OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway.

OBJECTIVE To provide medication reference for duloxetine use in clinical settings， particularly for patients with depression in primary medical institutions in Xinjiang that lack therapeutic drug monitoring conditions. METHODS The medical records of 281 depression inpatients taking duloxetine in the First Affiliated Hospital of Xinjiang Medical University from January 2022 to December 2023 were retrospectively collected. They were divided into training set （196 cases） and test set （85 cases） in the ratio of 7∶3. Feature selection was performed by encapsulating random forests （RF） with recursive feature elimination. Four machine learning algorithms， namely support vector machine， RF， extreme gradient boosting （XGBoost） and artificial neural network， were used to construct duloxetine blood concentration prediction model. The prediction performance of the models was evaluated and compared by coefficient of determination （R2）， mean absolute error （MAE） and root mean squared error （RMSE）. The feature of the selected optimal model was explained by Shapley additive explanation method， and the importance ranking of the features and the influence on the prediction results of duloxetine blood concentration were determined. RESULTS A total of 29 characteristic variables were selected， including age， ethnicity， body mass index（BMI）， etc. XGBoost showed the highest R2 （0.808）， and the lowest MAE （7.644） and RMSE （10.808）. The ranking of feature importance for predicting the blood concentration of duloxetine was as follows： BMI＞age＞other 20 feature sets （including liver and kidney function and biochemical indicators）＞daily dosage＞comorbidities＞combination therapy＞ethnicity＞white blood cell count＞hemoglobin＞height. CONCLUSIONS XGBoost model possesses the best prediction performance of duloxetine blood concentration； BMI and age have a greater impact on the prediction of duloxetine blood concentration.

ObjectiveTo analyze the distribution characteristics of traditional Chinese medicine （TCM） syndrome elements in different risk populations of heart failure complicated with type 2 diabetes. MethodsClinical data of 675 type 2 diabetes patients were retrospectively collected. Lasso-multivariate Logistic regression was used to construct a clinical prediction nomogram model. Based on this， 441 non-heart failure patients were divided into a low-risk group （325 cases） and a high-risk group （116 cases） according to the median risk score of heart failure complicated with type 2 diabetes. TCM diagnostic information （four diagnostic methods） was collected for both groups， and factor analysis was applied to summarize the distribution of TCM syndrome elements in different risk populations. ResultsLasso-multivariate Logistic regression analysis identified age， disease duration， coronary heart disease， old myocardial infarction， arrhythmia， absolute neutrophil count， activated partial thromboplastin time， and α-hydroxybutyrate dehydrogenase as independent risk factors for heart failure complicated with type 2 diabetes. These were used as final predictive factors to construct the nomogram model. Model validation results showed that the area under the curve （AUC） of the receiver operating characteristic （ROC） curve for the modeling group and validation group were 0.934 and 0.935， respectively. The Hosmer-Lemeshow test （modeling group P = 0.996， validation group P = 0.121） indicated good model discrimination. Decision curve analysis showed that the curves for All and None crossed in the upper right corner， indicating high clinical utility. The low-risk and high-risk groups each obtained 14 common factors. Preliminary analysis revealed that the main disease elements in the low-risk group were qi deficiency （175 cases， 53.85%）， dampness （118 cases， 36.31%）， and heat （118 cases， 36.31%）， with the primary locations in the spleen （125 cases， 38.46%） and lungs （99 cases， 30.46%）. In the high-risk group， the main disease elements were yang deficiency （73 cases， 62.93%）， blood stasis （68 cases， 58.62%）， and heat （49 cases， 42.24%）， with the primary locations in the kidney （84 cases， 72.41%） and heart （70 cases， 60.34%）. ConclusionThe overall disease characteristics in different risk populations of type 2 diabetes patients with heart failure are a combination of deficiency and excess， with deficiency being predominant. Deficiency and heat are present throughout. The low-risk population mainly shows qi deficiency with dampness and heat， related to the spleen and lungs. The high-risk population shows yang deficiency with blood stasis and heat， related to the kidneys and heart.

