This study identified blood-entering components of Anshen Dropping Pills and explored their anti-insomnia effects and mechanisms. The main blood-entering components of Anshen Dropping Pills were detected and identified by UPLC-Q-TOF-MS/MS. The rationality of the formula was assessed by using enrichment analysis based on the relationship between drugs and symptoms, and core targets of its active components were selected as the the potential anti-insomnia targets of Anshen Dropping Pills through network pharmacology analysis. Furthermore, protein-protein interaction(PPI) network, Gene Ontology(GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed on the core targets. An active component-core target network for Anshen Dropping Pills was constructed. Finally, the effects of low-, medium-, and high-dose groups of Anshen Dropping Pills on sleep episodes, sleep duration, and sleep latency in mice were measured by supraliminal and subliminal pentobarbital sodium experiments. Moreover, total scores of the Pittsburgh sleep quality index(PSQI) scale was used to evaluate the changes before and after the treatment with Anshen Dropping Pills in a clinical study. The enrichment analysis based on the relationship between drugs and symptoms verified the rationality of the Anshen Dropping Pills formula, and nine blood-entering components of Anshen Dropping Pills were identified by UPLC-Q-TOF-MS/MS. The network proximity revealed a significant correlation between eight components and insomnia, including magnoflorine, liquiritin, spinosin, quercitrin, jujuboside A, ginsenoside Rb_3, glycyrrhizic acid, and glycyrrhetinic acid. Network pharmacology analysis indicated that the major anti-insomnia pathways of Anshen Dropping Pills involved substance and energy metabolism, neuroprotection, immune system regulation, and endocrine regulation. Seven core genes related to insomnia were identified: APOE, ALB, BDNF, PPARG, INS, TP53, and TNF. In summary, Anshen Dropping Pills could increase sleep episodes, prolong sleep duration, and reduce sleep latency in mice. Clinical study results demonstrated that Anshen Dropping Pills could decrease total scores of PSQI scale. This study reveals the pharmacodynamic basis and potential multi-component, multi-target, and multi-pathway effects of Anshen Dropping Pills, suggesting that its anti-insomnia mechanisms may be associated with the regulation of insomnia-related signaling pathways. These findings offer a theoretical foundation for the clinical application of Anshen Dropping Pills.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Tandem Mass Spectrometry/methods* ; Sleep Initiation and Maintenance Disorders/metabolism* ; Mice ; Network Pharmacology ; Male ; Chromatography, High Pressure Liquid ; Humans ; Protein Interaction Maps/drug effects* ; Sleep/drug effects* ; Female ; Adult

Objective To investigate the alterations of cerebral blood flow(CBF)in type 2 diabetic mellitus(T2DM) patients without cognitive impairment by using arterial spin labeling(ASL)technique.Methods A total of 23 T2DM patients without cognitive impairment and 23 healthy controls(HC)matched by age,sex,and education attainment were recruited.Their clinical data were collected,and neuropsychological tests and cerebral magnetic resonance imaging were performed.Then,the outcomes of clinical features,neuropsychological tests,and global and regional CBF were compared between the two groups.The significant regional zCBF(z-transformed relative CBF)values were extracted and correlated with clinical data and neuropsychological scores in T2DM patients,controlling age,sex,and education.Results No significant difference was found in whole brain CBF between the two groups(P=0.155),while significantly higher CBF was identified in the left superior temporal gyrus and left insula in the T2DM group(Gaussian random field correction,initial threshold P < 0.001,cluster level P < 0.05).No correlation was observed between the significant regional zCBF values and the clinical data or the neuropsychological scores in T2DM patients(all P>0.05).Conclusion Alterations in cerebral hemodynamics may precede cognitive function changes in T2DM,suggesting that the ASL technique is promising for early monitoring of cerebral hemodynamic changes associated with cognitive impairment in patients with T2DM.
Humans ; Diabetes Mellitus, Type 2/physiopathology* ; Cerebrovascular Circulation ; Middle Aged ; Male ; Female ; Magnetic Resonance Imaging ; Case-Control Studies ; Cognitive Dysfunction ; Neuropsychological Tests ; Aged

