Osteoporosis is a common bone disease， whose incidence is still on the rise， posing great challenges to patients and society. This review mainly studies the pathogenesis of osteoporosis from the aspects of oxidative stress， inflammatory response， and glucolipotoxicity-induced injury and clarifies the efficacy and mechanism of some active ingredients of traditional Chinese medicine against osteoporosis through the integration of in vitro and in vivo experiments. The experimental results suggest that some active ingredients can improve bone resorption markers and maintain bone homeostasis by modulating inflammation， oxidative stress， etc. These active ingredients regulate osteoporosis through the receptor activator of nuclear transcription factor-κB （NF-κB） ligand （RANKL） pathway， osteoprotegerin （OPG） pathway， Wnt/β-catenin pathway， NF-κB pathway， mitogen-activated protein kinase （MAPK） pathway， adenosine monophosphate （AMP）-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） pathway， and oxidative stress pathway. This review provides ideas for the progress of the prevention and treatment of osteoporosis with the active ingredients of traditional Chinese medicine， aiming to provide new potential lead compounds and reference for the development of innovative drugs and clinical therapy for the treatment of osteoporosis.

OBJECTIVE To systematically evaluate medication risk prediction models for hospitalized adult patients and provide references for their development and clinical application. METHODS Databases including PubMed， Embase， Web of Science， CNKI， Wanfang data， VIP and CBM were searched for studies on medication risk prediction models from their inception to May 2024. After screening the literature， extracting data， and evaluating the quality of the literature， descriptive analysis was performed on the results of the included studies. RESULTS A total of 13 studies were included， involving 12 models. Nine studies used Logistic regression algorithm for modeling， and the number of included predictive factors ranged from 3 to 11； the area under the receiver operating characteristic curve ranged from 0.65 to 0.865. The literature quality evaluation results showed that 10 studies had high risk of bias； 10 studies had high applicability risk. A total of 31 predictive factors were extracted， including 15 items of basic patient information， 3 test indicators， and 5 items of medication information， and 8 others. CONCLUSIONS The existing medication risk prediction models for hospitalized adult inpatients are mainly Logistic regression algorithm， with predictive factors mainly focusing on basic indicators such as demographics. The overall prediction performance of the models needs to be improved， and the overall risk of bias is relatively high.

The Baveno Cooperation is a consortium of internationally renowned experts committed to setting standards for the clinical management of patients with advanced chronic liver disease, with a particular emphasis on complications related to portal hypertension. Updated every five years and endorsed by major scientific societies, the Baveno recommendations have significantly influenced clinical practice and improved patient outcomes worldwide. The latest Baveno consensus, Baveno VII, provided a series of recommendations that have shifted our understanding of chronic liver disease and portal hypertension and profoundly shaped clinical practice. However, many areas of research remain to be explored in the short to intermediate term to enable a more personalized medicine approach. This review highlights some of the most relevant advancements introduced in Baveno VII and discusses future challenges.
Hypertension, Portal/therapy* ; Humans

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

[Objective] To investigate the pathological characteristics of false-positive lesions of prostate cancer on ⁶⁸Ga-PSMA-11 PET/CT based on the pathology of whole mount specimens, in order to more accurately assess the degree of malignancy within the prostate tissue and avoid overdiagnosis and unnecessary treatment. [Methods] A total of 77 patients who underwent ⁶⁸Ga-PSMA-11 PET/CT before radical prostatectomy in Nanjing Drum Tower Hospital during Jan.2018 and Dec.2022 were retrospectively analyzed.The pathology of whole mount specimens was detected.Two nuclear physicians examined all imaging plates without knowing the pathological results.Two pathological physicians completed all pathological diagnosis without knowing the imaging results.The pathological characteristics of false-positive lesions were determined by matching ⁶⁸Ga-PSMA-11 PET/CT and pathological specimens.To analyze the pathological features of false-positive lesions, true-negative lesions were randomly delineated and defined.The pathological features of false-positive and true-negative lesions were analyzed and compared using Fisher exact test. [Results] After the imaging and pathological sections were matched, 21(16.3%) false-positive lesions were identified.The pathological characteristics of the 21 false-positive lesions were as follows: 16 (76.2%) simple atrophy with cyst formation, 3(14.3%) prostatic nodular hyperplasia, and 2(9.5%) inflammation.The pathological characteristics of 21 true-negative lesions were: 13(61.9%) normal glands, 5(23.8%) prostatic nodular hyperplasia and 3(14.3%) simple atrophy with cyst formation.Fisher exact test showed that the proportion of simple atrophy with cyst formation in the pathological features of false-positive lesions and true-negative lesions was statistically significant (76.2% vs.14.3%, P<0.001). [Conclusion] Simple atrophy with cyst formation may be a characteristic pathological type of the false-positive lesions of prostate cancer on ⁶⁸Ga-PSMA-11 PET/CT.

