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In order to investigate the effect of temperature shock action parameters on the methane adsorption and desorption of mudstone, a temperature shock modification test was conducted on the mudstone in the roof of 15303 working face of 15# coal seam in Sihe Coal Mine using orthogonal test method. The 3 factors and 4 levels were hot shock temperature of 50, 100, 150 and 200 ℃, cold shock temperature of −10, −30, −50 and −70 ℃, and the number of shock cycles of 1, 3, 5 and 7. The volumetric method was used to determine the characteristic parameters of adsorption and desorption of mudstone under different action parameters and to investigate the influence mechanism in terms of pore structure. The results showed that the mudstone methane adsorption and desorption capacity increased after modification with different action parameters, and the effects on the saturation adsorption capacity, Langmuir pressure, specific surface area and most probable pore size were in the following order: heat shock temperature > number of cycles > cold shock temperature; the effects on the desorption rate, diffusion coefficient and pore volume were in the following order: number of cycles > cold shock temperature > heat shock temperature. The saturation adsorption capacity increased the most at the heat shock temperature of 200 ℃, the cold shock temperature of −50 ℃ and the number of shock cycles of 3 times, 23.29%, 15.60% and 19.15% respectively; the final desorption rate increased the most at the heat shock temperature of 150 ℃, the cold shock temperature of −70 ℃ and the number of shock cycles of 5 times, 7.15%, 11.54% and 11.14% respectively. In terms of pore structure, the saturated adsorption capacity of the mudstone has a good linear relationship with the specific surface area and the most available pore size, and the desorption rate has a good linear relationship with the pore capacity, while the specific surface area and pore volume of the modified mudstone are increased and the most probable pore size is reduced resulting in increased methane adsorption and desorption capacity of the mudstone. In terms of surface properties, the modification reduces the surface roughness, increases the mudstone-water contact angle and reduces the surface energy.

Abstract The optimal timing and type of hematopoietic stem cell transplantation (HSCT) for treating peripheral T-cell lymphoma (PTCL) remain controversial. This retrospective real-world study investigated the application pattern and outcomes of HSCT in China. The analysis encompassed 408 PTCL patients with a median age of 45.5 years, all of whom received initial adequate therapy at five hospitals. Among patients with nodal PTCL who responded effectively to first-line therapy (the “responders”, n = 127) and subsequently underwent HSCT consolidation (n = 47, 37.0%), 93.6% received auto-HSCT, while 6.4% underwent allo-HSCT. Front-line auto-HSCT showed potential for long-term disease control in nodal PTCL responders. Among non-nodal PTCL responders (n = 80) with HSCT (n = 26, 32.5%), 46.2% underwent allo-HSCT and 53.8% received auto-HSCT. Upfront allo-HSCT provides longer progression-free survival (PFS) for non-nodal PTCL responders, with lower 3-year cumulative incidence of relapse (CIR) (16.7% vs. 56.0%) and comparable non-relapse mortality (NRM) (10.4% vs. 11.0%) compared to auto-HSCT. For patients who achieved remission with second-line salvage regimens, allo-HSCT was the primary choice (82.4%) for non-nodal PTCL, while auto-HSCT was more common (82.4%) in nodal PTCL. Nodal PTCL patients underwent auto-HSCT after ≥ 3 lines of treatment had a higher 3-year CIR (81.0%) compared to those treated in the first (26.0%) or second line (26.0%). Non-nodal PTCL patients underwent allo-HSCT after ≥ 3 lines had a higher 3-year NRM (37.5%) compared to after first (10.4%) or second line treatment (8.5%). These findings highlight distinct HSCT application patterns for PTCL in China, emphasizing the impact of early disease control and upfront consolidative HSCT.

Acute graft-versus-host disease (aGVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and contributes to high morbidity and mortality. However, our current understanding of the development and progression of aGVHD after allo-HSCT remains limited. To identify the potential biomarkers for the prevention and treatment of aGVHD during the early hematopoietic reconstruction after transplantation, we meticulously performed a comparative analysis of single-cell RNA sequencing data from post-transplant patients with or without aGVHD. Prior to the onset of aGVHD, monocytes in the peripheral blood of patients with aGVHD experienced a dramatic rise and activation on day 21 post-transplantation. This phenomenon is closely aligned with clinical cohort results obtained from blood routine examinations. Furthermore, in vitro co-culture experiments showed that peripheral blood monocytes extracted from patients with aGVHD approximately 21 days post-transplantation induced a significantly higher proliferation rate of allogeneic T cells compared to those from patients without aGVHD. Our study indicates that monocytes could be a crucial early clinical risk factor for the development of aGVHD, and this insight could potentially guide the timing of monitoring efforts, recommending assessments at the pivotal juncture of approximately day 21 post-transplantation, shedding fresh light on the significance of early hematopoietic regeneration in relation to the onset of aGVHD.

