BACKGROUND:Previous studies have found that neohesperidin can delay bone loss in ovariectomized mice and has the potential to treat osteoporosis,but its specific mechanism of action remains to be explored. OBJECTIVE:To explore the key targets and possible mechanisms of neohesperidin in the treatment of osteoporosis based on bioinformatics and cell experiments in vitro. METHODS:The gene expression dataset related to osteoporosis was obtained from GEO database,and the differentially expressed genes were screened and analyzed in R language.The osteoporosis-related targets were screened from GeneCards and DisGeNET databases,and the neohesperidin-related targets were screened from ChEMBL and PubChem databases,and the common targets were obtained by intersection of the three.The String database was used to construct the PPI network of intersection genes,and the key targets were screened.The DAVID database was used for GO and KEGG enrichment analysis.The AutoDock software was used to verify the molecular docking between the neohesperidin and the target protein.The effect of neohesperidin on osteogenic differentiation of C57 mouse bone marrow mesenchymal stem cells was detected.Complete medium was used as blank control group;osteogenic induction medium was used as the control group;and osteogenic induction medium containing different concentrations of neohesperidin(25,50 μmol/L)was used as experimental group.The expression of alkaline phosphatase,the degree of mineralization,the expression of osteogenic-related genes and target genes during osteogenic differentiation of cells were measured at corresponding time points. RESULTS AND CONCLUSION:(1)9 253 differentially expressed genes,2 161 osteoporosis-related targets,and 326 neohesperidin-related targets were screened.There were 53 common targets among the three.All 53 genes were up-regulated in osteoporosis samples.The PPI network screened the target gene PRKACA of research significance.GO function and KEGG pathway enrichment analysis showed that neohesperidin's treatment of osteoporosis through PRKACA target mainly depended on biological processes such as protein phosphorylation and protein autophosphorylation,acting on endocrine resistance,proteoglycan in cancer,and estrogen signaling pathway to play a therapeutic role.Molecular docking results showed that neohesperidin had a certain binding ability to the protein corresponding to the target PRKACA.(2)The results of alkaline phosphatase staining showed that neohesperidin could promote the expression of alkaline phosphatase in the early stage of osteogenic differentiation of mesenchymal stem cells.Alizarin red staining showed that neohesperidin could promote the mineralization of osteogenic differentiation of mesenchymal stem cells.RT-qPCR results showed that neohesperidin could increase the mRNA expression of alkaline phosphatase,PRKACA,and osteocalcin.(3)These results indicate that neohesperidin may promote osteogenic differentiation through PRKACA target on the estrogen signaling pathway to prevent and treat osteoporosis.

B7-H3 (CD276), an immune checkpoint protein of the B7 family, exhibits significant upregulation in solid tumors and hematologic malignancies, exerting a crucial role in their pathophysiology. The distinct differential expression of B7-H3 between tumors and normal tissues and its multifaceted involvement in tumor pathogenesis position it as a promising therapeutic target for tumors. In the context of acute myeloid leukemia (AML), B7-H3 is prominently overexpressed and closely associated with unfavorable prognoses, yet it has remained understudied. Despite various ongoing clinical trials demonstrating the potential efficacy of immunotherapies targeting B7-H3, the precise underlying mechanisms responsible for B7-H3-mediated proliferation and immune evasion in AML remain enigmatic. In view of this, we comprehensively outline the current research progress concerning B7-H3 in AML, encompassing in-depth discussions on its structural attributes, receptor interactions, expression profiles, and biological significance in normal tissues and AML. Moreover, we delve into the protumor effects of B7-H3 in AML, examine the intricate mechanisms that underlie its function, and discuss the emerging application of B7-H3-targeted therapy in AML treatment. By juxtaposing B7-H3 with other molecules within the B7 family, this review emphasizes the distinctive advantages of B7-H3, not only as a valuable prognostic biomarker but also as a highly promising immunotherapeutic target in AML.

