Effects of the Oat Hay Feeding Method and Compound Probiotic Supplementation on the Growth, Antioxidant Capacity, Immunity, and Rumen Bacteria Community of Dairy Calves.

This study aimed to investigate the effects of the oat hay feeding method and compound probiotics (CMP) on the growth, health, serum antioxidant and immune indicators, rumen fermentation, and bacteria community of dairy calves from 3 to 5 months of age. Forty-eight female Holstein calves (80 ± 7 days of age, 93.71 ± 5.33 kg BW) were selected and randomly divided into four groups. A 2 × 2 factorial design was adopted for the experiment, with the factors of the oat hay feeding method (fed as free-choice or 16.7% in the diet) and compound probiotics (CMP) inclusion (0.15% or 0%) in the pelleted starter. The results showed that, compared with giving oat hay as free-choice, feeding a diet of 16.7% oat hay increased the pelleted starter intake at 1-84 d (p < 0.05), with an average daily gain (ADG) at 61-84 d (p = 0.02); adding CMP to the pelleted starter did not significantly affect body weight, and reduced the fecal index (p < 0.05). Feeding 16.7% oat hay increased the concentration of IgA, IgG, and IgM (p < 0.01), while adding CMP increased the catalase (p < 0.01) and decreased the concentration of malondialdehyde (p < 0.01) in serum. Feeding 16.7% oat hay increased the ruminal concentration of propionic acid (p < 0.05) and isobutyric acid (p = 0.08), and decreased the ruminal pH (p = 0.08), the concentration of acetic acid (p < 0.05), and the ratio of acetic acid to propionic acid (p < 0.01). Feeding 16.7% oat hay reduced the relative abundance of ruminal Firmicutes, Unidentified-Bacteria, Actinobacteria, Prevotella, NK4A214-group, Olsenella, and Actinobacteriota (p < 0.05); adding CMP increased the relative abundance of ruminal Prevotella, Rikenellaceae-RC9-gut-group, Ruminococcus, NK4A214-group, and Ruminococcus (p < 0.05), and decreased the abundance of Desulfobacterora, Prevotella-7, and Erysipelotricaceae-UCG-002 (p < 0.05). In conclusion, feeding a diet of 16.7% oat hay increased the pelleted starter intake and average daily gain, while slightly reducing the ruminal pH values; adding CMP to the pelleted starter resulted in reduced diarrhea incidence, increased serum antioxidant capacity and immunity, as well as ruminal richness and diversity of microorganisms in dairy calves from 3 to 5 months of age.

Identification of actionable targets for breast cancer intervention using a diversity outbred mouse model.

HER2-targeted therapy has improved breast cancer survival, but treatment resistance and disease prevention remain major challenges. Genes that enable HER2/Neu oncogenesis are the next intervention targets. A bioinformatics discovery platform of HER2/Neu-expressing Diversity Outbred (DO) F1 Mice was established to identify cancer-enabling genes. Quantitative Trait Loci (QTL) associated with onset ages and growth rates of spontaneous mammary tumors were sought. Twenty-six genes in 3 QTL contain sequence variations unique to the genetic backgrounds that are linked to aggressive tumors and 21 genes are associated with human breast cancer survival. Concurrent identification of TSC22D3, a transcription factor, and its target gene LILRB4, a myeloid cell checkpoint receptor, suggests an immune axis for regulation, or intervention, of disease. We also investigated TIEG1 gene that impedes tumor immunity but suppresses tumor growth. Although not an actionable target, TIEG1 study revealed genetic regulation of tumor progression, forming the basis of the genetics-based discovery platform.

Review and comment rules of national key monitoring drug prescriptions （medical orders） / 中国药房

In order to standardize the review and comment of national key monitoring drug prescriptions （medical orders） by medical institutions at all levels， the Sichuan Academy of Medical Sciences·Sichuan Provincial People’s Hospital took the lead in compiling the Review and Comment Rules of National Key Monitoring Drugs prescriptions （Medical Orders） herein after referred to as the Rules in accordance with the Second Batch of National Key Monitoring Rational Drug Use List （hereinafter referred to as the List） issued by the National Health Commission confirmed in Jan. 13， 2023. According to the laws and drug instructions issued by the national drug regulatory department， clinical guidelines and expert consensus， combined with the actual situation of patients （including age， body weight， liver and kidney function）， the writing group classified the common and unreasonable drug use problems for 30 kinds of drugs included in the List and develop the review and comment details. After two rounds of Delphi method questionnaire research and experts’ online meetings， and reviewed by the steering committee， the final Rules was formed. The Rules aim to provide reference for the evaluation of the rational use of drugs included in the List by medical institutions， so as to realize the standardized management of key monitoring drugs， promote the rational drug use in medical institutions， and ensure the safety of drug use for patients.

