Inflammatory bowel disease (IBD) is characterized by chronic relapsing intestinal inflammation and encompasses ulcerative colitis (UC) and Crohn's disease (CD). IBD has emerged as a global healthcare problem. Clinically efficacious therapeutic agents are deficient. This study concentrates on models of ulcerative colitis with the objective of discovering novel therapeutic strategies. Previous investigations have established that schisandrin A demonstrates anti-inflammatory effects in vitro, concurrently enhancing the transcriptional activity of farnesoid X receptor (FXR). FXR inversely modulates the transcriptional activity of NF-κB, which has an important role in regulating inflammatory responses. Consequently, the current study was to explore the safeguarding influence of schisandrin A on ulcerative colitis and delineate the mechanism by which it regulates this effect through the FXR signaling pathway. The effect of schisandrin A on the mRNA levels of inflammatory factors was evaluated in RAW264.7 cells. The dual luciferase reporter gene assay was used to verify the relationship between schisandrin A and FXR targeting. The animal experiments were performed in accordance with the regulations of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval No. PZSHUTCM2304250005). Acute ulcerative colitis was induced in wild-type or FXR knockout C57BL/6 mice by drinking 3% dextran sodium sulfate (DSS) for 7 days, and schisandrin A was administered via gavage for a continuous treatment period of 7 days. The body weight and faecal were monitored daily. The mRNA levels of inflammatory factors in colon tissue and FXR target genes were measured by RT-qPCR. The findings revealed that schisandrin A, in vitro, impeded the lipopolysaccharide (LPS)-induced elevation in mRNA levels of inflammatory factors and schisandrin A could augment transcriptional activity of FXR. In wild-type mice, schisandrin A significantly improved weight loss, colon shortening, loose stools and blood in stools in mice with acute ulcerative colitis, and schisandrin A significantly reduced the expression of pro-inflammatory factors genes and significantly increased the expression of FXR target genes in colon tissues. In FXR knockout mice, the administration of schisandrin A failed to yield ameliorative effect on acute ulcerative colitis in mice. In conclusion, schisandrin A can reduce intestinal inflammation through the FXR signaling pathway to alleviate acute ulcerative colitis in mice. Implications arise that Schisandra lignans could serve as lead compounds for drug development aimed at inflammatory bowel disease.

Sepsis-induced coagulopathy(SIC),a critical and potentially lethal condition arising from sepsis,results in endothelial damage and significant coagulation dysregulation,making it a major factor contributing to mortality among sepsis patients.Early diagnosis and treatment of SIC are expected to improve the prognosis of sepsis patients.In 2019,the International Society on Thrombosis and Hemostasis(ISTH)issued the first guidelines for the diagnosis and treatment of SIC,but there are no corresponding protocols in China.Therefore,Chinese Society of Thrombosis,Hemostasis and Critical Care,Chinese Medicine Education Association,and Chinese People's Liberation Army Professional Committee of Critical Care Medicine jointly formulated the"Chinese Expert Consensus on the Diagnosis and Treatment of Sepsis-induced Coagulopathy(2024 edition)."This consensus includes 5 parts:pathogenesis,classification,laboratory approaches,diagnosis and treatment,with a total of 14 evidence-based recommendations to guide clinical practice.

Objective To investigate the role of magnesium ion(Mg2+)in cisplatin-induced acute kidney injury(Cis-AKI)in kidney organoids and HK-2 cells,as well as the potential mechanism.Methods Initially,we utilized human-derived induced pluripotent stem cells(iPSCs)to construct kidney organoids,and then built a Cis-AKI model based on kidney organoids.HE staining was used to observe the structure of kidney organoids,and immunofluorescence staining was used to observe the localization of markers and the expression of cleaved caspase-3.qRT-PCR was conducted to detect mRNA levels of tubular and glomerular markers,as well as inflammatory factors.Subsequently,the kidney organoids were randomly divided into control group,cisplatin group(Cis group),and Mg2+pretreatment group(Cis+Mg2+group).CCK-8 and ATP content assays were employed to evaluate the cell viability of renal tubular epithelial cells.TUNEL staining was performed to detect the apoptosis of renal tubular epithelial cells.Western blot was utilized to detect the expression of apoptosis-associated proteins(Bcl-2,Bax,cleaved caspase-3)and organic cation transporter 2(OCT2).Immunofluorescence was used to detect the localization and expression of OCT2.Results On the 10th day,the tubular structure in kidney organoids was visible,with abundant expression of renal markers.Treatment with 10 μmol/L cisplatin resulted in structural damage to kidney organoids,significantly increased expression of cleaved caspase-3 and mRNA levels of inflammatory factors,and significantly decreased ATP content.Compared with the Cis group,the Cis+Mg2+group showed increased ATP content in kidney organoids,reduced number of TUNEL-positive cells,significantly decreased expression of apoptosis-associated proteins,and significantly decreased expression of OCT2.However,there was no significant improvement in HK-2 cell viability,the number of TUNEL-positive cells,or apoptosis-associated proteins in the Cis+Mg2+group,and HK-2 cells did not express OCT2.Conclusion Kidney organoid is an ideal in vitro model to study the pathogenesis and treatment of Cis-AKI.Mg2+pretreatment can significantly reduce the damage of kidney organoids induced by cisplatin,and the mechanism may be related to the downregulation of OCT2.

