ObjectiveTo observe the inhibitory effect of the Weiliuan mixture （WLAHJ） on the subcutaneous xenograft tumor of MKN-74 gastric cancer cells， and explore the potential anti-gastric cancer mechanism of WLAHJ by using transcriptomic sequencing technology to reveal related genes and pathways. Methods30 Balb/c nude mice were randomly divided into model， low-， medium-， and high-dose（15，30，45 g·kg^-1） WLAHJ and 5-FU （0.025 g·kg^-1） groups to build a subcutaneous xenograft tumor model with MKN-74 human gastric cancer cells. After modeling，each group was continuously treated with the corresponding drugs for 28 days. During the treatment period， the body weight and tumor size of the mice were observed and recorded every 2 days. At the end of the treatment， the mice were sacrificed， and required samples were collected to calculate the tumor inhibition rate of WLAHJ on the subcutaneous xenograft tumor. High-throughput transcriptomic sequencing （RNA-seq） technology was used to analyze the differentially expressed genes in the subcutaneous tumor tissues of the model group and the medium-dose WLAHJ group， thus exploring the potential mechanism of WLAHJ in gastric cancer intervention. Immunofluorescence experiments were conducted to detect the protein expression levels of glutathione peroxidase 4 （GPX4）， solute carrier family 7 member 11 （SLC7A11）， transferrin receptor protein-1 （TFR-1）， and acyl-CoA synthetase long-chain family member 4 （ACSL4） in subcutaneous xenograft tumors of each group. Cell counting kit-8（CCK-8） and colony formation assays were used to detect the viability and anti-proliferative ability of human gastric cancer AGS and MKN-74 cells at different concentrations of WLAHJ. Kits were used to detect the levels of Fe²⁺， reactive oxygen species （ROS）， malondialdehyde （MDA）， and superoxide dismutase （SOD） activity in cells. Western blot was used to detect the expression levels of GPX4， SLC7A11， TRF-1， ACSL4， spermidine/spermine N1-acetyltransferase 1 （SAT1）， arachidonic acid 15-lipoxygenase （ALOX15）， and key proteins in the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. ResultsThe mechanism of WLAHJ in gastric cancer intervention may be related to ferroptosis and the PI3K/Akt /mTOR signaling pathway. The growth of subcutaneous xenograft tumors in nude mice of the WLAHJ and 5-FU groups（P<0.05，P<0.01）， GPX4， and SLC7A11 dropped significantly（P<0.01）， while TFR-1， ACSL4， SAT1， and ALOX15（P<0.05，P<0.01）increased significantly compared with those in the model group. The levels of ROS， Fe²⁺， and MDA increased in the WLAHJ and 5-FU groups and the proliferation of gastric cancer cells， SOD activity， the ratios of phosphorybation （p）-mTOR/mTOR， p-PI3K/PI3K， and p-Akt/Akt protein expressions（P<0.05，P<0.01）decreased compared with those in the blank group. ConclusionThe mechanism of WLAHJ in treating gastric cancer may be related to the regulation of the PI3K/ Akt /mTOR signaling pathway to intervene in ferroptosis.

Objective To analyze the clinical parameters of esophageal cancer patients before and during neoadjuvant chemotherapy,as well as to explore the related factors and predictive value that affect the efficacy of neoadjuvant chemotherapy for esophageal cancer.Methods A total of 194 patients with esophageal cancer who underwent neoadjuvant chemotherapy at the First Affiliated Hospital of Guangxi Medical University from 2020 to 2023 were selected as the research subjects.The treatment process and outcomes of the patients were followed up,and they were divided into an effective group and an ineffective group according to the effi-cacy.Differences were compared in clinical parameters between two groups of patients before and during treat-ment,screen for factors that may affect efficacy,correlation analysis was conduct to explore the correlation be-tween relevant factors and the efficacy of neoadjuvant chemotherapy,and the predictive value of relevant fac-tors were analyzed using receiver operating characteristic(ROC)curve analysis.Results There was a statisti-cally significant difference(P＜0.05)in the average cycle cost,lowest WBC value,lowest PLT value,inci-dence of nausea,transaminase abnormalities,and hair loss between the two groups.Logistic regression analysis showed that average cycle cost,transaminase abnormalities,and hair loss were related factors affecting neoad-juvant chemotherapy for esophageal cancer.Spearman correlation analysis showed that the above indicators had a certain correlation with the efficacy of neoadjuvant chemotherapy for esophageal cancer.ROC curve a-nalysis showed that the area under the curve(AUC)for predicting the efficacy of neoadjuvant chemotherapy in esophageal cancer by combining transaminase abnormalities,average cycle cost,and hair loss was 0.758(95％CI:0.683-0.832)Conclusion There is a certain correlation between average cycle cost,transaminase abnormalities,and hair loss and the effectiveness of neoadjuvant chemotherapy for esophageal cancer,which has certain predictive value for the efficacy of neoadjuvant chemotherapy for esophageal cancer.

