Clinicians need to focus on various points in the diagnosis and treatment of insomnia.This article prescribed the treatment protocol based on the unique features,such as insomnia in the elderly,women experiencing specific physiologi-cal periods,children insomnia,insomnia in sleep-breathing disorder patients,insomnia in patients with chronic liver and kidney dysfunction.It pro-vides some reference for clinicians while they make decision on diagnosis,differentiation and treat-ment methods.

Objective:To explore the quality improvement in the organization structure and management model of the integrated community child health services.Methods:This was a qualitative study, including two parts: cause analysis and service improvement suggestions. In the analysis part the data mining was conducted to identify valuable patterns and relationships in the comprehensive child health services. Semi-structured interviews were conducted with 12 relevant department heads and health workers of the comprehensive child health service team at Gumei Community Health Service Center in December 2023, and the causes of the key problems were explored. In the service improvement part, focus group discussions were held to propose suggestions, then improvement measures were formulated to address the identified problems.Results:Through data mining and semi-structured interviews, the key problems were identified: information isolation among multiple departments and lack of coordination mechanism in the comprehensive child health service team. A team organizational structure based on the "three definite" principle was established. The organizational structure should include the pediatric family doctor team, general practitioner management team and departments of pediatrics, maternal and child health care, immunization and child rehabilitation; the management model should include a cross-department resource and information sharing mechanism, the pediatric family doctor model, optimization and integration of physical space, and enhancement of publicity activities for the comprehensive child health services.Conclusion:Based on the analysis in Gumei health service center, this study identified key problems in community integrated child health services, and proposes the quality improvement measure in the organizational structure and management model of the service team.

Purpose/Significance To explore the feasibility of applying blockchain technology to the current healthcare system of hos-pitals,and to achieve the purpose of protecting patients'privacy to the greatest extent possible at a lower cost.Method/Process 505 questionnaires are randomly distributed and collected from people of different age groups in Beijing,Tianjin,Shanghai and Shenzhen who have a certain degree of understanding of blockchain technology,and the results are analyzed.Result/Conclusion Different age groups are highly concerned about personal privacy and privacy protection,and are willing to accept blockchain as an emerging technology.There is a greater demand and acceptance for the application of blockchain technology in the primary health care systems.

Objective:To develop a machine learning algorithm based on habitat imaging(HI),which can be used in the grading of gliomas by using multimodal magnetic resonance imaging(MRI),so as to construct the model of support vector machine(SVM)and the visualized heterogeneous regions of gliomas.Methods:A total of 335 glioma patients were collected from the 2019 brain tumor segmentation(BraTS)challenge competition of World Health Organization(WHO),which included 259 cases with high-grade gliomas(HGG)and 76 cases with low-grade gliomas(LGG).Subregions were divided based on HI technology.The PyRadiomics open-source package was used to extract the image features of region of interest(ROI),and to screen the features that stronger correlated with the high and low-grade gliomas.An SVM model was used to classify and predict the screened feature data.The heterogeneity of gliomas in images was analyzed through visualized characterization.The efficacy of glioma grading was assessed by using the area under curve(AUC)of the receiver operating characteristic(ROC)curve.Results:The AUC of test set exceeded 90%.The average accuracy of the performance indicators of test set was(92.74±2.88)%,and the average sensitivity was(93.90±2.10)%,and the average specificity was(90.36±4.59)%,and the average F1 score was(95.24±0.66)%when the tumors were divided into six habitat regions.The SVM model could showed important sub-regions in glioma grading in three-dimensional space.Conclusion:The study method based on HI has significant advantages in glioma grading,which can effectively realize visualized heterogeneity of tumor and construct model of the heterogeneity of tumor.

Objective To explore the distribution of traditional Chinese medicine(TCM)syndrome elements in patients with multi-drug resistant bacteria-infected pneumonia.Methods Clinical data of 126 patients with multi-drug resistant bacteria-infected pneumonia admitted to the intensive care unit of Lung Disease Centre of Qingdao Hospital of Traditional Chinese Medicine from May 2020 to July 2022 were retrospectively collected.The clinical data included the patients'gender,age,underlying diseases,history of bad additions of smoking and alcohol,multi-drug resistant bacteria,and the information of four diagnostic methods of TCM,etc.The disease-nature syndrome elements in patients with drug-resistance to various strains of drug-resistant bacteria were extracted,and then deficiency-excess syndrome differentiation was carried out.Results(1)A total of 201 strains of multi-drug resistant bacteria were detected in 126 patients with multi-drug resistant bacterial pneumonia.The main pathogenic species were Gram-negative bacteria,and the proportion accounted for 95.52%(192/201),which was significantly higher than that of Gram-positive bacteria[4.48%(9/201)],with a statistically significant difference(χ2 = 166.612,P＜0.001).Klebsiella pneumoniae accounted for the highest percentage of 23.38%in the gram-negative bacterium.(2)A total of 12 syndrome elements were extracted from the 126 patients.The excess syndrome elements were predominated by phlegm and heat,and the deficiency syndrome elements were predominated by yin deficiency.There was no statistically significant difference in the distribution of yin deficiency,blood deficiency,heat,phlegm,fluid-retention and damp syndrome elements among patients with different strains of drug-resistant bacterial infection(P＞0.05).(3)Of the 126 patients,62 cases(49.21%)had simple excess syndrome,one case(0.79%)had simple deficiency syndrome,and 63 cases(50.00%)had concurrent deficiency-excess syndrome.Among the 126 patients,there were 19 cases of single syndrome element,41 cases of concurrent two-syndrome element,49 cases of concurrent three-syndrome element,16 cases of concurrent four-syndrome element,and one case of concurrent five-syndrome element.And the combined syndrome element of phlegm-heat-yin deficiency occurred most frequently for 26 times.Conclusion Gram-negative bacteria are the primary infectious pathogens for the patients with multi-drug resistant bacterial infections,and the TCM syndrome elements of the patients are characterized by the concurrence of deficiency and excess and simple excess syndrome,mainly manifesting as phlegm,heat,and yin deficiency.

