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.

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.

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.

Objective:To evaluate the efficacy and safety of traditional Chinese medicine(TCM)in the treatment of male im-mune infertility(MII)by meta-analysis.Methods:We retrieved randomized controlled trial(RCT)on the treatment of male im-mune infertility with traditional Chinese medicine from the databases of WanFang,Chinese Biomedical Literature,Cochrane Library,Weipu,PubMed and CNKI,and performed methodological quality assessment of the RCTs identified and statistical analysis and evalua-tion of the publication bias using the RevMan5.4 software.Results:Totally,25 RCTs(2 563 cases)were included in this study.Compared with Western medicine alone in the treatment of MII,TCM achieved a significantly higher total effectiveness rate(OR=6.35,95% CI:4.96-8.13,P<0.000 01),negative conversion rate of seminal plasma anti-sperm antibodies(OR=4.52,95% CI:2.72-7.51,P<0.000 01),negative rate of serum anti-sperm antibodies(OR=2.98,95% CI:2.23-3.96,P<0.000 01),sperm concentration(MD=15.56,95% CI:11.32-19.79,P<0.000 01),grade a sperm motility(MD=3.85,95% CI:1.91-5.79,P=0.000 01),grade a+b sperm motility(MD=13.77,95% CI:7.06-20.48,P<0.000 1),sperm viability(MD=10.32,95% CI:6.78-13.86,P<0.000 01)and pregnancy rate(OR=3.53,95% CI:2.68-4.63,P<0.000 01),but a lower rate of adverse reactions(OR=0.06,95% CI:0.01-0.23,P<0.000 01).There was no statistically significant difference in the percentage of morphologically abnormal sperm between TCM and Western medicine alone in the treatment of MII(MD=-7.53,95% CI:-15.50-0.44,P=0.06).Conclusion:TCM has a definite effectiveness and high safe in the treatment of male immune infertility.

The steroid constituents in the 75% ethanol extract of Cyanotis arachnoidea and their anti-HSV-1 activities in vitro were investigated in this study. The ethyl acetate fraction of the extract was isolated and purified using silica gel, ODS, Sephadex LH-20 column chromatography, and semi-preparative HPLC. Structural identification was conducted based on spectroscopic data. Ten steroid compounds were isolated and identified, namely makisterone A 3-acetate(1), makisterone A 2-acetate(2), makisterone A(3), ajugasterone C 2-acetate(4), ajugasterone C(5), 20-hydroxyecdysone 2-acetate(6), 20-hydroxyecdysone 3-acetate(7), podecdysone C(8), rubrosterone(9), and poststerone(10). Compounds 1 and 2 are new steroid compounds. The anti-HSV-1 activities of compounds 1-10 were evaluated using the CPE inhibition method. Vero cells were used in the experiment, with acyclovir as the positive control. The results showed that compounds 9 and 10 showed anti-HSV-1 activity, with EC_(50) values of 83.11 and 103.62 μg·mL~(-1), respectively.
Herpesvirus 1, Human/drug effects* ; Antiviral Agents/isolation & purification* ; Animals ; Chlorocebus aethiops ; Steroids/isolation & purification* ; Vero Cells ; Drugs, Chinese Herbal/isolation & purification* ; Molecular Structure

Objective:This study aims to evaluate the incidence of postoperative malnutrition in colorectal cancer patients who underwent curative colorectal cancer surgery using the Golbal Leadership Initiative on Malnutrition(GLIM)criteria,and to explore the impact of malnutrition defined by the GLIM criteria on short-term clinical outcomes in patients with colorectal cancer.Method:We included a prospective cohort of 171 patients who underwent curative colorectal cancer surgery in Chongqing JiuLongpo People's Hospital from September 2022 to May 2023.Nutritional Risk Screening 2002(NRS 2002)was used for nutritional risk screening and GLIM criteria was used for the diagnosis of malnutrition.To compare the short-term postoperative clinical outcomes between the well-nourished group and the malnourished group under the GLIM criteria.Logistic regression analysis was conducted to analyze the risk factors of postoperative complications.Result:Among the included cases,nutritional screening data showed that 74(43.27％)patients were considered to be at risk of malnutrition(NRS 2002≥3),while based on GLIM criteria,63 patients(36.84％)were diagnosed as malnutrition.Univariate logistic regression analysis showed that GLIM-defined malnutrition was associated with total postoperative complications[odds ratio:2.075(95％CI:1.292～3.333),P=0.002].Multivariat analysis showed that women,BMI＜18.5kg/m2,smoking history,low differentiation of tumor,sarcopenia,laparotomy,low prealbumin,were independent risk factors for total postoperative complications.Conclusions:The nutritional diagnosis based on the GLIM criteria can effectively reflect the preoperative nutritional status of patients with colorectal cancer.GLIM-defined preoperative malnutrition can predict the risk of short-term complications in colorectal cancer patients who underwent curative colorectal cancersurgery.

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

Humans ; Female ; Deep Learning ; Ovarian Neoplasms/genetics* ; Carcinoma, Ovarian Epithelial/genetics* ; Neural Networks, Computer ; RNA

The powder modification technology was used to improve the powder properties and microstructure of Dioscoreae Rhizoma extract powder, thereby solving the problem of poor solubility of Dioscoreae Rhizoma formula granules. The influence of modifier dosage and grinding time on the solubility of Dioscoreae Rhizoma extract powder was investigated with the solubility as the evaluation index, and the optimal modification process was selected. The particle size, fluidity, specific surface area, and other powder properties of Dioscoreae Rhizoma extract powder before and after modification were compared. At the same time, the changes in the microstructure before and after modification was observed by scanning electron microscope, and the modification principle was explored by combining with multi-light scatterer. The results showed that after adding lactose for powder modification, the solubility of Dioscoreae Rhizoma extract powder was significantly improved. The volume of insoluble substance in the liquid of modified Dioscoreae Rhizoma extract powder obtained by the optimal modification process was reduced from 3.8 mL to 0 mL, and the particles obtained by dry granulation of the modified powder could be completely dissolved within 2 min after being exposed to water, without affecting the content of its indicator components adenosine and allantoin. After modification, the particle size of Dioscoreae Rhizoma extract powder decreased significantly, d_(0.9) decreased from(77.55±4.57) μm to(37.91±0.42) μm, the specific surface area and porosity increased, and the hydrophilicity improved. The main mechanism of improving the solubility of Dioscoreae Rhizoma formula granules was the destruction of the "coating membrane" structure on the surface of starch granules and the dispersion of water-soluble excipients. This study introduced powder modification technology to solve the solubility problem of Dioscoreae Rhizoma formula granules, which provided data support for the improvement of product quality and technical references for the improvement of solubility of other similar varieties.
Powders ; Solubility ; Technology, Pharmaceutical ; Technology ; Plant Extracts ; Particle Size