Mitophagy-regulated Necroptosis plays a vital role in the nephrotoxicity of Fumonisin B1 in vivo and in vitro.

Fumonisin B1 (FB1), one of the most widely distributed mycotoxins found in grains and feeds as contaminants, affects many organs including the kidney once ingested. However, the nephrotoxicity of FB1 remains to be further uncovered. The connection between necroptosis and nephrotoxicity of FB1 has been investigated in this study. The results showed that mice exposed to high doses of FB1 (2.25 mg/kg b.w.) developed kidney damage, with significant increases in proinflammatory cytokines (Il-6, Il-1ß), kidney injury-related markers (Ngal, Ntn-1), and gene expressions linked to necroptosis (Ripk1, Ripk3, Mlkl). The concentration-dependent damage effects of FB1 on PK-15 cells contain cytotoxicity, cellular inflammatory response, and necroptosis. These FB1-induced effects can be neutralized by pretreatment with the necroptosis inhibitor Nec-1. Additionally, FB1 caused mitochondrial damage and mitophagy in vivo and in vitro, whereas Mdivi-1, a mitophagy inhibitor, prevented these effects on PK-15 cells as well as, more crucially, necroptosis. In conclusion, the RIPK1/RIPK3/MLKL signal route of necroptosis, which may be controlled by mitophagy, mediated nephrotoxicity of FB1. Our findings clarify the underlying molecular pathways of FB1-induced nephrotoxicity.

Comparison of the PADUA and IMPROVE scores in assessing venous thromboembolism risk in 42,257 medical inpatients in China.

Venous thromboembolism (VTE) is a major contributor to hospital mortality and disability-adjusted life-year (DALY) loss. Multiple guidelines recommend using the Padua or IMPROVE scores to stratify VTE risk in hospitalized medical patients. However, the IMPROVE score is not recommended in Chinese guidelines, and there is very little evaluation of its clinical application and effectiveness in the Chinese population. The objective of this study is to compare the efficacy of the Padua and IMPROVE scoring models for assessing VTE risk in Chinese medical inpatients. We conducted a retrospective analysis of the clinical characteristics and thrombotic risk of 42,257 medical inpatients at a tertiary hospital in Guangdong, China, between 2021 and 2022. Logistic regression was used to assess thrombotic risk factors. The Receiver Operating Characteristic (ROC) curves, Area Under the Curve (AUC), sensitivity, and specificity were employed to evaluate the performance of the two models. Of the 42,257 patients included, 948 (2.24%) experienced VTE during hospitalization. According to the Padua score, 3,7513 (88.78%) of patients were considered low risk, while 4,744 (18.22%) were classified as high risk. The IMPROVE score identified 20,744 (49.09%) of patients as low risk, 20799(49.22%) as intermediate risk, and 714(1.69%) as high risk. The AUC for the Padua score was 0.735 (95% CI: 0.717-0.753), with a sensitivity of 49.4% and specificity of 89.6%. For the IMPROVE score, the AUC was 0.711 (95% CI: 0.693-0.729), with a sensitivity of 32.5% and specificity of 99.0%. The DeLong test, used to compare the AUCs, yielded a z-value of 1.886 with a P-value of 0.059, indicating no statistical difference. When assessing VTE risk in patients with stroke, cancer, nephrotic syndrome, and critical illness (ICU/CCU stay), both scoring models showed comparable predictive performance with AUCs ranging between 0.7 and 0.8. Both the Padua score and IMPROVE score have good predictive ability for VTE events during hospitalization in medical patients. Among them, the IMPROVE score has objective assessment items, simpler operation, and more detailed risk stratification, which is beneficial for clinicians to take physical and pharmacological preventive measures at different levels.ChiCTR2200056903, February 22, retrospectively registered.

Is the expression of different discrete emotions related to time? Evidence from online Chinese reviews using sentiment analysis and human behavior dynamics.

