Aim To investigate the effect of Huangqi injection(HI)and Huangqi oral solution(HO)on cisplatin-induced nephrotoxicity(CIN)based on un-targeted metabolomics technology and the underlying mechanisms.Methods Sprague Dawley(SD)rats were randomly divided into the blank group,cisplatin(CDDP)model group,HI treatment group,and HO treatment group,then the CIN model was built with low dose multiple intraperitoneal injections of CDDP.Pre-liminary evaluation of the renal protective efficacy of HI and HO was performed by measuring serum creatinine(Scr),blood urea nitrogen(BUN),and organ indi-ces.Further screening and identification of potential biomarkers(PBs)related to CIN and HI/HO pharma-cological effects were attained through metabolomics studies of renal tissues,and pathway enrichment analy-sis was conducted.Results HI and HO significantly restored the abnormal increase in renal function indica-tors and abnormal decrease in organ indices caused by CDDP,as well as significantly improved the abnormal renal metabolic profile induced by CDDP,indicating that both HI and HO had good alleviating effects on CIN.HI significantly reversed 47 out of 54 CIN related PBs,mainly involving metabolic pathways such as glycerophospholipid metabolism,tryptophan metabo-lism,pantothenate and CoA biosynthesis;HO signifi-cantly reversed 18 out of 54 CIN related PBs,mainly involving metabolic pathways such as taurine and hypo-taurine metabolism,ascorbate and aldarate metabo-lism,pentose and glucuronate interconversions.Con-clusions Both HI and HO have significant alleviating effects on CIN.In the short term,HI salleviating effect is superior to that of HO.Overall,the mechanisms by which both alleviate CIN are mainly related to regula-ting lipid metabolism,amino acid metabolism.

In proton therapy,prompt gamma-ray imaging is considered as one of the most promising methods for assessing proton beam range.Prompt gamma-ray imaging detector evaluates the proton beam range based on the prompt gamma-ray distribution obtained by the prompt gamma-ray imaging system,which enables high-precision measurement of the proton beam range.Herein a proton beam range verification algorithm is designed for the newly developed prototype of the range verification detector(pixelated prompt gamma-ray imaging detector),which verifies the range estimation accuracy of the prototype for different phantoms and different energies of homogeneous media through Monte Carlo simulation.The results show that the accuracy of the proton beam range verification algorithm is within 0.5 mm of the safety margin error of the Bragg peak,and the measurement accuracy is significantly improved with the increase of the number of protons,indicating that the prototype algorithm is feasible for proton beam range verification.

Objective:To evaluate the safety and efficacy of the probiotic Bifidobacterium longum subsp. longum BL21 (BL21) in preventing radiation-induced diarrhea (RID) in cervical cancer patients during radiotherapy (RT) and to investigate the intestinal microbiota in the patients. Methods:This study was a prospective, single-arm, phase Ⅱ clinical trial, involving cervical cancer patients treated with radical and adjuvant RT. From the first day of RT, participants took one pack of BL21 powder (containing 20 billion colony-forming unit(CFU) of Bifidobacterium longum subsp. longum BL21) orally every day until the end of RT. The occurrence of adverse events and RID during RT were assessed as per Common Terminology Criteria for Adverse Events ( CTCAE) v5.0. In this way, the safety and efficacy of BL21 in preventing RID were evaluated. Additionally, the intestinal microbiota in fecal samples collected from the patients before and after RT were analyzed using 16S rRNA sequencing. Results:A total of 35 cervical cancer patients were enrolled in this study, with 29 cases incorporated for the final analysis. No serious adverse event related to the administration of BL21 was observed. The patients exhibited slight RID, with the majority (22/29) developing no or grade 1 RID during RT. The microbiota in the fecal samples showed decreased alpha diversity after RT, as indicated by the Chao1 ( P = 0.002) and Shannon ( P = 0.005) indices. Furthermore, these samples exhibited a notably higher abundance of genus Clostridium (LDA score = 3.98). The fecal samples from patients with grade 1 RID or no RID post-RT exhibited higher alpha diversity than those from patients with grade 2 RID or above post-RT (Chao1: P = 0.07, Shannon: P = 0.28), as well as a high abundance of genera Gemmiger (LDA score = 4.48) and Dorea (LDA score = 3.83). Conclusions:The administration of BL21 to cervical cancer patients during RT is simple, convenient, safe, and effective in preventing RID, thus warranting further investigation.

