ObjectiveTo observe the effects of modified Chaihu Shugansan on the calmodulin-dependent protein kinase Ⅱ（CaMKⅡ）/cAMP-response element binding protein （CREB） signaling pathway in the hippocampus and heart tissue of a rat model with myocardial ischemia and depression and explore the mechanism by which this formula prevents and treats coronary heart disease combined with depression. MethodsThe model of myocardial ischemia combined with depression was established by high-fat diet， intraperitoneal injection of isoproterenol （ISO）， and chronic unpredictable mild stress （CUMS）. A total of 108 SD male rats were randomly divided into normal group， model group， high （23.4 g·kg^-1）， medium （11.7 g·kg^-1）， and low （5.85 g·kg^-1） dose groups of modified Chaihu Shugansan， CaMKⅡ inhibitor （KN93） group， and KN93 + high， medium， and low dose groups of modified Chaihu Shugansan， with 12 rats in each group. From the first day of modeling to the end of modeling， drugs were administered once a day. In the seventh and eighth weeks， the KN93 group and the KN93 + high， medium， and low dose groups of modified Chaihu Shugansan were intraperitoneally injected with KN93 three times weekly. At the end of the eighth week， behavioral tests including sucrose preference， open field， and elevated plus maze were conducted. Electrocardiogram （ECG） lead Ⅱ changes were observed in each group of rats， and hematoxylin-eosin （HE） staining was performed to observe changes in heart tissue. Serum levels of triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein （HDL）， low-density lipoprotein （LDL）， and lactate dehydrogenase （LDH） were measured by using an enzyme-labeled instrument. Creatine kinase （CK） and creatine kinase-MB （CK-MB） were detected by ultraviolet spectrophotometry， while serum monocyte chemoattractant protein-1 （MCP-1） was measured by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression of CaMKⅡ and CREB in hippocampal and heart tissue， and Western blot was performed to assess protein expression of CaMKⅡ， phosphorylated （p）-CaMKⅡ， CREB， and p-CREB. ResultsCompared to the normal group， the model group showed significant reductions in sucrose preference rate， total activity distance in the open field， number of entries into the center area of the open field， and percentage of entries into the open arms of the elevated plus maze （P<0.01）. The ECG showed ST-segment elevation， and HE staining showed serious degeneration of myocardial fibers， disordered arrangement， and infiltration of a large number of inflammatory cells. In addition， serum TC and LDL levels increased （P<0.01）， and HDL level decreased （P<0.01）. CK， CK-MB， LDH， and MCP-1 levels significantly increased （P<0.05， P<0.01）. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB decreased in the hippocampal tissue （P<0.05， P<0.01）， but those increased in the heart tissue （P<0.01）. Compared to the model group， the high， medium， and low dose groups of modified Chaihu Shugansan showed improvements in these abnormalities. The KN93 group had reduced sucrose preference， total activity distance in the open field， number of entries into the center area of the open field， and percentage of entries into the open arms of the elevated plus maze （P<0.01）， as well as decreased serum CK， CK-MB， LDH， and MCP-1 levels （P<0.05， P<0.01）. KN93 also reduced ST-segment elevation， alleviated the degeneration degree of myocardial fibrosis， and lowered inflammatory cell infiltration. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB in both the hippocampal and heart tissue were reduced （P<0.05， P<0.01）. The KN93 + high， medium， and low dose groups of modified Chaihu Shugansan showed further improvements in these abnormalities compared to the KN93 group. ConclusionThe modified Chaihu Shugansan exerts antidepressant and myocardial protective effects in rats with myocardial ischemia and depression， possibly related to bidirectional regulation of the CaMKⅡ/CREB signaling pathway， with the high-dose modified Chaihu Shugansan showing the best effects.

