BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

Objective:To understand the prevalence of insufficient physical activity among adults aged ≥18 years in China and to explore the influencing factors.Methods:The China Chronic Disease and Risk Factor Surveillance was conducted in 298 counties/districts in China in 2018, covering 31 provinces (autonomous regions, municipalities). A multi-stage stratified cluster random sampling method was used to select permanent residents aged ≥18 years. A questionnaire including Global Physical Activity Questionnaire was used to collect information about the participants' demographic characteristics and physical activity through face-to-face interview. A total of 183 769 participants completed the survey. After complex data weighting, the prevalence of insufficient physical activity, occupation, transportation, and leisure-time physical activity time was analyzed. Multivariate logistic regression models were used to analyze the influencing factors related to insufficient physical activity.Results:The prevalence of insufficient physical activity among adults aged ≥18 years was 22.3% (95% CI: 20.9%-23.7%) in China in 2018, with males [24.4% (95% CI: 23.0%-25.8%)] significantly higher than females [20.2% (95% CI: 18.6%-21.8%)]. Adults aged 70 years and above [28.4% (95% CI: 26.9%-29.9%)] were significantly higher than adults in other age groups, followed by adults aged 18-29 years [26.4% (95% CI: 24.4%- 28.3%)] and 30-39 years [23.4% (95% CI: 21.5%-25.3%)], and tended to increase with increasing education and total sedentary behavior time ( P<0.001). The weekly occupation, transportation, and leisure-time physical activity time appeared 958.6 (95% CI: 911.4-1 005.8) minutes, 234.5 (95% CI: 224.7- 244.2) minutes, and 88.6 (95% CI: 83.5-93.7) minutes, respectively. Multivariate logistic regression analysis showed that males, adults living in rural areas or northern China, ≥70 years, with junior high school education, an annual household income per capita <6 000 yuan and institutional/clerical/ technical occupation and longer total sedentary behavior time were related to a higher prevalence of insufficient physical activity. Conclusions:In China, over one-fifth of the adults had lower physical activity levels. Adults who are male, young adults, more educated, institutional/clerical/technical occupation, and with more extended total sedentary behavior are the populations that need to be focused on to promote physical activity-related health.

Objective:To study the effects of rolling blood pump parameters and blood concentration on hemolysis during extracorporeal circulation.Methods:According to the extracorporeal hemolysis experiment standard, an extracorporeal circulation experimental device was built to analyze the influences of circulation time (0 ~ 90 min), blood flow rate (1~4 L/min), and blood volume fraction (60%, 70%) on the hemolysis of blood samples in the circulatory system. The results of hemolysis were analyzed using first-order linear regression.Results:The longer the blood pump circulation time, the greater the hemolysis rate; the higher the blood flow rate, the greater the hemolysis rate. When the flow rate is 1 and 2 L/min, the hemolysis rate curve has an inflection point that changes with time, i.e. when the circulation time exceeds 30 min, the slope of the hemolysis rate curve suddenly increases. However, when the flow rate is 3 and 4 L/min, the hemolysis mutation phenomenon is not obvious. Compared to the blood sample with blood volume fraction of 70%, a blood sample with a blood volume fraction of 60% is less prone to hemolysis.Conclusions:The longer the blood pump circulation time and the higher the blood flow rate, the more easily the red blood cells are destroyed, i.e. the hemolysis rate is directly proportional to the circulation time and blood flow rate. When the circulation time increases to a certain degree, an inflection point appears in the hemolysis rate curve, and the hemolysis trend will be significantly enhanced.

Objective:To study the relationship between compartmental kneeosteoarthritis (KOA) and osteoporosis (OP).Methods:A total of 118 KOA patients with 50~80 years old and 16.5~38 of body mass index (BMI) were selected as the KOA group, in which the patient with OP caused by secondary factors were excluded. 42 patients who did not suffer from KOA who matched the age of patients in the KOA group were selected. The age, BMI, bone mineral density (BMD) and other data of the two groups of patients were collected. The correlation analysis between KOA and OP was conducted to determine the degree of correlation, so as to reveal the relationship between the incidence, progression, prognosis of KOA and OP.Results:BMD was correlated with BMI. BMD was negatively correlated with age. The incidence of KOA and OP was correlated with age. There is a large correlation between KOA and OP, and the probability of KOA associated with OP is high. For KOA patients, OP is less likely to be accompanied by a higher BMI, while OP is more likely to be accompanied by a lower BMI.Conclusions:OP is one of the pathogenic factors of KOA. KOA patients should be treated with anti-OP before and after surgery.

OBJECTIVE： To provide reference for optimizing the treatment of children with infective endocarditis. METHODS： Clinical pharmacists provide whole process pharmaceutical care for a child with congenital heart disease and infective endocarditis admitted to our hospital in April 2017.  According to the individual situation of child， when therapy efficacy was poor， medication suggestions were put forward by timely referring to the guide and literature as well as combined with pharmacists’ work experience. RESULTS： After treatment with vancomycin at normal dose of 38 mg/（kg·d）， the vancomycin blood concentration （1.3 μg/mL） was low， and the treatment effect was poor. Clinical pharmacist made two suggestions to adjust the dose of vancomycin. The first dose was 45 mg/（kg·d）， the second dose was 60 mg/（kg·d）； pediatrician adopt clinical pharmacist recommendations completely. After treatment， the child’s body temperature was normal； vancomycin blood trough concentration increased to 5.8-6.5 μg/mL， and the disease was controlled. CONCLUSIONS： During vancomycin treatment of infective endocarditis in children， clinical pharmacists should provide pharmaceutical care throughout the course and pay close attention to the blood trough concentration of vancomycin in order to ensure the rational use of drugs in children.

