ObjectiveTo investigate the influence of empagliflozin combined with donafenib or lenvatinib on the pharmacokinetic parameters of each drug， and to provide a reference for combined medication in clinical practice. MethodsA total of 48 healthy male Sprague-Dawley rats were divided into 8 groups： empagliflozin group 1 and 2， donafenib group， lenvatinib group， donafenib pretreatment+empagliflozin group， lenvatinib pretreatment + empagliflozin group， empagliflozin pretreatment+donafenib group， and empagliflozin pretreatment+lenvatinib group， with 6 rats in each group. The doses of empagliflozin， donafenib， and lenvatinib were 2.5 mg/kg， 40 mg/kg， and 1.2 mg/kg， respectively. The rats in the empagliflozin group， donafenib group， and lenvatinib group were given a blank solvent by gavage for 7 consecutive days， followed by a single dose of empagliflozin， donafenib， or lenvatinib on day 7 after the administration of the blank solvent； the rats in the pretreatment groups were given the pretreatment drug by gavage for 7 consecutive days， followed by a single dose of drug combination on day 7 after administration of the pretreatment drug. Blood samples were collected at different time points， and plasma was separated to measure the concentration of each drug. A validated ultra-performance liquid chromatography-tandem mass spectrometry method was used to measure the plasma concentrations of donafenib， lenvatinib， and empagliflozin， and a non-compartmental model was used to calculate the main pharmacokinetic parameters of each drug （area under the plasma concentration-time curve ［AUC］， time to peak ［T_max］， peak concentration ［C_max］， and half-life time ［t_1/2］）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. ResultsCompared with the empagliflozin group， the donafenib pretreatment+empagliflozin group had significant increases in the AUC_0-t and AUC_0-∞ of empagliflozin （P=0.011 and 0.008）， while the lenvatinib pretreatment+empagliflozin group had no significant change in the AUC of empagliflozin， with a slightly shorter T_max （P=0.019）. Compared with the donafenib group， the empagliflozin pretreatment+donafenib group had significant increases in the AUC_0-t and AUC_0-∞ of donafenib （P=0.027 and 0.025）， as well as a significant increase in C_max （P=0.015） and significant reductions in CLz/F and Vz/F （P=0.005 and 0.004）； compared with the lenvatinib group， the empagliflozin pretreatment+lenvatinib group had a reduction in the t_1/2 of lenvatinib by approximately 5 hours （P=0.002）， with a trend of reduction in AUC_0-t （P0.05）. ConclusionEmpagliflozin combined with donafenib may alter the pharmacokinetic parameters of both drugs， leading to a significant increase in the exposure levels of both drugs， and efficacy and adverse reactions should be monitored during co-administration. There are no significant changes in the exposure levels of empagliflozin and lenvatinib during co-administration.

Objective To investigate the clinical characteristics,diagnosis and treatment of severe combined peri-odontal-endodontic lesions in a double-rooted maxillary lateral incisor with a palatal radicular groove and to provide a reference for clinical diagnosis and treatment.Methods A patient with a double-rooted left maxillary lateral incisor with a palatal radicular groove and severe combined periodontal-endodontic lesions underwent complete root canal thera-py and intentional replantation,and a retrospective analysis of the management of this type of patient was performed based on the literature.Results The 3-year follow-up examination revealed no discomfort,good healing of the upper left lateral incisor,no pathological loosening,and a palatal gingival sulcus was found at a depth of approximately 1 mm.Review of the literature showed that the prognosis of the affected tooth and the choice of treatment plan were correlated with the length and depth of extension of the lingual groove toward the root,the periodontal condition and the pulpal sta-tus of the affected tooth.For minor PRGs or for affected teeth with no loss of pulpal viability,flap surgery and odonto-plasty can be used to avoid endodontic treatment or retreatment.For deep or long lingual grooves that result in signifi-cant loss of periodontal tissue,endodontic treatment,odontoplasty,or closure of the grooves and guided tissue regenera-tion are needed.In the case of PRGs with double root formation,the affected tooth can be preserved via root canal thera-py,removal of the small root and filling with apical restorative material,and intentional replantation.Conclusion In cases of severe combined periodontal-endodontic lesions due to palatal radicular grooves occurring in double-rooted maxillary lateral incisors,clinical presentation and imaging can prevent missed diagnoses,and appropriate treatment should be based on the length and depth of lingual grooves extending toward the roots,periodontal conditions,and pulp-al status of the affected teeth.

