ObjectiveTo explore the mechanism of Shouhui Tongbian capsules in treating constipation based on the research foundation of its active components combined with network pharmacology and animal experiments. MethodsThe drug components were imported into SwissTargetPrediction to predict the targets of Shouhui Tongbian capsules， and constipation-related targets were collected from disease databases. A protein-protein interaction （PPI） network was constructed for the common targets shared by Shouhui Tongbian capsules and constipation to screen key targets， which was followed by gene ontology （GO） function and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment analyses. A "bioactive component-target-pathway" network was constructed， and the core components of Shouhui Tongbian capsules in treating constipation were screened based on the topological parameters of this network. Molecular docking was employed to predict the binding affinity of core components to key targets. A mouse model of constipation was constructed to screen the key pathways and targets of the drug intervention in constipation. ResultsThe PPI network revealed six key constipation-related targets： protein kinase B （Akt1）， B-cell lymphoma-2 （Bcl-2）， glycogen synthase kinase-3β （GSK-3β）， cyclooxygenase-2 （PTGS2）， estrogen receptor 1 （ESR1）， and epidermal growth factor receptor （EGFR）. The KEGG pathway analysis showed that the phosphatidylinositol 3-kinase （PI3K）/Akt signaling pathway was the most enriched. The topological parameter analysis of the "bioactive component-target-pathway" network screened out the top 10 core components： auranetin， isosinensetin， naringin， diosmetin， quercetin， apigenin， luteolin， hesperidin， isorhapontigenin， and chrysophanol. Molecular docking results showed that the 10 core components had strong binding affinity with the 6 key targets. Animal experiments showed that after intervention with different doses of Shouhui Tongbian capsules， the time to the first black stool excretion was reduced and the fecal water content and small intestine charcoal propulsion rate of mice were improved. After treatment with Shouhui Tongbian capsules， the colonic mucosal injury and glandular arrangement were alleviated， and the muscle layer thickness was increased. Western blot results showed that Shouhui Tongbian capsules recovered the expression of apoptosis-related molecules mediated by the PI3K/Akt pathway in the colonic tissue of constipated mice. Terminal-deoxynucleotidyl transferase-mediated nick end labeling （TUNEL） results showed that the cell apoptosis rate of the colon significantly reduced after intervention with Shouhui Tongbian capsules. ConclusionThe results of network pharmacology and animal experiments confirmed that Shouhui Tongbian capsules can treat constipation through multiple targets and pathways. The capsules can effectively intervene in loperamide-induced constipation in mice by regulating the constipation indicators and reducing cell apoptosis in the colon tissue via activating the PI3K/Akt signaling pathway.

Chronic constipation （CC） is one of the most common functional gastrointestinal diseases. At present， the overall therapeutic effect of CC is still not satisfactory worldwide， which seriously affects the quality of life and social function of patients. The etiology and pathophysiological mechanism of constipation are still unclear. It involves comprehensive factors such as heredity， social psychology， diet， intestinal flora imbalance， intestinal motility disorder， visceral sensitivity change， pelvic floor muscle group dysfunction and enteric nervous system （ENS） disorder. Among them， the abnormal factors of the brain-gut-microbiome axis are particularly significant. The brain-gut-microbiome axis is a complex network of interactions between the intestine and the brain， integrating and coordinating the physiological functions and pathological processes of the gastrointestinal tract. Microorganisms in the intestinal lumen play an important role in it， and can communicate with the intestinal tract and the central nervous system through nerve， endocrine and immune pathways. As a key brain-gut peptide in the regulation pathway of the brain-gut-microbiome axis， 5-hydroxytryptamine （5-HT） is involved in the regulation of gastrointestinal motility， sensation and secretion. The abnormal conduction of the 5-HT signaling pathway is closely related to the occurrence and development of constipation. Traditional Chinese medicine（TCM） is a unique precious resource in China， which has good curative effects and safety. In recent years， it has received extensive attention in the treatment of constipation. TCM and active ingredients， acupuncture and massage specifically regulate 5-HT signal transmission， so that the expressions of related molecules tend to be suitable for individual disease state levels to effectively improve constipation symptoms， with unique advantages. Therefore， this study used ''constipation''， ''intestinal flora''， ''5-HT''， and ''traditional Chinese medicine'' as the keywords to search PubMed， China National Knowledge Infrastructure （CNKI） and other literature databases. The correlation between 5-HT and constipation as well as brain-gut-microbiome axis and the research progress of TCM intervention in the 5-HT signaling pathway in the treatment of constipation were reviewed in order to explore the potential therapeutic value of 5-HT system in this disease and provide references for subsequent research.