Objective To investigate the effects of inhibiting KDM2A gene on the proliferation,invasion and migration of liver cancer cells and its possible regulatory mechanism.Methods Forty pairs of HCC tissues and their adjacent normal counterparts were collected from 2014 to 2017 in Tongji Hospital,Tongji Medical College Affiliated to Huazhong University of Science and Technology.Human liver cancer cell lines HepG2,Huh7,HCCLM3,MHCC-97H and normal liver cells LO2 were cultured in vitro.The mRNA and protein expression levels of KDM2A in HCC tissues and cells were detected by qRT-PCR and Western blotting.Huh7 cells were taken and set up as follows:(1)si-NC group(transfected with si-NC)and si-KDM2A group(transfected with si-KDM2A);(2)mimic-NC group(transfected with mimic-NC),miRNA-29a-3p mimic group(transfected with miRNA-29a-3p mimic),inhibitor-NC group(transfected with inhibitor-NC)and miRNA-29a-3p inhibitor group(transfected with miRNA-29a-3p inhibitor).The mRNA and protein expression levels of KDM2A were detected by qRT-PCR and Western blotting.The invasion and migration of cells were detected by Transwell,the proliferation of cells was detected by CCK-8 methods.The online databases TargetScan,miRDIP,miRWalk,Starbase and miRDB were used to predict the binding sites of KDM2A and miR-29a-3p.The KDM2A 3'-UTR(WT)or KDM2A 3'-UTR(MUT)report plasmid was co-transfected with NC-miRNA or miR-29a-3p mimics respectively for 48 h in 293T cells,and the luciferase activity was detected by the luciferase reporter gene detection system.Results Compared with adjacent normal counterparts,the relative mRNA and protein expression levels of KDM2A in HCC tissues increased significantly(P＜0.05).Compared with LO2,the relative mRNA and protein expression levels of KDM2A in HepG2,Huh7,HCCLM3 and MHCC-97H increased significantly(P＜0.05).Compared with si-NC group,the proliferation,invasion and migration of Huh7 cells in si-KDM2A group decreased significantly(P＜0.05 or P＜0.01).The analysis results of TargetScan,miRDIP,miRWalk,Starbase and miRDB showed that there were binding sites between KDM2A and miR-29a-3p.The results of the dual luciferase reporter assay showed that miR-29a-3p mimic significantly reduced KDM2A-MUT luciferase activity(P＜0.01).After overexpression of miRNA-29a-3p,the relative mRNA and protein expression levels of KDM2A were decreased(P＜0.01),the proliferation,invasion and migration abilities were decreased(P＜0.05)in Huh7 cells.After inhibiting the expression of miRNA-29a-3p,the relative mRNA and protein expression levels of KDM2A were increased(P＜0.05),the proliferation,invasion and migration abilities were enhanced(P＜0.05)in Huh7 cells.Conclusion Inhibiting the expression of KDM2A can reduce the proliferation and migration ability of Huh7 cells.miR-29a-3p may be the upstream regulator of KDM2A and participate in the occurrence and development of hepatocellular carcinoma.

Objective:To investigate the independent influencing factors of body mass index (BMI) growth risk during breast cancer treatment and establish a predictive model, and validate its predictive efficacy.Methods:A retrospective cohort study was conducted by a convenience sampling method. 306 eligible breast cancer patients underwent follow-up at the Tianjin Medical University Cancer Hospital between January and May 2023 were selected as the modeling group. The BMI changes of the modeling group patients were monitored during the study period. Patients with BMI changed < ± 0.5 kg/m 2 were classified as the stable group, while those with BMI changed ≥ 0.5 kg/m 2 were classified as the growth group. Factor analysis was conducted, and a predictive model was established. The fitting effect was verified by the Hosmer-Lemeshow test, and the receiver operating characteristic (ROC) curve was drawn to verify the model′s predictive ability. 110 eligible breast cancer patients underwent follow-up at the Tianjin Medical University Cancer Hospital between June and August 2023 were selected as the validation group to verify the predictive effect of the model. Results:The age of the modeling group patients was (48.89 ± 7.78) years, BMI was (25.53 ± 1.39) kg/m 2 and the age of the validation group patients was (50.18 ± 7.70) years, BMI was(24.31 ± 0.86) kg/m 2, both groups were female, there were no significant differences between the two groups (all P>0.05). Axillary lymph node dissection ( OR=4.196, 95% CI 3.512-9.158), chemotherapy duration ( OR=2.002, 95% CI 1.001-3.003), premenopausal status ( OR=3.257, 95% CI 1.244-3.733), low health behavior capacity ( OR=5.977, 95% CI 2.878-7.893), and low physical activity ( OR=3.755, 95% CI 1.244-11.733) were identified as independent influencing factors of BMI change during breast cancer treatment (all P<0.05). The predictive model was P=0.915, with the ROC curve area of 0.950, a J-index of 0.785, a sensitivity of 0.971, and a specificity of 0.814. Internal and external validation of the model in the validation group revealed a sensitivity of 0.858, a specificity of 0.887, and an accuracy of 97.3%. Conclusion:The predictive model exhibited excellent performance and can serve as a valuable tool for formulating nursing intervention strategies to maintain the BMI stability of breast cancer patients during treatment.