Objective: To explore the effects and possible mechanisms of the drug pair Cornus officinalis and Radix achyranthis bidentatae (SYR-NX) on improving hypertensive kidney damage. Method: SYR-NX, a formulation of Cornus officinalis and Radix Achyranthis Bidentatae with a dose ratio 1:2.5, was used in this experiment. We investigated the effects of SYR-NX on spontaneously hypertensive rats (SHR) fed with a high-salt diet and Human Kidney-2 (HK2) cells exposed to hypoxia. After 8 weeks of treatment with SYR-NX, blood pressure was tested, and β 2-Microglobulin(β2-MG), blood creatinine (S-cr), endothelial nitric oxide synthase (eNOS), nicotinamide adenine dinucleotide phosphate (NADPH), M2 pyruvate kinase (PKM2), adenosine triphosphate (ATP), pyruvate, lactate, connective tissue growth factor (CTGF) and tumor necrosis factor-α (TNF-α)were measured. HK2 cells pre-treated with SYR-NX were cultured in a three-gas hypoxic incubator chamber (5 % CO2, 1 % O2, 94 % N2) for 12 h, and then eNOS, PKM2, NADPH, ATP, pyruvate, lactate, CTGF and TNF-α were assessed. Results: SYR-NX significantly reduced SBP, DBP, β2-MG, S-cr, PKM2, pyruvate, lactate, CTGF and TNF-α, and increased eNOS, NADPH, and ATP. Conclusion: SYR-NX can regulate metabolic reprogramming through eNOS and improves hypertensive kidney injury.

China is rich in coal-measure gas reserves. However, the complex geological conditions of coal-measure gas reservoirs make it costly and inefficient to mine a single gas-bearing system, and difficult to co-mine multiple gas-bearing systems. How to improve the permeability and compatibility of coal reservoirs is the key issue in development of coal-measure gas. In order to explore effective methods to improve the structure of coal reservoirs, the evolution characteristics of sandstone pore-fracture in the top plate of coal seams under the cyclic impacts of high temper-ature (200 ℃) and low temperature (−196 ℃) were investigated. The development of sandstone pore-fracture before and after high- and low-temperature impacts was characterized using industrial micro-CT. The CT data of the specimens before and after impact were filtered and homogenized using digital image and three-dimensional reconstruction techniques. The changes of volume, surface area, porosity and fractal dimension of distribution complexity of sandstone pore-fracture after 0, 1, 5, 10 and 15 high- and low-temperature impacts were qualitatively and quantitatively analyzed. The results shown that, (1) High- and low-temperature cyclic impacts promoted the development, expansion and connectivity of pore-fracture, and the sprouting of secondary fracture in sandstone. The impacts contributed to the expansion of micro pore-fracture to form larger macro fracture. (2) The volume, surface area, porosity and fractal dimension of distribution complexity of sandstone pore-fracture varied logarithmically with the increase of the number of temperature impacts, and the growth tended to increase first and then decrease. The increase of its area and porosity reached a maximum of 15.48% and 20.98%, respectively, after the 5th impact effect. (3) High- and low-temperature cyclic impacts weakened the binding force between the sandstone matrix and broke the original static equilibrium. The variation curve of sandstone porosity with the number of scanned layers evolved into a "C-like" shape, which indicated that the binding force at the ends of the sandstone was more attenuated.

IntroductionRetrospective studies have suggested that Ursodeoxycholic Acid (UDCA) provide a protective effect against SARS-CoV-2 infection, particularly in patients with liver disease. However, it is uncertain whether this finding can be extended to the allogeneic hematopoietic stem cell transplantation (allo-HSCT) cohort. Therefore, we aim to examine the protective potential of UDCA against SARS-CoV-2 infection in recently received allo-HSCT patients.MethodsDuring the initial Omicron variant wave in China (December 2022 to February 2023), we conducted a prospective observational study involving 91 hospitalized patients who had undergone allo-HSCT within the previous 6 months as part of the National Longitudinal Cohort of Hematological Diseases (NICHE). Throughout hospitalization, we continuously monitored the status of COVID-19 using SARS-CoV-2 PCR kits or SARS-CoV-2 Antigen Rapid Tests.ResultsAmong these patients, 67.0% (n = 61) were confirmed to have contracted SARS-CoV-2 infection. For the 52 patients evaluated, 23.1% experienced a severe or critical clinical course. There was no difference in the infection rate or severity of COVID-19 between the UDCA group and the non-UDCA group. We found that only patients transplanted between 3 and 6 months ago demonstrated a higher risk of SARS-CoV-2 infection compared to those who received allo-HSCT within 3 months (Odds Ratio [OR]: 3.241, 95% Confidence Interval [CI]: 1.287-8.814, P = 0.016). But other clinical factors, such as administration of UDCA, showed no difference. Notably, only age ≥38 years old remained as an independent risk factor for a severe clinical course of SARS-CoV-2 infection (OR: 3.664, 95% CI: 1.129-13.007, P = 0.035).ConclusionThe effectiveness of UDCA in protecting newly allo-HSCT recipients against SARS-CoV-2 infection remains unconfirmed. Presently, the most effective strategy appears to be minimizing exposure to SARS-CoV-2.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT04645199, identifier NCT04645199.