Objective To explore the effect and mechanism of quercetin on osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs).Methods BMSCs were divided into a blank control group(Control)and quercetin(Quercetin)low-dose group(4.8 mL/kg),medium-dose group(9.6 mL/kg),and high-dose group(19.2 mL/kg)intervened with drug-containing serum,while the positive control group was treated with osteogenic differentiation medium,respectively.The cell cycle was analysed by flow cytometry,cell proliferation was detected by MTT assay,cell activity was determined by Alkaline phosphatase(ALP)assay kit,and calcified nodule formation was observed by alizarin red staining.The expression of β-catenin and the key factors of osteogenic differentiation,runt-related transcription factor 2(RUNX2)and osteocalcin(OCN),were detected by qPCR and Western blot,respectively.Results Compared with the control group,quercetin-containing serum significantly promoted the proliferation of BMSCs(P=0.000205,P=0.000063)and enhanced the formation of calcium nodules,and increased osteogenic and ALP activity after osteogenic differentiation.The results of qPCR and Western blot showed that the quercetin group significantly up-regulated the mRNA and protein expression of β-catenin(P<0.0001),RUNX2(P<0.0001)and OCN(P<0.0001)during osteogenic differentiation.Conclusion Quercetin can effectively promote the osteogenic differentiation of BMSCs,and its mechanism is achieved by activating the Wnt/β-catenin signaling pathway and up-regulating the expression of the osteogenesis-related transcription factor RUNX2.

Objective:To analyze and summarize the efficacy and safety of thalidomide in the treatment of refractory systemic juvenile idiopathic arthritis（sJIA）.Methods:The clinical data of ten patients with refractory sJIA admitted to Department of Nephrology and Immunology in Children's Hospital of Hebei Province from January 2015 to March 2022 were collected，and the clinical manifestations，efficacy and safety of thalidomide in the treatment of refractory sJIA were analyzed retrospectively. Systemic juvenile arthritis disease activity score（sJADAS）was used to evaluate the efficacy of the treatment. Statistical analysis was performed by repeated measurements using general linear models.Results:Among the 10 children（4 males and 6 females）with refractory sJIA，the average age of onset was（7.5±3.3）years. Seven patients were complicated with macrophage activation syndrome at an early stage of disease.The average course of disease was（4.4±1.7）years，and the longest course of disease was 8.3 years. Before the application of thalidomide，all the 10 children experienced relapses（ranging from 2 to 10 times）. The indices of 10 children treated with thalidomide at 6 months and 12 months were compared with those before treatment. Peripheral blood leukocytes［（10.19±3.67）×10 9/L，（8.53±2.83）×10 9/L vs.（16.11±7.81）×10 9/L， F=7.918，11.084， P=0.020，0.009］，C-reactive protein［19.13（0.38，35.21）mg/L，8.05（0.10，18.00）mg/L vs. 59.34（24.20，131.90）mg/L， F=7.030，12.731， P=0.026，0.006］，sJADAS scores［6.00（1.50，12.50）scores，3.00（0，12.50）scores vs. 20.00（11.50，28.00）scores， F=14.710，17.870， P=0.004，0.002］were decreased significantly. The doses of prednisone［0.13（0，0.45）mg/（kg·d），0.02（0，0.06）mg/（kg·d）vs. 0.42（0.16，1.47）mg/（kg·d）， F=5.890，7.623， P=0.041，0.022］were significantly decreased.All the differences were statistically significant. Prednisone was successfully discontinued in 7 cases. Tocilizumab was gradually withdrawn in 3 cases，and tocilizumab administration interval was prolonged in 1 case. None of the 10 children had serious adverse reactions. Conclusion:Thalidomide is clinically effective in the treatment of sJIA，and can reduce the required dose of prednisone and prolong the tocilizumab free remission.

