ObjectiveTo study on the different therapeutic effects and potential mechanisms of Rhei Radix et Rhizoma（RH） before and after steaming with wine on constipation model mice. MethodsFifty-four male ICR mice were randomly divided into control group， model group， lactulose group（1.5 mg·kg^-1）， high， medium and low dose groups of RH and RH steaming with wine（PRH）（8， 4， 1 g·kg^-1）. Except for the control group， the constipation model was replicated by gavage of loperamide hydrochloride（6 mg·kg^-1） in the other groups. After 2 weeks of modeling， each administration group was gavaged with the corresponding dose of drug solution， and the control and model groups were given an equal volume of normal saline， 1 time/d for 2 consecutive weeks. After administration， the feces were collected for 16S rRNA sequencing， the levels of gastrin（GAS）， motilin（MTL）， interleukin-6（IL-6）， γ-interferon（IFN-γ） in the colonic tissue were detected by enzyme-linked immunosorbent assay（ELISA）， the histopathological changes of colon were observed by hematoxylin-eosin（HE） staining， flow cytometry was used to detect the proportion changes of CD4⁺， CD8⁺ and regulatory T cell（Treg） in peripheral blood. ResultsCompared with the control group， the model group showed significantly decrease in fecal number in 24 h， fecal quality and fecal water rate（P<0.01）， the colon was seen to have necrotic shedding of mucosal epithelium， localized intestinal glands in the lamina propria were degenerated， necrotic and atrophied， a few lymphocytes were seen to infiltrate in the necrotic area in a scattered manner， the contents of GAS and MTL， the proportions of CD4⁺， CD8⁺ and Treg were significantly reduced（P<0.01）， the contents of IL-6 and IFN-γ were significantly elevated（P<0.05， P<0.01）. Compared with the model group， the fecal number in 24 h， fecal quality and fecal water rate of high-dose groups of RH and PRH were significantly increased（P<0.05， P<0.01）， the pathological damage of the colon was alleviated to varying degrees， the contents of GAS， MTL， IL-6 and IFN-γ were significantly regressed（P<0.05， P<0.01）， and the proportions of CD4⁺ and CD8⁺ were significantly increased（P<0.01）， although the proportion of Treg showed an upward trend， there was no significant difference. In addition， the results of intestinal flora showed that the number of amplicon sequence variant（ASV） and Alpha diversity were decreased in the model group compared with the control group， and there was a significant difference in Beta diversity， with a decrease in the relative abundance of Lactobacillus and an increase in the relative abundances of Bacillus and Helicobacter. Compared with the model group， the ASV number and Alpha diversity were increased in the high-dose groups of RH and PRH， and there was a trend of regression of Beta diversity to the control group， the relative abundance of Lactobacillus increased， and the relative abundances of Bacillus and Helicobacter decreased. ConclusionRH and PRH can improve dysbacteriosis， promote immune system activation， inhibit the release of inflammatory factors for enhancing the gastrointestinal function， which may be one of the potential mechanisms of their therapeutic effect on constipation.