Objective:To compare the pregnancy outcomes of luteal phase and follicular phase progestin-primed ovarian stimulation protocol with clomiphene citrate supplementation(LPPOS+CC and FPPOS+CC)in young women with diminished ovarian reserve(DOR).Methods:A total of 483 women aged≤35 years with DOR,who underwent in vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI)/embryo transfer(ET)with controlled ovarian stimulation using LPPOS+CC(n=257)or FPPOS+CC(n=226)protocols during June 2018 and December 2021 at the First Affiliated Hospital of Wenzhou Medical University,were included in this retrospective study.The baseline characteristics,superovulation results,laboratory related indicators between the two groups,and the pregnancy outcomes of women who achieved at least one high-quality cleavage-stage embryo or good-morphology blastocyst were compared between the two groups.Results:No statistically significant differences were identified between the groups with respect to age,duration of infertility,proportion of secondary infertility,previous failed cycles,body mass index,anti-Müllerian hormone,antral follicle count,basal luteinizing hormone level,basal progesterone level,number of oocytes retrieved,oocyte maturation rate,high-quality cleavage-stage embryo cycle rate,the percentage of women with profound pituitary suppression,live birth rate and preterm birth rate(all P＞0.05).The LH levels on the day of trigger[4.0(2.7,5.3)vs.5.1(3.2,7.2)IU/L],the percentage of women with LH levels of＞10 IU/L on the trigger day(3.13%vs.10.67%),and the two pronucleus(2PN)rate of ICSI oocytes(72.16%vs.79.56%)were significantly lower in the LPPOS+CC group than those in the FPPOS+CC group(P＜0.05 or P＜0.01).The duration of stimulation[11(9,12)vs.9(8,11)d],the consumption of total gonadotropin[2213(1650,2700)vs.2000(1575,2325)IU],the progesterone levels on the day of trigger[1.3(0.8,2.9)vs.0.9(0.6,1.2)ng/mL],the clinical pregnancy rate[61.88%vs.46.84%],and implantation rate[42.20%vs.31.07%]in the LPPOS+CC group were significantly higher than those in the FPPOS+CC group(all P＜0.01).Conclusion:Compared to FPPOS+CC,the LPPOS+CC protocol appears to have better pregnancy outcomes for young women with DOR undergoing IVF/ICSI-ET.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Objective:To discuss the inhibitory effect of microRNA-487a(miR-487a)on the M2 polarization of tumor-associated macrophages(TAMs)in gastric cancer,and to clarify its effect on the proliferation,invasion,and migration of the gastric cancer AGS cells.Methods:The TAMs from gastric cancer tissue and adjacent normal tissue macrophages(NTMs)from adjacent tissue of the primary gastric cancer patients were isolated and cultured.The human monocyte THP-1 cells were induced in vitro to differentiate into TAMs,and the differentiated M0,M1,and M2 macrophages were cultured for 24 h by conditioned medium(CM)to obtain the TAMs,M1-TAMs,and M2-TAMs respectively.The TAMs were transfected and then divided into blank group,inhibitor-NC group,miR-487a inhibitor group,miR-487a inhibitor+si-NC group,and miR-487a inhibitor+si-TIA1 group.The transfection efficiencies of the cells in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods.The M2-TAMs were co-cultured with the AGS cells,and divided into AGS group,AGS+inhibitor-NC group,AGS+miR-487a inhibitor group,AGS+miR-487a inhibitor+si-NC group,and AGS+miR-487a inhibitor+si-TIA1 group.RT-qPCR method was used to detect the expression levels of miR-487a and lymphocyte intracytoplasmic antigen-1(TIA1)mRNA in TAMs from gastric cancer tissue and NTMs from adjacent normal tissue in various groups;Western blotting method was used to detect the expression level of TIA1 protein in TAMs from gastric cancer tissue and NTMs from adjacent normal tissue and TAMs in various groups;flow cytometry was used to detect the levels of CD206 and CD163 in TAMs in various groups;enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of interleukin-10(IL-10),transforming growth factor-beta(TGF-β),vascular endothelial growth factor A(VEGF-A),and arginase-1(Arg-1)in culture supernatant of the TAMs cells;CCK-8 assay was used to detect the proliferative activity of the AGS cells in various groups;wound healing assay was used to detect the migration rates of the AGS cells in various groups;Transwell assay was used to detect the number of invasion AGS cells in various groups.Results:The RT-qPCR results shoued that compared with NTMs from adjacent tissue,the expression level of miR-487a in the TAMs from gastric cancer tissue was significantly increased(P<0.01)and the expression level of TIA1 mRNA was significantly decreased(P<0.01).Compared with TAMs,the expression level of miR-487a in M1-TAMs was significantly decreased(P<0.01),and the expression level of TIA1 mRNA was increased(P<0.01);the expression level of miR-487a in M2-TAMs was significantly increased(P<0.01),and the expression level of TIA1 mRNA was decreased(P<0.01).After transfection,compared with blank group and inhibitor-NC group,the expression level of miR-487a in the cells in miR-487a inhibitor group was significantly decreased(P<0.01),indicating successful transfection.The Western blotting results showed that compared with NTMs from adjacent normal tissue,the expression level of TIA1 protein in TAMs from gastric cancer tissue was decreased(P<0.01);compared with TAMs,the expression level of T1A1 protein in M1-TAMs was significantly increased(P<0.01),and the expression of TIA1 protein in M2-TAMs was significantly decreased(P<0.01);after co-transfection,compared with inhibitor-NC group,the expression level of TIA1 protein in the cells in miR-487a inhibitor group was significantly increased(P<0.01);compared with miR-487a inhibitor+si-NC group,the expression level of TIA1 protein in the cells in miR-487a inhibitor+si-TIA1 group was significantly decreased(P<0.01).The flow cytometry results showed that compared with blank group and inhibitor-NC group,the levels of CD206 and CD163 in the cells in miR-487a inhibitor group were significantly decreased(P<0.01);after co-transfection,compared with inhibitor-NC group,the levels of CD206 and CD163 in the cells in miR-487a inhibitor group were significantly decreased(P<0.01);compared with miR-487a inhibitor+si-NC group,the levels of CD206 and CD163 in the cells in miR-487a inhibitor+si-TIA1 group were significantly increased(P<0.01).The ELISA results showed that compared with blank group and inhibitor-NC group,the levels of IL-10,TGF-β,VEGF-A,and Arg-1 in culture supernatant of the TAMs in miR-487a inhibitor group were significantly decreased(P<0.01);after co-transfection,compared with inhibitor-NC group,the levels of IL-10,TGF-β,VEGF-A,and Arg-1 in culture supernatant of the TAMs in miR-487a inhibitor group were significantly decreased(P<0.01);compared with miR-487a inhibitor+si-NC group,the levels of IL-10,TGF-β,VEGF-A,and Arg-1 in culture supernatant of the TAMs in miR-487a inhibitor+si-TIA1 group were significantly increased(P<0.01).The CCK-8 assay results showed that compared with AGS group,the proliferation activity of the cells in AGS+inhibitor-NC group was significantly increased(P<0.01);compared with AGS+inhibitor-NC group,the proliferation activity of the cells in AGS+miR-487a inhibitor group was significantly decreased(P<0.01);compared with AGS+miR-487a inhibitor+si-NC group,the proliferation activity of the cells in AGS+miR-487a inhibitor+si-TIA1 group was significantly increased(P<0.01).The wound healing assay results showed that compared with AGS group,the migration rate of the cells in AGS+inhibitor-NC group was significantly(P<0.05);compared with AGS+inhibitor-NC group,the migration rate of the cells in AGS+miR-487a inhibitor group was significantly decreased(P<0.01);compared with AGS+miR-487a inhibitor+si-NC group,the migration rate of the cells in AGS+miR-487a inhibitor+si-TIA1 group was significantly increased(P<0.05).The Transwell assay results showed that compared with AGS group,the number of invasion AGS cells in AGS+inhibitor-NC group was significantly increased(P<0.01);compared with AGS+inhibitor-NC group,the number of invasion AGS cells in AGS+miR-487a inhibitor group was significantly decreased(P<0.01);compared with AGS+miR-487a inhibitor+si-NC group,the number of invasion AGS cells in AGS+miR-487a inhibitor+si-TIA1 group was significantly increased(P<0.01).Conclusion:Silencing the miR-487a expression can inhibit the M2 polarization of the gastric cancer-associated macrophages by targeted upregulation of TIA1,and suppress the proliferation,migration,and invasion of the gastric cancer cells.