Construction of evaluation indicator system for promoting common prosperity of health care in Zhejiang province / 中华医院管理杂志

Objective:To establish a set of scientific and reasonable indicator system of common prosperity in the field of health, so as to promote the construction and evaluation of the demonstration area of common prosperity with high quality of health.Methods:According to the requirements of promoting common prosperity demonstration area with high quality of health in Zhejiang province, the initial indicator pool was established through literature research and theoretical analysis in July 2021, and experts were convened to carry out expert brainstorming to determine indicator system in the form of meetings. Delphi method was used to conduct two rounds of expert consultation on the indicator system.Finally, the analytic hierarchy process and percentage weight method were used to calculate the indicator weight value.Results:The final indicator system included 4 first-level indicators and 30 second-level indicators. Among the first-level indicators, the weight values of the development, equilibrium, inclusiveness, and sustainability were 0.326 4, 0.242 8, 0.245 8, and 0.185 0. There were 8 second-level indicators in developmental indicator dimension, of which the indicator with the highest weight was the per capita health expectancy. The balance indicator dimension included 6 second-level indicators, of which the indicator with the highest weight was the per capita financing difference of basic medical insurance between the urban workers with the urban-rural residents. The inclusive indicator dimension included 6 second-level indicators, and the proportion of personal health expenditure to total health expenditure had the highest weight. The sustainability indicator dimension included 10 second-level indicators, and the proportion of government health expenditure in fiscal expenditure had the highest weight.Conclusions:The indicator system constructed in this research could provide certain guidance and reference for promoting the construction of common prosperity in health, and provide some reference for follow-up research in this field.

Acute COVID-19 severity and 16-month mental morbidity trajectories in patient populations of six nations

BACKGROUNDThe aim of this multinational study was to assess the development of adverse mental health symptoms among individuals diagnosed with COVID-19 in the general population by acute infection severity up to 16 months after diagnosis. METHODSParticipants consisted of 247 249 individuals from seven cohorts across six countries (Denmark, Estonia, Iceland, Norway, Scotland, and Sweden) recruited from April 2020 through August 2021. We used multivariable Poisson regression to contrast symptom-prevalence of depression, anxiety, COVID-19 related distress, and poor sleep quality among individuals with and without a diagnosis of COVID-19 at entry to respective cohorts by time (0-16 months) from diagnosis. We also applied generalised estimating equations (GEE) analysis to test differences in repeated measures of mental health symptoms before and after COVID-19 diagnosis among individuals ever diagnosed with COVID-19 over time. FINDINGSA total of 9979 individuals (4%) were diagnosed with COVID-19 during the study period and presented overall with a higher symptom burden of depression (prevalence ratio [PR] 1{middle dot}18, 95% confidence interval [95% CI] 1{middle dot}03-1{middle dot}36) and poorer sleep quality (1{middle dot}13, 1{middle dot}03-1{middle dot}24) but not with higher levels of symptoms of anxiety or COVID-19 related distress compared with individuals without a COVID-19 diagnosis. While the prevalence of depression and COVID-19 related distress attenuated with time, the trajectories varied significantly by COVID-19 acute infection severity. Individuals diagnosed with COVID-19 but never bedridden due to their illness were consistently at lower risks of depression and anxiety (PR 0{middle dot}83, 95% CI 0{middle dot}75-0{middle dot}91 and 0{middle dot}77, 0{middle dot}63-0{middle dot}94, respectively), while patients bedridden for more than 7 days were persistently at higher risks of symptoms of depression and anxiety (PR 1{middle dot}61, 95% CI 1{middle dot}27-2{middle dot}05 and 1{middle dot}43, 1{middle dot}26-1{middle dot}63, respectively) throughout the 16-month study period. CONCLUSIONAcute infection severity is a key determinant of long-term mental morbidity among COVID-19 patients.