Objective:To investigate the effect of 4-octyl itaconate(4-OI)on transforming growth factor-β1(TGF-β1)-induced lung fibroblast-to-myofibroblast differentiation and related mechanisms.Methods:TGF-β1 was employed to induce the differentiation of the human embryonic lung fibroblast cell line MRC-5, and the effect of 4-OI on lung fibroblast-to-myofibroblast differentiation was examined.Cytotoxicity of 4-OI on MRC-5 cells was detected by the CCK-8 assay.Western blot was used to detect the protein levels of α-smooth muscle actin(α-SMA), collagen 1α1(COL1A1), fibronectin(FN), phosphorylated and total Smad2/3, and nuclear facor-E2 related factor 2(Nrf2).Real-time fluorescence quantitative PCR was used to detect the mRNA expression of α-SMA, COL1A1 and FN.Reactive oxygen species(ROS)levels were assessed by fluorescence microscopy and flow cytometry.Intracellular glutathione(GSH)concentrations were measured by spectrophotometry.Results:Pretreatment with 4-OI was able to inhibit TGF-β1-induced protein overexpression of α-SMA, COL1A1 and FN( F=122.8, 51.5, 27.2, all P<0.05), and increased mRNA levels( F=29.83, 51.62, 94.82, all P<0.01).In addition, 4-OI inhibited TGF-β1-mediated phosphorylation of Smad2/3 proteins in a dose-dependent manner( F=21.80, 36.69, P<0.01 for both).Pretreatment with 4-OI also reversed increased ROS levels( P<0.01)induced by TGF-β1 and enhanced GSH concentrations via disinhibition of TGF-β1( P<0.05).The inhibitory effect of TGF-β1 on Nrf2 expression was alleviated and Nrf2 nuclear translocation was uplifted by 4-OI pretreatment( P<0.05).After silencing Nrf2, 4-OI was unable to inhibit the increased protein expression of COL1A1 induced by TGF-β1, but was still able to inhibit the increased expression of α-SMA and FN protein induced by TGF-β1( P<0.05). Conclusions:4-OI could inhibit lung fibroblast-to-myofibroblast differentiation partially via Nrf 2 activation.

Objective:To evaluate the optimization effect of transcutaneous electrical acupoint stimulation (TEAS) combined with moderate sedation with propofol (TEAS-propofol balanced anesthesia) for gastrointestinal endoscopy.Methods:This was a single-blind randomized controlled trial. American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients, aged 18-64 yr, undergoing elective gastrointestinal endoscopy at the Endoscopic Diagnosis and Treatment Center of the Affiliated Hospital of Qingdao University from May to August 2022, were divided into 2 groups using the block random allocation method: conventional anesthesia group (group C) and TEAS-propofol balanced anesthesia group (group TPB). Patients received moderate sedation with propofol plus routine anesthesia with fentanyl 50 μg in group C. In TPB group, TEAS was performed at bilateral Neiguan, Hegu and Zusanli acupoints before surgery until the end of surgery, and patients received propofol for moderate sedation (Modified Observer′s Assessment of Alertness/Sedation scale score was 3). The efficacy and safety of anesthesia and parameters related to outcomes were observed and recorded.Results:In this study, 66 patients were recruited, with 33 in each group, the failure rate of anesthesia in both groups was 3%, and no reflux or aspiration was found. Compared with group C, no significant changes were found in the patients′ satisfaction on the same day, intraoperative pain response score, incidence of intraoperative adverse reactions (tachycardia, hypertension, bucking and body movement), awake time, consumption of propofol, rate of intraoperative awareness and rate of patients hoping to receive the same anesthesia method again postoperatively ( P>0.05), the patients′ satisfaction was significantly increased on the next day ( P<0.05), the incidence of intraoperative respiratory depression, physician satisfaction, and degree of postoperative dizziness and nausea were significantly reduced ( P<0.05), and the discharge time and time to the complete recovery of normal behavior function was significantly shortened in group TPB ( P<0.05). Conclusions:The combination of TEAS at bilateral Neiguan, Hegu and Zusanli acupoints with moderate sedation using propofol for gastrointestinal endoscopy is not only safe and effective, but also beneficial to the postoperative outcome of patients, and the effect is better than that of conventional anesthesia with propofol and fentanyl.