Objective:To compare the similarities and differences of macrophage activation syndrome（MAS）combined with systemic juvenile idiopathic arthritis（sJIA）versus with juvenile onset systemic lupus erythematosus（JSLE）.Methods:The clinical data of 48 children with MAS admitted to the Department of Nephrology and Immunology in Children's Hospital of Hebei Province from May 2015 to January 2023 were retrospectively analyzed. The patients were divided into sJIA-MAS and JSLE-MAS group，and the clinical manifestations，laboratory indicators and treatment of the two groups were compared.Results:Among the 48 children（14 males and 34 females）with MAS，the average age of onset was 9.5（3.0，11.8）years. There were 28 cases（11males and 17 females）of sJIA-MAS and 20 cases（3 males and 17 females）of JSLE- MAS. All the 48 children with MAS had fever and hyperferinemia，and the fever with sJIA-MAS was mostly continued fever or remittent fever. Respiratory tract infection was the most common trigger in sJIA-MAS［15 cases（53.6%）］，and disease activity was the most common trigger in JSLE-MAS［13 cases（65.0%）］.Additionally，viral infections（EB virus and cytomegalovirus）were also one of the triggers in MAS［sJIA：7 cases（25%），JSLE：4 cases（20%）］.Compared with JSLE-MAS，the number of days with fever［15.0（12.0，21.0）days vs. 6.0（4.0，9.5）days， Z=-3.812， P=0.001］and the length of hospital stay［29.0（26.3，39.8）days vs.26.0（19.3，30.8）days， Z=-1.958， P=0.049］were longer in sJIA. Compared with JSLE-MAS，ALT［（685.32±561.67）U/L vs.（139.61±124.44）U/L， t=4.973， P=0.001］，AST［784.00（235.25，1 251.25）U/L vs.189.50（53.25，374.08）U/L， Z=-3.283， P=0.001］，CRP［11.48（3.56，28.89）mg/L vs.1.91（0.53，8.98）mg/L， Z=-3.200， P=0.001］，ferritin［32 167.0（12 384.8，65 963.8）μg/L vs.2 003.5（922.5，11 430.0）μg/L， Z=-4.130， P=0.001］，ferritin max/ESR min［1 353.35（355.75，4 342.53）vs.91.92（34.94，291.53）， Z=-4.120， P=0.001］were higher in sJIA.The decrease of CRP was greater in sJIA［80.04（45.64，143.71）mg/L vs.10.20（6.27，25.64）mg/L， Z=-4.433， P=0.001］.Compared with sJIA-MAS，peripheral white blood cell counting［4.05（2.90，7.73）×10 9/L vs.1.56（1.15，3.47）×10 9/L， Z=-3.577， P=0.001］and platelet counting［（162.68±92.19）×10 9/L vs.（110.10±72.99）×10 9/L， t=2.118， P=0.040］were lower in JSLE-MAS. Kidney involvement was more common in JSLE-MAS［10 cases（50%）vs.0 cases（0%）， χ 2=17.684， P=0.001］.There was no significant difference in the incidence of sJIA-MAS and JSLE-MAS meeting the criteria of hemophagocytic lymphohistiocytosis［6 cases（21.4%）vs.5 cases（25.0%）， χ 2=0.084， P=0.772］. Conclusion:Compared with JSLE-MAS，sJIA-MAS is more dangerous and difficult to control，while JSLE-MAS involves more organs，among which the blood system and kidney are more common.

Objective:To establish a tissue based assay and in-house cell based assay combined system to screen anti-metabotropic glutamate receptor 1 antibodies in a case of previously idiopathic encephalitis with prominent cerebellar ataxia and make the final diagnosis, and to summarize and analyze clinical characteristics and treatment response of the disease.Methods:A middle-aged woman admitted to Department of Neurology, People's Liberation Army General Hospical Accredited to the Sixth Medical Center in January 9, 2020, who presented with acute dizziness, unsteady gait and developed head titubation, repeated language and calculation impairment was reported. The patient′s serum and cerebrospinal fluid were firstly tested with commercial kits for conventional neural antibodies.Then samples were incubated with rat hippocampus, cerebellum and human embryonic kidney 293 cells transfected with metabotropic glutamate receptor 1 plasmid to screen extra antibodies by indirect immunofluorescence method. By reviewing literature, physical functions of metabotropic glutamate receptor 1 and clinical features of anti-metabotropic glutamate receptor 1 antibodies associated encephalitis were summarized.Results:The patient was neural antibodies negative with commercial kits. Further investigation showed neuropil staining pattern after her serum and cerebral spinal fluid were incubated with rat brain slices. The characteristic "Medusa head" staining pattern of Purkinje cells in cerebellum was also noticed. Along with her previous head titubation symptom, an in-house cell based assay using human embryonic kidney 293 cells transfected with metabotropic glutamate receptor 1 plasmid was developed and proved the existence of anti-metabotropic glutamate receptor 1 antibodies. The final diagnosis of anti-metabotropic glutamate receptor 1 antibodies associated encephalitis was made. One-year follow-up revealed her serum antibodies titers dramatically decreased and cerebrospinal fluid antibodies were negative after using steroids and intravenous immunoglobulin, but still left prominent cerebellum atrophy and severe ataxia.Conclusions:Anti-metabotropic glutamate receptor 1 antibodies may cause acute encephalitis. Cerebellar ataxia and head titubation are characteristic symptoms of metabotropic glutamate receptor 1 autoimmunity. The response to immunotherapies is limited and patients may have severe neurological deficits.

