are needed to scientifically develop MHA that meets patients' needs.

Objective:To construct an evaluation index system for the core competence of hospital specialist service operation assistants and provide reference for the evaluation of such competence.Methods:From January to March 2022, literature analysis and behavioral event interviews were used to initially establish a core competence evaluation index system of hospital specialist service operation assistants, based on the Donabedian model. Subsequently, the Delphi expert consultation method was applied to conduct correspondence consultation, inviting experts to evaluate the contents and importance of the index system, using analytic hierarchy process to determine the weights of the indexes at all levels.Results:Two rounds of expert consultation were carried out, and the valid recovery rate of the questionnaire was 100%. The familiarity coefficient of the second round of correspondence was 0.87, the basis of judgment coefficient was 0.90, and the authority coefficient was 0.89. The final evaluation index system for core competence of hospital specialist service operation assistant consisted of 3 first-level indexes, 13 second-level indexes and 81 third-level indexes. The weight of the first-level index structure index was 0.266, and the highest weight among the second-level indexes was the operational development ability (0.083), while the highest weight among the third-level indexes of operational development ability was the comprehensive coordination ability (0.193); The weight of the first-level index process index was 0.405, and the corresponding second-level and third-level indexes with the highest weight were department operation practice work (0.157) and reasonable resource allocation (0.303), respectively; The weight of the first-level index result index was 0.329, and the corresponding second-level and third-level indexes with the highest weight were the weight of medical quality and safety (0.103) and drug adverse reaction reporting rate (0.237), respectively.Conclusions:The evaluation index system constructed in this study proves scientific and reasonable in weight assignment, proving a reference for the management of the specialist service operation assistants.

Objective To investigate the HIV-1 genotype and distribution of newly diagnosed HIV-1 cases in Fujian Province in 2020, so as to provide insights into formulation of the precise AIDS control strategy in the province. Methods Newly diagnosed HIV-1 cases without antiretroviral therapy (excluding AIDS patients) were randomly sampled from each city of Fujian Province in 2020 at a proportion of 50% of the mean number of HIV-infected cases reported across 9 cities of Fujian Province during the past three years. Subjects’ demographic and epidemiological data were collected and blood samples were collected. The HIV-1 pol gene was amplified using nested reverse-transcription PCR assay, and the gene sequences were used for HIV-1 genotyping and phylogenetic analysis. The gene sequences were uploaded to the HIV Drug Resistance Database (http://hivdb.stanford.edu) for genotypic drug resistance assays, and the scores and level of HIV drug resistance were estimated using the HIVDB Algorithm version 9.5. Results A total of 1 043 newly diagnosed HIV-1 cases were reported in Fujian Province in 2020, and 936 gene sequences were successfully obtained following sequencing of blood samples. There were 9 HIV-1 genotypes characterized in blood samples from 936 newly diagnosed HIV-1 cases, with CRF07_BC (52.1%) and CRF01_AE (30.4%) as predominant subtypes, followed by CRF08_BC (4.9%), CRF55_01B (3.0%), subtype C (2.5%), subtype B (2.1%), CRF85_BC (1.7%), CRF59_01B (0.3%) and CRF65_CPX (0.1%), and unidentified subtypes were found in 26 blood samples. HIV-1 drug resistance was detected in 43 out of the 936 newly diagnosed HIV-1 cases, with 4.6% prevalence of HIV-1 drug resistance prior to therapy, and the highest drug resistance was found in the HIV CRF59_01B subtype, followed by in CRF08_BC, B, C, CRF01_AE, CRF07_BC and other subtypes, with a significant difference in the genotype-specific prevalence of HIV-1 drug resistance (χ² = 45.002, P < 0.05). Conclusions There was a HIV-1 genotype diversity in Fujian Province in 2020, and emerging recombinant and drug-resistant HIV-1 strains were detected and spread across patients and regions. Monitoring of HIV-1 genotypes is recommended to be reinforced for timely understanding of the transmission and spread of novel recombinant and drug-resistant HIV-1 strains.