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.

Objective To analyze the PLCβ4 gene mRNA expression and its clinical significance in hepatocellular carcinoma (HCC) based on TCGA database. Methods Based on the data on 424 clinical samples (including 374 cases of HCC tissues and 50 cases of nontumor liver tissues) in the TCGA database, Kaplan–Meier method, Cox regression analysis, and immune infiltration analysis were performed to evaluate the relationship between PLCβ4 gene and the clinical characteristics and survival prognosis of HCC patients. Correlation analysis between PLCβ4 gene and 24 types of immune cells was applied to investigate the relationship between PLCβ4 gene and immune cell infiltration and mRNA expression level of TP53 gene, a high-frequency mutation gene in HCC. In addition, paraffin sections of highly, moderately, and poorly differentiated tumor tissues and normal liver tissues from HCC patients were collected. The histopathological observation was carried out via HE staining method, and the expression levels of PLCβ4 and Ki-67 proteins in each clinical sample were verified through the immunohistochemical method. Results The expression level of PLCβ4 gene in HCC was significantly higher than that in normal tissues (P<0.01), and all patients in the PLCβ4 high-expression group had a significantly longer overall survival than those in the low-expression group (P<0.05), which suggested that PLCβ4 substantially affected the prognosis of HCC patients. Correlation analysis showed that the expression level of PLCβ4 gene was highly correlated with immune cell infiltration and the expression level of TP53 gene. As verified by clinical sample experiments, HE staining experiments and immunohistochemical results revealed that PLCβ4 gene expression in HCC tissue samples was significantly higher than that in normal tissues (P<0.001), and it was negatively correlated with the degree of differentiation. Conclusion PLCβ4 may serve as an independent prognostic factor in HCC and is expected to be a novel molecular target for HCC treatment.

OBJECTIVE To investigate the attenuation and synergism of Hugan buzure recipe （HBR） combined with oxaliplatin on hepatocellular carcinoma tumor bearing nude mice and its mechanism. METHODS Eight nude mice were selected from 40 nude mice as the blank group （normal saline）， and the remaining nude mice were inoculated with hepatoma cells Huh7 to establish the tumor-bearing model. The 32 modeled nude mice were randomly allocated to four groups： model group （normal saline， ig）， HBR group （0.69 g/kg， ig）， oxaliplatin group （10 mg/kg， ip）， and combination group （intraperitoneal injection of 0.69 g/kg HBR+intragastric administration of 10 mg/kg oxaliplatin）， with 8 mice in each group. Administer drug/normal saline once a day for 32 consecutive days； administer subcutaneous injection once every 7 days for a total of 5 times. During the experiment， the general condition of nude mice in each group was observed， and the tumor volume was measured every 4 days. On the 30th day of administration， the thermal stimulation paw withdrawal latency of nude mice in each group were detected. The tumor inhibition rate， spleen coefficient， the number of red blood cells， white blood cells and platelets in the whole blood of nude mice in each group， and the content of aspartate aminotransferase （AST） and creatinine in serum were detected after the end of administration. HE staining was used to observe the pathological changes in tumor tissues in nude mice in each group. The expression of microtubule-associated protein 1 light chain 3 （LC3），selective autophagy adaptor protein p62， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， and Caspase-3 protein in tumor tissues. RESULT Compared with the model group， the tumor volume， tumor weight， white blood cells，red blood cells in the whole blood and spleen coefficients of nude mice in the oxaliplatin group were significantly decreased （P＜0.01）； the thermal stimulation paw withdrawal latency， AST and creatinine in serum were significantly increased （P＜0.05 or P＜0.01）. Compared with the oxaliplatin group， the tumor volume and tumor weight of nude mice in the combination group were significantly decreased （P＜0.01）； the white blood cells， red blood cells and platelets in the whole blood and spleen coefficients of nude mice were significantly increased （P＜0.05 or P＜0.01）； the thermal stimulation paw withdrawal latency， AST and creatinine in serum were significantly decreased （P＜0.01）； the expression levels of LC3， Bax and Caspase-3 proteins in tumor tissues of nude mice were significantly increased （P＜0.01）， and the expression levels of p62 and Bcl-2 proteins were significantly decreased （P＜0.01）. CONCLUSIONS HBR enhances the tumor inhibition rate of oxaliplatin by inducing apoptosis and autophagy， and can alleviate the peripheral neurotoxicity， hematological toxicity， hepatorenal toxicity， and immune organ toxicity caused by oxaliplatin in nude mice.