BACKGROUND: The prevalence of hypertension is high among Chinese adults, thus, identifying non-hypertensive individuals at high risk for intervention will help to improve the efficiency of primary prevention strategies. METHODS: The cross-sectional data on 9699 participants aged 20 to 80 years were collected from the China National Health Survey in Gansu and Hebei provinces in 2016 to 2017, and they were nonrandomly split into the training set and validation set based on location. Multivariable logistic regression analysis was performed to develop the diagnostic prediction model, which was presented as a nomogram and a website with risk classification. Predictive performances of the model were evaluated using discrimination and calibration, and were further compared with a previously published model. Decision curve analysis was used to calculate the standardized net benefit for assessing the clinical usefulness of the model. RESULTS: The Lasso regression analysis identified the significant predictors of hypertension in the training set, and a diagnostic model was developed using logistic regression. A nomogram with risk classification was constructed to visualize the model, and a website ( https://chris-yu.shinyapps.io/hypertension_risk_prediction/ ) was developed to calculate the exact probabilities of hypertension. The model showed good discrimination and calibration, with the C-index of 0.789 (95% confidence interval [CI]: 0.768, 0.810) through internal validation and 0.829 (95% CI: 0.816, 0.842) through external validation. Decision curve analysis demonstrated that the model was clinically useful. The model had a higher area under receiver operating characteristic curves in training and validation sets compared with a previously published diagnostic model based on Northern China population. CONCLUSION This study developed and validated a diagnostic model for hypertension prediction in Gansu Province. A nomogram and a website were developed to make the model conveniently used to facilitate the individualized prediction of hypertension in the general population of Han and Yugur.
Adult ; Humans ; Asian People ; China/epidemiology* ; Cross-Sectional Studies ; Health Surveys ; Hypertension/epidemiology* ; Nomograms ; Ethnicity

AIM: To explore the role and mechanism of silent mating type information regulator 2 homolog 3 (SIRT3) in attenuation of intestinal ischemia-reperfusion (I/R) injury by dexmedetomidine in mice. METHODS: Twenty-four healthy male C57BL mice were divided into 4 groups randomly (n=6): sham operation group (Sham group), intestinal ischemia-reperfusion group (I/R group), dexmedetomidine group (Dex group), SIRT3 inhibitor 3-TYP group (3-TYP group). Superior mesenteric artery was clamped for 45 min followed by reperfusion for 2 h to establish intestinal I/R model in I/R group, Dex group, and 3-TYP group. Sham group received sole sham operation. 1 h prior to onset of ischemia, 3-TYP was injected into mice in 3-TYP group intraperitoneally (5 mg/kg, diluted to 0.3 mL), and 0.3 mL normal saline into mice in Dex group intraperitoneally. 30 min prior to onset of ischemia, dexmedetomidine was injected into mice in 3-TYP group and Dex group intraperitoneally (25 μg/kg, diluted to 0.3 mL). 1 h and 30 min prior to onset of ischemia, 0.3 mL normal saline was injected into mice in Sham group and I/R group intraperitoneally, respectively. 2 h of after reperfusion, the mice were sacrificed under anesthesia. Intestinal tissues were took and observed for pathological changes under light microscope after HE staining, and the injury was assessed via the Chiu's score method, and activities of SIRT3 and superoxide dismutase 2 (SOD2) were detected via spectrophotometry, and malondialdehyde (MDA) via spectrophotometry. RESULTS: The pathological injury was exacerbated, and the Chiu's score, the MDA level elevated remarkably, while the activity level of SIRT3 and SOD2 declined remarkably in I/R group, Dex group and 3-TYP group compared to Sham group (P<0.05). The pathological injury was alleviated, and the Chiu's score declined remarkably in Dex group and 3-TYP group compared to I/R group (P<0.05); and the MDA level declined remarkably, while activity level of SIRT3 and SOD2 elevated remarkably in Dex group compared to I/R group (P<0.05); and there was no significant difference both in the activity level of SIRT3 and SOD2 and in the MDA level between 3-TYP group and I/R group. The pathological injury was exacerbated, and the Chiu's score, the MDA level elevated remarkably, while the activity level of SIRT3 and SOD2 declined remarkably in 3-TYP group compared to Dex group (P<0.05). CONCLUSION: SIRT3 and its downstream SOD2 are involved in mediating the effect of attenuation of intestinal ischemia-reperfusion injury through inhibiting oxidative stress response by dexmedetomidine.