ObjectiveTo conduct a systematic review of the effect of active music therapy on cognitive function for older adults with cognitive impairment based on International Classification of Diseases, the 11th Revision (ICD-11), and International Classification of Functioning, Disability and Health (ICF). MethodsA PICO framework was constructed. Thematic keyword searches were conducted in databases including PubMed, Web of Science, Embase, CNKI, VIP, and Wanfang data, for literature on the effect of active music therapy on cognitive function for older adults with cognitive impairment, published up to November 5th, 2023. Information on authors, countries, publication date, sample characteristics, study designs, intervention methods, measurement tools and outcomes were extracted. The methodological quality of the researches was evaluated using the Physiotherapy Evidence Database (PEDro) scale. ResultsEight researches from six countries were included, which were all randomized controlled trials involving 356 older adults with mild cognitive impairment and dementia. The articles were published from 2014 to 2020, with an average of 7.4 of the PEDro scale. Active music therapy was used by singing and playing instruments. Interventions took place in hospitals, nursing homes, and health centers. The intervention duration ranged from mostly 30 to 60 minutes a time, with a few 120 minutes a time. Interventions were implemented mostly one to three times a week, lasting from eight to twelve weeks. Health outcomes focused on cognitive function, including overall cognitive function, executive function, attention function and memory function. ConclusionA theoretical framework for the benefits of active music therapy on the cognitive function for older adults with cognitive impairment has been constructed based on ICD-11 and ICF. Active music therapy can improve overall cognitive function, executive function, attention function and memory function for older adults with cognitive impairment.

Objective To explore the risk factors for myocardial injury in esophagogastric variceal bleeding(EGVB)patients with liver cirrhosis during hospitalization.Methods A case-control trial was conducted on 235 EGVB patients admitted to our hospital between May 2021 and July 2022.Their basic information,laboratory results and relevant data during hospitalization were collected.According to their myocardial enzyme profiles during hospitalization,they were divided into myocardial injury group(n=46)and non-myocardial injury group(n=189).Univariate regression analysis and clinical correlation analysis were used to preliminarily screen the risk factors for myocardial injury secondary to EGVB caused by liver cirrhosis.Then,multivariate logistic regression analysis was used to further screen the risk factors.A nomogram was constructed based on the selected risk factors and the occurrence of myocardial injury.Receiver operating characteristic(ROC)curve was plotted to analyze the independent predictive value of these factors alone or combined together.Calibration curve analysis and internal verification were utilized to evaluate the predictive performance of the nomogram model.Subgroup verification was performed in the myocardial infarction group.Results Univariate analysis revealed that statistical differences were observed in age,sex,hypertension,renal disease,underlying diseases,vomiting,leukocytosis,increased alanine aminotransferase(ALT)or aspartate aminotransferase(AST),albumin,red blood cell hematocrit(HCT),international normalized ratio(INR),endoscopy within 6 h after admission,and Child-Pugh(CP)class between the myocardial injury group and the non-myocardial injury group(P＜0.01).Multivariate logistic regression analysis showed that age(P=0.014,OR=1.153,95％CI:1.030～1.291),underlying diseases(P=0.005,OR=1.122,95％CI:1.032～2.437),and albumin(P=0.012,OR=0.449,95％CI:0.241～0.837)were independent risk factors for inhospital myocardial injury in EGVB patients with liver cirrhosis.The AUC value of the above indicators combined together for predicting myocardial injury was 0.902.Hosmer-Lemeshow test and calibration curve analysis indicated that the nomogram had good prediction consistency(Chi-square=12.88,P=0.615).Internal verification correctly distinguished 86.4％of verification objects.Subgroup analysis of myocardial injury patients showed that albumin was also an independent risk factor for in-hospital myocardial injury in this population(AUC=0.80).Conclusion Age,underlying diseases,and albumin level are independent risk factors for in-hospital myocardial injury in EGVB patients with liver cirrhosis.Albumin level can be used as an independent risk factor for predicting myocardial infarction.Combination of the above 3 indicators has a high diagnostic value in early identification and prevention of myocardial injury in this patient population.