Objectives: The online behavior of online users has taken on complex and diverse characteristics, and posting product reviews on e-commerce platforms is no exception. In fact, reviews contain rich and multi-dimensional discrete emotional information, and whether there is a relationship between the expression of these different discrete emotions and the time interval between product purchase and review posting as well as their related characteristics are the issues that this study needs to analyze and solve in depth. Methods: Based on the OCC model (named after three proposers) of psychological emotional cognitive evaluation theory as the basis for emotion classification, the study used the massive amounts of Chinese reviews of mobile phones on the Chinese e-commerce platform Jingdong Mall as the research object, applied supervised machine learning methods to classify discrete emotions, and constructed a large corpus containing satisfaction, disappointment, admiration, reproach, love, and hate; then the study delved into the distribution and behavioral dynamics characteristics of consumers' comments containing the different discrete emotions at different "purchase-comment" time intervals. Results: The results showed that the first peak of the distribution curves of the six discrete emotions at different "purchase-comment" time intervals occurs on the first day after purchase and then decreases gradually but at different rates. The three curves for satisfaction, love, and hate emotions also show a second peak on the eleventh day, which is more similar to the bimodal distribution, implying that the corresponding product reviews are more objective. In addition, the distribution of reviews containing the six discrete emotions at different "purchase-comment" time intervals follows a power-law distribution and has the temporal characteristics of human behavioral dynamics, that is, "strong paroxysms and weak memory". However, the reviews containing the admiration and reproach emotions were most intensively written by consumers after the purchase, indicating that the service provided by the seller, logistics, and e-commerce platform stimulates more consumers to give quick responses and detailed reviews. Conclusion: This study is not only of great significance for exploring the internal mechanisms of consumer discrete emotional expression but also provides important decision-making references for potential consumer purchasing decisions, product updates for developers, marketing strategy formulation for marketing teams, and service improvement for sellers, logistics companies, and e-commerce platforms.

3D-printed near-infrared-light-responsive on-demand drug-delivery scaffold for bone regeneration.

Although several bioactive 3D-printed bone scaffolds loaded with multiple kinds of biomolecules for enhanced bone regeneration have been recently developed, the manipulation of on-demand release profiles of different biomolecules during bone regeneration remains challenging. Herein, a 3D-printed dual-drug-loaded biomimetic scaffold to regulate the host stem cell recruitment and osteogenic differentiation in a two-stage process for bone regeneration was successfully fabricated. First, a chemotactic small-molecule drug, namely, simvastatin (SIM) was directly incorporated into the hydroxyapatite/collagen bioink for printing and could be rapidly released during the early stage of bone regeneration. Further, near-infrared (NIR)-light-responsive polydopamine-coated hydroxyapatite nanoparticles were designed to deliver the osteogenic drug, i.e., pargyline (PGL) in a controllable manner. Together, our scaffold displayed an on-demand sequential release of those two drugs and could optimize their therapeutic effects to align with the stem cell recruitment and osteoblastic differentiation, thereby promoting bone regeneration. The results confirmed the suitable mechanical strength, high photothermal conversion efficiency, good biocompatibility of our scaffold. The scaffold loaded with SIM could efficiently accelerate the migration of stem cells. In addition, the scaffold with on-demand sequential release promoted alkaline phosphatase (ALP) activity, significantly upregulated gene expression levels of osteogenesis-related markers, and enhanced new-bone-formation capabilities in rabbit cranial defect models. Altogether, this scaffold not only offers a promising strategy to control the behavior of stem cells during bone regeneration but also provides an efficient strategy for controllable sequential release of different biomolecule in bone tissue engineering.

The pathogenesis of hyperlipidemic acute pancreatitis caused by pancreatic duct hypertension / 临床肝胆病杂志

Compared with acute pancreatitis caused by other factors， hyperlipidemic acute pancreatitis often has a higher rate of severe conditions， greater difficulties in predicting prognosis， and a more complex and unclear pathogenesis. At present， the pathogenesis of hyperlipidemic acute pancreatitis may be associated with the elevation of serum free fatty acids， but the lipid-lowering treatment regimens do not reduce the incidence rate of this disease. Recent studies have further confirmed that pancreatic duct hypertension is an important pathogenesis of acute pancreatitis. The latest research advances have shown that hyperlipidemia can lead to pancreatic duct obstruction by causing pancreatic duct hyperplasia， forming protein embolism at the biliary-pancreatic junction， and damaging the secretory function of the pancreatic duct， while pancreatic duct obstruction can in turn cause pancreatic duct obstruction. This article reviews the latest research advances in hyperlipidemia in causing pancreatic duct obstruction and emphasizes that pancreatic duct hypertension is one of the important pathogeneses of hyperlipidemic acute pancreatitis， which will provide new ideas for exploring the pathogenesis of hyperlipidemic acute pancreatitis.

Clinical effect of levosimendan combined with recombinant human brain natriuretic peptide in the treatment of acute heart failure / 重庆医学