Objective To investigate the serum levels of semaphorin 3E(Sema3E)in patients with intracranial aneurysms,revealing the correlation between Sema3E and 1-month poor prognosis after interventional embolization.Methods This study was a prospective single-center cohort study,recruiting 102 consecutive patients with intracranial aneurysms who underwent interventional surgery from June 2020 to January 2022 in our hospital.Among them,11 patients were excluded.Clinical and radiological profiles were collected.Peripheral blood was collected after admission,and serum Sema3E levels were determined by enzyme-linked immunosorbent assay.All the aneurysms were treated with endovascular coil embolization or stent-assisted coil embolization.The primary outcome was evaluated with the Glasgow Outcome Scale(GOS)1 month after interventional therapy.The favorable outcome was defined as a GOS score of 4-5,and a poor outcome was defined as a GOS score of 1-3(severe disability,vegetative state,or death).Univariate and multivariate logistic regression analyses were used to identify potential prognostic factors after interventional therapy.Results The average age of 91 patients with intracranial aneurysm was 59.9±11.0 years old,including 70 cases(76.9%)with favorable prognosis and 21 cases(23.1%)with poor prognosis.The mean preoperative Glasgow Coma Scale(GCS)score of the poor prognosis group(9.4±4.5)was significantly lower than that of the favorable prognosis group(13.3±2.5;P<0.001).In the poor prognosis group,the Hunt-Hess grade(3.6±0.6 vs.2.0±1.3,P<0.001)and the serum Sema3E levels[(6.21±1.58)μg/L vs.(4.38±1.77)μg/L,P<0.001]were significantly higher than those in the favorable prognosis group.Logistic regression analysis showed the Hunt-Hess grade(OR =7.150,P =0.003),stent-assisted coil embolization(OR =15.777,P =0.010),and the serum Sema3E level(OR =1.756,P =0.027)were independent prognostic factors for intracranial aneurysms after interventional therapy.Conclusions The serum Sema3E level is closely correlated with the severity of intracranial aneurysms.The serum Sema3E level is a prognostic factor for interventional treatment,which can be used as a biomarker for predicting poor outcomes.

OBJECTIVE To investigate the mechanism of Cichorium glandulosum in the treatment of liver fibrosis by using network pharmacology and experimental validation. METHODS A "component-target-pathway" network was constructed with the help of TCMSP, Pubchem, SwissTargetPrediction and Genecards databases, and the STRING database was used to predict the targets of Cichorium glandulosum against liver fibrosis. KEGG and GO enrichment analysis was performed in the DAVID database, and molecular docking of active ingredients and key targets was docked in AUTODOCK. PDGF-BB was used to induce activation of cells and verify the effects of six compounds, including quercetin, quercetin, chicoric acid, caffeic acid, chlorogenic acid, and isochlorogenic acid, on the proliferation, apoptosis, and liver fibrosis indicators of HSC-T6 cells. Western blotting was used to detect the expression of Ras, ERK1, ERK2, C-fos, and JNK proteins in HSC-T6 cells. RESULTS Network pharmacology screened 239 common targets between the components and liver fibrosis, PPI analysis showed that SRC, STAT3, HSP90AA1 and other targets were key targets, KEGG analysis showed that the pathways affected by Cichorium glandulosum included cancer pathways, metabolic pathways, etc. GO analysis predicted that Cichorium glandulosum mainly affected processes such as signal transduction. The molecular docking results showed that the target that could bind well with the components MAPK1, and the components that could bind well with the target aesculetin, caffeic acid and chlorogenic acid. Compared with the model group, the inhibition effect of the six compounds on PDGF-BB-induced HSC-T6 cell activation was stronger, and all 6 compounds had the effects to reverse the index of liver fibrosis, in which aesculetin had the strongest activity(P<0.01). The expression of Ras, ERK1, ERK2, C-fos, and JNK in HSC-T6 cells decreased after the interventions of 6 compounds. CONCLUSION Each component of Cichorium glandulosum has different anti liver fibrosis effects, which are related to the inhibition of ERK/RAS pathway activation.

OBJECTIVE To screen out the pharmacodynamic substances of Cistanches Herba aqueous extracts, explore the basis of the pharmacodynamic substances and their mechanism of action in the treatment of diabetic nephropathy(DN), based on the spectral relationship between the mass spectral peak areas of different elution sites of Cistanches Herba aqueous extracts and their anti-DN effects. METHODS UPLC-Orbitrap-MS/MS technique was used to characterise the chromatographic peaks; MTT method was used to detect the effects of different elution sites of Cistanches Herba aqueous extract on the proliferation of high glucose and high fat HK-2 cells; grey correlation analysis and partial least squares method were used to analyse the spectral relationship between mass spectrometry peak area and anti-DN activity. MTT method was used to determine the anti-DN activities of the individual components of Cistanches Herba aqueous extract; biochemical kit and ELISA were used to determine the levels of oxidative indicators(SOD, GSH-P) and inflammatory factors(IL-1β, TNF-α, TGF-β); Western blotting was used to detect the expression of apoptosis-related proteins. RESULTS UPLC-Orbitrap-MS/MS technique speculated and identified 72 common compounds; In Cistanches Herba aqueous extracts, water, 20% ethanol, and 40% ethanol-eluted sites differentially increased the proliferation rate of HK-2 cells in a high-sugar, high-fat environment; Partial least squares and grey correlation analyses showed that the constituents of the aqueous extracts of Cistanches Herba with greater anti-DN contributions were 8-epideoxymatricinic acid, geniposidic acid, pinoresinol, betaine and syringin, et al. MTT assay reveals that 8-epi-deoxystrychnic acid and geniposidic acid had significant proliferative effects on HK-2 cells in a high glucose and high fat environment; Biochemical kit and ELISA showed that 8-epideoxystrychnic acid and geniposidic acid were able to up-regulate the activity of SOD and GSH-Px, and at the same time they had an inhibitory effect on the expression of inflammatory factors IL-1β, TNF-α and TGF-β. Western blotting results showed that 8-epideoxystrychnic acid and geniposidic acid were able to down-regulate and up-regulate the markers of dermal mesenchymal transition: α-SMA, Collagen Ⅰ and E-cadherin, and they could exert anti-DN effects by inhibiting the PI3K-Akt pathway. CONCLUSION The two compounds, 8-epideoxystrychnic acid and geniposidic acid, which are screened by the spectroeffective relationship of anti-DN among the many chemical constituents contained in Cistanches Herba, can affect oxidative stress, inflammation and epithelial-mesenchymal transformation of renal tubular cells by inhibiting the PI3K-Akt signalling pathway, and improve renal pathology, degree of fibrosis and renal function, which will be useful for the in-depth study of aqueous extracts of Cistanches Herba in the treatment of DN.