ObjectiveTo analyze the characteristics and influencing factors of elderly hospitalized patients with carbapenem-resistant gram-negative bacillus (CRO) infection in the intensive care unit (ICU) of a gradeⅡ level A general hospital in Yangpu District of Shanghai, and to provide scientific basis for the prevention and control of hospital-acquired CRO infection in such hospitals. MethodsThe clinical data of elderly ICU patients (age ≥60 years) from January 2019 to December 2023 were retrospectively collected. A total of 122 cases with hospital-acquired CRO infection were used as the case group, and a total of 68 cases with carbapenem-sensitive gram-negative (CSO) infection were used as the control group. The clinical characteristics of the two groups were analyzed, and univariate analysis and logistic regression analysis were performed for screening for possible influencing factors on hospital-acquired CRO infection. ResultsThe main pathogens of CRO infection were carbapenem-resistant Acinetobacter baumannii (CRAB) (53 cases, 43.44%) and carbapenem-resistant Klebsiella pneumoniae (CRKP) (46 cases, 37.70%), and 17 patients (13.93%) had more than two types of CRO infection. Among the CRO infection, the main sites were lower respiratory tract infection (58 cases, 47.54%), ventilator-associated pneumonia (21 cases, 17.21%), and catheter-associated urinary tract infections (16 cases, 13.11%). The incidence rate of poor prognosis was higher in the CRO infection group (54.10%) than that in the CSO infection group (36.76%) (P=0.021). The results of univariate analysis showed that male, history of hospitalization within three months, chronic respiratory disease, hypoproteinemia, anemia, and history of invasive procedures prior to infection, including indwelling central venous catheter, invasive mechanical ventilation, urinary catheter, gastric tube placement and parenteral nutrition, in addition, heparin anticoagulation, the use of broad-spectrum penicillin, third-generation cephalosporins, fluoroquinolones, carbapenems, carbapenems combined with fluoroquinolones, carbapenems combined with glycopeptides, use of ≥3 antibiotics and long time of antibiotic use prior to infection were all associated with the CRO infection (P<0.05). The results of logistic regression analysis showed that use of carbapenems (OR=7.739, 95%CI: 2.226‒26.911), ≥3 types of antibiotics (OR=6.307, 95%CI: 1.674‒23.754), invasive mechanical ventilation (OR=4.082, 95%CI: 1.795‒9.281), urinary catheter (OR=3.554, 95%CI: 1.074‒11.758), and comorbid hypoproteinemia (OR=4.741, 95%CI: 2.039‒11.022) and diabetes (OR=3.245, 95%CI: 1.344‒7.839) were positively correlated with the risk of CRO infection. ConclusionConcurrent use of carbapenems with multiple other antibiotics, as well as the use of invasive mechanical ventilation, urinary catheter, and comorbid hypoproteinemia and diabetes, may be associated with an increased influencing of CRO infection. More attention should be paid to the prevention and control of infection in elderly patients with the above-mentioned risk factors, and active screening of drug-resistant bacteria should be strengthened. Besides, the rational use of broad-spectrum antibiotics such as carbapenems, avoiding unnecessary invasive operations, and paying attention to patient nutrition and blood glucose control all can reduce the incidence of CRO infection and help to improve clinical outcomes.