ABSTRACTObjectives To determine the impact of pretransplant measurable residual disease (pre-MRD) and the efficacy of maintenance therapy in t(8;21) acute myeloid leukemia (AML) patients after allogeneic hematopoietic cell transplantation (allo-HCT).Methods We retrospectively analyzed 100 t(8;21) AML patients who underwent allo-HCT between 2013 and 2022. 40 patients received pre-emptive therapy including immunosuppressant adjustment, azacitidine, and donor lymphocyte infusion (DLI) combined with chemotherapy. 23 patients received prophylactic therapy, including azacitidine or chidamide.Results Patients with a positive pre-MRD (pre-MRDpos) had a higher 3-year cumulative incidence of relapse (CIR) (25.90% [95% CI, 13.87%–39.70%] vs 5.00% [95% CI, 0.88%–15.01%]; P = 0.008). Pre-MRDpos patients were less likely to have a superior 3-year disease-free survival (DFS) (40.83% [95% CI, 20.80%–80.16%]) if their MRD was still positive at 28 days after transplantation (post-MRD28pos). The 3-year DFS and CIR were 53.17% (95% CI, 38.31% – 73.80%) and 34.87% (95% CI, 18.84% – 51.44%), respectively, for patients receiving pre-emptive interventions after molecular relapse. The 3-year DFS and CIR were 90.00% (95%CI, 77.77% – 100%) and 5.00% (95%CI, 0.31% – 21.10%), respectively, for high-risk patients receiving prophylactic therapy. In most patients, epigenetic-drug-induced adverse events were reversible with dose adjustment or temporary discontinuation.Conclusion Patients with pre-MRDpos and post-MRD28pos were more likely to have higher rates of relapse and inferior DFS, even after receiving pre-emptive interventions. Prophylactic therapy may be a better option for high-risk t(8;21) AML patients; however, this warrants further investigation.

Due to its high mortality, incidence and disability rates, ischemic stroke poses heavy economic burdens to families and society. Zuogui Pill (ZGP) is a classic Chinese medicine for tonifying the kidney, which is effective for the recovery of neurological function after ischemic stroke. However, Zuogui Pill has not been evaluated for its potential effects on ischemic strokes. Using network pharmacology, the research aimed to explore the mechanisms of Zuogui Pill on ischemic stroke, which were further validated in SH-SY5Y cells injured by oxygen and glucose deprivation/reperfusion (OGD/R). Network analysis of Zuogui Pill identified 86 active ingredients and 107 compound-related targets correlated with ischemic stroke. Additionally, 11 core active compounds were obtained, such as Quercetin, beta sitosterol, and stigmasterol. Most of the compounds have been proven to have pharmacological activities. Based on pathway enrichment studies, Zuogui Pill may exert neuroprotection through MAPK signaling, PI3K-Akt signaling and apoptosis, as well as enhance neurite outgrowth and axonal regeneration effect via mTOR signaling, p53 signaling and Wnt signaling pathways. In vitro experiment, the viability of ischemic neuron treated with Zuogui Pill was increased, and the ability of neurite outgrowth was significantly improved. Western blot assays shown that the pro-neurite outgrowth effect of Zuogui Pill on ischemic stroke may be relate to PTEN/mTOR signal pathway. The results of the study provided new insights into Zuogui Pill’s molecular mechanism in treatment of ischemic stroke, as well as clinical references for its use.

Introduction The risk of death significantly increased from stage 3 chronic kidney disease (CKD) onward. We aimed to construct a novel nomogram to predict the overall survival (OS) of patients afflicted with CKD from stage 3–5. Methods A total of 882 patients with stage 3–5 CKD were enrolled from the NHANES 2001–2004 survey. Data sets from the 2003–2004 survey population were used to develop a nomogram that would predict the risk of OS. The 2001–2002 survey population was used to validate the nomogram. Least absolute shrinkage and selection operator (Lasso) regression was conducted to screen the significant predictors relative to all-cause death. The multivariate Cox regression based on the screened factors was applied to effectively construct the nomogram. The performance of the nomogram was evaluated according to the C-index, the area under the receiver operating characteristic curve (AUC), and the calibration curve with 1000 bootstraps resample. Kaplan–Meier’s curves were used for testing the discrimination of the prediction model. Results Five variables (age, urinary albumin-to-creatinine ratio (UACR), potassium, cystatin C (Cys C), and homocysteine) were screened by the Lasso regression. The nomogram was constructed using these factors, as well as the CKD stage. The included factors (age, CKD stage, UACR, potassium, Cys C, and homocysteine) were all significantly related to the death of CKD patients, according to the multivariate Cox regression analysis. The internal validation showed that this nomogram demonstrates good discrimination and calibration (adjusted C-index: 0.70; AUC of 3-, 5-, and 10-year OS were 0.75, 0.78, and 0.77, respectively). External validation also demonstrated exceedingly similar results (C-index: 0.72, 95% CI: 0.69–0.76; AUC of 3-, 5-, and 10-year OS were 0.76, 0.79, and 0.80, respectively). Conclusions This study effectively constructed a novel nomogram that incorporates CKD stage, age, UACR, potassium, Cys C, and homocysteine, which can be conveniently used to facilitate the individualized prediction of survival probability in patients with stage 3–5 CKD. It displays valuable potential for clinical application.