Huoxin Pill () Attenuates Cardiac Fibrosis by Suppressing TGF-β1/Smad2/3 Pathway in Isoproterenol-Induced Heart Failure Rats / 中国结合医学杂志

OBJECTIVE@#To evaluate the effects of Huoxin Pill (, HXP) on cardiac fibrosis and heart failure (HF) in isoproterenol (ISO)-induced HF rats.@*METHODS@#Thirty Wistar rats were randomly divided into 5 groups including control, HF, isosorbide mononitrate (ISMN), HXP low (HXP-L), and HXP high (HXP-H) groups (n=6 for each group) according to the complete randomization method. Rats were pretreated with ISMN (5 mg/kg daily), low concentration of HXP (10 mg/kg daily) or high concentration of HXP (30 mg/kg daily) or equal volume of saline by intragastric administration for 1 week, followed by intraperitoneal injection of ISO (10 mg/kg, 14 days), and continually intragastric administrated with above medicines or saline for additional 6 weeks. The effects of HXP treatment on the cardiac function, heart weight index (HWI), pathological changes, and collagen content were further assessed. Moreover, the role of HXP on activation of transforming growth factor- β 1 (TGF-β 1)/Smads pathway was further explored using immunohistochemistry (IHC) and Western-blot assay.@*RESULTS@#HXP treatment significantly alleviated the decrease of ejection fraction (EF) and fractional shortening (FS), while decreased the elevation of left ventricular end-systolic volume (LVESV) in ISO-induced HF rats (P<0.05). Moreover, HXP treatment obviously attenuated the increase of HWI and serum level of creatine kinase MB (CK-MB, P<0.05), as well as pathological changes in ISO-induced HF rats. Further determination indicated that HXP treatment alleviated the elevation of collagen I and collagen III protein expression in cardiac tissues of ISO-induced HF rats. Furthermore, HXP treatment significantly down-regulated the increase of TGF-β 1 and p-Smad2/3 protein expression in cardiac tissues of HF rats (P<0.05), while did not affect the expression of total Smad2/3.@*CONCLUSIONS@#HXP attenuated heart failure and cardiac fibrosis in ISO-induced HF rats by suppression of TGF-β 1/Smad2/3 pathway.

Effect of Fushengong Prescreption on Regulation-antagonism Effect of ACE-AngⅡ-AT1R Axis and ACE2-Ang(1-7)-MASR Axis of Rats with Chronic Renal Failure / 中国实验方剂学杂志

Objective:To study the effect of Fushengong prescreption on the regulation-antagonism effect of angiotensin converting enzyme-angiotensin Ⅱ-angiotensin Ⅱ 1 receptor （ACE-AngⅡ-AT1R） axis and angiotensin converting enzyme 2-angiotensin （1-7）-Mas receptor［ACE2-Ang（1-7）-MASR］ axis of rats with chronic renal failure（CRF）， and to explore its mechanism of delaying the development of CRF. Method:The 65 male SD rats were randomly divided into normal group （<italic>n</italic>=10） and modeling group （<italic>n</italic>=55）. The normal group was routinely reared， while the modeling group were administered by gavage with 0.25 g·kg^-1d^-1adenine suspension for 28 days. After the model was successfully established， the survival model rats were randomly divided into model group， benazepril group（0.01 g·kg^-1·d^-1）and low，medium and high dose of Fushengong prescreption groups （4，8，16 g·kg^-1·d^-1）. The normal group and model group were administered the same volume of normal saline by gavage， lasted for 28 days. After the experiment， systolic blood pressure （SBP） and diastolic blood pressure （DBP） of caudal artery were measured， and 24-hour urine was collected to determine 24-hour urine protein （24 h U-pro）. The content of serum creatinine（SCr） and blood urea nitrogen （BUN） in the serum were measured， the histological morphology was observed by hematoxylin eosin（HE）staining， and the degree of renal interstitial fibrosis was observed by Masson staining. Enzyme linked immunosorbent assay （ELISA） was used to determine the contents of AngⅡ， Ang （1-7） and Cystatin C （CysC） in serum and renal homogenate. The protein level of ACE， ACE2， AT1R and MASR were detected by Western blot. The expression of ACE and ACE2 protein in renal tissues were detected by immunohistochemistry. Result:Compared with normal group， the expression levels of SCr， BUN and CysC in model group were significantly increased（<italic>P</italic><0.05）， the content of AngⅡ in serum and kidney tissues were significantly increased， the content of Ang （1-7） were significantly decreased（<italic>P</italic><0.05）， the expression of ACE and AT1R protein in renal tissues were significantly increased（<italic>P</italic><0.05）， and the expression of ACE2 and MASR protein were significantly decreased（<italic>P</italic><0.05）. Compared with model group and benazepril group， after the intervention with Fushengong prescreption， the serum SCr，BUN and CysC decreased（<italic>P</italic><0.05），the content of AngⅡ in serum and kidney tissues decreased significantly，Ang（1-7） increased significantly（<italic>P</italic><0.05）， the expression of ACE and AT1R protein in renal tissues decreased significantly（<italic>P</italic><0.05）， ACE2 and MASR protein increased significantly（<italic>P</italic><0.05）. The high-dose Fushengong prescreption has the best effect. The high， medium and low-dose effects of Fushengong prescreption were dose-dependent. Conclusion:Fushengong prescreption improved renal function and pathological change of kidney in adenine-induced rats with chronic renal failure. The mechanism may be related to the inhibition of ACE-AngⅡ-AT1R axis and promotion of ACE2-Ang（1-7）-MASR axis ，which leads to the delaying of the progression of chronic renal failure.