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.

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 effect and mechanism of Humulus lupulus Linn.extract on ovariectomized osteoporosis rats.Methods Sixty female SD rats were randomly divided into sham surgery group,model group,positive control group(estradiol valerate,0.105 mg·kg-1),low-,medium-and high-dose(65.625,131.120,196.875 mg·kg-1)Humulus lupulus Linn.extract groups,with 10 rats in each group.Except for the sham surgery group,other groups had their ovaries removed.After surgery,rats were given drugs once daily by intragastric administration for 90 days.HE staining was used to observe the morphological changes of rat tibia.Bone morphometric parameters were measured,as well as trabecular number(Tb.N),trabecular thickness(Tb.Th),trabecular separation(Tb.Sp),and trabecular area(Tb.Ar)were calculated.Furthermore,we detected the biomechanical status of rat femur,such as maximum load,elastic modulus,and fracture strength.ELISA was used to detect the level of serum estrogen(E2),tartrate-resistant acid phosphatase(TRACP5b),osteocalcin(OC)and bone-specific alkaline phosphatase(BALP)in rats.Serum alkaline phosphatase(ALP)content was measured by using a fully automated biochemical analyzer.RT-PCR and Western Blot were used to detect mRNA and protein expression levels of OPG,RANKL,ERα,ERβ,Wnt16 and β-catenin in rat tibia.Results Compared with the sham surgery group,the tibial trabeculae of the model group was broken,the bone marrow cavity was enlarged,and osteoporotic structure was found.Tb.N,Tb.Th and Tb.Ar of tibia were significantly decreased(P＜0.05),and Tb.Sp was significantly increased(P＜0.05).The maximum load,elastic modulus and fracture strength of femur were significantly decreased(P＜0.05).Serum E2 content was significantly decreased(P＜0.05),and serum TRACP5b,OC,ALP and BALP contents were significantly increased(P＜0.05).The mRNA and protein expressions of OPG,OPG/RANKL,ERα,ERβ,β-catenin and Wnt16 were significantly decreased(P＜0.05),while the mRNA and protein expressions of RANKL were significantly increased(P＜0.05).Compared with model group,positive control group and high-dose Humulus lupulus Linn.extract group had improved the above indexes(P＜0.05).Conclusion Humulus lupulus Linn.extract has a certain preventive and therapeutic effect on postmenopausal osteoporosis,and its mechanism may be related to the regulation of Wnt/β-catenin signaling pathway and the regulation of OPG/RANK/RANKL signaling pathway.

【Objective】 To investigate the risk factors and predictive effectiveness of prostate imaging reporting and data system (PI-RADS) score for patients with clinically significant prostate cancer (CsPCa) whose PI-RADS score was 3, so as to provide evidence for the diagnosis and treatment. 【Methods】 The clinical and multi-parameter magnetic resonance imaging (mpMRI) data of 153 CsPCa patients treated during Jan.2017 and Dec.2021 whose PI-RADS score was 3 were retrospectively analyzed. With PI-RADS score of 3 as the independent risk factor for CsPCa, the other relevant independent risk factors in predicting CsPCa were evaluated. 【Results】 Univariate and multivariate analyses showed that prostate-specific antigen (PSA) density and apparent dispersion coefficient (ADC) were independent risk factors for the diagnosis of CsPCa (P<0.05). Analysis of receiver operating characteristic (ROC) curve showed that combined PSA density and ADC were more effective than PSA density and ADC alone (P<0.05). 【Conclusion】 The combination of PSA density and ADC can guide clinicians to identify high-risk CsPCa patients from patients with PI-RADS score of 3 points.