OBJECTIVE To standardize the management of patients’ self-carried medicines dispensed by Pharmacy Intravenous Admixture Services （PIVAS） of our hospital， improve the quality of medical care， and ensure the safety of patients’ medication. METHODS Based on evidence-based methodology， the research literature of domestic medical institutions on the management of patients’ self-carried medicines was systematically searched and analyzed， and the data on the use of patients’ self- carried medicines in our hospital from February to April 2023 were extracted based on our hospital’s information system. A fishbone diagram of the difficulties in constructing patients’ self-carried medicines within PIVAS of our hospital was drawn through brainstorming， thereby establishing a refined whole-process management system for patients’ self-carried medicines in PIVAS. The effectiveness of the system was evaluated through the indicators， including dispensing volume， error rate， and so on. RESULTS & CONCLUSIONS A total of 15 papers were included， covering descriptive studies on the reasons for the use of patients’ self- carried medicines， current status of their use， management system， management methods， management suggestions. There were 12 clinical departments in our hospital with a high proportion of patients using self-carried medicines， among which the pediatric neurology department had the most use of patients’ self-carried medicines， accounting for 10.65%. In terms of dosage form， injectable drugs accounted for 13.68%， all of anticancer drug were uniformly dispensed by our hospital’s PIVAS. PIVAS in our hospital had successfully constructed the management system for dispensing patients’ self-carried medicines， which included the processes of drug reception and preservation， medical document retention， doctor’s order review， drug placement， dispensing， review and transportation. After the implementation of the system， from May 2023 to October 2024， our hospital’s PIVAS dispensed 654 bags of patients’ self-carried medicines in total，with a monthly average of 36 bags. Zero error management 5）；was realized for all patients’ self-carried medicines. The system operates stably and effectively， thereby ensuring the high-quality dispensing of patients’ self-carried medicines in PIVAS of our hospital.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Objective To explore the relationship between serum Krüppel-like factor 5(KLF5)and actinin-4 with prognosis of hepatocellular carcinoma(HCC)treated with transcatheter arterial chemoembolization(TACE).Methods From March 2015 to March 2020,130 HCC patients admitted into the Second Affiliated Hospital were collected as study subjects and divided into HCC group and 86 patients with liver cirrhosis were collected as control group.After 3 years of postoperative follow-up,HCC patients were sub-divided into survival group(n=38)and mortality group(n=92)based on their survival outcomes.ELISA was applied to detect the level of serum KLF5 and actinin-4 in each group and analyzed the correlation between serum KLF5 and actinin-4 levels.Cox regression was applied to analyze the risk factors affecting the prognostic mortality of HCC patients;Receiver operating char-acteristic curve(ROC)was plotted to evaluate the predictive value of serum KLF5 and actinin-4 levels for the prognostic mortality of HCC patients.Results The serum level of KLF5 and actinin-4 in the mortality group was significantly higher than those in the survival group(P＜0.05);There was a positive correlation between serum level of KLF5 and actinin-4 in HCC patients(P＜0.001);Low differentiation,staging(CNLC)stage IIIa of China liver cancer staging(CNLC),vascular invasion and elevated level of KLF5 and actinin-4 were risk factors for prognostic mortality in HCC patients(P＜0.05);The area under the curve(AUC)of serum KLF5 and acti-nin-4 alone and in combination for predicting mortality in HCC patients was 0.835,0.866,and 0.936,respec-tively,showing a high level of combined predicting function(Zcombination-KLF5=2.792,P=0.005,Zcombi-nation-actinin-4=2.014,P=0.044).Conclusions Serum level of KLF5 and actinin-4 l found in HCC patients has a high predictive value for prognosis.

BACKGROUND: Current replacement procedures for stenosis or occluded arteries using prosthetic grafts have serious limitations in clinical applications, particularly, endothelialization of the luminal surface is a long-standing unresolved problem.METHOD: We produced a cell-based hybrid vascular graft using a bioink engulfing adipose-derived mesenchymal stromal cells (ADSCs) and a 3D bioprinting process lining the ADSCs on the luminal surface of GORE-Tex grafts. The hybrid graft was implanted as an interposition conduit to replace a 3-cm-long segment of the infrarenal abdominal aorta in Rhesus monkeys. RESULTS: Complete endothelium layer and smooth muscle layer were fully developed within 21 days post-implantation, along with normalized collagen deposition and crosslinking in the regenerated vasculature in all monkeys. The regenerated blood vessels showed normal functionality for the longest observation of more than 1650 days. The same procedure was also conducted in miniature pigs for the interposition replacement of a 10-cm-long right iliac artery and showed the same long-term effective and safe outcome. CONCLUSION This cell-based vascular graft is ready to undergo clinical trials for human patients.

Cholestatic liver disease is a common disease that causes bile flow dysfunction due to various reasons. The etiology of cholestatic liver disease is complexed, and therapeutic drugs are extremely limited. To date, ursodeoxycholic acid is the only FDA-approved drug for treating primary biliary cirrhosis, whereas its efficacy is limited to early stage of the disease, therefore novel drugs are urgently needed. Nuclear receptors become therapeutic hotspot target in cholestasis since these receptors play a key role in regulating bile acid homeostasis. Peroxisome proliferator-activated receptor (PPAR) is an important nuclear receptor involved in regulating multiple mechanisms of cholestasis in vivo. It can improve intrahepatic cholestasis by inhibiting bile acid synthesis, reducing bile acid toxicity, affecting the expression of bile acid metabolic enzymes and transporters, and can play an anti-inflammatory, anti-oxidation and anti-fibrosis role. A number of studies have shown that PPAR agonists represented by fibrates alone or in combination can improve liver function indexes, inflammatory factors and fibrosis markers in patients with cholestasis. This review analyzes and summarizes the lastest advances in the molecular mechanism of PPAR as a therapeutic target for cholestasis and drug treatment in development or have been used in clinical.