BACKGROUND:With computer-aided design,melt electrowriting technology can precisely construct 3D tissue engineering scaffolds with specific morphology,which has attracted increasing attention in tissue engineering. OBJECTIVE:To elaborate on the progress of melt electrowriting technology in tissue engineering in recent years. METHODS:PubMed and CNKI were used to retrieve articles about applications of melt electrowriting technology in tissue engineering.The search time was from March 2008 to February 2023.The search terms were"melt electrowriting,melt electrospinning,electrospinning,tissue engineering,scaffold,regeneration"in English and"melt electrowriting,electrospinning,tissue engineering"in Chinese.A preliminary screening of articles was performed by reading the titles and abstracts.Finally,69 articles were included for review. RESULTS AND CONCLUSION:(1)Melt electrowriting technology can achieve precise layer-by-layer deposition of fibers compared to traditional electrospinning technology,which better simulates the complex structure of natural tissues.Compared to other 3D printing technologies,smaller-diameter fibers can be prepared by melt electrowriting technology,resulting in highly ordered porous structures.(2)By combining with other scaffold preparation techniques or materials,such as fused deposition modeling,solution electrospinning technology,and hydrogel,melt electrowriting technology shows great potential in preparing complex tissue engineering scaffolds,which provides certain possibilities for achieving complex tissue regeneration.(3)The regeneration of complex tissues often involves blood vessels,nerves,and soft and hard tissues at the same time.The regeneration of blood vessels and nerves is of great significance to realize the physiological reconstruction of tissues.However,soft and hard tissues have certain difficulties to realize the coordinated regeneration of both due to their different biological and mechanical properties.Melt electrowriting technology has certain advantages in the field of bionic scaffolds due to its good biocompatibility,the ability to prepare multi-scale scaffolds and high porosity.

BACKGROUND:Semen cuscutae has the effect of tonifying the liver and kidney system and benefiting the essence.The main pathogenesis of osteoarthritis is deficiency of the liver and kidneys.Therefore,it is hypothesized that there is a link between semen cuscutae and osteoarthritis. OBJECTIVE:To explore the potential relationship between osteoarthritis and semen cuscutae and validate the mechanism of semen cuscutae based on the network pharmacology and molecular docking analysis. METHODS:First,the active ingredients and targets of semen cuscutae were screened in TCMSP,and the genes related to osteoarthritis were collected in the disease databases GeneCard's,OMIM and TTD.The intersected genes were taken and then subjected to a series of analyses and screened for hub genes.Through the enrichment analysis of hub genes,the pathway of semen cuscutae acting on osteoarthritis was selected.The role of hub genes was verified by molecular docking.Therefore,the appropriate active ingredients of semen cuscutae were selected for experimental verification. RESULTS AND CONCLUSION:There were 11 active ingredients of semen cuscutae,66 intersection target genes of semen cuscutae and osteoarthritis,and 12 hub genes,including tumor necrosis factor,interleukin 1B,TP53,RAC-alpha serine/threonine protein kinase(AKT1),vascular endothelial growth factor A,matrix metalloproteinase 9,prostaglandin peroxidase 2,cystatinase 3,epidermal growth factor,peroxisome proliferator-activated receptor gamma,interleukin 10,vascular cell adhesion factor 1.After the enrichment analysis of the hub genes,the classical inflammatory pathway,nuclear factor-κB signaling pathway,was selected for subsequent validation of semen cuscutae to alleviate osteoarthritic inflammation.Through the results obtained after molecular docking of each active ingredient and the hub gene of the pathway prostaglandin peroxidase 2,sesamin with the highest affinity was selected for subsequent cell experiments,and the experimental results confirmed that sesamin,the active ingredient of semen cuscutae,could reduce the expression of cyclooxygenase 2 by inhibiting the nuclear factor-κB signaling pathway induced by interleukin-1β.To conclude,sesamin,the active ingredient of semen cuscutae,reduces the expression of cyclooxygenase 2 by inhibiting the nuclear factor-κB signaling pathway induced by interleukin-1β,thereby improving inflammation in osteoarthritis and expanding the therapeutic effect of semen cuscutae in osteoarthritis.