Protein as the allergens could lead to allergy. In addition, a widespread class of allergens were known as glycans of N-glycoprotein. N-glycoprotein contained oligosaccharide linked by covalent bonds with protein. Recently,studies implicated that allergy was associated with glycans of heterologous N-glycoprotein found in food, inhalants, insect toxins, etc. The N-glycan structure of N-glycoprotein allergen has exerted an influence on the binding between allergens and IgE, while the recognition and presentation of allergens by antigen-presenting cells (APCs) were also affected. Some researches showed thatN-glycan structure of allergen was remodeled by N-glycosidase, such as cFase I, gpcXylase, as binding of allergen and IgE partly decreased. Thus, allergic problems caused by N-glycoproteins could potentially be solved by modifying or altering the structure ofN-glycoprotein allergens, addressing the root of the issue. Mechanism of N-glycans associated allergy could also be elaborated through glycosylation enzymes, alterations of host glycosylation. This article hopes to provide a separate insight for glycoimmunology perspective, and an alternative strategy for clinical prevention or therapy of allergic diseases.

ObjectiveExisting artificial vision devices can be divided into two types: implanted devices and extracorporeal devices, both of which have some disadvantages. The former requires surgical implantation, which may lead to irreversible trauma, while the latter has some defects such as relatively simple instructions, limited application scenarios and relying too much on the judgment of artificial intelligence (AI) to provide enough security. Here we propose a system that has voice interaction and can convert surrounding environment information into tactile commands on head and neck. Compared with existing extracorporeal devices, our device can provide a larger capacity of information and has advantages such as lower cost, lower risk, suitable for a variety of life and work scenarios. MethodsWith the latest remote wireless communication and chip technologies, microelectronic devices, cameras and sensors worn by the user, as well as the huge database and computing power in the cloud, the backend staff can get a full insight into the scenario, environmental parameters and status of the user remotely (for example, across the city) in real time. In the meanwhile, by comparing the cloud database and in-memory database and with the help of AI-assisted recognition and manual analysis, they can quickly develop the most reasonable action plan and send instructions to the user. In addition, the backend staff can provide humanistic care and emotional sustenance through voice dialogs. ResultsThis study originally proposes the concept of “remote virtual companion” and demonstrates the related hardware and software as well as test results. The system can not only achieve basic guide functions, for example, helping a person with visual impairment to shop in supermarkets, find seats at cafes, walk on the streets, construct complex puzzles, and play cards, but also can meet the demand for fast-paced daily tasks such as cycling. ConclusionExperimental results show that this “remote virtual companion” is applicable for various scenarios and demands. It can help blind people with their travels, shopping and entertainment, or accompany the elderlies with their trips, wilderness explorations, and travels.