Aim To investigate the effect of Huangqi injection(HI)and Huangqi oral solution(HO)on cisplatin-induced nephrotoxicity(CIN)based on un-targeted metabolomics technology and the underlying mechanisms.Methods Sprague Dawley(SD)rats were randomly divided into the blank group,cisplatin(CDDP)model group,HI treatment group,and HO treatment group,then the CIN model was built with low dose multiple intraperitoneal injections of CDDP.Pre-liminary evaluation of the renal protective efficacy of HI and HO was performed by measuring serum creatinine(Scr),blood urea nitrogen(BUN),and organ indi-ces.Further screening and identification of potential biomarkers(PBs)related to CIN and HI/HO pharma-cological effects were attained through metabolomics studies of renal tissues,and pathway enrichment analy-sis was conducted.Results HI and HO significantly restored the abnormal increase in renal function indica-tors and abnormal decrease in organ indices caused by CDDP,as well as significantly improved the abnormal renal metabolic profile induced by CDDP,indicating that both HI and HO had good alleviating effects on CIN.HI significantly reversed 47 out of 54 CIN related PBs,mainly involving metabolic pathways such as glycerophospholipid metabolism,tryptophan metabo-lism,pantothenate and CoA biosynthesis;HO signifi-cantly reversed 18 out of 54 CIN related PBs,mainly involving metabolic pathways such as taurine and hypo-taurine metabolism,ascorbate and aldarate metabo-lism,pentose and glucuronate interconversions.Con-clusions Both HI and HO have significant alleviating effects on CIN.In the short term,HI salleviating effect is superior to that of HO.Overall,the mechanisms by which both alleviate CIN are mainly related to regula-ting lipid metabolism,amino acid metabolism.

ObjectiveTo study the chemical constituents of Bidens pilosa and the in vitro antiproliferative activity of some compounds against gastric cancer cells. MethodsThe chemical constituents were isolated and purified by methods such as silica gel column chromatography， preparative thin layer chromatography， medium pressure preparation chromatography， semi-preparative high performance liquid chromatography（HPLC） and recrystallization， their structures were identified on the basis of physicochemical properties， spectral data and circular dichroism spectra. Thiazole blue（MTT） assay was used to determine the in vitro inhibitory activityies of some isolated compounds against human gastric cancer SGC-7901 cells， and molecular docking was used to predict their potential targets. ResultsTwenty-five compounds were isolated from the petroleum ether fraction of B. pilosa and identified as bidpillignan A（1）， 5α， 8α-epidioxy-（22E， 24R）-ergosta-6， 22-diene-3β-ol（2）， 3β-hydroxysitost-5-en-7-one（3）， （20R）-6β-hydroxystigmasta-4， 22-dien-3-one（4）， 3β-hydroxylstigmasta-5， 22-dien-7-one（5）， （22E， 24S）-24-methyl-5α-choleata-7， 22-diene-3β， 5α， 6β-triol（6）， stigamast-5-ene-3β， 7α-diol（7）， stigmast-5， 22-diene-3β， 7α-diol（8）， 7β-hydroxysitosterol（9）， stigmasterol（10）， artabotrol（11）， cosmosoic acid（12）， ent-4（15）-eudesmene-1β， 6α-diol（13）， clovandiol（14）， 1H-indole-3-carboxaldehyde（15）， 6， 7-dimethoxycoumarin（16）， 3'， 4'-dimethoxyquercetin（17）， 8， 8'-bis-（dihydroconiferyl）-diferuloylate（18）， hydroxydihydrobovolide（19）， 2-deacetyl-11β， 13-dihydroxyxanthinin（20）， loliolide（21）， pubescone（22）， （+）-dehydrovomifoliol（23）， 2， 3-dihydroxypropyl palmitate（24） and n-hexadecane acid（25）. Among them， compound 1 was a new compound， compounds 3-9， 11-12， 18-20， 22-23 were first isolated from Bidens genus plants， and compounds 13 and 14 were isolated from this plant for the first time. Compounds 17 and 18 showed good in vitro proliferation inhibitory activities against SGC-7901 cells with the half inhibitory concentrations（IC₅₀） of 3.11， 7.22 μmol·L^-1， respectively. Molecular docking results showed that the potential targets of the two exerting anti-gastric cancer activity might be vascular endothelial growth factor receptor 2（VEGFR2） and poly（adenosine diphosphate-ribose） polymerase 7（PARP7）. ConclusionOne new compound， 14 genus first compounds， and 2 species first compounds were isolated from B. pilosa， among which compounds 17 and 18 processed anti-gastric cancer cell proliferation activity in vitro， and the targets may be VEGFR2 and PARP7.

