BACKGROUND: Angiotensin receptor neprilysin inhibitors (ARNIs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) are the cornerstones in treating heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) are included in HFrEF treatment guidelines. However, the effect of SGLT-2i and the five drugs on HFrEF have not yet been systematically evaluated. METHODS: PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) from inception dates to September 23, 2022. Additional trials from previous relevant reviews and references were also included. The primary outcomes were changes in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter/dimension (LVEDD), left ventricular end-systolic diameter/dimension (LVESD), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV), left ventricular end-systolic volume index (LVESVI), and left ventricular end-diastolic volume index (LVEDVI). Secondary outcomes were New York Heart Association (NYHA) class, 6-min walking distance (6MWD), B-type natriuretic peptide (BNP) level, and N-terminal pro-BNP (NT-proBNP) level. The effect sizes were presented as the mean difference (MD) with 95% confidence interval (CI). RESULTS: We included 68 RCTs involving 16,425 patients. Compared with placebo, ARNI + BB + MRA + SGLT-2i was the most effective combination to improve LVEF (15.63%, 95% CI: 9.91% to 21.68%). ARNI + BB + MRA + SGLT-2i (5.83%, 95% CI: 0.53% to 11.14%) and ARNI + BB + MRA (3.83%, 95% CI: 0.72% to 6.90%) were superior to the traditional golden triangle ACEI + BB + MRA in improving LVEF. ACEI + BB + MRA + SGLT-2i was better than ACEI + BB + MRA (-8.05 mL/m 2 , 95% CI: -14.88 to -1.23 mL/m 2 ) and ACEI + BB + SGLT-2i (-18.94 mL/m 2 , 95% CI: -36.97 to -0.61 mL/m 2 ) in improving LVEDVI. ACEI + BB + MRA + SGLT-2i (-3254.21 pg/mL, 95% CI: -6242.19 to -560.47 pg/mL) was superior to ARB + BB + MRA in reducing NT-proBNP. CONCLUSIONS: Adding SGLT-2i to ARNI/ACEI + BB + MRA is beneficial for reversing cardiac remodeling. The new quadruple drug "ARNI + BB + MRA + SGLT-2i" is superior to the golden triangle "ACEI + BB + MRA" in improving LVEF. REGISTRATION PROSPERO; No. CRD42022354792.
Humans ; Heart Failure/physiopathology* ; Stroke Volume/physiology* ; Angiotensin Receptor Antagonists/therapeutic use* ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use* ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use* ; Randomized Controlled Trials as Topic ; Mineralocorticoid Receptor Antagonists/therapeutic use* ; Adrenergic beta-Antagonists/therapeutic use*