MicroRNA-23a reduces lipopolysaccharide-induced cellular apoptosis and inflammatory cytokine production through Rho-associated kinase 1/sirtuin-1/nuclear factor-kappa B crosstalk / 中华医学杂志(英文版)

BACKGROUND@#MicroRNAs are closely associated with the progression and outcomes of multiple human diseases, including sepsis. In this study, we examined the role of miR-23a in septic injury.@*METHODS@#Lipopolysaccharide (LPS) was used to induce sepsis in a rat model and H9C2 and HK-2 cells. miR-23a expression was evaluated in rat myocardial and kidney tissues, as well as H9C2 and HK-2 cells. A miR-23a mimic was introduced into cells to identify the role of miR-23a in cell viability, apoptosis, and the secretion of inflammatory cytokines. Furthermore, the effect of Rho-associated kinase 1 (ROCK1), a miR-23a target, on cell damage was evaluated, and molecules involved in the underlying mechanism were identified.@*RESULTS@#In the rat model, miR-23a was poorly expressed in myocardial (sham vs. sepsis 1.00 ± 0.06 vs. 0.27 ± 0.03, P < 0.01) and kidney tissues (sham vs. sepsis 0.27 ± 0.03 vs. 1.00 ± 0.06, P < 0.01). Artificial overexpression of miR-23a resulted in increased proliferative activity (DNA replication rate: Control vs. LPS vs. LPS + Mock vs. LPS + miR-23a: H9C2 cells: 34.13 ± 3.12 vs. 12.94 ± 1.21 vs. 13.31 ± 1.43 vs. 22.94 ± 2.26, P < 0.05; HK-2 cells: 15.17 ± 1.43 vs. 34.52 ± 3.46 vs. 35.19 ± 3.12 vs. 19.87 ± 1.52, P < 0.05), decreased cell apoptosis (Control vs. LPS vs. LPS + Mock vs. LPS + miR-23a: H9C2 cells: 11.39 ± 1.04 vs. 32.57 ± 2.29 vs. 33.08 ± 3.12 vs. 21.63 ± 2.35, P < 0.05; HK-2 cells: 15.17 ± 1.43 vs. 34.52 ± 3.46 vs. 35.19 ± 3.12 vs. 19.87 ± 1.52, P < 0.05), and decreased production of inflammatory cytokines, including interleukin-6 (Control vs. LPS vs. LPS + Mock vs. LPS + miR-23a: H9C2 cells: 59.61 ± 5.14 vs. 113.54 ± 12.30 vs. 116.51 ± 10.69 vs. 87.69 ± 2.97 ng/mL; P < 0.05, F = 12.67, HK-2 cells: 68.12 ± 6.44 vs. 139.65 ± 16.62 vs. 143.51 ± 13.64 vs. 100.82 ± 9.74 ng/mL, P < 0.05, F = 9.83) and tumor necrosis factor-α (Control vs. LPS vs. LPS + Mock vs. LPS + miR-23a: H9C2 cells: 103.20 ± 10.31 vs. 169.67 ± 18.84 vs. 173.61 ± 15.91 vs. 133.36 ± 12.32 ng/mL, P < 0.05, F = 12.67, HK-2 cells: 132.51 ± 13.37 vs. 187.47 ± 16.74 vs. 143.51 ± 13.64 vs. 155.79 ± 15.31 ng/mL, P < 0.05, F = 9.83) in cells. However, ROCK1 was identified as a miR-23a target, and further up-regulation of ROCK1 mitigated the protective function of miR-23a in LPS-treated H9C2 and HK-2 cells. Moreover, ROCK1 suppressed sirtuin-1 (SIRT1) expression to promote the phosphorylation of nuclear factor-kappa B (NF-κB) p65, indicating the possible involvement of this signaling pathway in miR-23a-mediated events.@*CONCLUSION@#Our results indicate that miR-23a could suppress LPS-induced cell damage and inflammatory cytokine secretion by binding to ROCK1, mediated through the potential participation of the SIRT1/NF-κB signaling pathway.

