OBJECTIVE To investigate the improvement effect and potential mechanism of Qingxue xiaozhi jiangtang formula on insulin resistance （IR） in type 2 diabetes mellitus （T2DM） rats. METHODS T2DM rat model was established by intraperitoneal injection of 30 mg/kg streptozotocin combined with high-fat and high-sugar diet. The rats were randomly divided into normal control group， model group， Qingxue xiaozhi jiangtang formula low-dose and high-dose groups （6.525， 13.05 g/kg， calculated by raw material） and metformin group （positive control， 0.18 g/kg）， with 8 rats in each group. Administration groups were given relevant medicine intragastrically； normal control group and model group were given constant volume of normal saline intragastrically， once a day， for consecutive 6 weeks. Body mass and fasting blood glucose （FBG） were determined， and oral glucose tolerance test was conducted. Serum fasting insulin （FINS） level was measured to calculate the insulin resistance index （HOMA-IR） and insulin sensitivity index （ISI）. Additionally， the level of serum lipids， liver function， oxidative stress indicators and inflammatory factors were assessed. The phosphorylation levels of kinase R-like endoplasmic reticulum kinase （PERK） and forkhead box O1 （FOXO1） protein in liver tissue of rats were determined. RESULTS Compared with model group， the body weight， ISI， the levels of high-density lipoprotein cholesterol and superoxide dismutase were increased significantly in Qingxue xiaozhi jiangtang formula high-dose group and metformin group （P＜0.05）； FBG， blood glucose level at 120 minutes of glucose loading， area under the curve of glucose， FINS， HOMA-IR， low-density lipoprotein cholesterol， total cholesterol， triglyceride， alanine transaminase， aspartate transaminase， alkaline phosphatase， malondialdehyde， interleukin-6， tumor necrosis factor-α， and C-reactive protein levels were significantly reduced （P＜ Δ0.05）； the pathological damage of liver tissue had significantlyimproved， and the phosphorylation levels of PERK and FOXO1 proteins in liver tissue were significantly decreased （P＜0.05）. CONCLUSIONS Qingxue xiaozhi jiangtang formula can regulate glucose and lipid metabolism， inflammation factor and oxidative stress levels， and alleviate insulin resistance in T2DM rats. Its mechanism of action may be related to the inhibition of the PERK/FOXO1 signaling pathway.

Objective:To explore the effective components and potential mechanisms of Xiefei Lishui Prescription in the treatment of heart failure.Methods:Ultra high-performance liquid chromatography tandem four stage rod time of flight mass spectrometry (UPLC-Q-TOF-MS) technology was used to analyze and identify the active components of Xiefei Lishui Prescription. Drug targets were predicted through the Swiss Target Prediction database, and disease targets were collected from Gene Cards, Dis GENET, and TTD databases. The intersection of drug targets and disease targets was screened using a STRING database for protein interaction to identify core targets. The core targets were included in the DAVID database for GO enrichment and KEGG analysis. Finally, molecular docking validation was performed between the drug components and the corresponding core targets.Results:The results identified 10 active components of Xiefei Lishui Prescription, and 8 potential active components were screened using network pharmacology for the treatment of heart failure with Xiefei Lishui Prescription, corresponding to 160 related action targets. A total of 1 305 disease-related targets were collected, and a total of 51 targets ad 17 core targets were included in the string database for protein interaction analysis. GO functional enrichment and KEGG analysis indicated that the mechanism of Xiefei Lishui Prescription in treating heart failure may be related to pathways such as protein binding, ATP binding, and negative regulation of the VEGF signaling pathway and T cell receptor pathway during apoptosis. The molecular docking results showed that baicalin exhibited good binding activity with ESR1, sorghum isoflavones with ESR1, and quercetin with AKT1, EGFR, IL2, and ABCB1.Conclusion:Xiefei Lishui Prescription may exert therapeutic effects on heart failure through multiple pathways by targeting ESR1, AKT1, EGFR, and other targets.

Myocardial fibrosis is characterized by pathological remodeling of extracellular matrix,which is a common pathological change during the development of various cardiovascular diseases.Qi transformation dysfunction in the zang-fu organs,subtle substance accumulation,and endogenous turbid evil production lead to the occurrence of diseases.The theory of turbid blood is widely used to elucidate the pathological changes of diseases and guide the prevention and treatment.Turbid blood,as a special pathogenic factor and pathological product,plays a crucial role in the oxidative stress process of myocardial fibrosis.Qi deficiency of the heart and spleen,stagnation of turbid blood,impaired blood circulation in the heart,and the inability to maintain the oxidative-reductive system balance of myocardial cells are the root causes of disease onset.Accumulation of turbid blood,intermingled phlegm and blood stasis,blockage of heart vessels,and accumulation of metabolic waste products contribute to disease progression.Prolonged turbidity accumulation leads to cardiac enlargement,scattered mental state,and pathological remodeling of the extracellular matrix,indicating a severe disease stage.Early treatment focuses on strengthening the vital qi and spleen,reducing turbidity and recovering clarity.In the middle stage,the key is to resolve phlegm,eliminate stasis,and promote clarity while removing turbidity.In the late stage,detoxification,turbidity elimination,and restoring clarity are emphasized.By adhering to the characteristics of the pathological mechanism and using traditional Chinese medicine intervention,it is possible to suppress oxidative stress,prevent pathological remodeling of the extracellular matrix,and improve myocardial fibrosis.