ObjectiveTo establish a UHPLC-MS/MS quantitative method for the determination of glucuronic acid， tartaric acid， glycolic acid， malic acid， lactic acid， citric acid， DL-2-hydroxybutyric acid sodium， mandelic acid， benzilic acid， hydroxycaprylic acid， lactobionic acid， gluconic acid and N-acetylneuraminic acid in cosmetics. MethodsSamples were prepared by ultrasonic extraction， cleansed by precipitating reagent and followed by high-speed centrifugation of the extraction solution. The supernatant was filtered by 0.22 μm Millipore filter. The continued filtrate was taken for analysis. A reversed phase column， Poroshell 120 EC-C₁₈ （2.7 μm， 4.6 mm×1 000 mm） was used with 0.1% formic acid buffer and acetonitrile as the mobile phase under the condition of gradient elution. The analytes were detected with electrospray ionization source in negative ion mode （ESI^-） and multiple reactions monitoring （MRM）， and quantified by external standard curve. ResultsThe method showed a good linearity of glucuronic acid， tartaric acid， malic acid， DL-2-hydroxybutyric acid sodium， benzilic acid， hydroxycaprylic acid and N-acetylneuraminic acid within the concentration range of 50.0‒2 000.0 μg·L^-1 （r>0.995）. The method showed a good linearity of glycolic acid， lactic acid， citric acid and mandelic acid within the concentration range of 100.0‒5 000.0 μg·L^-1 （r>0.995）. The method showed a good linearity of lactobionic acid and gluconic acid within the concentration range of 50.0‒5 000.0 μg·L^-1 （r>0.995）. The recoveries were in the range of 92.3%‒114.1%； the relative standard deviations （RSD） were in the range of 0.9%‒6.0% （n=3）. The detection limits of glucuronic acid， tartaric acid， malic acid， citric acid， DL-2-hydroxybutyric acid sodium， mandelic acid， benzilic acid， hydroxycaprylic acid， lactobionic acid， gluconic acid and N-acetylneuraminic acid were 0.003% while the detection limits of glycolic acid， lactic acid and mandelic acid were 0.006%. In 10 batches of commercially available cosmetics， eight batches showed positive result. ConclusionThe UHPLC-MS/MS method is efficient， sensitive and accurate and is applicable to the determination of 13 α-hydroxy acidic components in cosmetics.

Chronic constipation （CC） is one of the common and frequent functional gastrointestinal diseases in clinic. At present， the overall therapeutic effect of CC is still not satisfactory in China and abroad， which seriously affects the quality of life of patients. The pathophysiological mechanism of constipation has not been fully elucidated， and studies have mainly focused on the dysfunction of the enteric nervous system （ENS）， abnormalities of Cajal interstitial cells （ICCs）， alterations in mucosal immune function （low-grade intestinal inflammation， intestinal barrier damage， and immune activation）， abnormalities of gastrointestinal hormones， dysregulation of intestinal flora， and dysfunctions of intestinal dynamics. Traditional Chinese medicine （TCM） is a unique and precious resource in China with good efficacy and safety. TCM and its active ingredients can effectively treat constipation， and its mechanism of action needs to be further investigated. Signaling pathways are involved in the development of constipation， which is one of the main targets in the study of pathological mechanisms of constipation and the pharmacological study of therapeutic drugs. Therefore， the authors searched PubMed， China National Knowledge Infrastructure （CNKI）， and other literature databases with the keywords of ''constipation''， ''signaling pathway''， and ''traditional Chinese medicine'' to systematically summarize the signaling pathways related to constipation regulated by TCM. The comprehensive analysis shows that TCM mainly plays a role in regulating autophagy， apoptosis， and proliferation and ensuring anti-oxidative stress， anti-inflammation， and protection of intestinal barrier of ICCs by modulating signaling pathways such as stem cell factor/tyrosine kinase receptor （SCF/c-kit）， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， 5-hydroxytryptophan （5-HT）， mitogen-activated protein kinases （MAPK）， and Toll-like receptors （TLRs）. TCM regulates neurotransmitter secretion and intestinal water metabolism to improve constipation. This demonstrates the advantages of multi-level， multi-target， and multi-level effects of TCM， and in-depth research can provide new ideas for exploring the pathogenesis of constipation and developing new drugs.