Regulatory effects of miR-138 and RUNX3 on Th1/Th2 balance in peripheral blood of children with cough variant asthma / 中国当代儿科杂志

OBJECTIVES@#To study the expression levels of microRNA-138 (miR-138) and Runt-related transcription factor 3 (RUNX3) in peripheral blood of children with cough variant asthma (CVA) and their regulatory effects on Th1/Th2 balance.@*METHODS@#Sixty-five children with CVA (CVA group) and 30 healthy children (control group) were enrolled. Peripheral venous blood samples were collected for both groups, and CD4@*RESULTS@#Compared with the control group, the CVA group showed significantly decreased levels of IFN-γ and IL-2 from CD4@*CONCLUSIONS@#MiR-138 regulates Th1/Th2 balance by targeting RUNX3 in children with CVA, providing a new direction for the treatment of CVA.

Clinical significance of the deep learning algorithm based on contrast-enhanced CT in the differential diagnosis of gastric gastrointestinal stromal tumors with a diameter ≤ 5 cm / 中华胃肠外科杂志

Objective: Contrast-enhanced CT is an important method of preoperative diagnosis and evaluation for the malignant potential of gastric submucosal tumor (SMT). It has a high diagnostic accuracy rate in differentiating gastric gastrointestinal stromal tumor (GIST) with a diameter greater than 5 cm from gastric benign SMT. This study aimed to use deep learning algorithms to establish a diagnosis model (GISTNet) based on contrast-enhanced CT and evaluate its diagnostic value in distinguishing gastric GIST with a diameter ≤ 5 cm and other gastric SMT before surgery. Methods: A diagnostic test study was carried out. Clinicopathological data of 181 patients undergoing resection with postoperative pathological diagnosis of gastric SMT with a diameter ≤ 5 cm at Department of Gastrointestinal Surgery of Renji Hospital from September 2016 to April 2021 were retrospectively collected. After excluding 13 patients without preoperative CT or with poor CT imaging quality, a total of 168 patients were enrolled in this study, of whom, 107 were GIST while 61 were benign SMT (non-GIST), including 27 leiomyomas, 24 schwannomas, 6 heterotopic pancreas and 4 lipomas. Inclusion criteria were as follows: (1) gastric SMT was diagnosed by contrast-enhanced CT before surgery; (2) preoperative gastroscopic examination and biopsy showed no abnormal cells; (3) complete clinical and pathological data. Exclusion criteria were as follows: (1) patients received anti-tumor therapy before surgery; (2) without preoperative CT or with poor CT imaging quality due to any reason; (3) except GIST, other gastric malignant tumors were pathologically diagnosed after surgery. Based on the hold-out method, 148 patients were randomly selected as the training set and 20 patients as the test set of the GISTNet diagnosis model. After the GISTNet model was established, 5 indicators were used for evaluation in the test set, including sensitivity, specificity, positive predictive value, negative predictive value and the area under the receiver operating curve (AUC). Then GISTNet diagnosis model was compared with the GIST-risk scoring model based on traditional CT features. Besides, in order to compare the accuracy of the GISTNet diagnosis model and the imaging doctors in the diagnosis of gastric SMT imaging, 3 radiologists with 3, 9 and 19 years of work experience, respectively, blinded to clinical and pathological information, tested and judged the samples. The accuracy rate between the three doctors and the GISTNet model was compared. Results: The GISTNet model yielded an AUC of 0.900 (95% CI: 0.827-0.973) in the test set. When the threshold value was 0.345, the sensitivity specificity, positive and negative predictive values of the GISTNet diagnosis model was 100%, 67%, 75% and 100%, respectively. The accuracy rate of the GISTNet diagnosis model was better than that of the GIST-risk model and the manual readings from two radiologists with 3 years and 9 years of work experience (83% vs. 75%, 60%, 65%), and was close to the manual reading of the radiologist with 19 years of work experience (83% vs. 80%). Conclusion: The deep learning algorithm based on contrast-enhanced CT has favorable and reliable diagnostic accuracy in distinguishing gastric GIST with a diameter ≤ 5 cm and other gastric SMT before operation.