BackgroundPrior research has shown inconclusive findings regarding the relationship between blood pressure variability (BPV) in acute ischemic stroke (AIS) and functional outcomes. Most research has examined the connection between short-term BPV during the early 24–72 h after the occurrence of ischemic stroke and functional prognosis. We sought to determine the relationship between daily BPV at 7 days of commencement and functional outcomes during the 3 months following AIS.MethodsAltogether, 633 patients with AIS admitted within 72 h of commencement were enrolled. AIS was defined as the time from the onset of symptoms to 7 days. Throughout this period, blood pressure (BP) was recorded twice daily (casual BP cuffs). The daily BPV, with standard deviation (SD) and coefficient of variation (CV), was calculated and matched to the functional results. The adverse outcome was characterized as a modified Rankin scale (mRS)≥3, which comprised the recurrence of stroke, clinical intracranial bleeding, and death.ResultsIn total, 633 participants were included, and the incidence of adverse outcomes was 14.06% (89/633). There was a significant positive correlation between daily BPV and adverse outcomes but not between mean BP and risk. Smooth curve fitting revealed a U-shaped connection between the mean BP and adverse clinical outcomes. Multivariable logistic regression analysis showed an independent correlation between daily BPV and an adverse outcome in the top vs. bottom quartile of systolic BPV (odds ratio [OR] = 2.4, 95% confidence interval [CI]: 1.17–4.96, P = 0.018 for SD; OR = 2.4, 95% CI: 1.17–4.93, P = 0.017 for CV) during a 3-month follow-up period. Identical results have been reported for diastolic BPV.ConclusionIrrespective of BP level, elevated daily systolic BPV and diastolic BPV in AIS were associated with an increased risk of adverse outcomes within 3 months. We also discovered a U-shaped association between the mean BP and adverse clinical outcomes. These findings suggested that BPV should be a risk factor for adverse outcomes after ischemic stroke, which provided new insight into BP management strategy.

BackgroundAdjacent segment disease (ASD) is a common complication after lumbar fusion and is still traditionally treated by open surgery. In recent years, with the development of minimally invasive techniques, percutaneous endoscopic surgery(PES) has been used for the treatment of ASD after lumbar fusion due to its unique benefits. Nevertheless, it remains unclear about its significant clinical efficacy and advantages over conventional open surgery.ObjectivesTo evaluate the clinical efficacy and safety of PES in the treatment of ASD after lumbar fusion.Study designA systematic review and meta-analysis studies about the role of PES in managing ASD after lumbar fusion.MethodsA systematic search review was conducted in PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, VIP, WanFang, and SinoMed databases from the start of their construction to 15 November 2021. Eligible studies included references to clinical trials of PES for ASD after open lumbar fusion. Observations included pain relief, recovery of postoperative function, overall excellent rates, and indicators of the advantages of minimally invasive surgery compared to conventional surgery. Postoperative complications and recurrence rates were also recorded.ResultsA total of 24 studies, including 20 single-arm studies and 4 clinical control studies, all involving 928 patients were included. A total of 694 patients were included in the single-arm analysis. The results of the single-arm meta-analysis showed that PES could significantly reduce low back and leg pain and improve the functional status of the lumbar spine in patients with ASD after open lumbar fusion compared to preoperatively, and had good clinical efficacy after surgery. A total of 234 patients were included in the four clinically controlled studies, and the results of the meta-analysis showed that PES could clearly reduce pain and improve lumbar function, with no significant difference in efficacy between PES and open surgery. However, PES has a lower surgical incision, less intraoperative bleeding, and shorter operative time and length of hospital stay compared to open surgery. Moreover, it has a lower rate of postoperative recurrence as well as complications and a longer duration of efficacy.ConclusionsOn the basis of the available clinical literature and the results of this study, PES could achieve satisfactory clinical effects in ASD treatment after lumbar fusion. Compared with conventional open surgery, PES can not only obtain similar clinical results, but also had the advantages of less trauma and faster recovery. Nevertheless, a randomized controlled study is still needed to validate the findings of this study.Trial registrationSystematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022298387.

ObjectiveTo systematically review the efficacy and safety of sacubitril and valsartan in treating acute myocardial infarction complicated with heart failure and to observe whether it can further improve patients’ cardiac function, delay left ventricular remodeling, and reduce major adverse cardiovascular events (MACEs).MethodsElectronic databases including Pubmed, Embase, the Web of Science, Cochrane Library, Scopus, CNKI, Wanfang Data, and VIP were searched. The search period was from the establishment of the database to March 2022 to search for relevant controlled trials. Two investigators independently screened the literature, extracted data, and assessed the risk of bias. Revman5.3 and Stata14 software were used for statistical analysis.ResultsA total of 13 studies, with 6,968 patients were included. Meta-analysis results showed that sacubitril-valsartan increased left ventricular ejection fraction (LVEF) and decreased NT-proBNP level was better at 6 months and within 3 months of follow-up compared with the control group (P < 0.00001), but there was no significant difference at the 12-month follow-up (P > 0.05). Sacubitril-valsartan reducing LVEDD [MD = −2.55, 95%CI(−3.21, −1.88), P < 0.00001], LVEDVI [MD = −3.61, 95%CI(−6.82, −0.39), P = 0.03], LVESVI [MD = −3.77, 95%CI(−6.05, −1.49), P = 0.001], and increasing the distance of the 6-min walk test [MD = 48.20, 95%CI(40.31, 56.09), P < 0.00001] were more effective. Compared with ACEI/ARB, the use of ARNI can further reduce the total incidence of adverse cardiovascular events [RR = 0.72, 95%CI(0.62, 0.84), P 0.05). In terms of the incidence of adverse reactions, the incidence of cough in ARNI was lower than that in ACEI/ARB group [RR = 0.69, 95%CI(0.60, 0.80), P < 0.00001], but the incidence of hypotension was higher [RR = 1.29, 95%CI(1.18, 1.41), P < 0.00001], and the adverse reactions of hyperkalemia, angioedema and renal insufficiency were not increased (P > 0.05).ConclusionThe use of sacubitril-valsartan sodium in patients with acute myocardial infarction complicated with heart failure can significantly improve cardiac function and reverse ventricular remodeling, reducing the risk of re-hospitalization for heart failure. There is no apparent adverse reaction except easy cause hypotension.Systematic trial registration[www.ClinicalTrials.gov], identifier [CRD42022322901].