Myocardial infarction is the most common cause of heart failure,and myocardial remodeling can occur after infarction,thus contributing to the progression of heart failure.The occurrence of post-infarction ventricular remode-ling is closely related to m6A methylation.m6A methylation is a reversible and highly dynamic process.This process is mainly mediated by m6A methylation positive and negative regulatory enzymes and is involved in the occurrence of post-in-farction myocardial remodeling through mechanisms such as cellular autophagy.This article mainly reviews relevant litera-ture in recent years.Firstly,a brief introduction is given to m6A methylation,followed by an introduction to the role of m6A methylase in regulating myocardial remodeling.Finally,a summary analysis is conducted on the mechanism of m6A methylation in regulating myocardial remodeling from the perspectives of autophagy,inflammation,cell apoptosis,calcium ion homeostasis,extracellular matrix remodeling,and ferroptosis.The feasibility of using m6A methylation serological de-tection as a diagnostic tool for myocardial remodeling after myocardial infarction is discussed,in order to provide reference for related research.

Objective: To comprehensively assess the current status of extrauterine growth restriction (EUGR) in very preterm infants (VPI) and its associated factors in Chinese neonatal intensive care units (NICU). Methods: In this cohort study, 6 179 preterm infants born at <32 weeks' gestation were included, who were admitted to 57 hospitals in the China Neonatal Network in 2019 and hospitalized for ≥7 days. EUGR was evaluated by a cross-sectional definition (weight at discharge<10^th percentile for postmenstrual age), a longitudinal definition (decline in weight Z score>1 from birth to discharge), and weight growth velocity. The comparison between infants with and without EUGR was conducted by t-test, Mann-Whitney U test or χ² test as appropriate. Multivariable Logistic regression models were used to evaluate associations between EUGR with different definitions and maternal and neonatal factors, clinical practices, and neonatal morbidities. Results: A total of 6 179 VPI were enrolled in the study, with a gestational age of (29.8±1.5) weeks and birth weight of (1 365±304) g; 56.2% (3 474) of them were male. Among them, 48.4% (2 992 VPI) were cross-sectional EUGR and 74.9% (4 628 VPI) were longitudinal EUGR. Z score of weight was (0.13±0.78) at birth and decrease to (-1.35±0.99) at discharge. The weight growth velocity was 10.13 (8.42, 11.66) g/(kg·d). Multivariate Logistic regression analysis showed that among the influential factors that could be intervened after birth, late attainment of full enteral feeds (OR_adjust=1.01, 95%CI 1.01-1.02, P<0.001; OR_adjust=1.01, 95%CI 1.01-1.02, P<0.001), necrotizing enterocolitis≥Ⅱstage (OR_adjust=2.64, 95%CI 1.60-4.35, P<0.001; OR_adjust=1.62, 95%CI 1.10-2.40, P<0.001) and patent ductus arteriosus (OR_adjust=1.94, 95%CI 1.50-2.51, P<0.001; OR_adjust=1.63, 95%CI 1.29-2.06, P<0.001) were all associated with increased risks of both cross-sectional and longitudinal EUGR. In addition, late initiation of enteral feeds (OR_adjust=1.06, 95%CI 1.02-1.09, P=0.020) and respiratory distress syndrome (OR_adjust=1.45, 95%CI 1.24-1.69, P<0.001) were all associated with cross-sectional EUGR. Breast milk feeding (OR_adjust=1.33, 95%CI 1.05-1.68, P<0.001) was associated with a higher risk of longitudinal EUGR. Conclusions: The incidence of EUGR in VPI in China is high. Some modifiable risk factors provide priorities to improve postnatal growth for VPI. Nutritional management of VPI and the efforts to decrease the incidence of complications are still the focus of clinical management in China.
Female ; Humans ; Infant, Newborn ; Male ; Cohort Studies ; East Asian People ; Infant, Premature ; Infant, Premature, Diseases ; Infant, Very Low Birth Weight ; Intensive Care Units, Neonatal

Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.
Infant ; Infant, Newborn ; Male ; Humans ; Female ; Ductus Arteriosus, Patent/drug therapy* ; Infant, Premature ; Cross-Sectional Studies ; Ibuprofen/therapeutic use* ; Infant, Very Low Birth Weight ; Persistent Fetal Circulation Syndrome ; Infant, Premature, Diseases/therapy*