Venous thromboembolism (VTE) is a complication in children with acute lymphoblastic leukemia (ALL). The Chinese Children's Cancer Group-ALL-2015 protocol was carried out in China, and epidemiology, clinical characteristics, and risk factors associated with VTE were analyzed. We collected data on VTE in a multi-institutional clinical study of 7640 patients with ALL diagnosed in 20 hospitals from January 2015 to December 2019. First, VTE occurred in 159 (2.08%) patients, including 90 (56.6%) during induction therapy and 108 (67.92%) in the upper extremities. T-ALL had a 1.74-fold increased risk of VTE (95% CI 1.08-2.8, P = 0.022). Septicemia, as an adverse event of ALL treatment, can significantly promote the occurrence of VTE (P < 0.001). Catheter-related thrombosis (CRT) accounted for 75.47% (n = 120); and, symptomatic VTE, 58.49% (n = 93), which was more common in patients aged 12-18 years (P = 0.023), non-CRT patients (P < 0.001), or patients with cerebral thrombosis (P < 0.001). Of the patients with VTE treated with anticoagulation therapy (n = 147), 4.08% (n = 6) had bleeding. The VTE recurrence rate was 5.03% (n = 8). Patients with VTE treated by non-ultrasound-guided venous cannulation (P = 0.02), with residual thrombus (P = 0.006), or with short anticoagulation period (P = 0.026) had high recurrence rates. Thus, preventing repeated venous puncture and appropriately prolonged anticoagulation time can reduce the risk of VTE recurrence.
Humans ; Child ; Venous Thromboembolism/etiology* ; East Asian People ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology* ; Risk Factors ; Thrombosis/chemically induced* ; China/epidemiology* ; Anticoagulants/adverse effects* ; Recurrence

This paper focused on the research progress of the assessment methods of carers′ fall concern for the elderly. The content of this review included the definition of carers′ fall concern, and the advantages and disadvantages of various assessment method of carers′ fall concern for the caregivers to the elderly, such as qualitative interviews, questionnaires, and scales. Through this review, the authors hoped to provide a reference for selecting or developing a localized carers′ fall concern assessment tool.

Objective:To investigate the effects of early intervention with low-dose dobutamine on pneumonia complicated with sepsis.Methods:We retrospectively analyzed the clinical data of 200 patients with pneumonia complicated by sepsis who received treatment in the First People's Hospital of Taizhou from January 2015 to January 2018. We divided these patients into control and observation groups with 100 patients/group according to different treatment methods. The control group was treated with immunoglobulin and methylprednisolone and given ventilator-assisted ventilation. The observation group was given low-dose dobutamine based on the treatments given in the control group. Clinical efficacy, pulmonary function, the incidence of adverse reactions, length of hospital stay, time to dyspnea disappearance, organ failure rate, and mortality were compared between the two groups.Results:Total response rate was significantly higher in the observation group than in the control group [96.0% (96/100) vs. 77.0% (77/100), χ2 = 15.45, P < 0.05]. After treatment, improvements in the pulmonary function indexes [forced vital capacity, forced expiratory volume in one second, and forced expiratory volume in one second/forced vital capacity] in the observation group were superior compared with those in the control group ( t = -15.25, -34.56, -3.77, all P < 0.001). Length of hospital stay and time to dyspnea disappearance in the observation group were (4.23 ± 0.89) days and (3.21 ± 0.58) days, respectively, which were significantly shorter than those in the control group [(8.96 ± 1.58) days, (7.26 ± 0.24) days, t = -26.08, -64.52, both P < 0.001]. The incidence of adverse reactions, incidence of organ failure, and mortality in the observation group were 2.0% (2/100), 1.0% (1/100) and 2.0% (2/100) respectively, which were significantly lower than those in the control group [18.0% (18/100), 20.0% (20/100), 10.0% (10/100), χ2 = 16.80, 19.20, 5.67, all P < 0.05). Conclusion:Early intervention with low-dose dobutamine for the treatment of pneumonia complicated by sepsis can greatly improve clinical efficacy, reduce adverse reactions, decrease the incidence of organ failure and mortality, improve pulmonary function, and shorten the length of hospital stay and time to dyspnea disappearance.