Effect of Fushengong Prescription on p38 MAPK Signal Pathway of Rats with Chronic Renal Failure / 中国实验方剂学杂志

Objective:To observe the effects of Fushengong prescription on p38 mitogen-activated protein kinase（p38 MAPK） signal pathway of rats with chronic renal failure（CRF），and to explore its mechanism of reducing inflammatory reaction of renal tissues and delaying the progress of renal interstitial fibrosis. Method:The 55 male Sprague-Dawley rats were randomly divided into normal group，model group， and low，medium and high dose groups of Fushengong prescription，with 11 rats in each group.The normal group was routinely reared， and the other four groups of rats were fed a diet containing 0.5% adenine to produce a model of CRF， which was continuously molded for 21 days.After successful modeling，all rats switched to conventional feed.Normal group and model group were given normal saline 20 mL·kg-1，and each group of Fushengong prescription was given 4，8，16 g·kg-1 of water prescription once a day for 30 days.After the experiment，Masson staining was used to observe the degree of renal interstitial fibrosis.The expression of monocyte chemotactic protein-1（MCP-1） in renal tissues was detected by immunohistochemistry. The expression of phosphorylated p38 mitogen-activated protein kinase（p-p38 MAPK） and transformed growth factor-β1（TGF-β1） in renal tissues were detected by Western blot. Result:Compared with normal group，the renal interstitial collagen deposition increased significantly，the average optical density value of MCP-1 and the expression levels of p-p38 MAPK and TGF-β1 also increased significantly in model group （P<0.05）. Compared with model group，the renal interstitial collagen deposition reduced significantly，the average optical density value of MCP-1 and the protein expression levels of p-p38 MAPK and TGF-β1 also decreased significantly in each dose group of Fushengong prescription（P<0.05）. Conclusion:Fushengong prescription can effectively inhibit the expression of related inflammatory factors in the renal tissue of CRF rats，so as to reduce the inflammatory response in the renal tissue and delay the progress of renal interstitial fibrosis，the mechanism of which may be related to inhibit the activation of p38 MAPK signal transduction pathway.

Effect of Fushengong Prescription on Wnt/β-catenin Signaling Pathway in Kidney of Rats with Chronic Renal Failure / 中国实验方剂学杂志

Objective:To observe the effects of Fushengong prescription on secretory glycoprotein （Wnt）/β-serial protein （β-catenin） signaling pathway in kidney of rats with chronic renal failure （CRF），and to further explore its mechanism of releasing the aggregation of extracellular matrix（ECM），inhibiting renal tubule interstitial fibrosis （TIF） and prolonging the progression of CRF. Method:A total of 55 SD male rats were randomly divided into the normal group，the model group，and the low， medium and high dose groups of Fushengong prescription，with 11 rats in each group.The normal group was routinely reared and the other 4 groups of rats were used to establish CRF model with 0.5% adenine fodder， fed them continuously for 21 d. After successful modeling，all model rats were switched to conventional feed. Normal saline （NS） was given the normal group and the model group by 20 mL·kg-1·d-1， the low， middle and high dose groups rats of Fushengong prescription were given intragastric administration Fushengong prescription according to the body weight of 4， 8， 16 g·kg-1，once a day，continuous gavage for 30 d. After the experiment，the pathomorphism change of renal tissues of rats was measured by Masson staining， the expression of Wnt4 and β-catenin mRNA in the kidney tissues were observed by the method of Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， the expression of Wnt4，β-catenin and matrix metalloproteinase-7（MMP-7） protein of renal tissues were detected by the methods of Western blot. The expression of Wnt4， β-catenin protein of renal tissues were detected by the methods of immunohistochemistry （IHC）. Result:Compared with normal group，renal tubule interstitial fibrosis of renal tissues increased distinctly and the expression of Wnt4，β-catenin and MMP-7 protein increased significantly in the model group. Wnt4 and β-catenin mRNA also increased significantly in model group（P<0.01）. Compared with model group， the expression of Wnt4， β-catenin and MMP-7 protein in the Fushengong prescription groups decreased obviously （P<0.05）. The expression of Wnt4 and β-catenin mRNA in Fushengong prescription groups also decreased obviously. Conclusion:The mechanism of Fushengong prescription can release the aggregation of ECM，inhibit TIF and delay the progression of CRF，which may be related with the activation of Wnt/β-catenin signal pathway.