ObjectiveTo observe the efficacy of Huoxue Jiedu Formulas （活血解毒方药， HJF） as an adjunctive treatement for patients with binding of stasis and toxin syndrome during the vulnerable period after acute myocardial infarction （AMI） percutaneous coronary intervention （PCI） surgery， and to explore its potential mechanism from the perspective of serum neutrophil extracellular traps （NETs）. MethodsA total of 129 patients with binding of stasis and toxin syndrome within 6 months after PCI for AMI were enrolled and divided into a treatment group （65 cases） and a control group （64 cases） based on patients' willingness to take Chinese herbal medicine. The control group received standard western medical therapy alone， while the treatment group additionally received HJF， one dose daily. Both groups were treated for four weeks. Before and after treatment， TCM syndrome scores were assessed. Seattle angina questionnaire （SAQ） was used to record angina stability and frequency scores， while the short form-36 health survey （SF-36） was employed to assess quality of life across eight dimensions， including physical functioning， role-physical， bodily pain， general health， vitality， social functioning， role-emotional， and mental health. The Pittsburgh sleep quality index （PSQI） was used to evaluate sleep quality， and the patient health questionnaire-15 （PHQ-15） was used to assess psychosomatic symptoms； Duke activity status index （DASI） was used to measure daily physical activity. Serum levels of neutrophil extracellular traps （NET） markers including myeloperoxidase-DNA （MPO-DNA）， neutrophil elastase-DNA （NE-DNA）， and citrullinated histone H3 （CitH3） were measured in 20 patients from the treatment group. ResultsAfter treatment， TCM syndrome score， PSQI score and PHQ-15 score in both groups significantly decreased， while DASI score， angina stability and frequency scores， and all eight dimensions of the SF-36 scale significantly increased （P＜0.05）. Compared to the control group， the treatment group had significantly lower TCM syndrome scores and significantly higher DASI， angina stability and frequency scores （P＜0.05）， as well as higher scores in the SF-36 dimensions of physical functioning， role-physical， social functioning， bodily pain， and vitality （P＜0.05）. After treatment， serum levels of MPO-DNA， CitH3， and NE-DNA in the treatment group were significantly reduced （P＜0.05）. ConclusionHJF combined with conventional therapy can significantly improve angina symptoms， TCM syndrome scores， and psychosomatic conditions in patients with binding of stasis and toxin syndrome during the vulnerable period after AMI. It also enhances quality of life， sleep quality， and daily physical activity. The underlying mechanism may be associated with the inhibition of serum NETs level.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease with high global prevalence and long course, which affects more than 30% of the population and seriously endangers human health. Lipid metabolism plays an important role in the occurrence and development of MASLD. An increasing number of studies have shown that active ingredients in traditional Chinese medicine can regulate lipid metabolism to improve MASLD. Due to the obvious advantages of multi-target regulation and fewer side effects, the active ingredients have shown great potential and value for application. However, the pathological mechanism of MASLD is intricate and the active ingredients of traditional Chinese medicine can improve MASLD from multiple aspects, there is currently a lack of systematic discussion on lipid metabolism. Therefore, this review focuses on lipid metabolism and reviews the latest research progress of active ingredients from traditional Chinese medicine in ameliorating MASLD from the aspects of lipid uptake, lipid synthesis, lipid oxidation, lipid secretion, etc., in order to provide more theoretical references for active ingredients of traditional Chinese medicine in regulating lipid metabolism to improve MASLD.

Objective:To systematically evaluate the effects of "Internet+" nursing intervention mode on negative emotion and pregnancy outcome of infertility patients.Methods:PubMed, Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang, VIP and Chinese Biomedical Literature Database were searched to collect randomized controlled tria related to the effects of "Internet+" nursing interventions on patients with infertility from the inception to August 10th 2023. Two researchers conducted independent quality evaluation, evidence extraction and summary of the literature. Meta-analysis was performed by RevMan 5.4 software.Results:A total of 11 studies were included with a total of 1 596 patients. The Meta-analysis showed that nursing interventions based on "Internet+" significantly improved the anxiety of patients with infertility ( SMD=-1.09, 95% CI-1.76- -0.43, P< 0.01), depression ( SMD=-0.98, 95% CI-1.42- -0.54, P<0.01), biochemical pregnancy rate ( OR=1.67, 95% CI 1.14- 2.44, P<0.01), clinical pregnancy rate ( OR=1.83, 95% CI 1.22- 2.73, P<0.01), but no effect on infertility pressure ( MD=-3.81, 95% CI-15.10- 7.47, P>0.05). Conclusions:The interventions based on "Internet+" can effectively improve anxiety, depression and pregnancy outcome, but there is no adequate evidence of a reduction on infertility stress in patients.

OBJECTIVE To investigate the mechanism of Cistanche deserticola in the treatment of inflammatory bowel disease （IBD）. METHODS The active components of C. deserticola were screened based on TCMSP and literature reports. The targets of active ingredients were obtained via Swiss Target Prediction platform. Then the disease targets were obtained by searching GeneCards and OMIM databases. PPI network and “drug-compound-disease-target” network were constructed. The core components and core targets were screened. GO and KEGG enrichment analyses were performed， and molecular docking verification was conducted for core targets and core components. The IBD mice model was established and divided into model group， positive control group （dexamethasone， 0.4 mg/kg） and C. deserticola extract group （100， 200， 400 mg/kg）； blank control group was set， with 8 mice in each group. Each group was given relevant medicine， once a day， for 7 consecutive days. Disease activity index （DAI） score and colon length were calculated， and the pathological morphology of the colon of mice was observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， myeloperoxidase （MPO），tumor necrosis factor-α （TNF-α）] in colon tissue， and protein expressions of core targets were detected. RESULTS A total of 39 active ingredients and 232 potential targets of C. deserticola in the treatment of IBD were obtained. The treatment of IBD with C. deserticola might be related to core components such as quercetin， suchilactone， β-sitosterol and cistanoside H， and core targets such as TNF， AKT1， STAT3， EGFR and SRC. GO and KEGG pathway analysis predicted that the biological processes of C. deserticola in the treatment of IBD were mainly related to protein phosphorylation， and negative regulation of apoptosis， mainly involving PI3K/AKT and EGFR tyrosine kinase inhibitor resistance signaling pathways. The results of molecular docking showed that the binding energy between the core components and core target of C. deserticola was less than －4.7 kJ/mol. Animal experiment results showed that after intervention with C. deserticola extract， the body weight and colon length of mice significantly increased （P＜0.05 or P＜0.01）， while DAI decreased significantly （P＜0.05 or P＜0.01）. The congestion and edema of colon mucosa were significantly reduced， and the pathological score of colon tissue was significantly decreased （P＜0.05 or P＜0.01）； the levels of IL-6， IL-1β， MPO and TNF-α， as well as the protein expressions of PI3K， phosphorylated PI3K （p-PI3K）， EGFR， TNF- α， STAT3， phosphorylated STAT3 （p-STAT3）， AKT1， phosphorylated AKT1 （p-AKT1） and SRC in colon tissue were reduced significantly （P＜0.05 or P＜0.01）， while the level of IL-10 was significantly increased in model group （P＜0.01）. CONCLUSIONS C. deserticola may alleviate IBD by regulating the SRC/EGFR/PI3K/AKT signaling pathway.