Objective:To investigate the influence of nutritional therapy on short-term efficacy of gastric cancer patients with malnutrition after radical gastrectomy.Methods:The prospec-tive randomized control study was conducted. The clinicopathological data of patients with malnutri-tion after radical resection of gastric cancer who were admitted to the Zhongshan Hospital of Fudan University from December 2020 to December 2022 were selected. Based on random number table, all patients were allocated into the nutritional therapy group and the control group. Patients in the nutritional therapy group were given dietary guidance and daily oral nutrition supplements for 90 days after discharge, while patients in the control group were only given the same dietary guidance. Observation indicators: (1) grouping situations of the enrolled patients; (2) follow-up; (3) comparison of nutritional indicators at 90 days after discharge; (4) comparison of inflammation and physical function indicators at 90 days after discharge; (5) comparison of clinical outcome indicators at 90 days after discharge. Measurement data with normal distribution were expressed as Mean± SD, and independent sample t test was used for comparison between groups. Measurement data with skewed distribution were expressed as M(IQR), and non-parameter rank sum test was used for comparison between groups. Count data were expressed as absolute numbers or percentages, and chi-square test was used for comparison between groups. Comparison of ordinal data was conducted using the chi-square test. Results:(1) Grouping situations of the enrolled patients. A total of 187 patients were selected for eligibility. There were 131 males and 56 females, aged (65±12)years. Of the 187 patients, there were 95 patients in the nutritional therapy group and 92 patients in the control group, respectively. The gender (male, female), age, cases with cardiovascular complications, cases with respiratory complications, cases with diabetes, surgical methods (partial gastrectomy, total gastrectomy), tumor staging (Ⅰ stage, Ⅱ stage, Ⅲ stage), body mass, body mass index (BMI), skeletal muscle index, albumin (Alb), hemoglobin (Hb), neutrophil-to-lymphocyte ratio (NLR), 6-minutes walking distance, grip strength were 68, 27, (64±12)years, 21, 4, 7, 59, 36, 17, 27, 51, (59±11)kg, (21.5±3.1)kg/m 2, (42±7)cm 2/m 2, (39±5)g/L, (112±25)g/L, 2.3(8.0), (456±97)m, (29±8)kg in patients of the nutritional therapy group, versus 63, 29, (66±13)years, 22, 3, 9, 56, 36, 14, 24, 54, (58±11)kg, (21.1±2.9)kg/m 2, (42±7)cm 2/m 2, (39±4)g/L, (111±26)g/L, 2.2(8.4), (459±98)m, (29±8)kg in patients of the control group, showing no significant difference in the above indicators between the two groups ( χ2=0.21, t=-1.29, χ2=0.09, 0, 0.35, 0.03, 0.51, t=0.80, 0.85, 0.19, 0.14, 0.16, Z=-0.28, t=-0.17, 0.43, P>0.05). (2) Follow-up. All 187 patients were followed up for 90 days after surgery. During the follow-up period, all patients had good compliance and were able to follow the dietary guidance. Five patients in the nutrition therapy group experienced diarrhea and nausea adverse reactions, which were relieved after symptomatic treatment. No adverse reactions were found in the control group. (3) Comparison of nutritional indicators at 90 days after discharge. The body mass, body mass loss, BMI, skeletal muscle index, Alb, Hb were (58±10)kg, 2(6)kg, (21.0±2.9)kg/m 2, (41±7)cm 2/m 2, (41±4)g/L, (125±18)g/L in patients of the nutritional therapy group, versus (56±10)kg, 3(6)kg, (20.4±2.7)kg/m 2, (39±7)cm 2/m 2, (41±4)g/L, (121±21)g/L in patients of the control group. There were significant differences in body mass loss and skeletal muscle index between the two groups ( Z=-4.70, t=2.39, P<0.05), and there was no significant difference in body mass, BMI, Alb, and Hb ( t=1.30, 1.51, 0.80, 