Background: Myocardial ischemia/reperfusion (I/R) injury is associated with multiple serious clinical manifestations. Autophagy is upregulated in a short period of ischemia and further enhanced during reperfusion phase, which was considered as a “double-edged sword” in the pathological process of myocardial I/R injury. In addition, NLRP3 inflammasome triggers myocardial inflammatory response, which leads to cardiomyocyte death via pyroptosis and promotes subsequent myocardial remodelling. Qishen Yiqi Dripping Pill (QSYQ) has been recognized as a potential protective agent of cardiovascular diseases.Objective: We predicted the bioactive compounds, targets and pathways of OSYQ intervening on myocardial I/R injury by network pharmacology. Furthermore, we investigated the effect of QSYQ on myocardial I/R injury and explored its underlying mechanism via autophagy and NLRP3 Inflammasome.Methods: Bioactive compounds, targets of QSYQ and relevant targets of myocardial I/R injury were collected from public databases. The protein-protein interaction network, Gene ontology and KEGG pathway enrichment analysis were carried out to screen the key compounds, target genes, functional annotation and pivotal pathways. Molecular docking was used to validate the binding association between target genes and key bioactive ingredients. Furthermore, sixty SD rats were randomized into four groups: 1) sham, 2) model, 3) captopril and 4) QSYQ pretreatment (14 days before and after surgery). Each arm was subjected to ischemia/reperfusion surgery except sham arm (30 min coronary ligation, then reperfusion). Left ventricular (LV) function were evaluated and the hearts were used to evaluate size of myocardial infarction, cardiomyocyte fibrosis, and myocardial autophagosomes.Results: The network pharmacology revealed the mechanism of QSYQ intervening on myocardial I/R injury might be related to NOD-like receptor signaling pathway, PI3K-Akt signaling pathway, autophagy-animal, etc., Molecular-docking suggested the core target proteins had good binding association with bioactive compounds of QSYQ. The experiment confirmed that QSYQ attenuated myocardial infarct size, decreased inflammatory infiltration and collagen fiber deposition and alleviated the autophagosome and myocardium ultrastructure injury, leading to LV systolic function improvement. The possible mechanism of cardioprotection was due to regulating autophagy-related proteins, activating PI3K/Akt-mTOR signaling pathway, and inhibiting activation and assembly of NLRP3 inflammasome.Conclusion: QSYQ ameliorated myocardial I/R injury via suppressing excessive autophagy and NLRP3 Inflammasome.

Abstract Sparganii rhizoma (SL) has potential therapeutic effects on gastric cancer (GC), but its main active ingredients and possible anticancer mechanism are still unclear. In this study, we used HPLC-Q-TOF–MS/MS to comprehensively analyse the chemical components of the aqueous extract of SL. On this basis, a network pharmacology method incorporating target prediction, gene function annotation, and molecular docking was performed to analyse the identified compounds, thereby determining the main active ingredients and hub genes of SL in the treatment of GC. Finally, the mRNA and protein expression levels of the hub genes of GC patients were further analysed by the Oncomine, GEPIA, and HPA databases. A total of 41 compounds were identified from the aqueous extract of SL. Through network analysis, we identified seven main active ingredients and ten hub genes: acacetin, sanleng acid, ferulic acid, methyl 3,6-dihydroxy-2-[(2-hydroxyphenyl) ethynyl]benzoate, caffeic acid, adenine nucleoside, azelaic acid and PIK3R1, PIK3CA, SRC, MAPK1, AKT1, HSP90AA1, HRAS, STAT3, FYN, and RHOA. The results indicated that SL might play a role in GC treatment by controlling the PI3K-Akt and other signalling pathways to regulate biological processes such as proliferation, apoptosis, migration, and angiogenesis in tumour cells. In conclusion, this study used HPLC-Q-TOF–MS/MS combined with a network pharmacology approach to provide an essential reference for identifying the chemical components of SL and its mechanism of action in the treatment of GC.