Objective:To evaluate the clinical efficacy and safety of sulodexide soft capsules in treating proteinuria after renal transplantation, as well as its impact on graft function.Methods:The clinical data from 80 recipients who developed proteinuria after renal transplantation and were treated with sulodexide soft capsules during regular follow-up at the outpatient department of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from March 1, 2019, to March 1, 2023, were retrospectively analyzed. Proteinuria levels, graft function, safety-related indicators (coagulation function), and adverse events were compared before treatment and at 1, 2, 3, 6, and 12 months after treatment. Based on efficacy, recipients were divided into a satisfactory efficacy group (67 cases) and a general efficacy group (13 cases). Univariate and multivariate logistic regression analyses were conducted to stratify baseline data and explore factors influencing efficacy.Results:Among the 80 recipients, 63 (78.75%) had mild proteinuria and 17 (21.25%) had moderate proteinuria. The overall treatment response rate was 91.25% (73/80). Drug-related adverse events occurred in 12 patients (15.0%). Median urinary protein excretion at 1, 2, 3, 6, and 12 months post-treatment was 0.35 (0.20, 0.55) g/24 h, 0.30 (0.17, 0.44) g/24 h, 0.23 (0.15, 0.39) g/24 h, 0.21 (0.13, 0.32) g/24 h, and 0.15 (0.10, 0.23) g/24 h, respectively, all significantly lower than the pre-treatment level of 0.52 (0.43, 0.90) g/24 h (all P<0.001). The median urinary albumin-to-creatinine ratios at the corresponding time points were 99.15 (45.33, 201.13) μg/mg, 77.20 (43.30, 176.20) μg/mg, 57.50 (31.35, 173.75) μg/mg, 53.55 (25.90, 142.00) μg/mg, and 39.05 (20.53, 103.60) μg/mg, also significantly reduced compared to the pre-treatment value of 152.05 (71.90, 271.23) μg/mg ( P=0.012, P=0.003, P<0.001, P<0.001, P<0.001, respectively). At 12 months post-treatment, the serum creatinine level (132.86±36.86 μmol/L) showed a statistically significant improvement compared to the pre-treatment level (146.60±48.42 μmol/L) ( P=0.045). Univariate analysis indicated that satisfactory efficacy was associated with the time of proteinuria onset post-transplantation, the interval between proteinuria onset and treatment initiation, and recipient age ( HR= 1.001, 95% CI: 1.001-1.020, P=0.043; HR = 1.034, 95% CI: 1.009-1.058, P=0.006; HR=1.058, 95% CI: 1.003-1.116, P=0.040). Stratified univariate analysis revealed that proteinuria onset within 2 years post-transplantation, treatment initiation within 2 years of proteinuria onset, and age younger than 45 years were significantly associated with satisfactory efficacy ( HR=5.524, 95% CI: 1.510-20.207, P=0.010; HR= 7.800, 95% CI: 2.104-28.920, P=0.002; HR=5.972, 95% CI: 1.497-23.822, P=0.011). Multivariate analysis identified the interval between proteinuria onset and treatment initiation as an independent factor influencing satisfactory efficacy ( HR=1.025, 95% CI: 1.010-1.093, P=0.015). Conclusions:Sulodexide effectively reduces proteinuria after renal transplantation, particularly in mild-to-moderate or early-onset cases, while maintaining stable allograft function without significant adverse effects

OBJECTIVE To prepare reactive oxygen species(ROS)-responsive methotrexate(MTX)-modified paclitaxel(PTX)/icariin(ICA)micelles(MTX-oxi-Ms@PTX/ICA),and perform technology optimization and in vitro anti-tumor effect evaluation.METHODS Synergistic toxicity concentration range of PTX and ICA was screened by synergistic toxicity test.The micelles were prepared by thin film hydration method,and their technology was optimized by response surface methodology.The fundamental characteristics of the micelles prepared by the optimal technology were evaluated.The micelles'cytotoxicity,targeting ability to renal carcinoma RENCA cells of mice,and their inhibitory effects on invasion and migration were assessed.RESULTS Results of synergistic toxicity experiments demonstrated that the strongest synergistic effect occurred when PTX concentrations ranged from 2.5 to 10 μmol/L and ICA concentrations ranged from 5 to 15 μmol/L.The optimal technology of MTX-oxi-Ms@PTX/ICA was determined to include 80 mg Soluplus?,Soluplus? and TPGS1000 mass ratio of 4:1(mg/mg),2 mg DSPE-PEG2000-TK-PEG5000,2 mg DSPE-PEG2000-MTX,1 mg PTX,and 1.5 mg ICA,with a hydration temperature of 35 ℃ and a formulation volume of 5 mL.Under the optimal conditions,average encapsulation efficiency of PTX and ICA in 3 batches of MTX-oxi-Ms@PTX/ICA reached 92.75％,the critical micelle concentration(CMC)was 0.007 9 mg/mL,the particle size was(62.09±1.68)nm,the polydispersity index(PDI)was 0.046±0.032,and the Zeta potential was(-2.47±0.15)mV.Within 30 days of placement,there was no significant change in particle size and polydispersity index of micelle.In vitro release experiments showed that MTX-oxi-Ms@PTX/ICA released drugs more rapidly in oxidative environments.The half maximal inhibitory concentration of MTX-oxi-Ms@PTX/ICA against RENCA cells was(5.170±0.036)μmol/L.In vitro cellular uptake experiments indicated that compared with unmodified micelles,MTX modified micelles had stronger targeting effects on cancer cells,and also significantly enhanced the inhibitory ability of invasion and migration of RENCA cells(P＜0.05).CONCLUSIONS MTX-oxi-Ms@PTX/ICA micelles are successfully prepared,which exhibit high encapsulation efficiency,low critical micelle concentration,and good stability.These micelles demonstrate significant cytotoxicity against RENCA cells and effectively inhibit cancer cell invasion and migration.