Objective:To investigate the cognition and learning habits of different types of postgraduates and evaluate learning effect and its potential risk factors on clinical epidemiology in a medical college, so as to provide relevant data for improving the teaching method and learning effect of clinical research methods for postgraduates.Methods:A cross-sectional study design was conducted to enroll all the postgraduates of Grade 2020 in a military medical school. A self-filled questionnaire was adopted to collect data. The discrepancy of cognition and learning habits between different types of postgraduates was evaluated by univariate analysis. Discussion was conducted to clarify the potential risk factors of learning effect. t tests or Mann-Whitney U tests were conducted to test the differences between groups for continuous variables. Chi-squared tests or McNemar tests were applied to evaluate the difference between groups for categorical variables. Results:A total of 652 postgraduate students were enrolled for analysis, including 409 master students (62.7) and 243 doctoral students (37.3). The proportion of doctoral students who have heard of clinical epidemiology ( χ2=19.99, P<0.001), who have learned clinical epidemiology ( χ2=9.20, P=0.002), who are interested in ( χ2=11.41, P=0.001) and think the course is important ( χ2=10.71, P=0.001), who previewed before class( χ2=11.21, P=0.001), reviewed after class ( χ2=3.29, P=0.001) and actively discuss in class ( χ2=11.64, P=0.001) is significantly higher than that of master students, the difference was statistically significance. The average score of all the postgraduates was (5.50±1.62) points before teaching and (7.47±1.90) points after teaching, the difference was statistically significant ( t=-23.49, P<0.001). After teaching, the grades of full-time students improved more than that of part-time graduate students, there was statistical significance in the master group ( t=4.41, P<0.001), while not in the doctor group ( t=0.94, P=0.351). Conclusions:The mastery of key points on clinical epidemiology have significantly improved after teaching among the postgraduates of different types. Different teaching methods and processes should be adopted to the variety of postgraduates according to their knowledge foundations and shortcomings. Besides, standardizing their learning habits are of certain significance to improve the learning effect.

OBJECTIVE To explore the efficacy and safety of intra-articular injection of ropivacaine combined with alfentanil for postoperative analgesia in patients who underwent knee arthroscopic surgery. METHODS A total of 60 patients who underwent knee arthroscopic surgery were collected from the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture from March to September in 2022， and then divided into trial group and control group with random number table method， with 30 cases in each group. The control group received intra-articular injection of 0.25% ropivacaine 50 mg， and the trial group received intra-articular injection of 0.25% ropivacaine 50 mg+alfentanil 0.15 μg/kg.The first postoperative remedial analgesia time， the total amount of postoperative remedial drugs， numerical rating scale at rest （NRS-R） scores， numerical rating scale at movement （NRS-M） scores， heart rate， mean arterial blood pressure， and pulse oxygen saturation during exercise at different monitoring time points after surgery， the incidence of adverse drug reactions such as hypotension， respiratory depression， nausea， and vomiting after surgery were compared between 2 groups. RESULTS Compared with the control group， the first postoperative remedial analgesia time was significantly longer in the trial group， and the total amount of postoperative remedial drugs was significantly reduced （P＜0.001）. The trial group had lower NRS-R and NRS-M scores at each monitoring time point， with statistically significant differences （P＜0.001）， and there was an interactive effect between time and groups （P＜0.001）. The changes in heart rate， mean arterial blood pressure， and pulse oxygen saturation of patients in the trial group were relatively small， with no statistically significant differences （P＞0.05）， and there was no interactive effect between time and groups （P＞0.05）. There was no statistical significance in the incidence of adverse drug reactions between 2 groups， such as postoperative hypotension， respiratory depression， nausea， vomiting （P＞0.05）. CONCLUSIONS The intra- articular injection of ropivacaine combined with alfentanil shows good efficacy and safety for post-knee arthroscopic analgesia， and significantly prolongs the analgesic duration of ropivacaine.