Objective: To investigate the clinical value of coefficient of variation of heart rate and blood pressure in rapid identification of children with suspected orthostatic intolerance(OI). Methods: This was a retrospective study. The medical records of 379 children with OI were collected, who were admitted to the Department of Pediatrics of Qilu Hospital of Shandong University from January 2015 to January 2020. Another 20 out-patient children without syncope or syncope aura were selected as control. According to the results of standing test and head-up tilt test (HUTT), all the patients with OI were divided into the following 4 groups: vasovagal syncope (VVS) group, postural tachycardia syndrome (POTS) group, POTS combined with VVS (POTS+VVS) group and HUTT negative group. Then, coefficient of variation of systolic pressure (SBP_CV), coefficient of variation of diastolic pressure (DBP_CV) and coefficient of variation of heart rate (HR_CV) in standing test and HUTT were calculated. Kruskal-Wallis test was used for comparison among the five groups, and Dunnett's T3 method for comparison between two groups. Paired t test was used to compare the coefficient of variation between supine and erect position and tilt position in each group. The predictive values of HR_CV,SBP_CV and DBP_CV for negative HUTT were evaluated by receiver operating characteristic (ROC) curve. Results: Among the 379 children, there were 79 in HUTT negative group, 208 in VVS group, 52 in POTS group, and 40 in POTS+VVS group. The SBP_CV of supine-erect position of the control group, HUTT negative group, VVS group, POTS group, POTS+VVS group were (3.8±1.0)%, (5.3±2.2)%, (6.6±3.4)%, (5.9±3.6)%, (6.9±2.8)%, respectively. Similarly, the SBP_CV of supine, erect and head-up tilt position were (4.5±0.8)%, (6.0±1.9)%, (7.1±2.6)%, (6.0±2.1)%, (7.3±2.5)%; the DBP_CV of supine-erect position were (7.3±1.2)%, (9.1±3.7)%, (9.1±4.9)%, (9.1±4.8)%, (11.6±4.6)%; the DBP_CV of supine, erect and tilt position were (7.4±1.1)%, (9.4±2.9)%, (10.1±3.8)%, (9.2±3.3)%, (11.0±4.7)%; the HR_CV of supine-erect position were (7.6±2.6)%, (12.9±3.7)%, (16.2±4.3)%, (21.2±5.9)%, (24.9±5.3)%; and the HR_CV of supine, erect and tilt position were (8.1±1.6)%, (10.1±2.7)%, (14.1±4.3)%, (15.6±3.7)%, (18.9±4.0)%, respectively. All the indexes showed significant differences among the five groups (χ²=21.91, 25.47, 19.82, 14.65, 104.52, 92.51, all P<0.05). ROC curve analysis showed that when the SBP_CV and HR_CV of supine-erect position reached 4.4% and 10.5%, the area under the curve of ROC were 0.713 and 0.877, the sensitivity of predicting negative HUTT were 58.2% and 78.5%, and the specificity were 80.0% and 95.0%, respectively. Conclusions: Coefficient of variation of heart rate and blood pressure may serve as potential diagnostic indexes in evaluating autonomic function of OI patients. SBP_CV ≥ 4.4% or HR_CV ≥ 10.5% of supine-erect position could be an indication of HUTT.