Objective To study the application effects of different inferior vena cava filters(IVCF)placed in the renal vein for the treatment of deep vein thrombosis(DVT).Methods A total of 102 patients with lower limb DVT who underwent renal vein IVCF at the Second People's Hospital of Baoshan from January 2021 to June 2022 were selected.According to the type of IVCF,patients were divided into a retrievable group(n=51)and a permanent group(n=51).The two groups were compared in terms of filter placement conditions,perioperative limb circumference differences,D-dimer,fibrinogen,venous recanalization scores,venous recanalization rates,as well as complications and recurrence-free survival status 12 months post-operation.Results The surgical success rate was 100%.The differences in limb circumference above the knee(15 cm)and below the knee(10 cm)at 1 day,3 days,and 7 days post-operation were significantly reduced compared to pre-operative measurements and showed a downward trend(P<0.05).D-dimer and fibrinogen levels at 1 day,3 days,and 7 days post-operation were also significantly reduced compared to pre-operative levels,with a downward tren(P<0.05).The venous recanalization scores at 7 days post-operation were significantly lower than pre-operative scores in both groups(P<0.05).The incidence of postoperative complications in the retrievable group was lower than that in the permanent group(P<0.05).Conclusion The placement of a retrievable IVCF on the renal vein for endovascular treatment of DVT has significant therapeutic effects,can adjust the circumference difference of the lower limb,improve coagulation function,and reduce the incidence of complications and recurrence.

Protein arginine methyltransferase 5 (PRMT5) exhibits elevated expression levels in a variety of cancers and has emerged as a critical target for cancer therapy in recent years. However, first-generation PRMT5 inhibitors have exhibited inadequate selectivity, leading to significant hematological toxicity, thus limiting their clinical utility. The second-generation PRMT5 inhibitors have shown marked improvement in safety and efficacy by selectively targeting MTAP-null tumor cells without impacting normal cells. This review systematically summarizes the biological and functional roles of PRMT5 in MTAP-deficient tumor cells, and comprehensively analyzes the research and development process, molecular binding mechanisms, and the latest advancements in clinical trials of the five second-generation PRMT5 inhibitors currently under investigation, aiming to provide valuable insights for further in-depth studies in this field.

Nanomaterials(Ce-CS)with oxidase-like properties were synthesized in one step using L-cystine(CS)and ammonium cerium nitrate(CAN)as raw materials for detection of acetaminophen(APAP).The morphology,structure and elements composition of Ce-CS were characterized by scanning electron microscopy(SEM),energy dispersive X-ray spectroscopy(EDS),nitrogen adsorption specific surface area analysis(BET),X-ray diffraction(XRD),infrared spectroscopy(IR)and X-ray photoelectron spectroscopy(XPS).The Ce-CS with peroxidase-like activity could catalyze the oxidation of colorless 3,3′,5,5′-tetramethylbenzidine(TMB)into blue oxided TMB(oxTMB),which had a significant absorption peak at 652 nm.Under the optimal catalytic conditions,i.e.,reaction temperature of 25℃(room temperature),pH=4.0,Ce-CS concentration of 1 mg/mL,and reaction time of 10 min,the catalytic mechanism and kinetics of Ce-CS were studied.When APAP existed in the reaction system,it could inhibit the peroxidase-like activity of Ce-CS,reduced the absorbance at 652 nm(A652),and the absorbance difference at 652 nm(ΔA652)had a good linear relationship with concentration of APAP in the range of 50-2000 μmol/L(R2=0.996),with a detection limit(S/N=3)of 0.1 μmol/L.This method was applied to detection of APAP in oral liquid and river water samples,with recoveries of 98.0%-102.0%,demonstrating the potential of Ce-CS as an oxidase substitute in drug analysis and environmental monitoring.