The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 μmol/L) with or without Ang II (0.4 μmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.
Rats ; Mice ; Animals ; Rats, Sprague-Dawley ; Angiotensin II/pharmacology* ; Fibroblasts ; Mice, Inbred C57BL ; Fibrosis ; Collagen/pharmacology* ; Collagen Type I/metabolism* ; RNA, Messenger/metabolism* ; Myocardium/pathology*

The biological samples of oral genetic diseases and rare diseases are extremely precious. Collecting and preserving these biological samples are helpful to elucidate the mechanisms and improve the level of diagnose and treatment of oral genetic diseases and rare diseases. The standardized construction of biobanks for oral genetic diseases and rare diseases is important for achieving these goals. At present, there is very little information on the construction of these biobanks, and the standards or suggestions for the classification and coding of biological samples from oral and maxillofacial sources, and this is not conducive to the standardization and information construction of biobanks for special oral diseases. This consensus summarizes the background, necessity, principles, and key points of constructing the biobank for oral genetic diseases and rare diseases. On the base of the group standard "Classification and Coding for Human Biomaterial" (GB/T 39768-2021) issued by the National Technical Committee for Standardization of Biological Samples, we suggest 76 new coding numbers for different of biological samples from oral and maxillofacial sources. We hope the consensus may promote the standardization, and smartization on the biobank construction as well as the overall research level of oral genetic diseases and rare diseases in China.

Objective:To investigate the independent influencing factors of wound drainage tube time delay in patients with breast cancer and establish a predictive model.Methods:Patients admitted to Tianjin Medical University Cancer Hospital from January to November 2021 were selected as the research objects. They were divided into sword modeling group (156 cases) and verification group (86 cases) according to the admission time. Delayed time to postoperative wound drainage and extubation in breast cancer patients was the end point, 95 cases of 156 patients in the modeling group whose extubation time was less than or equal to 7 days were set as the normal group, 61 cases whose extubation time were more than 7 days were set as delayed group, and the influencing factors of the two groups were compared to establish the prediction model, Hosmer-Lemeshow test was conduct to verify the fitting effect, used the ROC curve to verify the prediction model performance.Results:Univariate and multivariate Cox proportional hazards regression analysis showed that patients' high BMI, related basic disease history, operation mode, axillary lymph node dissection, breast tumor size (T3, T4) and drainage fluid volume 48 hours (≥50 ml) after operation were independent influencing factors for wound drainage tube time delay ( P<0.05). The prediction model was P=0.822, and the area under the ROC curve was 0.877, and the Youden index was 0.605, the sensitivity was 0.736, and the specificity was 0.869. The research data of 86 cases in the validation group were used as the test set for internal and external validation of the model, and the model verification was 96.51%. Conclusion:This prediction model has a good effect, providing a reference basis for clinical medical workers.

BACKGROUND: Hypertension is associated with stroke-related mortality. However, the long-term association of blood pressure (BP) and the risk of stroke-related mortality and the influence path of BP on stroke-related death remain unknown. The current study aimed to estimate the long-term causal associations between BP and stroke-related mortality and the potential mediating and moderated mediating model of the associations. METHODS: This is a 45-year follow-up cohort study and a total of 1696 subjects were enrolled in 1976 and 1081 participants died by the latest follow-up in 2020. COX proportional hazard model was used to explore the associations of stroke-related death with baseline systolic blood pressure (SBP)/diastolic blood pressure (DBP) categories and BP changes from 1976 to 1994. The mediating and moderated mediating effects were performed to detect the possible influencing path from BP to stroke-related deaths. E value was calculated in the sensitivity analysis. RESULTS: Among 1696 participants, the average age was 44.38 ± 6.10 years, and 1124 were men (66.3%). After a 45-year follow-up, a total of 201 (11.9%) stroke-related deaths occurred. After the adjustment, the COX proportional hazard model showed that among the participants with SBP ≥ 160 mmHg or DBP ≥ 100 mmHg in 1976, the risk of stroke-related death increased by 217.5% (hazard ratio [HR] = 3.175, 95% confidence interval [CI]: 2.297-4.388), and the adjusted HRs were higher in male participants. Among the participants with hypertension in 1976 and 1994, the risk of stroke-related death increased by 110.4% (HR = 2.104, 95% CI: 1.632-2.713), and the adjusted HRs of the BP changes were higher in male participants. Body mass index (BMI) significantly mediated the association of SBP and stroke-related deaths and this mediating effect was moderated by gender. CONCLUSIONS In a 45-year follow-up, high BP and persistent hypertension are associated with stroke-related death, and these associations were even more pronounced in male participants. The paths of association are mediated by BMI and moderated by gender.
Adult ; Blood Pressure/physiology* ; China/epidemiology* ; Follow-Up Studies ; Humans ; Hypertension ; Male ; Middle Aged ; Risk Factors ; Stroke