Blood Pressure ; Child ; Heart Rate ; Humans ; Orthostatic Intolerance/diagnosis* ; Postural Orthostatic Tachycardia Syndrome/diagnosis* ; Retrospective Studies ; Syncope, Vasovagal/diagnosis* ; Tilt-Table Test

Background/Aims: 17β-hydroxysteroid dehydrogenase 13 (HSD17B13) variants were recently reported to have significantly lower odds of non-alcoholic fatty liver disease (NAFLD). This is a two-part study that aimed to evaluate the association of HSD17B13 variants with NAFLD and its histological severity, and to identify the association of the variants with clinical outcomes in a cohort of biopsy-proven NAFLD patients. Methods: Consecutive biopsy-proven NAFLD patients and controls without fatty liver were recruited for this study between 2009 and 2014. Genotyping for HSD17B13 variants was performed using rhAmp assays. A total of 165 patients with NAFLD were monitored up until August 2019. Clinical outcomes were recorded. Results: HSD17B13 rs72613567 TA allele and rs6834314 G allele were associated with lower odds of non-alcoholic steatohepatitis (NASH) in the overall cohort and among ethnic Chinese, but not among ethnic Malays or Indians (P<0.05). During a mean follow-up of 89 months, 32 patients (19.4%) experienced at least one clinical outcome (cardiovascular events, n=22; liver-related complications, n=6; extra-hepatic malignancy, n=5; and mortality, n=6). The rs72613567 homozygous TA allele and the rs6834314 homozygous G allele were independently associated with a lower incidence of liver-related complications (hazard ratio [HR], 0.004; 95% confidence interval [CI], 0.00–0.64; P=0.033 and HR, 0.01; 95% CI, 0.00–0.97; P=0.048, respectively) and were associated with lower grade of hepatocyte ballooning among the ethnic Chinese. Conclusion HSD17B13 rs72613567 and rs6834314 variants were inversely associated with NAFLD and NASH, and were associated with lower incidence of adverse liver outcomes in a cohort of multi-ethnic Asian patients with NAFLD.

OBJECTIVE: To study the expression of B lymphocyte-induced mature protein-1 (BLIMP-1) in regulatory T cells (Tregs) of children with aplastic anemia (AA), and analyze its correlation with the number of Tregs and the levels of inhibitory cytokines interleukin (IL)-10 and transforming growth factor (TGF)-β in plasma. METHODS: The peripheral blood samples of 10 newly diagnosed AA children and 10 healthy children were collected for experiment. qPCR was used to detect FOXP3 and PRDM1 mRNA expression levels. Flow cytometry was used to detect the proportion of Tregs, the expression of BLIMP-1 in Tregs, and the levels of cytokines such as IL-2, IL-17A, IL-6, interferon (IFN)-γ, IL-10 and TGF-β in plasma. Pearson correlation model was used to evaluate the relationship between the expression of BLIMP-1 in Treg and the number of Tregs, as well as the levels of IL-10 and TGF-β in plasma. RESULTS: Compared with control group, the proportion of Tregs in peripheral blood of AA children was decreased significantly (P<0.001); The plasma levels of proinflammatory cytokines IL-2, IL-6 and IFN-γ in AA children were increased significantly (P=0.033, P=0.031, P=0.006), and IL-17A also was increased but the difference was not statistically significant (P=0.052), while anti-inflammatory cytokines IL-10 and TGF-β were significantly reduced (P=0.048, P=0.002). The relative expressions level of FOXP3 and PRDM1 mRNA in AA children were significantly lower than those in control group (P=0.037, P=0.016). The expression of BLIMP-1 protein in Tregs of AA children was significantly lower than that in control group (P<0.001). The expression level of BLIMP-1 protein in Tregs was positively correlated with the percentage of Tregs in lymphocytes (r=0.671, P=0.001), and was also positively correlated with the levels of IL-10 and TGF-β in plasma (r=0.500, P=0.029; r=0.486, P=0.030). CONCLUSION The expression of BLIMP-1 in Tregs of AA children is impaired, and the low expression of BLIMP-1 is related to the decrease of the number in Tregs and IL-10 and TGF-β expressions.