Background::Compared with human leukocyte antigen (HLA)-matched sibling donor (MSD) transplantation, it remains unclear whether haploidentical donor (HID) transplantation has a superior graft-versus-leukemia (GVL) effect for Philadelphia-negative (Ph-) high-risk B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to compare the GVL effect between HID and MSD transplantation for Ph- high-risk B-ALL.Methods::This study population came from two prospective multicenter trials (NCT01883180, NCT02673008). Immunosuppressant withdrawal and prophylactic or pre-emptive donor lymphocyte infusion (DLI) were administered in patients without active graft-versus-host disease (GVHD) to prevent relapse. All patients with measurable residual disease (MRD) positivity posttransplantation (post-MRD+) or non-remission (NR) pre-transplantation received prophylactic/pre-emptive interventions. The primary endpoint was the incidence of post-MRD+.Results::A total of 335 patients with Ph- high-risk B-ALL were enrolled, including 145 and 190, respectively, in the HID and MSD groups. The 3-year cumulative incidence of post-MRD+ was 27.2% (95% confidence interval [CI]: 20.2%-34.7%) and 42.6% (35.5%-49.6%) in the HID and MSD groups (P = 0.003), respectively. A total of 156 patients received DLI, including 60 (41.4%) and 96 (50.5%), respectively, in the HID and MSD groups ( P= 0.096). The 3-year cumulative incidence of relapse was 18.6% (95% CI: 12.7%-25.4%) and 25.9% (19.9%-32.3%; P = 0.116) in the two groups, respectively. The 3-year overall survival (OS) was 67.4% (95% CI: 59.1%-74.4%) and 61.6% (54.2%-68.1%; P = 0.382), leukemia-free survival (LFS) was 63.4% (95% CI: 55.0%-70.7%) and 58.2% (50.8%-64.9%; P= 0.429), and GVHD-free/relapse-free survival (GRFS) was 51.7% (95% CI: 43.3%-59.5%) and 37.8% (30.9%-44.6%; P= 0.041), respectively, in the HID and MSD groups. Conclusion::HID transplantation has a lower incidence of post-MRD+ than MSD transplantation, suggesting that HID transplantation might have a superior GVL effect than MSD transplantation for Ph- high-risk B-ALL patients.Trial registration::ClinicalTrials.gov: NCT01883180, NCT02673008.

Objective:To understand the status of life quality related to cough in lung cancer patients after video-assisted thoracoscopic surgery (VATS) and to explore its influencing factors based on enhanced recovery after surgery(ERAS).Methods:By using the convenience sample way, a total of 140 patients in lung cancer who were admitted to the VATS from Chinese Academy of Medical Science, Cancer Hospital were selected as study objects from June to August 2020. Mandarin Chinese version of the Leicester cough questionnaire(LCQ-MC) was used to measure the status of life quality related to cough in lung cancer patients after surgery.The influencing factors were analyzed by single factor analysis and multivariate linear regression analysis.Results:The score of LCQ-MC of patients after VATS (15.83±1.93) was significantly lower than before (19.03±1.64) ( t value was 17.149, P<0.01) . In terms of physiology,psychology and society, the score of LCQ-MC after VATS (4.88±0.84, 5.25±0.71, 5.70±0.73) was also apparently lower than before (6.23±0.77, 6.20±0.84, 6.60±0.72) ( t values were 14.816, 11.338,11.276, P<0.01).The single factor analysis indicated that life quality related to cough had some connections with age( F value was 3.274), cough condition before surgery ( t value was -2.174), operation methods ( F value was 2.837), the time of chest tube retained ( F value was 3.690) and drinking ( t value was -3.033) after VATS( P<0.05). The multiple-factor result showed that age, cough condition before surgery and the time of chest tube retained were the independent factors affecting the life quality related to cough in lung cancer patients after VATS( P<0.05). Conclusion:The lung cancer patients after VATS cough obviously, and their life quality is lower. At the same time, it has some effect on physiology, psychology and society to a certain extent. Medical staff should pay more attention to the elderly and who cough obviously and develop individual interventions before the surgery.After that, in order to remove the chest tube as early as possible, the guidance of pulmonary rehabilitation and mental nursing should be suggested to patients to improve their life quality.

microRNA (miRNA) is a class of 19-25 nucleotide highly conserved single-stranded non-coding RNA that is widely found in plants and animals. Their biological effect is to negatively regulate target gene expression at the post-transcriptional level through complementary pairing with mRNA. Intestinal I/R injury is more common in clinical practice, and ischemia-reperfusion will cause intestinal mucosal barrier damage, and it is related to the occurrence, development, and outcome of many clinical diseases. Many studies have shown that the miRNA subtype genes miR-34a-5p, miR-351-5p, miR-682, miR-21, etc. affect the intestinal I/R injury process to some extent by regulating a series of signal transduction. Therefore, revealing the role of miRNA in intestinal I/R injury and providing a new direction for the diagnosis and treatment of I/R.