1.32, P>0.05). (4) Comparison of inflammation and body function indicators at 90 days after discharge. The NLR, 6-minutes walking distance, grip strength were 2.1(5.1), (478±99)m, and (33±9)kg in patients of the nutritional therapy group, versus 2.2(5.7), (465±96)m, (30±8)kg in patients of the control group. There was a significant difference in grip strength between the two groups ( t=2.08, P<0.05), and there were no significant difference in NLR and 6-minutes walking distance ( Z=-1.28, t=0.91, P>0.05). (5) Comparison of clinical outcome indicators at 90 days after discharge. The quality of life score and readmission rate were (79±14)points, 4.2%(4/95) in patients of the nutritional therapy group, versus (78±16)points, 6.5%(6/92) in patients of the control group, showing no significant difference in the above indicators between the two groups ( t=0.58, χ2=0.14, P>0.05). Conclusion:Nutritional therapy with daily oral nutrition supplements can improve the short-term nutritional status and body function of patients with malnutrition after radical gastrectomy for gastric cancer.

BackgroundMental illness during pregnancy has become a major public health problem in China over the recent years， and depression is the most common psychological symptom during pregnancy. Current research efforts are directed towards the therapy on prenatal depression， whereas the construction of prediction model for prenatal depression risk has been little studied. ObjectiveTo construct a simple model for predicting the risk of prenatal depression， thus providing a valuable reference for the prevention of maternal depression during pregnancy. MethodsA total of 803 pregnant women attending three hospitals in Nanchong city were consecutively recruited from May 2021 to February 2022. A self-administered questionnaire was developed for the assessment of social demographic variables， obstetrical and general medical indexes and psychological status of all participants， and Self-rating Depression Scale （SDS） was utilized to screen for the presence of maternal depression. Subjects were randomly assigned into modelling group （n=635） and validation group （n=168） at the ratio of 8∶2 under simple random sampling with replacement. The candidate risk factors of maternal depression during pregnancy were screened using binary Logistic regression analysis， and the predictive model was constructed. Then the performance of the predictive model was validated using receiver operating characteristics （ROC） curve. Results① Lack of companionship （β=-0.692， OR=0.501， 95% CI： 0.289~0.868）， low mood during the last menstrual period （β=-1.510， OR=0.221， 95% CI： 0.074~0.656）， emotional stress during the last menstrual period （β=-1.082， OR=0.339， 95% CI： 0.135~0.853）， unsatisfactory relationship between mother-in-law and daughter-in-law （β=-1.228， OR=0.293， 95% CI： 0.141~0.609）， and indifferent generally relationship between mother-in-law and daughter-in-law （β=-0.831， OR=0.436， 95% CI： 0.260~0.730） were risk factors for prenatal depression in pregnant women （P<0.05 or 0.01）. ② Model for predicting the prenatal depression risk yielded an area under curve （AUC） of 0.698 （95% CI： 0.646~0.749）， the maximum Youden index was 0.357 in modelling group with the sensitivity and specificity was 0.606 and 0.751， and an AUC of 0.672 （95% CI： 0.576~0.767） and maximum Youden index of 0.263 in validation group with the sensitivity and specificity of 0.556 and 0.707. ConclusionThe simple model constructed in this study has good discriminant validity in predicting of the risk of prenatal depression. ［Funded by Nanchong Social Science Research Project of the 14th Five-Year Plan （number， NC21B165）］