Objective To study the clinical effect of levosimendan combined with recombinant human brain natriuretic peptide(rhBNP)on patients with acute heart failure.Methods A total of 100 patients with acute heart failure in the hospital from December 2019 to December 2021 were selected as the research sub-jects.According to different treatment options,the subjects were divided into the control group,levosimendan group,rhBNP group and combined treatment group,with 25 cases in each group.The control group received traditional conventional diuretic,tube expansion and other treatment;the levosimendan group was treated with levosimendan on the basis of the control group;the rhBNP group was treated with rhBNP on the basis of the control group;the combined treatment group was treated with levosimendan and rhBNP on the basis of the control group.The improvement of New York Heart Association(NYHA)classification,death,rehospitaliza-tion rate,6-minute walking distance,improvement of serological indicators and adverse reactions were recor-ded in each group.Results Before treatment,there was no significant difference in baseline data between the groups(P>0.05).On the 1 st and 3 rd day after treatment,the improvement of NYHA classification in the combined treatment group was better than that in the other groups(P<0.05),and the improvement of NY-HA classification in the levosimendan group and rhBNP group was better than that in the control group(P<0.05).The readmission rate within 6 months after treatment in the combined treatment group was lower than that in the other groups(P<0.05).At 5 and 9 days after treatment,the 6-minute walking distance in the combined treatment group was longer than that in the other groups(P<0.05).At 9 days after treatment,the left ventricular ejection fraction(LVEF)in the combined treatment group was higher than that in the other groups(P<0.05),and the level of N-terminal B-type natriuretic peptide(NT-proBNP)in the combined treatment group was lower than that in the other groups(P<0.05).No significant difference was found in the comparison of the occurrence of adverse reactions among the four groups(P>0.05).Conclusion The combina-tion of levosimendan and rhBNP in the treatment of patients with acute heart failure is superior to traditional treatment and monotherapy in early clinical improvement,and dose not increase the incidence of adverse reactions.

Comparison of the predictive value of venous thromboembolism assessment tools in medical inpatients / 中国实用护理杂志

Objective:A comparison was made between the predictive efficacy of the Padua Score and the simplified Assessment Scheme Recommended by Chinese experts (hereinafter referred to as the Simplified Method) for the risk assessment of venous thromboembolism (VTE) in medical inpatients, aiming to provide a reference for the clinical selection of appropriate risk assessment tools.Methods:A retrospective cohort study was conducted, selecting 42 257 internal medicine inpatients discharged from Peking University Shenzhen Hospital between May 1, 2021, and April 30, 2022, using a convenience sampling method. Data collected included general information upon admission, VTE-related information, occurrences of VTE during hospitalization, and results from the two assessment tools. The predictive efficacy of the tools was evaluated by plotting ROC curves and calculating AUC, sensitivity, specificity, positive predictive value, negative predictive value, and predictive accuracy.Results:Among 42 257 patients, there were 21 065 male and 21 192 female participants, aged (55.04 ± 15.17) years old. The incidence rate of VTE among medical inpatients was 2.24% (948/42 257). The AUC for Padua Score and the Simplified Method in medical patients were 0.735 (95% CI 0.717-0.753) and 0.582 (95% CI 0.561-0.602), respectively. Sensitivities were 49.4% and 18.2%, specificities were 89.6% and 98.1%, positive predictive values were 9.9% and 17.7%, negative predictive values were 98.7% and 98.1%, and predictive accuracy were 88.7% and 96.3%, respectively. The departments with the highest incidence rates of VTE during hospitalization were rehabilitation medicine, emergency, neurology, geriatrics, and respiratory medicine. Within these departments, the AUC values for the Padua Score and the Simplified Method were as follows: 0.864 and 0.612, 0.782 and 0.653, 0.792 and 0.664, 0.850 and 0.551, 0.867 and 0.664, respectively. Conclusions:The Padua Score demonstrated better predictive efficacy compared to the Simplified Method. However, the Simplified Method had more accessible assessment criteria and could serve as an initial VTE risk screening tool in emergency situations or when complete data are not available.

Iron overload regulates atherosclerotic activity of foam cells induced by oxLDL / 实用医学杂志

Objective To explore the roles of iron overload in pro-atherogenic activation of foam cells.Methods RAW264.7 and MOVAS cells were stimulated by oxLDL,ferrimine citrate and deferoxamine respectively.Prussian Blue and Oil Red O staining were used to detect iron deposition and foam cell.CCK-8 test,DHE probe,ELISA,RT-qPCR were performed to detect the cell death rate,reactive oxygen species(ROS)generation,lipid peroxidation molecules[glutathione peroxidase(GSH),glutathione peroxidase 4(GPX4),malondialdehyde(MDA)content]and the mRNA level of ATP binding cassette transporter A1(ABCA1),ATP binding cassette transporter G1(ABCG1),inductible nitris oxide synthase(iNOS),arginase-1(Arg-1),α-smooth muscle actin(α-SMA),smooth muscle 22 alpha(SM22a),osteopontin(OPN),Interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α).Results Iron overload could reduced reverse cholesterol transporters(ABCA1 and ABCG1),promote foam cells generation,increased cell death rate,induced the expression of lipid peroxidation molecules(GSH,GPX4,MDA),and promoted pro-inflammatory M1 marker of macrophage and synthetic marker expression of vascular smooth muscle cell(VSMC)and inflammatory cytokines(IL-1β,TNF-α).Conclusion Iron overload promotes the generation of foam cells derived from macrophages and smooth muscle cells and transform them into pro-atherosclerotic phenotype,aggravates cell lipid peroxidation and inflammatory reaction,which contributes to the progress of atherosclerosis.