Objective To investigate whether recombinant Newcastle disease virus(rL-RVG)induces iron death in gastric cancer cells through Nrf2-GCLC-GPX4 pathway.Methods After human gastric cancer HGC-27 cells were treated with rL-RVG,Newcastle disease virus(NDV)and PBS solution(control group),respectively,cell proliferation,invasion and migration were detected by CCK-8 assay and Transwell invasion assay and cell scratch test.Ferroptosis accelerator(erastin),and nuclear factor E2 related factor 2(Nrf2)accelerator(TBHQ)and inhibitor(ML385)were added respectively as controls.The content of malondialdehyde(MDA)in each treatment group was detected by lipid oxidation kit.The content of reactive oxygen species(ROS)was detected by DCFH-DA fluorescent probe and flow cytometry.Western blotting and immunofluorescence assay were employed to measure the expression levels of Nrf2-GCLC-GPX4 pathway related proteins.Results Compared with the control group,the survival rate of HGC-27 cells were significantly decreased after rL-RVG and NDV treatment in a dose-and time-dependent manner,and the effect was more significant in the rL-RVG treatment group(P＜0.05).The migration and invasion abilities of HGC-27 cells were obviously inhibited in the NDV and rL-RVG treatment groups,and the latter had more notable inhibition than the former.The protein levels of Nrf2,GCLC,SLC7A11 and GPX4 were statistically decreased(P＜0.05),and the contents of MDA and ROS were increased(P＜0.05)in the virus treatment groups than the control group,with the increasing or decreasing trend more significant in the rL-RVG group than the NDV group.What's more,the protein levels of SLC7A11 and GPX4 were decreased in the erastin group(P＜0.05).Compared with the control group,those of Nrf2,GCLC,SLC7A11 and GPX4 were increased in the TBHQ group and decreased in the ML385 group(P＜0.05),while the contents of MDA and ROS were decreased and increased respectively in the above 2 groups(P＜0.05).Compared with the rL-RVG group,the rL-RVG+TBHQ group and rL-RVG+ML385 group had enhanced and reduced protein expressio of Nrf2,GCLC,SLC7A11 and GPX4,respectively(P＜0.05),while the contents of MDA and ROS were in opposite trends(P＜0.05).Conclusion rL-RVG can induce ferroptosis of gastric cancer cells through Nrf2-GCLC-GPX4 pathway,and then inhibit the growth of tumor cells.