ObjectiveChronic kidney disease (CKD) patients are more likely to die from cardiovascular disease (CVD) than develop renal failure. This study aimed to develop a new nomogram for predicting the risk of cardiovascular death in CKD patients.MethodsThis study enrolled 1656 CKD patients from NHANES 2003 to 2006 survey. Data sets from 2005 to 2006 survey population were used to build a nomogram for predicting the risk of cardiovascular death, and the nomogram was validated using data from 2003 to 2004 survey population. To identify the main determinants of cardiovascular death, we performed univariate analysis and backward-stepwise regression to select the key factors. The probability of cardiovascular death for each patient in 5, 7, and 9 years was calculated using a nomogram based on the predictors. To assess the nomogram’s performance, the area under receiver operating characteristic curve (AUC) and the calibration curve with 1,000 bootstraps resamples were utilized. The prediction model’s discrimination was examined using cumulative incidence function (CIF).ResultsAge, homocysteine, potassium levels, CKD stage, and anemia were included in the nomogram after screening risk factors using univariate analysis and backward-stepwise regression. Internal validation revealed that this nomogram possesses high discrimination and calibration (AUC values of 5–, 7–, and 9-years were 0.79, 0.81, and 0.81, respectively). External validation confirmed the same findings (AUC values of 5–, 7– and 9-years were 0.76, 0.73, and 0.73, respectively). According to CIF, the established nomogram effectively differentiates patients at a high risk of cardiovascular death from those at low risk.ConclusionThis work develops a novel nomogram that integrates age, homocysteine, potassium levels, CKD stage, and anemia and can be used to more easily predict cardiovascular death in CKD patients, highlighting its potential value in clinical application.

Introduction After stage 3 CKD, the risk of adverse cardiovascular events increased significantly. Therefore, we performed a meta-analysis to investigate the cardiovascular protective effect of SGLT2 inhibitors in patients with stage 3/4 CKD with different baseline kidney function or underlying diseases. Method To identify eligible trials, we systematically searched the Embase, PubMed, Web of Science, and Cochrane library databases from inception to April 15, 2021. The primary cardiovascular outcome was defined as a combination of cardiovascular mortality and hospitalization due to heart failure. Baseline kidney functions (stage 3a CKD: eGFR45-59mL/min per 1.73m2, stage 3b CKD: eGFR30-44mL/min per 1.73m2, stage 4 CKD: eGFRResults In the present study, a total of eleven trials were included that involved a total of 27,823 patients with stage 3/4 CKD. The treatment and control groups contained 14,451 and 13,372 patients, respectively. In individuals with stage 3/4 CKD, SGLT2 inhibitors reduced the risk of primary cardiovascular outcomes by 26% (HR 0.74, [95% CI 0.69–0.80], I2 = 0.00%), by 30% in patients with stage 3a CKD (HR 0.70, [95% CI 0.59–0.84], I2 = 18.70%), by 23% in patients with stage 3b CKD (HR 0.77, [95% CI 0.66–0.90], I2 = 2.12%), and by 29% in patients with stage 4 CKD (HR 0.71, [95% CI 0.53–0.96], I2 = 0.00%). The risk of primary outcomes was reduced by 29% (HR 0.71, [95% CI 0.63–0.80], I2 = 0.00%) in patients with type 2 diabetes, by 28% (HR 0.72, [95% CI 0.56–0.93], I2 = 37.23%) in patients with heart failure with preserved ejection fraction, by 21% (HR 0.79, [95% CI 0.70–0.89], I2 = 0.00%) in patients with heart failure with reduced ejection fraction, and by 25% (HR 0.75, [95% CI 0.64–0.88], I2 = 0.00%) in patients with atherosclerotic cardiovascular disease. Conclusions For stage 3/4 CKD, SGLT2 inhibitors significantly decreased the risk of primary cardiovascular outcomes, and these benefits were consistent throughout the spectrum of different kidney functions, even in stage 4 CKD. There was no evidence of increased adverse outcomes across different baseline clinical complications, such as type 2 diabetes, heart failure, or atherosclerotic cardiovascular disease.

Background: At present, there are a variety of treatment strategies for percutaneous coronary intervention. The role of drug-coated balloon (DCB) in the treatment of side branch for de novo coronary bifurcated lesions (CBL) is unclear.Objective: To examine the effect of DCB in side branch protection for de novo CBL.Methods: Electronic databases, including Pubmed, Embase, the Web of science, Cochrance library, CNKI, CBM, WanFang Data and VIP were searched for studies that compared DCB with non-drug-coated balloon (NDCB) in side branch protection for de novo CBL from inception through July 7th, 2021. The primary outcome was target lesion revascularization (TLR). Secondary clinical outcomes included myocardial infarction (MI), cardiac death (CD). The angiographic outcomes included side branch late lumen loss (LLL), minimum lumen diameter (MLD), diameter stenosis (DS) and binary restenosis (BR). The target lesion failure (TLF) was also analyzed.Results: A total of 10 studies, including 5 randomized controlled trials and 5 non-randomized observational studies, with 934 patients were included. Meta-analysis results of angiographic outcomes suggested that DCB group had the less LLL, DS and BR and the higher MLD compared with NDCB group at follow-up (P < 0.05). Meta-analysis results of clinical outcomes suggested that the significant difference in the TLR, MI and CD between DCB group and NDCB group has not been found yet (P > 0.05). However, the MACE of DCB group was significantly less than that of NDCB group at 9-month follow-up [OR = 0.21, 95%CI (0.05, 0.84), P = 0.03] and 12-month follow-up [OR = 0.45, 95%CI (0.22, 0.90), P = 0.02]. In addition, there was no significant difference in TLF between DCB group and NDCB group (P > 0.05).Conclusions: DCB had great effect in side branch protection for de novo CBL at short and medium-term follow-up with no reduction in the procedural success rate.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=267426, PROSPERO [Identifier: CRD42021267426].