Optimized pathways for operations management in public hospitals under the DIP payment system / 现代医院

As the comprehensive reform of public hospitals enters a more challenging phase,the conventional extensive operation management no longer fulfills the requirements of high-quality development.This article investigates the current challen-ges in hospital operation management under the DIP payment system,proposes an optimized pathway as well as an outline for practical implementation.The proposed pathway suggests implementing a closed-loop resource allocation strategy integrating budg-et and performance based on disease groups and scores,establishing a cost management mechanism for enhancing resource effi-ciency,and development of a performance distribution system for stimulating self-management motivation among personnel.Addi-tionally,the article suggests the establishment of a Management Information System,aiming to provide practical references for en-hancing operational management capabilities in public hospitals under the DIP payment mode.

Comparison of efficacy and safety of direct thrombectomy and bridging thrombectomy in the treat-ment of acute anterior circulation large vessel occlusion stroke under different collateral circulation statuses / 新乡医学院学报

Objective To compare the safety and efficacy of direct thrombectomy versus bridging thrombectomy in the treatment of acute anterior circulation large vessel occlusion stroke under different collateral circulation statuses.Methods Totally 93 patients with acute anterior circulation ischemic stroke admitted to the First Affiliated Hospital of Xinxiang Medical University from September 2020 to March 2023 were selected as the research subjects.Patients were divided into direct throm-bectomy group(n=47)and bridging thrombectomy group(n=46)based on the type of thrombectomy.Patients in the direct thrombectomy group received direct intravascular thrombectomy,while patients in the bridging thrombectomy group received intravenous thrombolysis with alteplase combined with mechanical thrombectomy.According computed tomography angiography,the collateral circulation Tan classification was applied to divide the patients into good collateral circulation sub-group and poor collateral circulation sub-group.The modified thrombolysis in cerebral infarction grading(mTICI)was used to evaluate vessel recanalization.Head computed tomography plain scan was performed at 24-48 hours postoperatively to assess if there was hemorrhagic transformation,and modified Rankin Scale score was performed at 90 days postoperatively.Information such as imaging examination time,femoral artery puncture time,vessel recanalization time after thrombectomy,prognosis and spontaneous non-traumatic symptomatic intracerebral hemorrhage(SICH)were collected.Results The age,gender,baseline Alberta stroke program early computed tomography score,baseline national institutes of health stroke scale score,proportions of hypertension,diabetes and atrial fibrillation,baseline systolic pressure,creatinine,baseline blood glucose,platelet count,occlusion site,stroke etiologies and collateral circulation status of patients in the two groups were not statistically significantly different(P＞0.05).There were no significant differences in the post-admission imaging examination time,femoral artery puncture time,vessel recanalization time after thrombectomy,successful vascular reperfusion rate,good prognosis rate,mortality rate,and SICH incidence between the two groups(P＞0.05).The hemorrhagic transformation rate of patients in the direct thrombectomy group was significantly lower than that in the bridging thrombectomy group(P＜0.05).There were no significant differences in the post-admission imaging examination time,femoral artery puncture time,vessel recanalization time after thrombectomy,successful vascular reperfusion rate,good prognosis rate,mortality rate,and SICH incidence between patients with good collateral circulation and patients with poor collateral circulation in the two groups(P＞0.05).The hemorrhagic transformation rate of patients with good and poor collateral circulation in the direct thrombectomy group was significantly lower than that in the bridging thrombectomy group(P＜0.05).Conclusion Under different collateral circulation conditions,the safety and efficacy of direct thrombectomy and bridging thrombectomy in the treatment of acute anterior circulation large vessel occlusion stroke are similar,but bridging thrombectomy is more likely to result in cerebral hemorrhage transformation compared with direct thrombectomy.