Enhanced water solubility, antioxidant activity, and oral absorption of hesperetin by D-α-tocopheryl polyethylene glycol 1000 succinate and phosphatidylcholine / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Hesperetin, an abundant bioactive component of citrus fruits, is poorly water-soluble, resulting in low oral bioavailability. We developed new formulations to improve the water solubility, antioxidant activity, and oral absorption of hesperetin. Two nano-based formulations were developed, namely hesperetin-TPGS (D-α-tocopheryl polyethylene glycol 1000 succinate) micelles and hesperetin-phosphatidylcholine (PC) complexes. These two formulations were prepared by a simple technique called solvent dispersion, using US Food and Drug Administration (FDA)-approved excipients for drugs. Differential scanning calorimetry (DSC) and dynamic light scattering (DLS) were used to characterize the formulations' physical properties. Cytotoxicity analysis, cellular antioxidant activity assay, and a pharmacokinetic study were performed to evaluate the biological properties of these two formulations. The final weight ratios of both hesperetin to TPGS and hesperetin to PC were 1:12 based on their water solubility, which increased to 21.5- and 20.7-fold, respectively. The hesperetin-TPGS micelles had a small particle size of 26.19 nm, whereas the hesperetin-PC complexes exhibited a larger particle size of 219.15 nm. In addition, the cellular antioxidant activity assay indicated that both hesperetin-TPGS micelles and hesperetin-PC complexes increased the antioxidant activity of hesperetin to 4.2- and 3.9-fold, respectively. Importantly, the in vivo oral absorption study on rats indicated that the micelles and complexes significantly increased the peak plasma concentration (Cmax) from 2.64 μg/mL to 20.67 and 33.09 μg/mL and also increased the area under the concentration-time curve of hesperetin after oral administration to 16.2- and 18.0-fold, respectively. The micelles and complexes increased the solubility and remarkably improved the in vitro antioxidant activity and in vivo oral absorption of hesperetin, indicating these formulations' potential applications in drugs and healthcare products.

Analysis and evaluation of peer review results of a fund's three year research project / 中华医学科研管理杂志

Objective Based on the three years' peer review data of a project fund,the results of fund peer review were analyzed and evaluated,to provide references for further improvement of the peer review and management.Methods Based on the fund's peer review results of 2145 projects in three years,descriptive statistics,single-item identification index were adopted,as well as RJ normality test,t-test and other statistical methods,to analyze and assess the overall data of fund,project categories,individual scores,etc.Results The score distribution of the three year peer review project of the fund is almost normal distribution,and the overall consistency of peer review shows a better trend.The analysis shows that the peer review experts of the fund have better consistency in terms of project innovation,rationality and characteristics.While there were differences in the peer review of applicability.Conclusions The three year peer review data of the fund show that three years' evaluation results are reliable,reasonable,and the quality of evaluation is good,showing a better development trend in both project quality and expert consistency.

Applying Malmquist index to evaluate the output efficiency of scientific research in a hospital department / 中华医学科研管理杂志

Objective To study the dynamic changes of scientific research efficiency of 51 departments in a top three hospitals in Beijing from 2014 to 2016,and to provide reference information for improving the efficiency of scientific research in hospital departments.Methods The CCC model of DEA,BCC model were used for lateral analysis,and then Malmquist index was used for longitudinal analysis.Results There were 12 (23.53％) departments in 2014,11 (21.57％) departments in 2015,9 (17.65％) departments in 2016 data envelopment analysis was valid,from 2014 to 2016,41 (80.39％) departments of the hospital increased the total factor productivity.Conclusions The total factor productivity of the 51 departments in the hospital increased from 2014 to 2016,and technological progress was the main reason for its growth.

Analysis of the scientific research efficiency of hospital department based on stochastic frontier method / 中华医学科研管理杂志

Objective Based on the data of scientific research output in a top three hospital in Beijing from 2015 and 2016,stochastic frontier analysis is conducted to estimate the efficiency of scientific research performance in different departments of this hospital,so as to draw the impetus for the growth of departments.Methods According to the results of the stochastic frontier model,comprehensive analysis and evaluation are conducted for the research performance of various departments.Results The overall average technical efficiency of the hospital is 0.44,and improvement space for the technical efficiency of scientific research performance is still 0.56.There are significant differences in the technical efficiency of each department.Among the four major categories,the D section is higher than the technical efficiency of class A,B and C departments.Conclusions The overall technical efficiency of the hospital is not high,the level of scientific research output of the four types of departments is not balanced,which should be emphasized in the improvement of scientific research performance level.