Objective:To investigate the mechanism of proanthocyanidin (PA) in regulating the osteogenic differentiation of human periodontal ligament stem cells (PDLSCs), and to explore the effects of PA on the expression and nuclear translocation of transcription factor EB (TFEB) and on the autophagy-lysosome pathway.Methods:PDLSCs were divided into control group and PA group, which were subjected to RNA sequencing analysis (RNA Seq) to detect differentially expressed genes. The osteogenic differentiation ability and autophagy level were observed by real-time fluorescence quantitative PCR (RT-qPCR) analysis, alkaline phosphatase (ALP) staining and transmission electron microscope (TEM), respectively. Scratch assay and Transwell assay were used to detect the migration ability of PDLSCs. Lysotracker and immunofluorescence staining were used to detect the biogenesis of lysosomes. The total protein expression of transcription factor EB (TFEB) as well as that in cytoplasm and nucleus were detected by Western blotting. Confocal laser scanning microscope (CLSM) was used to observe the nuclear translocation of TFEB. The PDLSCs were treated with small interfering RNA (siRNA) technology to knock down the expression levels of TFEB gene with or without PA treatment. Western blotting was used to analyze the expressions of autophagy-related proteins Beclin1 and microtubule-associated protein 1 light chain 3 (LC3B), as well as osteogenic-related proteins runt-related transcription factor 2 (RUNX2), ALP, and osteocalcin in PDLSCs.Results:Compared with the control group, the osteogenic-related and autophagy-related genes showed differential expression in PDLSCs after PA treatment ( P<0.05). The mRNA expression levels of osteogenic-related genes RUNX2 (2.32±0.15) and collagen type Ⅰ alpha 1 (COL1α1) (1.80±0.18), as well as the autophagy related genes LC3B (1.87±0.08) and Beclin1 (1.63±0.08) were significantly increased in the PA group, compared with the control group (1.01±0.16, 1.00±0.10, 1.00±0.07, 1.00±0.06, respectively, all P<0.01). Compared with the control group, the PA group had higher ALP activity, and more autophagosomes and autophagolysosomes observed by TEM. PA promoted the migration of PDLSCs ( P<0.05) and the increased number of lysosomes and the expression of lysosomal associated membrane protein 1 (LAMP1). In the PA group, the relative expression level of total TFEB protein (1.49±0.07) and the nuclear/cytoplasmic expression of TFEB protein (1.52±0.12) were significantly higher than the control group (1.00±0.11, 1.00±0.13, respectively) ( t=6.43, P<0.01; t=5.07, P<0.01). The relative nuclear/cytoplasmic fluorescence intensity of TFEB in the PA group (0.79±0.09) was increased compared with the control group (0.11±0.08) ( t=8.32, P<0.01). Knocking down TFEB significantly reduced the expression of TFEB (1.00±0.15 vs 0.64±0.04), LAMP1 (1.00±0.10 vs 0.69±0.09), Beclin1 (1.00±0.05 vs 0.60±0.05), and LC3B Ⅱ/Ⅰ (1.00±0.06 vs 0.73±0.07) in PDLSCs ( P<0.05, P<0.05, P<0.01, P<0.01). When TFEB gene was knocked down, the expression levels of Beclin1 (1.05±0.11), LC3B Ⅱ/Ⅰ (1.02±0.09), RUNX2 (1.04±0.10), ALP (1.04±0.16), and osteocalcin (1.03±0.15) proteins were significantly decreased in the PA group compared with the pre-knockdown period (1.28±0.03, 1.44±0.11, 1.38±0.11, 1.62±0.11, 1.65±0.17, respectively) ( P<0.05, P<0.01, P<0.05, P<0.01, and P<0.01, respectively). Conclusions:PA promotes the osteogenic differentiation of PDLSCs through inducing the expression and nuclear translocation of TFEB and activating the autophagy-lysosome pathway.

Objective To explore the the correlation between cystatin C(Cys C),beta-2 microglobulin(β2-MG)and ischemic cerebral small vessel disease(CSVD)and its subgroups.Methods Totally 234 patients with CSVD were assigned to the study group,and 92 elderly people with no abnormal findings in head MRI were selected as controls.The CSVD patients were further divided into the subgroups of lacunar infarction(LI),white matter lesion(WML)and LI+WML.Each group was compared risk factors include the blood level of Cys C and β2-MG.Results There were statistically significant differences between CSVD group and control group in cystatin C(Cys C)and β2-MG(P<0.05).Cystatin C(Cys C)and β2-MG there were statistically significant differences between WML group and control group(P<0.05),and also between WML+LI group and control group(P<0.05).Logistic regression analysis and comparison across subgroups showed Cys C and β2-MG to be the common risk factors for WML group and WML+LI group inpatients with ischemic cerebral small vessel disease.Conclusion Cys C and β2-MG are the common risk factors for WML group and WML+LI group inpatients with ischemic cerebral small vessel disease.The risk factors vary across different CSVD subgroups.