Background: For anatomic total arthroscopic repair, cementless humeral fixation has recently gained popularity. However, few studies have compared clinical, radiographic, and patient-reported outcomes between cemented and press-fit humeral fixation, and none have performed follow-up for longer than 5 years. In this study, we compared long-term postoperative outcomes in patients receiving a cemented versus press-fit humeral stem anatomic arthroscopic repair. Methods: This study retrospectively analyzed 169 shoulders that required primary anatomic total shoulder arthroplasty (aTSA). Shoulders were stratified by humeral stem fixation technique: cementation or press-fit. Data were collected pre- and postoperatively. Primary outcome measures included range of motion, patient reported outcomes, and radiographic measures. Results: One hundred thirty-eight cemented humeral stems and 31 press-fit stems were included. Significant improvements in range of motion were seen in all aTSA patients with no significant differences between final cemented and press-fit stems (forward elevation: P=0.12, external rotation: P=0.60, and internal rotation: P=0.77). Patient reported outcome metrics also exhibited sustained improvement through final follow-up. However, at final follow-up, the press-fit stem cohort had significantly better overall scores when compared to the cemented cohort (visual analog score: P=0.04, American Shoulder and Elbow Surgeon Score: P<0.01, Simple Shoulder Test score: P=0.03). Humeral radiolucency was noted in two cemented implants and one press-fit implant. No significant differences in implant survival were observed between the two cohorts (P=0.75). Conclusions In this series, we found that irrespective of humeral fixation technique, aTSA significantly improves shoulder function. However, within this cohort, press-fit stems provided significantly better outcomes than cemented stems in terms of patient reported outcome scores.Level of evidence: III.

Methods: Among the patients who underwent TSA, 119 shoulders were retrospectively analyzed. Preoperative and postoperative clinical outcome data were collected. Linear regression analysis (univariate and multivariate) was conducted to evaluate the associations of clinical outcomes with age. Kaplan-Meier curves and Cox regression analyses were performed to evaluate implant survival. Results: At final follow-up, patients of all ages undergoing aTSA experienced significant and sustained improvements in all primary outcome measures compared with preoperative values. Based on multivariate analysis, age at the time of surgery was a significant predictor of postoperative outcomes. Excellent implant survival was observed over the course of this study, and Cox regression survival analysis indicated age and sex to not be associated with an increased risk of implant failure. Conclusions When controlling for sex and follow-up duration, older age was associated with significantly better patient-reported outcome measures. Despite this difference, we noted no significant effects on range of motion or implant survival.Level of evidence: IV.

Currently the main treatment of acute myeloid leukemia (AML) is chemotherapy combining hematopoietic stem cell transplantation. However, the unbearable side effect of chemotherapy and the high risk of life-threatening infections and disease relapse following hematopoietic stem cell transplantation restrict its application in clinical practice. Thus, there is an urgent need to develop alternative therapeutic tactics with significant efficacy and attenuated adverse effects. Here, we revealed that umbilical cord-derived mesenchymal stem cells (UC-MSC) efficiently induced AML cell differentiation by shuttling the neutrophil elastase (NE)-packaged extracellular vesicles (EVs) into AML cells. Interestingly, the generation and release of NE-packaged EVs could be dramatically increased by vitamin D receptor (VDR) activation in UC-MSC. Chemical activation of VDR by using its agonist 1α,25-dihydroxyvitamin D3 efficiently enhanced the pro-differentiation capacity of UC-MSC and then alleviated malignant burden in AML mouse model. Based on these discoveries, to evade the risk of hypercalcemia, we synthetized and identified sw-22, a novel non-steroidal VDR agonist, which exerted a synergistic pro-differentiation function with UC-MSC on mitigating the progress of AML. Collectively, our findings provided a non-gene editing MSC-based therapeutic regimen to overcome the differentiation blockade in AML.

Coronary microcirculation disorder after myocardial ischemia reperfusion （MIR） is a prominent problem in the treatment of coronary heart disease. According to the physiological commonality between “collaterals-sweat pore qi and fluid” and coronary microcirculation， and the evolution of the course of MIR， it is believed that “heart collateral stasis obstruction， sweat pore constraint and block” is the cause of coronary microcirculation disorder. The evolution of the pathogenesis can be divided into three periods. During the myocardial ischemia period， the pathogenesis is heart collaterals obstruction and sweat pores empty， while during the ischemia reperfusion period， it is internal formulation of deficiency wind， spasms of collaterals or slight heart collaterals obstruction； in the coronary microcirculation disorder period， sweat pores constraint and block， constraint transforming into heat， qi and fluid failing to diffuse are the pathogenesis. The corresponding treatment principle is assisting dredge with supplementation， and supplementing deficiency to dispel stasis； treating wind and blood simultaneously， and extinguishing wind to arrest convulsion； clearing heat and cooling blood， and diffusing qi and unblocking qi and fluid. Moreover， it is recommended to treat the heart and lungs simultaneously， and regulate the heart and liver at the same time.