Risk factors and prognosis of aspiration pneumonia in the elderly / 中华老年医学杂志

Objective:To analyze the disease characteristics of aspiration pneumonia and its risk factors.Methods:In this retrospective case-control study, analysis was conducted on data from 92 patients aged ≥ 60 years admitted to Beijing Jishuitan Hospital, Capital Medical University between June 1, 2018 and July 31, 2022, with aspiration pneumonia(AsP) as the primary diagnosis at the time of hospital discharge and from non-AsP patients admitted during the same period.The number of participants was matched at a 1∶1 ratio.Results:The average age of the AsP group was(80.88 ± 9.41) years and 57(62.0%) were men.The average age of the control group was(77.74 ± 10.98) years and 52(56.5%) were men.There was no statistically significant difference in age and sex ratio(age: t=1.973, P=0.060; sex ratio: χ2=0.661, P=0.416).Univariate analysis showed that, at admission, body mass index(BMI) and activities of daily living(ADL) scores of the AsP group were lower than those of the non-AsP group, the proportions of patients with gastroesophageal reflux disease, acute trauma, cerebrovascular disease, history of cerebral infarction/hemorrhage and sequelae of cerebrovascular disease were higher than those of the non-AsP group(all P<0.05), and the proportions of patients receiving feeding via indwelling nasogastric intubation and tracheal intubation were also higher in the AsP group(all P<0.05).The white blood cell count, the percentage of neutrophils and the procalcitonin level in the first round of tests were higher in the AsP group than those in the non-AsP group and the maximum values of the above parameters during hospitalization were also higher than those in non-AsP patients, while the levels of albumin and prealbumin were lower than those in the non-AsP group( P<0.05 for all).Chest CT showed that 83.7%(77/92) of patients with AsP had bilateral pneumonia, higher than 55.4%(51/92) in the non-AsP group( χ2=8.569, P=0.014).Multivariate Logistic regression analysis showed that male sex( OR=16.206, 95% CI: 1.268-207.191, P=0.032) was a risk factor for AsP, and BMI( OR=0.747, 95% CI: 0.582-0.959, P=0.022) and ADL score at admission( OR=0.945, 95% CI: 0.903-0.988, P=0.014) were protective factors against AsP.ADL score at admission( OR=0.951, 95% CI: 0.907-0.982, P=0.043), tumor history( OR=6.859, 95% CI: 1.484-31.700, P=0.014), history of cerebral infarction/intracerebral hemorrhage( OR=4.368, 95% CI: 1.087-17.511, P=0.038), history of chronic renal insufficiency( OR=5.820, 95% CI: 1.445-23.440, P=0.013), acute respiratory failure( OR=5.281, 95% CI: 1.237-22.545, P=0.013) and myocardial infarction( OR=9.466, 95% CI: 2.151-41.660, P=0.003) were independent factors affecting the prognosis of pneumonia in the elderly. Conclusions:Aspiration pneumonia in the elderly is more common in men and in individuals with low BMI and low ADL scores.There is no increased risk of mortality in people with AsP, compared with people without AsP, but some risk factors in AsP patients may lead to poor prognosis, calling for increased awareness and early intervention in clinical practice.

Preparation of soluble microneedles of Aconitum brachypodum alkaloids / 中成药

AIM To prepare the soluble microneedles of Aconitum brachypodum Diels alkaloids.METHODS Centrifugal molding method was adopted in the preparation of soluble microneedles.With chondroitin sulfate consumption,PVP K120 consumption and 40%ethanol consumption as influencing factors,piercing rate as an evaluation index,the formulation was optimized by Box-Behnken response surface method,after which the morphology,piercing performance,drug content and in vitro transdermal performance were investigated.RESULTS The optimal formulation was determined to be 123 mg for chondroitin sulfate consumption,298 mg for PVP K120 consumption,and 2.4 mL for 40%ethanol consumption,the piercing rate was 98.3%.The soluble microneedles were yellow and square patch with conoid needle,which could pierce aluminum foil and rat skin,along with the drug content of(0.94±0.025)mg.The soluble microneedle group demonstrated the accumulative permeability rate of 91.4%within 24 h,which was higher than that in the gel ointment group,and the permeability accorded with Higuchi equation.CONCLUSION The soluble microneedles of A.brachypodum alkaloids exhibit good mechanical strength,which can achieve effective transdermal delivery of drugs.

Relationship between early dialysis anemia status and prognosis in maintenance hemodialysis patients / 中华肾脏病杂志