Objective:To investigate the expression of serum galectin-3 in elderly patients with or without atrial fibrillation and to explore its impact on the prognosis of patients with atrial fibrillation.Methods:In this retrospective study, 100 patients aged 60 years or older treated at the Department of Geriatric Cardiovascular Medicine, Second Xiangyang Hospital, Central South University between March 2018 and September 2018 were enrolled.Based on electrocardiogram and previous history of atrial fibrillation, 73 participants were assigned to the atrial fibrillation group and 27 patients with sinus rhythm and no history of atrial fibrillation during the same period served as the control group.Elisa kits were used to measure the expression of galectin-3 in both groups, and echocardiography was used to measure the size of each cardiac chamber in patients.The Mann-Whitney test was used to compare galectin-3 levels between the two groups, and binary logistic regression analysis was used to determine risk factors for atrial fibrillation in the elderly.Kaplan-Meier survival curves and Cox proportional risk regression were used to analyze survival and the relationship between galectin-3 and prognosis.Results:Serum galectin-3 levels of patients in the atrial fibrillation group were higher than in the control group[(395.13±113.24)ng/L vs.(328.53±89.11)ng/L, t=2.626, P<0.01]. The level of galectin 3 in participants aged ≥ 65 years(n=48)was higher than in those aged<65 years(n=52), (414.01±105.03)ng/L vs.(343.11±106.01)ng/L( t=2.626, P<0.01). The galectin-3 level had a positive correlation with age( r=0.40, P<0.01), duration of atrial fibrillation( r=0.224, P<0.05)and C-reactive protein( r=0.305, P<0.01), but no correlation with N-terminal pro-B-type natriuretic peptide, atrial or ventricular size and the score of CHA2DS2-VASc in patients with atrial fibrillation, .Galectin-3 was a risk factor in patients with atrial fibrillation( P<0.01). Galectin-3 levels did not affect survival(log-rank=0.990)or prognosis( P>0.05)in patients with atrial fibrillation. Conclusions:Galectin-3 levels in elderly atrial fibrillation patients are higher than in people without atrial fibrillation and are positively correlated with age, duration of atrial fibrillation, and C-reactive protein.Galectin-3 is a risk factor for atrial fibrillation in elderly patients.

Objectives:To study the clinical significance of time to positive (TTP) of blood culture for neonatal sepsis.Methods:From August 2016 to June 2019, a retrospective study was conducted in patients with positive blood cultures admitted to the Neonatology Department of our hospital. The patients were assigned into different groups according to the species of pathogen, types of neonatal sepsis and the samples contaminated or not. TTP of different groups were analyzed.Results:A total of 307 cases with positive blood cultures were identified from 10 035 cases with blood culture specimens. Among the 307 cases, 162 were contaminated (the contaminated group) and 145 (1.4%) were diagnosed of neonatal sepsis (the pathogenic group). The proportion of TTP <24 h, 24~<48 h, 48~<72 h and ≥72 h in the 145 sepsis cases were 90.3% (131/145), 7.6% (11/145), 1.4% (2/145) and 0.7% (1/145), respectively. The median TTP was 9.0 h in early-onset sepsis (EOS) group and 11.5 h in late-onset sepsis (LOS) group. The median TTP of the contaminated group was 24.5 (19.9, 30.5)h, which was longer than 11.1 (8.1,16.2)h of the pathogenic group ( P<0.05). The median TTP of Gram (+) group was 14.0 (9.4,18.8)h, which was longer than 9.6 (7.5,11.3)h of Gram (-) group ( P<0.05). The median TTP of fungi group was 32.5 (25.5, 39.0) h, which was longer than 10.6 (8.1, 15.5)h of bacteria group ( P<0.05). Conclusions:Different pathogens has different TTP for neonatal sepsis. If blood culture maintains negative for more than 72 h, empiric use of antibiotics may be discontinued for patients of suspected sepsis without specific clinical manifestations or other lab results.