G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

Objective To investigate the effects of DNA demethylation drugs combined with histone deacetylase in-hibitors on fragile X mental retardation 1 neighbor protein (FMR1NB) expression and its promoter methylation in human oral cancer cells and try to find a strategy of weakening the heterogeneity of FMR1NB expression.Methods Human oral cancer cell lines Cal27 and SCC-9 were treated with decitabine (DAC) , an inhibitor of DNA meth-yltransferase, combined with trichostatin A (TSA) and valproic acid (VPA), inhibitors of histone deacetylase.Then reverse transcription-polymerase chain reaction (RT-PCR) , quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the expression of FMR1 NB and pyrosequencing was used to detect the methylation of FMR1NB promoter.Results Compared with the blank control group, DAC and its combination with TSA and VPA significantly induced the expression of FMR1NB mRNA and protein in Cal27 and SCC-9 cells.Compared with DAC alone group, FMR1NB mRNA expression of each DAC-combined drug groups significantly increased, but FMR1NB protein did not significantly change in Cal27 cells; for SCC-9 cells, except for DAC+TSA group, the mRNA and protein levels of FMR1NB significantly increased in all other groups.In addition, there was no signifi-cant difference in the expression of FMR1 NB mRNA and protein between the three-combined drugs group and two-combined drugs groups.Further methylation assay showed that the methylation level of the overall FMR1NB promot-er and its each CpG site measured were reduced to varying degrees in all treatment groups except for three-combina-tion drug group of SCC-9.Conclusion DAC and its combination with TSA and VPA can enhance the expression of FMR1NB by mediating the demethylation of FMR1NB promoter, wherein the enhanced expression effect of the com-bination of the two drugs is stronger, suggesting that they have the potential to weaken the heterogeneity of FMR1NB expression and improve the immunotherapy effect of oral cancer.

Objective To investigate the effect of interleukin-22(IL-22)on the activation of hepatic stellate cells(HSCs)and its mechanism.Methods The human HSC LX-2 cells were selected for the study,and the LX-2 cells induced by TGF-β1 were used to establish a model of HSC activation.LX-2 cells were treated with IL-22 at gradient concentrations,and Western blot and qRT-PCR were used to measure the expression levels of the activation markers COL1A1 and α-SMA and determine the appropriate working concentration and time of the drug.Western blot,qRT-PCR,and immunofluorescence assay were used to determine the levels of Fn14 and the markers for endoplasmic reticulum stress(ERS)and activation in activated HSCs treated by IL-22.ERS in LX-2 cells was induced by tunicamycin(TM),and Western blot and qRT-PCR were used to measure the levels of markers for ERS and activation in LX-2 cells treated by IL-22.TNF-like weak inducer of apoptosis(TWEAK)and small interfering RNA were used to upregulate and downregulate Fn14,and then the mRNA and protein expression levels of p-IRE1α,IRE1α,XBP1s,COL1A1,and α-SMA were measured.After LX-2 cells induced by TGF-β1 were treated by IL-22,TWEAK was used to upregulate Fn14,and Western blot and immunofluorescence assay were used to measure the levels of Fn14 and the markers for ERS and activation.The independent-samples t-test was used for comparison of continuous data between two groups;a one-way analysis of variance was used for comparison between multiple groups,and the Sidak's multiple comparison test was used for further comparison between two groups.Results Compared with the TGF-β1 group,the TGF-β1+IL-22 group had significant reductions in the protein and mRNA expression levels of COL1A1 and α-SMA,with a more significant effect after treatment with 10 ng/mL IL-22 for 24 hours(all P<0.01).Compared with the TGF-β1 group,the TGF-β1+IL-22 group had significant reductions in the expression levels of Fn14,p-IRE1α,and XBP1s(all P<0.05).Compared with the TM group,the TM+IL-22 group had significant reductions in the expression levels of p-IRE1α,XBP1s,COL1A1,and α-SMA(all P<0.05).Compared with the silenced control group,the Fn14 siRNA group had significant reductions in the expression levels of p-IRE1α,XBP1s,COL1A1,and α-SMA(all P<0.05).Compared with the normal control group,the TWEAK group had significant increases in the expression levels of Fn14,p-IRE1α,XBP1s,COL1A1,and α-SMA(all P<0.01).Compared with the TGFβ1+IL-22 group,the TGF-β1+IL-22+TWEAK group had significant increases in the expression levels of Fn14,p-IRE1α,XBP1s,COL1A1,and α-SMA(all P<0.05).Conclusion IL-22 negatively regulates ERS in HSCs by inhibiting Fn14,thereby inhibiting the activation of HSCs.