Objective:To analyze the status of anemia at the beginning of dialysis in maintenance hemodialysis (MHD) adult patients, and to explore the relationship between early dialysis anemia and early survival and long-term survival.Methods:It was a retrospective cohort study. The baseline demographic and clinical data of newly admitted MHD patients from January 1, 2013 to December 31, 2020 were retrospectively analyzed. According to the hemoglobin (Hb) level at the beginning of dialysis, the patients were divided into high Hb group (Hb≥110 g/L), middle Hb group (80 g/L≤Hb<110 g/L) and low Hb group (Hb<80 g/L). The baseline data among the three groups were compared, and the changing trend of Hb level in MHD patients during the 8 years was analyzed. The follow-up ended at peritoneal dialysis, kidney transplantation, death or on December 31, 2021. All-cause death event within 6 months after the initiation of dialysis was defined as early death, while all-cause death event more than 6 months after the initiation of dialysis was defined as long-term death. Kaplan-Meier survival curve was used to analyze the survival rate, and log-rank test was used to compare the survival rates among the three groups. Multivariate Cox regression analysis model was used to analyze the association between anemia (Hb<110 g/L) at the beginning of dialysis and both early and long-term mortality.Results:A total of 36 216 MHD patients were included in this study, with age of (61.3±15.5) years old and 22 163 males (61.20%). The Hb at the beginning of dialysis was (89.33±20.89) g/L. The compliance rate of Hb (≥110 g/L) was 16.43% (5 952/36 216). There were 12 232 patients (33.78%), 18 032 patients (49.79%), and 5 952 patients (16.43%) in low Hb group, middle Hb group, and high Hb group, respectively. There were statistically significant differences in gender distribution, age, serum creatinine, blood phosphorus, blood calcium, C-reactive protein, intact parathyroid hormone, blood leukocytes, platelets, serum albumin, triglyceride, total cholesterol, and proportions of chronic glomerulonephritis, diabetic nephropathy, diabetes mellitus, cardiovascular and cerebrovascular diseases, tumors, emporary catheter, long-term catheter and autologous arteriovenous fistula among the three groups (all P<0.05). During the 8-year period, the Hb level had an increased trend steadily each year, and Hb was (88.48±22.07) g/L, (88.52±21.43) g/L, (87.86±21.29) g/L, (88.93±20.69) g/L, (88.87±20.69) g/L, (90.03±20.47) g/L, (90.74±20.31) g/L and (90.31±20.54) g/L year by year. There were 2 176 early deaths (6.01%), and 6 557 long-term deaths (18.10%) by the end of follow-up. Kaplan-Meier survival curve showed that early survival rate of low Hb group was significantly lower than those of high Hb group (log-rank test, χ2=57.115, P<0.001) and middle Hb group (log-rank test, χ2=49.918, P<0.001), and long-term survival rates of low Hb group (log-rank test, χ2=107.097, P<0.001) and middle Hb group (log-rank test, χ2=47.430, P<0.001) were significantly lower than that of high Hb group. Multivariate Cox regression analysis showed that Hb<80 g/L at the beginning of dialysis was an independent influencing factor of early death (Hb ≥110 g/L as a reference, HR=1.307, 95% CI 1.096-1.559), and 80 g/L≤Hb<110 g/L and Hb<80 g/L at the beginning of dialysis were the independent influencing factors of long-term death (Hb≥110 g/L as a reference, HR=1.108, 95% CI 1.021-1.203; HR=1.228, 95% CI 1.127-1.339, respectively) in MHD patients. Conclusions:The compliance rate of Hb at the beginning of dialysis in MHD patients is low. Hb <80 g/L at the beginning of dialysis is an independent risk factor of early death, and Hb <110 g/L at the beginning of dialysis is an independent risk factor of long-term death in MHD patients.

Review of evaluation and influencing factors of oral drug absorption fraction / 药学学报

Fraction absorbed (Fa) is an important parameter to describe the absorption level of oral drugs, and an important basis for the development and optimization of the formulation process. Because it is easily confused with the concept of absolute bioavailability, it has not received enough attention from the industry. There are many complex factors affecting Fa. There are three time-related factors that directly affect the extent of Fa: the release time, the absorption time, and the residence time. The relationship between these three time-related factors determines the extent of Fa. Generally, we are more concerned about the apparent factors that affect the extent of Fa, including independent variables and covariates; The independent variables include administered dose, route, dosage form, etc. The covariates are divided into internal and external factors, and external factors include food factors, drug interactions, etc. Internal causes include age, sex, disease, etc. This paper analyzes and systematically combs how independent variables and covariates directly or indirectly affect the three time-related factors by affecting the body's physiology and internal environment, thus changing the complex process of Fa. Understanding this theoretical framework can better optimize the independent variables to reduce the impact of covariates on Fa. In addition, this paper also introduces the latest progress of prediction and evaluation of Fa, including the progress of complex dissolution device and the status of software prediction.

A network pharmacology-based approach to explore mechanism of kaempferol-7 -O -neohesperidoside against prostate cancer / 中国药理学通报