BACKGROUND:Previous literature reported that the fusion cage moved more than 2 mm from its original position,which means that the fusion cage moved backward.At present,clinical observation has found that the factors leading to the displacement of the fusion cage are complex,and the relationship between these factors and the cage retropulsion is not clear. OBJECTIVE:To explore the risk factors related to cage retropulsion after lumbar interbody fusion. METHODS:Retrospective analysis was conducted in 200 patients who underwent transforaminal lumbar interbody fusion surgery with a polyetheretherketone interbody fusion from February 2020 to February 2022.According to the distance from the posterior edge of the vertebral fusion cage to the posterior edge of the vertebral body after the operation(the second day after the removal of the drainage tube)and 1,3,6 and 12 months after the operation,patients were divided into cage retropulsion group(≥2 mm)and cage non-retropulsion group(<2 mm).The factors that may affect cage retropulsion,such as age,gender,body mass index,bone mineral density,operation time,bleeding,endplate injury,preoperative and postoperative interbody height,cage implantation depth,cage size,and segmental anterior convexity angle,were analyzed by univariate and logistic regression analysis. RESULTS AND CONCLUSION:(1)Posterior displacement of the fusion cage occurred in 15 cases(15/200).The differences in basic information such as age and body mass index between the two groups were not statistically significant.(2)The results of the univariate analysis were that gap height difference,time to wear a brace,segmental anterior convexity angle difference,bone mineral density,and age were related to posterior migration of the cage.(3)The results of logistic regression analysis were that cage size,endplate injury condition,and depth of cage implantation were risk factors for cage retropulsion.(4)These findings suggest that cage retropulsion after lumbar interbody fusion is caused by multiple factors,including segmental anterior convexity angle difference,bone mineral density,cage size,endplate damage,time to wear a brace,and depth of cage implantation.

Objective To evaluate the relationship between diabetic nephropathy(DN)and diabetic retinopathy(DR)in patients with type 2 diabetes mellitus(T2DM)based on imaging and clinical testing data.Methods Totally 600 T2DM patients who visited the First People's Hospital of Ziyang from March 2021 to December 2022 were included.The fundus photography and fundus fluorescein angiography were performed on all these patients and their age,gender,T2DM duration,cardiovascular diseases,cerebrovascular disease,hypertension,smoking history,drinking history,body mass in-dex,systolic blood pressure,diastolic blood pressure and other clinical data were collected.The levels of fasting blood glu-cose(FPG),triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipo-protein cholesterol(LDL-C),glycosylated hemoglobin(HbA1c),24 h urinary albumin(UAlb),urinary albumin to creati-nine ratio(ACR),serum creatinine(Scr)and blood urea nitrogen(BUN)were measured.Logistic regression was used to analyze the risk factors associated with DR.DR staging was performed according to fundus images,and the convolutional neural network(CNN)algorithm was used as an image analysis method to explore the correlation between DR and DN based on emission computed tomography(ECT)and clinical testing data.Results The average lesion area rates of DR and DN detected by the CNN in the non-DR,mild-non-proliferative DR(NPDR),moderate-NPDR,severe-NPDR and pro-liferative DR(PDR)groups were higher than those obtained by the traditional algorithm(TCM).As DR worsened,the Scr,BUN,24 h UAlb and ACR gradually increased.Besides,the incidence of DN in the non-DR,mild-NPDR,moderate-NPDR,severe-NPDR and PDR groups was 1.67％,8.83％,16.16％,22.16％and 30.83％,respectively.Logistic regression analysis showed that the duration of T2DM,smoking history,HbA1c,TC,TG,HDL-C,LDL-C,24 h UAlb,Scr,BUN,ACR and glomerular filtration rate(GFR)were independent risk factors for DR.Renal dynamic ECT analysis demonstrated that with the aggravation of DR,renal blood flow perfusion gradually decreased,resulting in diminished renal filtration.Conclusion The application of CCN in the early stage DR and DN image analysis of T2DM patients will improve the diag-nosis accuracy of DR and DN lesion area.The DN is worsening as the aggravation of DR.

The molar anchorage control in orthodontic treatment is a key concern of clinicians and a hot spot in the field of orthodontic clinical research.Good molar anchorage control is a prerequisite for the success of orthodontic treatment.In recent years,clear aligner treatment has been favored by orthodontists and patients because of its aesthetics,comfort and other advantages.However,the unique biomechanical mechanism of clear aligner system has brought new changes and challenges for dentists to understand the anchorage con-trol in orthodontics.This article provides a systematic review of the research methodology,clinical efficacy and enhanced strategy of mo-lar anchorage control in clear aligner treatment,with the aim to provide a reference for the clinical research and technical development of molar anchorage control in clear aligner treatment.