Objective To investigate the cryoprecipitate fracture hemorrhage clinical application value in the skull fracture hemorrhage,and provide reference for clinical treatment.Methods 80 patients with standard skull frac-ture hemorrhage were selected as the research subjects.The patients were randomly divided into observation group (40 cases)and the control group (40 cases).The control group was given hemostasis,dehydration,protecting stom-ach,antibacterial,nerve nutrition,reducing intracranial pressure,head up in bed and other symptomatic treatment.The observation group received the treatment besides in the control group and added the cryoprecipitate hemostasis,every time given 10U,every 6 -8h 1 time.According to the condition,they were given the cold sediment of 1 -3 times. Then,the cases that fit to give surgery we must cured them by the operation.After treatment 24h,the coagulation inde-xes were examined [prothrombin time (PT),activated partial thromboplastin time (APTT),thrombin time (TT),two D -dimer],plasma fibrinogen (Fbg),International Glasgow (GOS).Finally,we observed clinical prognosis in two groups.Results PT,APTT,TT were significantly shorter than before treatment in the observation group and the con-trol group(t =6.654,5.746,6.193 and 3.342,3.552,3.646,P <0.01 or P <0.05).The PT,APTT and TT of the observation group were significantly shorter than those in the control group (t =3.322,3.406,3.315,all P <0.05). Plasma Fbg was significantly higher than before treatment in two groups(t =5.762,3.592,P <0.01 or P <0.05). Fbg in the observation group was significantly higher than the control group(t =3.407,P <0.05).The clinical prog-nosis in the observation group was significantly better than the control group(χ2 =8.747,P <0.05).Conclusion Cryoprecipitate is a safe and efficient drug.It can effectively improve the blood coagulation dysfunction of patients with fracture of skull base,active endogenous coagulation system,improve hemostatic effect,and reduce the occurrence of progressive cerebral hemorrhage.Therefore,it can improve the prognosis of patients.

Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Down-Regulation ; drug effects ; Female ; Guanine Nucleotide Exchange Factors ; antagonists & inhibitors ; genetics ; metabolism ; Humans ; Indoles ; pharmacology ; MCF-7 Cells ; Maleimides ; pharmacology ; Protein Isoforms ; genetics ; metabolism ; Protein Kinase C ; antagonists & inhibitors ; genetics ; metabolism ; RNA Interference ; RNA, Small Interfering ; metabolism ; Receptor, ErbB-2 ; genetics ; metabolism ; Tetradecanoylphorbol Acetate ; toxicity

This study was aimed to observe the curative effect and safety of Danzhi Jiangtang Capsule ( DJC ) combined with atorvastatin on carotid artery intima-media thickness (IMT) in diabetes patients without hyper-tension . A total of 196 diabetes patients without hypertension with incrassate carotid artery IMT were randomly divided into the control group ( 98 cases ) and the treatment group ( 98 cases ) . The conventional diabetes thera-py was given to both groups . The atorvastatin of 20 mg/night was given to the control group . And the atorvas-tatin 20 mg/night added with DJC 9 . 0 g/night were given to the treatment group . The treatment course was
12 months . Carotid artery IMT , carotid atherosclerotic plaque area , FPG , FIns , HOMA-IR , HbA1c , blood lipids , hepatorenal function and etc . were examined before and after the treatment respectively . The results showed that there was a significant positive correlation between carotid artery IMT and FIns , HOMA-IR , HbAlc , LDL-C . After 12-month treatment , the total effectiveness is 85 . 87% in the treatment group . And there was significant difference compared with the control group ( P < 0 . 05 ) . The levels of FPG , FIns , HOMA-IR , HbAlc of the treatment group had no difference compared with the control group . Compared with the control group, TC and LDL-C of the treatment group was obviously decreased (P < 0.05). And HDL-C was significantly increased ( P < 0 . 05 ) . The carotid artery IMT of the treatment group decreased from ( 0 . 11 ±0 . 01 ) cm to ( 0 . 08 ± 0 . 01 ) cm . And compared with the control group , there was statistical significance ( P <0 . 05 ) . The carotid atherosclerotic plaque area of 58 cases in the treatment group decreased from ( 0 . 37 ±0.56) cm2 to (0.21 ± 0.25) cm2. However, there was no statistical significance compared to the control group. There were 5 adverse events in the control group and 9 adverse events in the treatment group . And there was no difference between two groups. It was concluded that DJC combined with atorvastatin can regulate lipid metabolism and reduce carotid artery IMT .

Objective To survey cervical myoelectric signals during craniocervical flexion, neutral and extension postures, and to explore the evidence that proper head position can alleviate cervical muscle fatigue in a lateral recumbent position. Methods Surface electromyography (sEMG) signals were detected from the sternocleidomastoid, upper trapezius and erector spinae muscles of 30 young subjects bilaterally during craniocervical flexion,neutral and extension postures in the left lateral recumbent position. The integrated trace area (IEMG) and median frequency (MF) were estimated. Results The average IEMG of the sternocleidomastoid muscles was significantly lower in flexion than in extension bilaterally. The average IEMG of the erector spinae muscles was lower in extension than in flexion bilaterally, and the difference was again significant. The IEMGs of the upper trapezius muscle showed no significant difference on average in the three postures bilaterally. There was no significant MF difference in any of the muscles. Conclusions The muscles in the cervical back were less activated during craniocervical extension in a lateral recumbent position. A little cranicocervical extension is optimal while resting in a lateral recumbent position.