Objective:To investigate the efficacy and safety of high intensity focused ultrasound(HIFU)com-bined with endometrial thermal Balloon ablation(TBEA)in the treatment of menorrhagia associated with adenomy-osis(AM).Methods:A retrospective cohort study was performed on clinical data of 77 patients with menorrhagia associated with adenomyosis(AM)in Mianyang Central Hospital from January 2021 to December 2022.According to different treatment methods,they were divided into HIFU combined with TBEA(HIFU+TBEA group,n=26)and HIFU combined with gonadotropin-releasing hormone agonist(GnRH-a)and levonorgestrel-releasing intrauterine system(LNG-IUS)(HIFU+drug group,n=51).The pictorial blood loss assessment chart(PBAC)at different fol-low-up time after HIFU ablation was used as the main outcome index,dysmenorrhea score(NRS),serum CA125 level,re intervention rate,treatment effectiveness rate and adverse reactions were used as the secondary out-come indexes.Evaluate the efficacy and safety of HIFU combined with TBEA in the treatment of menorrhagia as-sociated with AMby comparing the difference of outcome indexes between two groups before and after treatment at different times.Results:Compared with pre-treatment,the PBAC score,NRS score and CA125 level were signif-icantly decreased after treatment in both groups(P<0.05).Compared with HIFU+drug group,PBAC score of HIFU+TBEA group decreased more at 6,9 and 12 months after treatment(P<0.05),but there was no signifi-cant difference in PBAC score at 1 and 3 months after treatment(P>0.05).There was no significant difference in NRS scores between the two groups at 1,3,6,9 and 12 months after treatment(P>0.05).There was no signifi-cant difference in reintervention rate between HIFU+TBEA group(11.54% )and HIFU+drug group(21.57% )after treatment(P>0.05).There was no significant difference in treatment effectiveness between HIFU+TBEA group(80.77% )and HIFU+drug group(70.59% )(P>0.05).The adverse reactions of the two groups after treatment were graded as SIR A-B,and no serious adverse events occurred.Conclusions:The combination of HIFU and TBEA has good efficacy and safety in the treatment of AM,and can be used as a long-term manage-ment program for patients with no fertility needs,especially for AM patients with menorrhagia,which also has good clinical application value.

Objective:To investigate the efficacy and safety of high intensity focused ultrasound(HIFU)com-bined with endometrial thermal Balloon ablation(TBEA)in the treatment of menorrhagia associated with adenomy-osis(AM).Methods:A retrospective cohort study was performed on clinical data of 77 patients with menorrhagia associated with adenomyosis(AM)in Mianyang Central Hospital from January 2021 to December 2022.According to different treatment methods,they were divided into HIFU combined with TBEA(HIFU+TBEA group,n=26)and HIFU combined with gonadotropin-releasing hormone agonist(GnRH-a)and levonorgestrel-releasing intrauterine system(LNG-IUS)(HIFU+drug group,n=51).The pictorial blood loss assessment chart(PBAC)at different fol-low-up time after HIFU ablation was used as the main outcome index,dysmenorrhea score(NRS),serum CA125 level,re intervention rate,treatment effectiveness rate and adverse reactions were used as the secondary out-come indexes.Evaluate the efficacy and safety of HIFU combined with TBEA in the treatment of menorrhagia as-sociated with AMby comparing the difference of outcome indexes between two groups before and after treatment at different times.Results:Compared with pre-treatment,the PBAC score,NRS score and CA125 level were signif-icantly decreased after treatment in both groups(P<0.05).Compared with HIFU+drug group,PBAC score of HIFU+TBEA group decreased more at 6,9 and 12 months after treatment(P<0.05),but there was no signifi-cant difference in PBAC score at 1 and 3 months after treatment(P>0.05).There was no significant difference in NRS scores between the two groups at 1,3,6,9 and 12 months after treatment(P>0.05).There was no signifi-cant difference in reintervention rate between HIFU+TBEA group(11.54% )and HIFU+drug group(21.57% )after treatment(P>0.05).There was no significant difference in treatment effectiveness between HIFU+TBEA group(80.77% )and HIFU+drug group(70.59% )(P>0.05).The adverse reactions of the two groups after treatment were graded as SIR A-B,and no serious adverse events occurred.Conclusions:The combination of HIFU and TBEA has good efficacy and safety in the treatment of AM,and can be used as a long-term manage-ment program for patients with no fertility needs,especially for AM patients with menorrhagia,which also has good clinical application value.