ObjectiveTo observe the clinical efficacy and relative mechanism of the Modified Wenshen Yixin Formula （温肾益心方加减， MWYF） as an auxiliary treatment of coronary heart disease （CHD） complicated with hypothyroidism of spleen-kidney yang deficiency. MethodsA total of 135 CHD patients complicated with hypothyroidism and spleen-kidney yang deficiency were included and divided into control group （67 cases） and experimental group （68 cases） according to the patients' wishes of herbal medicine administration. The control group was given conventional western medicine， while the treatment group was additionally given MWYF， 1 dose per day； both groups were treated for 8 weeks. The traditional Chinese medicine （TCM） syndrome scores， angina scores， SF-36 scores， thyroid function indicators including thyroid stimulating hormone （TSH）， thyroxine （T4） and triiodothyronine （T3）， as well as serum cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， monocyte chemoattractant ligand 2 （CCL2）， and tumor necrosis factor-related activator protein （CD40L） levels before and after treatment were compared between the two groups. The dosage and reduction and discontinuation rate of thyroid hormone preparations after treatment were compared between the two groups. The effectiveness regarding TCM syndrome and angina pectoris was evaluated， and the safety was assessed. ResultsBias was adjusted by matching on propensity score， and 102 cases were finally included in the statistical analysis， with 51 cases in each group. The total effective rate regarding TCM syndrome ［94.12% （48/51） versus 64.71% （33/51）］， the total effective rate regarding angina pectoris ［80.39% （41/51） versus 62.75% （32/51）］， and the reduction and discontinuation rate of thyroid hormone preparation ［39.21% （20/51） versus 5.88% （3/51）］ were significantly higher in the experimental group than those in the control group （P＜0.05 or P＜0.01）. After treatment， the total TCM syndrome score， individual scores of major symptoms ， the major symptoms score， the secondary symptoms score， angina pectoris score， and TSH level were significantly reduced （P＜0.01）， while all dimensions of SF-36 scores， T4， T3， and cAMP levels significantly increased in both groups （P＜0.05 or P＜0.01）. The dosage of thyroid hormone preparations and the levels of cGMP， CCL2， and CD40L in the experimental group significantly decreased after treatment （P＜0.01）. When compared between the two groups after treatment， the total TCM syndrome score， the major symptoms score， the scores of individual major symptom （chest tightness， chest pain， fear of cold， cold limbs， waist and kness soreness and weakness）， the secondary symptoms score， angina pectoris score， TSH， cGMP， CCL2， and CD40L levels of the experimental group were significantly lower than those of the control group （P＜0.05 or P＜0.01）， while all dimension scores of SF-36， T4， T3， and cAMP levels were significantly higher （P＜0.01）. A total of three adverse events occurred during treatment， none of which were judged to be related to the interventions of this study. ConclusionMWYF can significantly ameliorate the TCM syndrome， angina pectoris， quality of life and thyroid function in CHD patients complicated with hypothyroidism and spleen-kidney yang deficiency， and can promote the reduction and disconti-nuation of thyroid hormone preparations. The mechanism may be related to the regulation of cAMP/cGMP balance， the regulation of hypothalamic-pituitary-thyroid metabolic axis and the reduction of immune inflammation.