Aim To explore the effect of kaempferol-7- 0-neohesperidoside (K70N) against prostate cancer (PCa) and the underlying mechanism. Methods The effect of K70N on the proliferation of PCa cell lines PC3, DU145, C4-2 and LNCaP was detected using CCK8 assay. The effect of K70N on migration ability of DU145 cells was determined by wound healing assay. The targets of K70N and PCa were screened from SuperPred and other databases. The common targets both related to K70N and PCa were obtained from the Venny online platform, a protein-protein interaction network (PPI) was constructed by the String and Cyto- scape. Meanwhile, the GO and KEGG functional enrichment were analyzed by David database. Then, a "drug-target-disease-pathway" network model was constructed. Cell cycle of PCa cells treated with K70N was analyzed by flow cytometry. The expressions of cycle-associated proteins including Skp2, p27 and p21 protein were detected by Western blot. Molecular docking between Skp2 and K70N was conducted by Sybyl X2. 0. Results K70N significantly inhibited the proliferation and migration of PCa cells. A total number of 34 drug-disease intersection targets were screened. The String results showed that Skp2 and p27, among the common targets, were the key targets of K70N for PCa treatment. Furthermore, GO and KEGG functional en-richment indicated that the mechanism was mainly related to the cell cycle. Flow cytometry showed that K70N treatment induced cell cycle arrest at the S phase. Compared with the control group, the protein expression level of Skp2 was significantly down-regulated, while the protein expression levels of p27 and p21 were up-regulated. The network molecular docking indicated that the ligand K70N had a good binding ability with the receptor Skp2. Conclusions K70N could inhibit the proliferation and migration of PCa cells, block the cell cycle in the S phase, which may be related to the regulation of cell cycle through the Skp2- p27/p21 signaling pathway.

CD19-Specific CAR-T Cell Treatment of 115 Children and Young Adults with Acute B Lymphoblastic Leukemia: Long-term Follow-up / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Chemotherapy has been the primary treatment for patients with B-cell acute lymphoblastic leukemia (B-ALL). However, there are still patients who are not sensitive to chemotherapy, including those with refractory/relapse (R/R) disease and those experiencing minimal residual disease (MRD) re-emergence. Chimeric antigen receptor-T lymphocytes (CAR-T) therapy may provide a new treatment option for these patients. @*Materials and Methods@#Our institution conducted a single-arm prospective clinical trial (ChiCTR-OPN-17013507) using CAR-T-19 to treat R/R B-ALL and MRD re-emergent patients. One hundred and fifteen patients, aged 1-25 years (median age, 8 years), were enrolled, including 67 R/R and 48 MRD re-emergent CD19-positive B-ALL patients. @*Results@#All patients achieved morphologic complete remission (CR), and within 1 month after infusion, 111 out of 115 (96.5%) patients achieved MRD-negative CR. With a median follow-up time of 48.4 months, the estimated 4-year leukemia-free survival (LFS) rate and overall survival (OS) rate were 68.7%±4.5% and 70.7%±4.3%, respectively. There were no significant differences in long-term efficacy observed among patients with different disease statuses before infusion (4-year OS: MRD re-emergence vs. R/R B-ALL, 70.6%±6.6% vs. 66.5%±6.1%, p=0.755; 4-year LFS: MRD re-emergence vs. R/R B-ALL, 67.3%±7.0% vs. 63.8%±6.2%, p=0.704). R/R B-ALL patients bridging to transplantation after CAR-T treatment had a superior OS and LFS compared to those who did not. However, for MRD re-emergent patients, there was no significant difference in OS and LFS, regardless of whether they underwent hematopoietic stem cell transplantation or not. @*Conclusion@#CD19 CAR-T therapy effectively and safely cures both R/R B-ALL and MRD re-emergent patients.

Implementation of surveillance,prevention and control of healthcare-asso-ciated infection in maternal and child healthcare institutions:A nation-wide investigation report / 中国感染控制杂志

Objective To investigate the implementation of surveillance,prevention and control measures for healthcare-associated infection(HAI)in maternal and child healthcare(MCH)institutions,and provide policy evi-dence for optimizing HAI prevention and control in MCH institutions.Methods Stratified sampling was conducted among the MCH institutions at provincial,municipal and county levels in 8 provinces/autonomous regions.A uni-fied questionnaire was designed and the online survey was conducted through"Questionnaire Star".Results The data from 123 MCH institutions were included in the analysis.90.24％of the MCH institutions carried out compre-hensive surveillance on HAI.The ratios of MCH institutions which implemented targeted surveillance on HAI in neonatal intensive care unit(NICU),surgical site infection,multidrug-resistant organisms(MDROs)and HAI in intensive care units(non-NICU excluded)were 89.66％,85.96％,80.77％,and 74.19％,respectively.51.22％MCH institutions adopted information surveillance system on HAI cases.94.31％MCH institutions carried out surveillance on hand hygiene compliance.Over 90％MCH institutions carried out surveillance on environment hy-giene in high-risk departments.71.54％MCH institutions conducted centralized cleaning,disinfection,sterilization and supply for reusable medical instruments in the central sterile supply department(CSSD).Over 90％MCH insti-tutions established three-level pre-examination triage systems.86.18％set up transitional wards.MCH institutions generally adopted a management model with established effective communication,full appointment visits,and sepa-rate visits for special medical groups,such as registered pregnant women,high-risk newborns,healthcare groups,and long-term rehabilitation patients.However,the ratio of institutions conducting on-line follow-up visits was less than 50％.Conclusion MCH institutions have generally carried out comprehensive and targeted surveillance on HAI.Information surveillance need to be facilitated.Hand hygiene and environmental hygiene surveillance has been popularized to a certain extent at all levels of MCH institutions.The cleaning,disinfection,sterilization,and supply processes of reusable medical devices in a few MCH institutions are not standardized.Special medical populations get effective management.On-line healthcare is to be further promoted.