Continuous expression of miR-431 during lung development in Sprague-Dawley rats / 中国当代儿科杂志

OBJECTIVE@#To study the role of miR-431 in lung development and morphology.@*METHODS@#According to the stage of lung development in rats, Sprague-Dawley rats at embryonic day 16 (E16), embryonic day (E19), embryonic day (E21), postnatal day 1 (P1), postnatal day 3 (P3), postnatal day 7 (P7), postnatal day 14 (P14) and 10 weeks after birth (P10 weeks) were selected, and lung tissue samples were collected for observation. Hematoxylin-eosin staining and transmission electron microscopy were performed to observe the morphology of lung tissue. Fluorescence in situ hybridization and real-time PCR were used to measure the expression of miR-431 during the critical stages of lung development (E19, E21 and P3).@*RESULTS@#The E19 group had the formation of the lamellar body and type II alveolar epithelial cells in the fetal lung tissue. The number of lamellar bodies increased with the increasing gestational age, with aggregation and excretion. Pulmonary alveoli formed rapidly, the lung interstitium became thinner, and the microvascular system became mature after birth. Fluorescence in situ hybridization and real-time PCR showed that the expression of miR-431 gradually decreased with the increasing gestational age (P<0.05).@*CONCLUSIONS@#The systematic and continuous morphological data of lung development is obtained in this experiment. In addition, miR-431 may play an important role in the negative regulation of lung development, which provides basis and direction for further research on the mechanism of lung development and related diseases.

Efficacy of inverso isomer of CendR peptide on tumor tissue penetration

The dense extracellular matrix and high interstitial fluid pressure of tumor tissues prevent the ability of anti-tumor agents to penetrate deep into the tumor parenchyma for treatment effects. C-end rule (CendR) peptides can enhance the permeability of tumor blood vessels and tumor tissues binding to neuropilin-1 (NRP-1), thus aiding in drug delivery. In this study, we selected one of the CendR peptides (sequence RGERPPR) as the parent l-peptide and substituted d-amino acids for the l-amino acids to synthesize its inverso peptide (RGERPPR). We investigated the NRP-1 binding activity and tumor-penetrating ability of (RGERPPR). We found that the binding affinity of (RGERPPR) with NRP-1 and the cellular uptake was significantly higher than that of RGERPPR. Evans Blue tests revealed that (RGERPPR) exhibited improved tumor-penetrating ability in C6, U87 and A549 tumor-bearing nude mice. Using nude mice bearing A549 xenograft tumors as a model, we found that the rate of tumor growth in the group co-administered with (RGERPPR) and gemcitabine (Gem) was significantly lower than the gemcitabine-treated group with a tumor suppression rate (TSR%) of 55.4%. Together, our results demonstrate that (RGERPPR) is a potential tumor-penetrating peptide.

Advances in models for predicting drug intestinal permeability / 药学学报

Intestinal permeability is one of key factors determing absorption of oral drug products. It is a big challenge to assess permeability of compounds with high accuracy and high efficacy during research and development process. In this review, the principles, strengths, weaknesses and advances of common intestinal permeability models are summarized, with focus on Ussing chamber and parallel artificial membrane permeability assay. In addition, future trends of permeability models are briefly discussed. This review may provide a reference to accessing permeability of lead compounds.

Analysis of the medical service capacity of primary healthcare in Zhejiang province / 中华医院管理杂志

Objective To analyze the medical service capacity of primary healthcare in Zhejiang province since the ongoing healthcare reform and put forward suggestions. Methods Key indicators of healthcare resources and medical service utilization from 2009 to 2015 reflecting the primary healthcare were identified,for a quantitative analysis in terms of the structure-process-outcome dimensions. Results In terms of structural service capacity,the average headcount growth rate of primary healthcare′s technical personnel was 5. 7% per year; the personnel competence structure kept improving; the hospital beds at primary institutions and their ratio among all were slightly decreased,with better devices and informatization. In terms of procedural service capacity,the proportion of primary institutions with contract-based services amounted to 89. 9%,with the standard contract signing rate up to 18. 8%. In terms of consequential service capacity,the average growth rate of the number of outpatient visits at primary institutions was 6. 3%. The amount and proportion of inpatients were slightly decreased,while the hospital bed utilization ratio was increased slightly. Conclusions It is necessary to further strengthen the training and introduction of primary healthcare professionals. The functional orientation of hospitals at various levels should be clarified, encouraging contract-signing of general practitioners, promote the medical insurance payment reform featuring the capitation payment at primary level,and improve the income distribution and incentive mechanism.