Objective    To study the safety of right vertical infra-axillary thoracotomy (RVIAT) in the repair of ventricular septal defect (VSD) and the optimal age for RVIAT. Methods    Between June 2014 and June 2018, 441 children underwent VSD repair via RVIAT in our hospital. According to the age, they were divided into four groups: a 4 months to 1 year old group (R1 group, n=123), a 1-2 years old group (R2 group, n=106), a 2-5 years old group (R3 group, n=166), a >5 years old group (R4 group, n=46). The clinical effects of the patients were compared. Results    All the operations were successfully performed and no serious complication was found in all groups. No statistical difference was observed in the operation time, blood loss during operation, thoracic drainage 24 h after operation among groups (P>0.05). The cardiopulmonary bypass time, aortic cross-blocking time and ICU stay time in the R1 and R2 groups were longer than those in the R3 and R4 groups (P<0.05). In the R1 group, the postoperative ventilating time and postoperative hospital stay time were longer, and the blood transfusion volume was more than those in the R3 and R4 groups (P<0.05). The incidence of postoperative complications was higher in the R4 group than that in the R1 and R3 groups (P<0.05). Conclusion    VSD repair via RVIAT may be more effective in children >2 years old, and 2-5 years old may be the optimal age.

Objective: To investigate the effects of self-made rehabilitation on lower extremity motor function in patients with stroke hemiplegia. Methods: In total, 60 stroke patients with hemiplegia who were unable to walk, were randomly assigned to the traction training belt plus routine rehabilitation group (experimental group) and routine rehabilitation group (control group),30 cases respectively. There were five outcomes: Fugl-Meyer Motor Assessment of the lower extremity(FMA-LE), Kendall method for Manual Muscle Testing(MMT), Berg Balance Scale(BBS), Functional Ambulation Classitication(FAC) and Activity of Daily Living(ADL). Results: For patients on therapy for 12 weeks, the results of both groups were statistically significant (t=-19.185--7.971, P <0.01) . The levels of FMA-LE, BBS and FAC were 29.6 ± 3.7 and 24.9 ± 5.9 (t=3.609, P <0.05) , 31(21, 40) and 22(10, 32)(t=-2.194, P <0.05), 3(3, 4) and 3(2, 3) (t=-2.270, P <0.05) in the test group and the control group, respectively. There was no significant difference in the levels of MMT and ADL (P >0.05). Conclusions The application of traction training belt tested in this study are significant efficacy in rehabilitation effects on lower extremity motor function, muscle strength, balance function and walking ability in stroke patients with hemiplegia, and is worth being promoted.

Objective: To revised the Taiwan version successful aging inventory (SAI), and verify its reliability and validity in urban elderly in mainland China. Methods: SAI was adjusted by culture and revised by pre-test to form a formal questionnaire. A sample of 600 elderly people in Guangzhou was chosen for a face-to-face questionnaire survey through convenient sampling. Half of the sample (n=300) was randomly selected for exploratory factor analysis, and the other was used to confirm the structural validity of SAI. Results: Exploratory factor analysis extracted six common factors, including health autonomy, economic security, life adaptation, society and relative relationship, study and family. The cumulative contribution rate of six common factors was 65.366%. The fitting indexes of confirmatory factor analysis were χ²/df=1.861, CFI=0.930, IFI=0.930, TLI=0.923, GFI=0.823, RMSEA=0.054, RMR=0.073. There were significant ceiling effects in the four dimensions of health autonomy, economic security, life adaptation, and family. The internal consistency coefficient (Cronbach's α) of SAI was 0.930, and the test-retest reliability was 0.943. An average score of SAI ≥ 3.95 points was considered successful aging. Conclusion Reliability and validity of SAI are good, which can be used to measure the successful aging status of Chinese elders and track the effectiveness of health promotion measures.