Objective To investigate the values of serum procalcitonin (PCT), anti-thrombin Ⅲ (AT-Ⅲ), D-dimer (D-D), fibrinogen (FIB), thrombin time (TT), activated partial thromboplastin time (APTT), and prothrombin time (PT) in the early diagnosis of pediatric sepsis. Methods A total of 82 children with sepsis in the Pediatric Intensive Care Unit (PICU) of General Hospital of Hunan University of Medicine from June 2020 to June 2023 were selected as sepsis group. Meanwhile, 90 children with respiratory tract infections in the general ward were included in general infection group, and 100 healthy children in the Department of Pediatric Health were selected as control group. The levels of serum PCT, AT-Ⅲ, D-D, FIB, TT, APTT and PT were compared among the three groups. Results Compared with the general infection group and the control group, the sepsis group had significantly higher serum PCT and D-D levels, prolonged TT, APTT and PT in the four-items of coagulation test, and reduced AT-Ⅲ and FIB levels (P < 0.05). The areas under the curve (AUCs) for the diagnosis of pediatric sepsis by serum PCT, AT-Ⅲ, D-D, PT, APTT, TT and FIB levels were 0.949, 0.174, 0.911, 0.869, 0.855, 0.834 and 0.242 respectively; among these indexes, serum PCT showed the highest diagnostic value, with the maximum Youden index at a cut-off value of 0.62 μg/L, and the diagnostic sensitivity and specificity were 86.6% and 79.0% respectively. The AUC for the combined diagnosis of pediatric sepsis by the seven indicators was 0.966. Conclusion The detection of serum PCT, AT-Ⅲ, D-D and four items of coagulation test is of great value in the early diagnosis and differential diagnosis of pediatric sepsis.

OBJECTIVE To investigate the effects of individualized dosing regimen on blood trough concentration of vancomycin and renal function in critically ill patients. METHODS According to relevant guidelines and the results of Vancomycin Calculator， clinical pharmacists formulated an individualized dosing regimen of vancomycin including loading dose and maintenance dose for critically ill patients based on the two independent variables of body weight and creatinine clearance rate. Using the method of retrospective study， patients who were admitted to the department of intensive care unit （ICU） of the Second Affiliated Hospital of Guangzhou Medical University and used the regimen from July 2018 to December 2021 were selected as the trial group， and patients who were treated with vancomycin and received blood drug concentration monitoring in ICU from January 2015 to June 2018 were recruited in the control group. The difference in trough concentration distribution and the incidence of acute kidney injury （AKI） after medication were compared between the two groups， the change of serum creatinine before and after medication in the trial group was analyzed. RESULTS Totally 197 patients were included in the trial group and 144 patients were in the control group. There was no significant difference between the two groups in the clinical information （gender， age， body weight， acute physiology and chronic health evaluation Ⅱ score， the proportion of patients with renal insufficiency， etc.） （P＞0.05）. The proportions of major infection sites （including lung， urinary， abdominal， blood and central nervous system） and treatment type （target or empirical treatment） also had no significant difference between the two groups （P＞0.05）. There was no significant difference in the attainment rate of ideal trough concentration （15-20 μg/mL） and the proportion of patients with trough concentration　＞20 μg/mL between the two groups （P＞0.05）， while the attainment rate of target trough concentration （10-20 μg/mL） and the proportion of patients with trough concentration ＜10 μg/mL were significantly different between the two groups （P＜0.05）. The attainment rate of target trough concentration in patients with chronic renal insufficiency in trial group was significantly higher than that in control group （P＜0.05）. There was no significant difference in the incidence of AKI and vancomycin-associated AKI between the two groups （P＞0.05）. In the trial group with medication duration ≥7 days ， the level of serum creatinine on the 7th day of treatment was increased significantly， compared with that on the 3rd day of treatment （P＜0.05）. CONCLUSIONS This individualized dosing regimen can improve the attainment rate of target trough concentration of vancomycin in critically ill patients， especially those with chronic renal insufficiency， during the first standardized monitoring， and not increase the risk of renal injury compared with previous empirical medication.