Objective:To explore the effect of augmented renal clearance(ARC)on 24-hour area under the concentration-time curve to minimum inhibitory concentration ratio(AUC 24/MIC)of vancomycin and prognosis in critical children, thus to provide proposal for individual dosage regimen. Methods:Sixty-five critical children treated with vancomycin, who suffered from sepsis/septic shock, were brought into this retrospective cohort study.According to estimate glomerular filtration rate, these children were divided into ARC group ( n=27) and normal group ( n=38). The influencing factor of AUC 24/MIC of vancomycin and therapy prognosis for two groups were detected and analyzed. Results:There were no significant differences between two groups in basic setting (age, sex, weight), scores of pediatric sequential organ failure assessment and pediatric risk of mortality Ⅲ, infection markers (C-reactive protein and procalcitonin), glutamic-pyruvic transaminase, hypoproteinemia, usage of diuretic and vasoactive agent( P>0.05). The patients from ARC group showed lower levels than those from normal group in AUC 24/MIC of vancomycin[375.2(300.8, 489.4) vs. 443.6(412.3, 593.2), Z=2.263, P=0.024] and it′s target achievement ratio (TAR)(40.7% vs. 76.3%, χ2=8.440, P=0.005). When usage of diuretic and vasoactive agent, the AUC 24/MIC of ARC group was lower than that of normal group( P<0.05). But there was no significant difference between ARC group and normal group regarding hypoproteinemia( P>0.05). The days of body temperature steady at least 48 hours[7.0(5.5, 9.0)d vs. 6.0(5.0, 8.0)d], the length of hospital stay[39.0(21.0, 58.0)d vs. 20.5(16.0, 28.0)d], the length of PICU stay[14.0(9.0, 31.5)d vs. 10.0(5.0, 15.0)d] were longer than those in normal group( P<0.05). There were no significant differences between ARC group and normal group regarding days of ventilation and infectious markers decreased at least 50%, as well as 28-days mortality( P>0.05). The multivariable analysis showed that the presence of ARC, hypoproteinemia, use of diuretics and vasoactive agent were significantly associated with AUC 24/MIC of vancomycin( P<0.05). Conclusion:ARC may down regulate levels of AUC 24/MIC and TAR of vancomycin.During ARC period, the usage of diuretic and vasoactive agent could affect the AUC 24/MIC of vancomycin.Individual dosage regimen should be employed for critical children suffered with ARC.

Background: Long coronavirus disease 2019 (COVID-19) in recovered patients (RPs) is gradually recognized by more people. However, how long it will last and the underlining mechanism remains unclear. Methods: We conducted a prospective follow-up study to evaluate the long-term symptoms and clinical indices of RPs at one-year after discharge from Union Hospital, Wuhan, China between December 2020 to May 2021. We also performed the 16S rRNA sequencing of stool samples from RPs and healthy controls (HCs) and analyzed the correlation between the gut microbiota and long COVID-19. Results: In total, 187 RPs were enrolled, among them, 84 (44.9%) RPs reported long COVID-19 symptoms at one-year after discharge. The most common long-term symptoms were cardiopulmonary symptoms, including chest tightness after activity (39/187, 20.9%), palpitations on exercise (27/187, 14.4%), sputum (21/187, 11.2%), cough (15/187, 8.0%) and chest pain (13/187, 7.0%), followed by systemic symptoms including fatigue (34/187, 18.2%) and myalgia (20/187, 10.7%), and digestive symptoms including constipation (14/187, 7.5%), anorexia (13/187, 7.0%), and diarrhea (8/187, 4.3%). Sixty-six (35.9%) RPs presented either anxiety or depression (42/187 [22.8%] and 53/187 [28.8%] respectively), and the proportion of anxiety or depression in the long symptomatic group was significantly higher than that in the asymptomatic group (41/187 [50.6%] vs. 25/187 [24.3%]). Compared with the asymptomatic group, scores of all nine 36-Item Short Form General Health Survey domains were lower in the symptomatic group (all P < 0.05). One hundred thirty RPs and 32 HCs (non-severe acute respiratory syndrome coronavirus 2 infected subjects) performed fecal sample sequencing.Compared with HCs, symptomatic RPs had obvious gut microbiota dysbiosis including significantly reduced bacterial diversities and lower relative abundance of short-chain fatty acids (SCFAs)-producing salutary symbionts such as Eubacterium_hallii_group, Subdoligranulum, Ruminococcus, Dorea, Coprococcus, and Eubacterium_ventriosum_group. Meanwhile, the relative abundance of Eubacterium_hallii_group, Subdoligranulum, and Ruminococcus showed decreasing tendencies between HCs, the asymptomatic group, and the symptomatic group. Conclusion This study demonstrated the presence of long COVID-19 which correlates with gut microbiota dysbiosis in RPs at one-year after discharge, indicating gut microbiota may play an important role in long COVID-19.

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.