Objective:To study combined adjuvant transcatheter arterial chemoembolization (TACE) with anti-tumor drug treatment on early hepatocellular carcinoma (HCC) recurrence in patients with microvascular invasion (MVI) after partial hepatectomy with curative intent.Methods:The clinical and pathological data of 169 patients with HCC who underwent partial hepatectomy with curative intent from January 2015 to December 2018 at the Affiliated Hospital of Qingdao University were retrospectively analyzed. MVI was diagnosed by postoperative histopathology. There were 147 males and 22 females, with the median age 56 years(ranged 32-79 years). The patients were divided into surgery group ( n=62, patients who did not receive adjuvant therapy), TACE group ( n=42, patients who only received TACE) and combined group ( n=65, patients who received TACE with anti-tumor drug) according to the therapies after resection. Patients in each group were further divided into grade M1 (mild) and grade M2 (severe) subgroups according to the severity of MVI. All patients were followed-up for observing tumor recurrence. The relapse-free survival in the three groups were compared using the Kaplan-Meier method and the log-rank test was used to compare the tumor-free survival rates. Results:The tumor-free survival rates of 169 patients at 1 and 2 years after operation were 59.2% and 40.8%. The tumor-free survival rates at 1 and 2 years after operation were 45.2% and 25.8% in surgery group, 61.9% and 40.5% in TACE group, 70.8% and 52.3% in combined group respectively. The differences among the three groups were significant: TACE group was better than surgery group, and combined group was better than TACE group, combined group was better than surgery group (all P<0.05). In TACE group and combined group, tumor-free survival rates of M1patients better than M2 patients, and the difference was significant ( P<0.05). Among M1 patients and M2 patients, tumor-free survival rates of combined group patients were better than surgery group and TACE group, the difference was significant (all P<0.05). The cumulative tumor-free survival rate was not significantly affected by different antineoplastic agents. Conclusion:Adjuvant TACE reduced the early recurrence rate of HCC patients with MVI. Adjuvant TACE combined with anti-tumor drug further reduced early tumor recurrence.

Objective:To investigate the effect of exercise both before and after myocardial infarction (MI) on microvessel density in the left ventricle, and on the mRNA and protein expression of vascular endothelial growth factor (VEGF) and its receptors.Methods:Ninety-six male Sprague-Dawley rats were randomly divided into a sedentary sham operation group (Sed-Sh), a pre-MI exercise sham operation group (PreE-Sh), a sedentary MI group (Sed-MI), a pre-MI exercise group (PreE-MI), a post-MI exercise group (PostE-MI) and a combined exercise group (ComE-MI). The rats of the exercise groups underwent 60min of treadmill training daily five times a week for five weeks, while those of the Sed-Sh and Sed-MI groups remained sedentary. Then all of the rats underwent either an operation to induce an acute MI (Sed-MI, PreE-MI, PostE-MI and ComE-MI groups) or a sham MI operation (Sed-Sh and PreE-Sh groups). Four weeks after the operation, the exercise groups underwent five days adaptive training, followed by 8 weeks of 60min of treadmill training daily, five times a week. All of the rats were then sacrificed. The microvessel densities in the infarcted and uninfarcted volumes were detected using Factor VIII-related antigen staining, while the mRNA expressions of VEGF and its receptors were examined using a real-time polymerase chain reaction. The protein expressions of VEGF and its receptors were measured using western blotting.Results:Compared with Sed-MI group, the average microvessel densities of the PostE-MI and ComE-MI groups had increased significantly, with the average density of the PostE-MI group significantly higher than that of the PreE-MI group, but significantly lower than the ComE-MI group′s average. Compared with the Sed-MI group, the average mRNA expression of VEGF and its receptors in the PostE-MI and ComE-MI groups was significantly higher, without significant differences between the two groups.Conclusions:Pre-MI exercise does not significantly improve left ventricular function or microvessel density, while post-MI exercise does, as it can upregulate the expression of VEGF and its receptors to activate VEGF signaling. The increase in microvessel density may benefit left ventricular remodeling and cardiac function.