Innovation and exploration of medical laboratory animal science teaching on the basis of a smart teaching environment / 中国比较医学杂志

Objective In the traditional laboratory zoology lecture environment,there is less teacher-student interaction,less student interest,and less engagement in learning.To improve the teaching quality of laboratory animal science,this teaching and research department was based on different teaching environments of multimedia and intelligent classrooms,theoretical course teaching of Medical Laboratory Animal Science as the research object,the course lecture format,teaching mode,teaching method,and other aspects of innovation and exploration.Methods This study used questionnaires to understand changes in student engagement in learning and preferences for smart classroom use,and NVivo qualitative analysis software was used to code student classroom behavior.Results The smart teaching environment resulted in higher student interest and more frequent teacher-student interaction in the classroom.Students were significantly more engaged in learning than in traditional teaching with higher correct rates on in-class and post-lesson exercises and a better grasp of concepts related to laboratory animal science.Conclusions A smart teaching environment brings students a better feeling and experience,improves their interest in laboratory animal science,increases classroom learning engagement,and achieves good teaching result.

Relationship between gratitude and academic burnout in college students / 中国心理卫生杂志

Objective:To explore the relationship between gratitude and academic burnout incollege students,as well as the role of psychological well-being and proactive coping in their relationship.Methods:A total of 1 038 college students from 4 universities were selected andassessedwith the Gratitude Scale(GQ-6),Flourishing Scale(FS),Proactive Coping Scale(PCS)and Maslach Burnout Inventory-General Survey(MBI-GS).SPSS macro pro-gram Process and Bootstrap method were used to test the mediating effect.Results:The MBI-GS scores were higher in boys than in girls(P＜0.01),and higher in those with left behind experience thanin those without left behind ex-perience(P＜0.001).The GQ-6 scores were negatively associated with the MBI-GS scores(β=-0.19,P＜0.001).PCS scores played an independent mediating role between GQ-6 scores and MBI-GS scores(Indirect effect=0.05,95％CI=0.02-0.09),while the scores of psychological well-being and proactive coping had a chain mediating effect between gratitude scores and academic burnout scores(Indirect effect=0.06,95％CI=0.03～0.01).Conclusion:It suggests that gratitude is related to academic burnout in college students,and proactive cop-ing plays an independent mediating role,while psychological well-being and proactive coping play a chain media-ting role.

Screening of hub genes and pathways of idiopathic non-cirrhotic portal hypertension and prediction of traditional Chinese medicine / 中国现代医生

Objective To with analyzing the gene expression profile of idiopathic non-cirrhotic portal hypertension(INCPH)by bioinformatics methods,we may obtain its key genes and signaling pathways to explore the molecular mechanism of INCPH and predict the potential traditional Chinese medicine.Methods The gene microarray dataset GSE77627 on INCPH was downloaded from gene expression omnibus(GEO)database,the data were normalized and screened for differential genes(DEGs)of INCPH using R language,and all DEGs were analyzed for gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment using Metascape database,and protein-protein interaction network was constructed by STRING database;meanwhile DEGs with the top 15 Degree values were screened as key genes using CytoHubba plugin.Subsequently,the key genes were mapped to each other with the medical ontology information retrieval platform(coremine medical)to screen potential Chinese herbal medicines for the treatment of INCPH with P<0.05,and the potent components that potential Chinese medicines have were screened from the TCMSP database,imported into Cytoscape software to construct a Chinese medicine correlation network map and predict the key targets.Results A total of 1880 DEGs were screened,including 1061 up-regulated and 819 down-regulated genes.DEGs were analyzed using the protein interaction database STRING and cytoHubba in Cytoscape software to obtain key genes,which were RPS27A,CDC42,EIF4E,MAPK1,PIK3R1,RPS6,RPS9,RPS8,RPL15,RPL27A,RPL24,RPL27,RPL26,RPL12 and MAPK14.The GO and KEGG analysis mainly involved gamete production and AGE-RAGE signaling pathway in INCPH.Conclusion The potential traditional Chinese medicines screened for INCPH are Ginseng Radix et Rhizoma,Salviae Miltiorrhizae Radix et Rhizoma,Scutellariae Radix,etc,which may be a potential source of molecular drugs for the treatment of INCPH.