Perihilar cholangiocarcinoma(PHC)is a common malignancy of biliary tract,for which surgery is the most effective treatment.However,its prognosis is not satisfactory even after surgical resection.In recent years,there have been some new advances in the surgical treatment of PHC.In this paper,we reviewed the existing literatures,demonstrated the current situation of preoperative biliary drainage,liver hyperplasia,hepatic resection,liver transplantation and minimally invasive surgery in the treatment of PHC,and prospected the future research direction.

Post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP)is one of the most common complications after endoscopic retrograde cholangiopancreatography(ERCP).Numerous PEP prediction models have been established based on different statistical methods at home and abroad.The PEP prediction model,as a tool for evaluating and screening high-risk populations,can provide a basis for medical staff to find high-risk PEP patients early and take effective preventive measures.In recent years,new PEP prediction models have appeared one after another,but there is still a lack of recognized reliable prediction models in clinic.This article reviews the research status of PEP risk prediction models,aim to provide a direction for establishing a more reliable,accurate,and practical PEP risk prediction model in the later period.

Aim To investigate the role and mecha-nism of CXC chemokine receptor 3(CXCR3)in hepa-toblastoma(HB).Methods The expression of CX-CR3 was detected by immunohistochemical and West-ern blot in 16 cases of HB tissue and adjacent normal liver tissue.The HB cells(Huh-6 and HepT1)were transfected with Con-shRNA,CXCR3-shRNA1,and CXCR3-shRNA2,respectively,and then divided into the Con-shRNA group,CXCR3-shRNA1 group,and CXCR3-shRNA2 group.Cell proliferation was detected by CCK-8 assay and EdU staining.Cell migration and invasion were detected by scratch and Transwell as-says.The expressions of β-catenin,c-Myc,cyclin D1,MMP-7 and MMP-9 were detected by Western blot.The tumor formation and tumor volume in each group were assessed using nude mouse xenograft tumor model,while the expressions of MMP-9 and Ki67 in tumor tissue were examined by immunohistochemistry.Results The expression of CXCR3 was up-regulated in HB tissue(P＜0.01).Compared to the Con-shR-NA group,the viability,proliferation,migration and invasion of Huh-6 and HepT1 cells in the CXCR3-shR-NA1 and CXCR3-shRNA2 groups were reduced(P＜0.01),the expressions of the Wnt/β-catenin signaling pathway related proteins were attenuated(P＜0.01),the tumor grew slowly and the volume was significantly reduced(P＜0.01),and the expressions of MMP-9 and Ki67 in tumor tissue decreased(P＜0.01).Con-clusions Downregulation of CXCR3 hinders the pro-liferation and migration of HB cells,potentially as-cribed to the attenuation of Wnt/β-catenin signaling regulation.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Objective To investigate the impact of lncRNA DSCAM-AS1 on the malignant biological behaviors of thyroid cancer(TC)cells by regulating the miR-150-5p/BRAF axis.Methods The expression of DSCAM-AS1 in TC cells was detected by qRT-PCR,and the best intervention cell line was screened.;the relationship between DSCAM-AS1,BRAF and miR-150-5p targeting regulation was verified by FISH,pull down and double Luciferase reporter gene experiment;The proliferation,migration and invasion of SW579 cells were detected;Western blot was applied to detect the expression of BRAF,E-Cadherin,and vimentin proteins;the tumor formation experiment in mice was applied to verify the effect of DSCAM-AS1 on TC tumor growth.Results DSCAM-AS1 was highly expressed in TC tissue and cells(P<0.05);There is a targeted regulation relationship between DSCAM-AS1,BRAF and miR-150-5p;inhibition of DSCAM-AS1 expression or overexpression of miR-150-5p obviously inhibited the proliferation,migration,invasion,and EMT of SW579 cells(P<0.05);Inhibition of miR-150-5p expression or overexpression of BRAF reversed the inhibitory effect of inhibition of DSCAM-AS1 expression or overexpression of miR-150-5p on the malignant behavior of SW579 cells(P<0.05);in vivo experiments showed that inhibiting the expression of DSCAM-AS1 obviously inhibited the growth of transplanted tumors in mice(P<0.05).Conclusion DSCAM-AS1 is up-regulated in TC cells,inhibiting the expression of LncRNA DSCAM-AS1 can inhibit the malignant progression of TC by regulating the miR-150-5p/BRAF signaling axis.