Depression is a mental disorder with high morbidity, disability and relapse rates. Ginkgo biloba extract (GBE), a traditional Chinese medicine, has a long history of clinical application in the treatment of cerebral and mental disorders, but the key mechanism remains incompletely understood. Here we showed that GEB exerted anti-depressant effect in mice through regulating gut microbial metabolism. GBE protected against unpredictable mild stress (UMS)-induced despair, anxiety-like and social avoidance behavior in mice without sufficient brain distribution. Fecal microbiome transplantation transmitted, while antibiotic cocktail abrogated the protective effect of GBE. Spatiotemporal bacterial profiling and metabolomics assay revealed a potential involvement of Parasutterella excrementihominis and the bile acid metabolite ursodeoxycholic acid (UDCA) in the effect of GBE. UDCA administration induced depression-like behavior in mice. Together, these findings suggest that GBE acts on gut microbiome-modulated bile acid metabolism to alleviate stress-induced depression.
Humans ; Mice ; Animals ; Depression/drug therapy* ; Gastrointestinal Microbiome ; Plant Extracts ; Ginkgo biloba

Objective:To examine the impact of pressure support ventilation(PSV)in combination with low inspired oxygen concentration on atelectasis during the emergence from general anesthesia in elderly patients undergoing robotic-assisted radical prostatectomy.Methods:In this prospective randomized controlled study, a total of 144 elderly patients, aged 65-80 years(average age: 71.4±4.4 years), who were undergoing elective robotic-assisted radical prostatectomy under general anesthesia, were divided into 4 groups(n=36 each)using the random number table method.The groups were as follows: PSV+ 40% fraction of inspiration oxygen(FiO 2)(P40 group), PSV+ 80%FiO 2(P80 group), spontaneous breathing+ 40%FiO 2(S40 group), and spontaneous breathing+ 80%FiO 2(S80 group). These methods were used during the general anesthetic emergence, which refers to the period from the end of the operation to extubation.Atelectasis aeration loss score was measured using ultrasound, and the oxygenation index(OI)was calculated through arterial blood gas analysis.These measurements were recorded at different time points: at the end of surgery(T 1), after extubation(T 2), 30 minutes after entering the post anesthesia care unit(PACU)(T 3), and 48 hours after surgery(T 4). The number of hypoxemia cases(defined as saturation of pulse oxygen <92%)during emergence and within 30 minutes of entering the PACU, as well as the incidence of postoperative pulmonary complications(PPCs)at T 4, were also recorded. Results:A total of 137 patients completed the study.Compared with the P40 group, the patients in the P80 group had higher atelectasis aeration loss scores at T 2[6.0(3.0)scores vs.4.0(2.0)scores; Z=-3.733, P<0.001], the S40 group[8.0(3.0)scores vs.4.0(2.0)scores; Z=-4.868, P<0.001], and the S80 group[9.0(3.0)scores vs.4.0(2.0)scores; Z=-6.835, P<0.001]. At T 3, the S40 group[7.0(2.0)scores vs.5.0(2.0)scores; Z=-4.631, P<0.001]and the S80 group[9.0(2.5)scores vs.5.0(2.0)scores; Z=-6.590, P<0.001]also had higher atelectasis aeration loss scores.There was no significant difference in the incidence of hypoxemia between the four groups during the recovery period( χ2=0.405, P=0.939)and in PACU( χ2=4.048, P=0.256). The incidence of PPCs in the four groups at 48 hours after operation was 5.9%(2/34), 11.4%(4/35), 8.6%(3/35), and 6.1%(2/33)respectively( χ2=0.947, P=0.814). Conclusions:The combination of positive end-expiratory pressure support ventilation(PSV)and low inspired oxygen concentration can effectively decrease the occurrence of atelectasis in elderly patients undergoing robotic-assisted radical prostatectomy during the emergence phase.This approach also helps in reducing the incidence of hypoxemia in the post-anesthesia care unit(PACU)and improves the postoperative oxygenation index.