Objective To investigate the role of sodium-hyaluronate-modified calcium peroxide nanoparticles(SH-CaO2 NPs)in inducing pyroptosis in human gastric cancer cells and its possible mechanisms.Methods Transmission electron microscopy(TEM),X-ray diffraction(XRD),infrared spectroscopy,and zeta potential test were used to confirm the synthesis of SH-CaO2 NPs.Cell scratch assay and CCK-8 assay were employed to observe the impacts of SH-CaO2 NPs on the migration and proliferation of human gastric cancer cell line HGC-27.The generation of reactive oxygen species(ROS)was observed with confocal laser scanning microscopy(CLSM)and quantified with flow cytometry in the cells after SH-CaO2 NPs treatment or with pretreatment with ROS inhibitor NAC.Furthermore,the effects of pretreatment of NLRP3 inhibitor(MCC950)and Caspase-1 inhibitor(VX765)on the proliferative activity and on expression of their own and their downstream GSDMD in HGC-27 cells were also investigated with CCK-8 assay,immunofluorescence assay and Western blotting.Results TEM images,XRD,infrared spectroscopy,and zeta potential test confirmed the successful preparation of SH-CaO2 NPs.Cell scratch assay and CCK-8 assay showed that application of SH-CaO2 NPs for 24 h significantly inhibited the proliferation of HGC-27 cells(P＜0.001),while,CLSM and flow cytometry indicated the treatment also promoted the production of ROS(P＜0.001).Pretreatment of ROS inhibitor NAC resulted in up-regulation of NLRP3,and increased expression levels of cleaved Caspase-1 and N-terminal fragment of GSDMD(P＜0.001),while pretreatment of both NLRP3 inhibitor and Caspase-1 inhibitor could reverse the process.Conclusion SH-CaO2 NPs inhibit cell viability of human gastric cancer,which may mediate the inflammatory response and pyroptosis by activating the ROS/NLRP3/Caspase-1/GSDMD signaling pathway.