Abstract Autologous hematopoietic stem cell transplantation (ASCT) remains an important postremission treatment for acute leukemia (AL). It is known that some prognostic factors, such as age, cytogenetic and molecular risk stratification, and minimal residual disease (MRD) status, are closely related to clinical outcomes following ASCT. Moreover, there are multiple measurements, including pretransplant treatment, stem cell mobilization and collection, conditioning regimens, and maintenance treatment after transplantation, that can affect prognosis after ASCT. Our clinical practice of ASCT should be better standardized to further improve patient outcomes. This review outlines optimization and quality control measures for ASCT developed at the Institute of Hematology and Blood Diseases Hospital of the Chinese Academy of Medical Sciences, the first established and largest autologous stem cell transplant center in China. These measures will enhance the development of best practices and strategies for AL ASCT therapies, thereby improving patient outcomes.

Yamanaka factors can reprogram somatic and cancer cells into induced pluripotent stem cells. Here, the authors show that the induction of these factors in acute myeloid leukemia leads to apoptosis of leukemia cells in vivo, and this is through modulation of chromatin accessibility to apoptotic genes and accompanied by H3K9me3 dysregulation.

Protection against hypoxia injury is an important therapeutic strategy for treating hypertensive nephropathy. In this study, the effects of Qian Yang Yu Yin granule (QYYY) on spontaneously hypertensive rats fed with high salt diet and HEK293T cells exposed to hypoxia were investigated. After eight weeks’ treatment of QYYY, blood pressure, serum creatinine, serum cystatin C, blood urea nitrogen, urinary β2-microglobulin, urinary N-acetyl-β-glucosaminidase, and urinary microalbumin were assessed. The changes of hypoxia-inducible factor-1α (HIF-1α), pyruvate kinase M2 (PKM2), glucose transport 1 (GLUT1), lactate dehydrogenase A (LDH-A), connective tissue growth factor (CTGF), transforming growth factor-β1 (TGF-β1), ATP, lactate, pyruvate, and pathology were also assessed in vivo. HEK293T cells pre-treated with QYYY and/or HIF-1α over expressing cells were cultured in a three gas hypoxic incubator chamber (5% CO2, 1% O2, 94% N2) for 12 h and then the expressions of HIF-1α, PKM2, GLUT1, LDH-A, CTGF, TGF-β1, ATP, lactate, and pyruvate were detected. Our results showed that QYYY promoted the indicators of renal inflammation and fibrosis mediated by HIF-1α/PKM2 positive feedback loop in vivo and vitro. Our findings indicated that QYYY treated hypertensive nephropathy by regulating metabolic reprogramming mediated by HIF-1α/PKM2 positive feedback loop.

Introduction: For chronic kidney disease (CKD) patients with or without cardiovascular diseases, the associations between leisure-time physical activity intensity (LTPA) and daily exercise time with mortality risk remain unclear. Method: This study enrolled 3279 CKD patients from National Health and Nutrition Examination Survey (NHANES) 2007–2014 survey. Patients were grouped into different groups according to LTPA intensity (none, moderate, vigorous) and duration (0 min, 0–30 min, 30–60 min, >60 min). We selected the confounders based on their connections with the outcomes of interest or a change in effect estimate of more than 10%. Multivariable-adjusted Cox proportional hazards models were used to examine the associations between LTPA and mortality. The three-knot cubic spline (10, 50, and 90%) was employed to investigate the relationship between the dose of LTPA duration and all-cause death. Patients were divided into different groups according to cardiovascular diseases (CVD). Results: A total of 564 all-cause death were recorded in this study. Multivariable Cox regression showed that moderate LTPA was associated with a reduced risk of mortality by 38% (hazard ratio (HR): 0.62, 95% confidence interval (CI): 0.44–0.88) in CKD patients, while vigorous LTPA did not have evident survival benefits (HR: 0.91, 95% CI: 0.46–2.64). Subgroups analysis demonstrated that those who engaged in moderate LTPA have a significantly lower risk of mortality (HR: 0.67, 95% CI: 0.47–0.95) in patients without CVD, while patients complicated with CVD did not benefit from the practice (HR: 0.61, 95% CI: 0.37–1.02). Physical exercise for more than 30 minutes was associated with a lower risk of mortality in general CKD patients (30–60 min: HR: 0.23, 95% CI: 0.09–0.58, >60 min: HR: 0.23, 95% CI: 0.08–0.63) and those without CVD (30–60 min/d: HR: 0.32, 95% CI: 0.12–0.83, >60 min/d: HR: 0.20, 95% CI: 0.06–0.71); however, this positive outcome was not seen in patients complicated with CVD (30–60 min/d: HR: 0.67, 95% CI: 0.11–4.04, >60 min/d: HR: 1.14, 95% CI: 0.14–9.11). Conclusions: Moderate LTPA for more than 30 minutes is associated with a reduced risk of mortality in general CKD patients and those without CVD. However, LTPA did not reduce the risk of mortality in CKD patients complicated with CVD.