AIM To prepare bergenin nanostructured lipid carriers,and to investigate their in vivo pharmacokinetics.METHODS The nanostructured lipid carriers were prepared by melting method.With solid lipid type,liquid lipid type,solid-liquid lipid ratio,lipid-drug ratio and poloxamer 188 concentration as influecing factors,encapsulation efficiency,drug loading and particle size as evaluation indices,the formulation was optimized by single factor test,after which the in vitro drug release was investigated,the stability was determined,and crystalline form analysis was performed.Eighteen rats were randomly assigned into three groups and given intragastric administration of the 0.5%CMC-Na suspensions of bergenin,physical mixture and bergenin solid dispersions(60 mg/kg),respectively,after which blood collection was made at 0.25,0.5,1,2,3,4,5,6,8,10,12 h,HPLC was adopted in the plasma concentration determination of bergenin,and main pharmacokinetic parameters were calculated.RESULTS The optimal formulation was determined to be glyceryl behenate as solid lipid,oleic acid as liquid lipid,4 ∶ 1 for solid-liquid lipid ratio,10 ∶ 1 as lipid-drug ratio 2.0%for poloxamer 188 concentration,the average concentration,drug loading,particle size and Zeta potential were(84.16±1.57)%,(7.73±0.27)%and(215.53±18.04)nm and-(37.56±2.03)mV,respectively.The nanostructured lipid carriers demonstrated the accumulative release rate of less than 50%within 240 min in simulated gastric fluid,which was 71.04%within 36 h in simulated intestinal fluid,along with good stability within 12 h in the latter.Bergenin existed in the nanostructured lipid carriers in an amorphous state.Compared with raw medicine and physical mixture,the nanostructured lipid carriers displayed prolonged tmax and t1/2(P<0.01),and increased Cmax,AUC0-t,AUC0-∞(P<0.01),whose relative bioavailability was enhanced to 6.08 times as compared with that of raw medicine.CONCLUSION Nanostructured lipid carriers can improve the stability and oral bioavailability of bergenin.

To explore the quality consistency evaluation method for multi-component traditional Chinese medicine and establish a dissolution evaluation method suitable for the characteristics of multi-component Chinese patent medicine, this study discussed the characteristics and advantages of the flow-through cell method in the dissolution evaluation of Chinese patent medicine by comparing the impact of the small cup method and the flow-through cell method on the dissolution behavior of water-soluble and lipid-soluble major active components of Danshen Tablets. Dissolution tests were performed using the small cup method as described in the 2020 edition of the Chinese Pharmacopoeia and the newly introduced flow-through cell method(closed-loop method) with water solution containing 0.5% SDS as dissolution medium. Cumulative dissolution curves of the water-soluble component salvianolic acid B and the lipid-soluble component tanshinone Ⅱ_A in Danshen Tablets were plotted, and fitting and similarity analysis of the dissolution models was conducted to identify the characteristics and advantages of the flow-through cell method. For the small cup method, 150 mL of water containing 0.5% SDS was used as the dissolution medium, with a rotation speed of 75 r·min~(-1) and a temperature of(37±0.5) ℃, and 3 mL of samples were taken at 15, 30 min, 1, 2, and 4 h, with fresh dissolution medium added at the same temperature and volume. For the flow-through cell method, a closed-loop system was used. Danshen Tablets were placed in the flow-through cell with approximately 6.7 g of glass beads, and 150 mL of water containing 0.5% SDS was used as the dissolution medium. The flow rate was set at 20 mL·min~(-1), and the temperature and sampling were the same as the small cup method. The results showed that compared with the small cup method, the flow-through cell method had stronger discriminative power and higher sensitivity in distinguishing the dissolution behavior of the two components, and could better reflect the differences in formulation quality, especially for water-insoluble lipid-soluble components. Given that there were no essential differences in the in vitro release kinetics between the two methods, the flow-through cell method could not only replace the traditional small cup method but also better guide the formulation development and identify quality issues of formulations.
Salvia miltiorrhiza ; Medicine, Chinese Traditional ; Tablets ; Water ; Lipids ; Solubility