Anemia, Aplastic ; Child ; Cytokines ; Flow Cytometry ; Forkhead Transcription Factors ; Humans ; Positive Regulatory Domain I-Binding Factor 1 ; T-Lymphocytes, Regulatory ; Transforming Growth Factor beta

Background/Aims: 17β-hydroxysteroid dehydrogenase 13 (HSD17B13) variants were recently reported to have significantly lower odds of non-alcoholic fatty liver disease (NAFLD). This is a two-part study that aimed to evaluate the association of HSD17B13 variants with NAFLD and its histological severity, and to identify the association of the variants with clinical outcomes in a cohort of biopsy-proven NAFLD patients. Methods: Consecutive biopsy-proven NAFLD patients and controls without fatty liver were recruited for this study between 2009 and 2014. Genotyping for HSD17B13 variants was performed using rhAmp assays. A total of 165 patients with NAFLD were monitored up until August 2019. Clinical outcomes were recorded. Results: HSD17B13 rs72613567 TA allele and rs6834314 G allele were associated with lower odds of non-alcoholic steatohepatitis (NASH) in the overall cohort and among ethnic Chinese, but not among ethnic Malays or Indians (P<0.05). During a mean follow-up of 89 months, 32 patients (19.4%) experienced at least one clinical outcome (cardiovascular events, n=22; liver-related complications, n=6; extra-hepatic malignancy, n=5; and mortality, n=6). The rs72613567 homozygous TA allele and the rs6834314 homozygous G allele were independently associated with a lower incidence of liver-related complications (hazard ratio [HR], 0.004; 95% confidence interval [CI], 0.00–0.64; P=0.033 and HR, 0.01; 95% CI, 0.00–0.97; P=0.048, respectively) and were associated with lower grade of hepatocyte ballooning among the ethnic Chinese. Conclusion HSD17B13 rs72613567 and rs6834314 variants were inversely associated with NAFLD and NASH, and were associated with lower incidence of adverse liver outcomes in a cohort of multi-ethnic Asian patients with NAFLD.

BACKGROUND: Hemorrhoids are one of the most common conditions that lead to surgery, and until now surgical hemorrhoidectomy has been the major effective treatment. Post-operative pain from hemorrhoidectomy has been experienced by thousands of patients and remains a major inconvenience of the operation. OBJECTIVE: This study evaluates the clinical efficacy of the pestle needle therapy, an acupoint stimulation method, for relief of post-hemorrhoidectomy pain. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This was a single-center, patient-assessor-blinded and randomized controlled trial with 154 patients receiving Milligan hemorrhoidectomy surgery. Eligible patients were randomly assigned to either a treatment group or a control group at a ratio of 1:1. The treatment group received the pestle needle therapy, with manual stimulation at Yaoshu (DU2), Mingmen (DU4), Changqiang (DU1), Chengshan (BL57), Erbai (EX-UE2) and the perianal points (1, 3, 5, 7, 9, and 11o'clock around the lesion); while the control group received a sham treatment with very light pressure. Three sessions of treatment were performed at 30 min, 4 h and 12 h after the surgery, and each lasted for 15 min. MAIN OUTCOME MEASURES: The primary outcome was post-operative pain measured with the visual analogue scale (VAS) at 12 h after surgery. The secondary outcomes included the VAS scores measured at 0.5, 2, 4, 6, 8, 24 and 48 h after surgery, the analgesic dose, the time and the VAS score of the patients' first defecation after surgery, as well as the Hamilton Rating Scale for Anxiety (HAMA) evaluated before discharge. RESULTS: The mean pain score of the treatment group was significantly lower than that of the control group (3.10 ± 1.27 vs 4.82 ± 1.29; P < 0.001) at 12 h after surgery. Compared with the control group, patients in the treatment group needed a smaller dose of analgesic within the first 24 hours after surgery (P = 0.002); and their HAMA scores before discharge were lower (4.07 ± 2.40 vs 5.10 ± 2.45, P = 0.009). Compared to the treatment group, patients in the control group had a greater time to the first defecation after surgery ([52.34 ± 15.72] h vs [27.08 ± 13.68] h; P < 0.001), but there was no difference in their VAS scores at the first defecation (P = 0.092). CONCLUSION The pestle needle therapy was effective for relieving pain, reducing anxiety and improving bowel function after hemorrhoidectomy, and it is worthy of clinical application.