Background: The association between Aldehyde dehydrogenase II (ALDH-2) rs671 polymorphism and essential hypertension (EH) risk or blood pressure (BP) levels remains unclear.Objective: To systematically review the influence of the aldehyde dehydrogenase II rs671 polymorphism on essential hypertension risk and blood pressure levels.Methods: The PubMed, EMbase, Web of Science, Cochrane Library, CNKI and CBM databases were electronically searched to identify case-control or cohort studies published prior to July 2019 that examined the association between the rs671 polymorphism and the risk of essential hypertension or blood pressure levels. A meta-analysis was conducted with Stata 15.1 software.Results: Twenty-two articles were included. Among these articles, 20 incorporated 30 individual studies evaluating the association between the rs671 polymorphism and EH (11,051 hypertensive patients and 15,926 normotensive controls), and 8 incorporated 12 individual studies evaluating the association between the rs671 polymorphism and BP (20,512 subjects). The results of the meta-analysis showed that the mutation of the rs671 polymorphism was associated with a significantly decreased risk of EH in all models: allelic model (OR = 0.80, 95% CI: 0.73–0.87), homozygous model (OR = 0.71, 95% CI: 0.63–0.80), heterozygous model (OR = 0.79, 95% CI: 0.72–0.87), dominant model (OR = 0.79, 95% CI: 0.71–0.87), and recessive model (OR = 0.76, 95% CI: 0.68–0.85). In the stratified analyses, significant associations were found for males, drinkers and population-based studies. Simultaneously, the A carriers had lower SBP (WMD = −1.78, 95% CI: −3.02 to −0.53) and DBP (WMD = −1.09, 95% CI: −1.58 to −0.61) levels than individuals with the GG homozygote.Conclusion: The collective findings of this meta-analysis suggested that the ALDH-2 rs671 polymorphism represented an important genetic marker in the development of hypertension. Considering the overall quality of evidence and the relatively small pooled sample size, more well-conducted high-quality studies are required to verify the above conclusion.Systematic Review Registration Number: PROSPERO (CRD42019129746).

ObjectiveDanhong Injection (DHI) has been widely used to treat various diseases in China for many years. The objective of this systematic review was to evaluate the efficacy of DHI combined with antihypertensive drugs for treatment of hypertensive nephropathy.MethodsSeven databases were searched from inception to September 21st, 2019. Randomized controlled trials comparing DHI combined with antihypertensive drugs versus antihypertensive drugs alone were extracted. The primary outcome was microalbuminuria (mALB). Secondary outcomes included systolic blood pressure (SBP), diastolic blood pressure (DBP), and serum creatinine (SCr).ResultsFifteen studies were included in the meta-analysis, which indicated that DHI combined with antihypertensive drugs has advantages compared with antihypertensive drugs alone for reducing mALB [weighted mean difference (WMD) = −12.86, 95% confidence interval (CI) (−14.72, −11.0), P < 0.01], lowering SBP [WMD = −2.84, 95% CI (−4.56, −1.12), P = 0.001] and DBP [WMD = −2.38, 95% CI (−4.34, −0.43), P = 0.017], and decreasing SCr [WMD = −40.45, 95% CI (−55.69, −25.21), P < 0.01].ConclusionThe combination of DHI with antihypertensive drugs appears to be more effective than antihypertensive drugs alone for treatment of hypertensive nephropathy. A moderate duration (≤4 weeks) of DHI administration is reasonable, and longer treatment with DHI should be avoided, according to the results of subgroup analysis.

Abstract Background The constitutive hyper-activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathways has frequently been associated with acute myeloid leukemia (AML). While many inhibitors targeting these pathways have been developed, the anti-leukemic effect was not as robust as expected. As part of the molecular link between PI3K/Akt and mTOR kinase, the role of Rheb1 in AML remains unexplored. Our study aims to explore the role of Rheb1 in AML and estimate whether Rheb1 could be a potential target of AML treatment. Methods The expressions of Rheb1 and other indicated genes were analyzed using real-time PCR. AML mouse model was established by retrovirus transduction. Leukemia cell properties and related signaling pathways were dissected by in vitro and in vivo studies. The transcriptional changes were analyzed via gene chip analysis. Molecular reagents including mTOR inhibitor and mTOR activator were used to evaluate the function of related signaling pathway in the mouse model. Results We observed that Rheb1 is overexpressed in AML patients and the change of Rheb1 level in AML patients is associated with their median survival. Using a Rheb1-deficient MLL-AF9 murine AML model, we revealed that Rheb1 deletion prolonged the survival of AML mice by weakening LSC function. In addition, Rheb1 deletion arrested cell cycle progression and enhanced apoptosis of AML cells. Furthermore, while Rheb1 deletion reduced mTORC1 activity in AML cells, additional rapamycin treatment further decreased mTORC1 activity and increased the apoptosis of Rheb1 Δ/Δ AML cells. The mTOR activator 3BDO partially rescued mTORC1 signaling and inhibited apoptosis in Rheb1 Δ/Δ AML cells. Conclusions Our data suggest that Rheb1 promotes AML progression through mTORC1 signaling pathway and combinational drug treatments targeting Rheb1 and mTOR might have a better therapeutic effect on leukemia.