Objective:To study the use of digital subtraction angiography (DSA) guided transnasal ileus tube placement in management of abdominal compartment syndrome (ACS) after liver transplantation.Methods:From January 2015 to December 2019, a total of 30 patients who developed ACS after liver transplantation who were admitted to the Transplantation Intensive Care Unit of Tianjin First Central Hospital were retrospectively studied. According to the way of decompression, these patients were divided into the study group and the control group. Patients in the control group were treated with conventional abdominal decompression, while patients in the study group were treated with DSA guided transnasal ileus tube placement based on management principles developed in conventional abdominal decompression. Changes in intra-abdominal pressure, treatment efficacy rates and liver functions were monitored in the two groups up to 7 days after abdominal decompression.Results:There were 23 males and 7 females, aged (53.4±11.6) years. After treatment, the IAP, portal venous blood flow velocity, bile drainage volume, ALT and AST in the study group were significantly better when compared with the findings before treatment: [IAP: (7.13±3.87) vs (22.73±2.09) mmHg, portal vein blood flow velocity: (34.76±10.31) vs (21.45±6.47) cm/s, bile drainage volume: (198.43±19.94) vs (80.72±9.52) ml/d, ALT: (158.92±67.56) vs (278.73±99.17) U/L, AST: (79.36±15.63) vs (196.71±89.05) U/L], ( P<0.05). After treatment, when compared with the control group, the IAP, portal vein blood flow velocity, bile drainage and TBil in the study group were significantly better [IAP: (7.13±3.87) vs (13.47±6.19) mmHg, portal vein blood flow velocity: (34.76±10.31) vs (24.98±8.54) cm/s, bile drainage: (198.43±19.94) vs (108.73±21.30) ml/d, TBil: (258.85±91.95) vs (343.69±89.45) μmol/L], ( P<0.05). In the control group, the IAP significantly decreased on the fourth day after treatment, ( P<0.05); compared with the significant difference in the study group on the second day after treatment ( P<0.05). After 7 days of treatment, the efficacy rate of the control group was 46.7% (7/15), compared to 86.7% (13/15) in the study group. The difference between the two groups was significant (χ 2=5.400, P<0.05). Conclusion:DSA guided transnasal ileus tube placement for treatment of abdominal compartment syndrome after liver transplantation resulted in a better treatment efficacy rate than conventional treatment.

Objective: To investigate the reversal effects in A549/DDP by standard substances (SS) from Traditional Chinese Medicine. Methods: Cell proliferation assays were performed to investigate the Resistant Index of A549/DDP and its tolerance to selected SS. The working concentrations of SS, IC5 calculated by nonlinear regressions, were applied as reversal doses to investigate the effects. Results: The resistant index of A549/DDP was 31.79. Tetramethylpyrazine and Matrine were well tolerated. Berberine hydrochloride, Dauricine, Oridomin exhibited dose-depend inhibitory effects on A549/DDP cell line. The working concentrations of them could effectively reverse the resistance of A549/DDP cell line to DDP. (P＜0.01) . Conclusion: The selected standard substances from Traditional Chinese Medicine were capable to reverse the resistance of A549/DDP cell line to DDP.

This study was aimed to illustrate the interaction mechanism between Chinese herbal medicines and CASP3 target,and to analyze the structural characteristics of CASP3 inhibitors.Molecular docking,molecular dynamics and binding energy were employed to analyze the interactions and mechanism between CASP3 target and ligands which were screened from a series of nature products.The results showed that the binding forces of tanshinone ⅡA and scutellarin with CASP3 target were stronger than others.And the theoretical stable structures of tanshinone ⅡA and scutellarin combined with CASP3 target were obtained by molecular dynamics method.It also can be found that hydrophobic interaction was crucial for tanshinone ⅡA binding to amino acid residues of CASP3 such as Phe256,Ser205 and Trp206.Meanwhile,one hydrogen bond was formed between ligand and receptor.The main interactions between scutellarin and CASP3 target were found to arise from hydrophobic effect in ligand and nine amino acid residues of receptor (such as Ser249,Trp214,and Trp206),four hydrogen bonds with different stabilities and electrostatic interaction.It was concluded that tanshinone ⅡA and scutellarin can form stable structures with CASP3 target.And their similar structures may be useful to screen effective CASP3 inhibitors.

In the present work, NiTi alloy substrates were activated by three different pretreatment processes. 5 X SBF1 and 5 X SBF2 concentrated simulated body fluids were prepared with citric acid buffer reagent, and then calcium phosphate coatings were formed quickly on NiTi alloy surface by accelerated biomimetic synthesis after pretreatment. The microstructure, composition and surface morphology of calcium phosphate coatings were studied. The results indicate that calcium phosphate coatings possess porous and net structure, which are composed of precipitated spherical particles with diameter less than 3 microm. The analysis of XRD shows that the main component of calcium phosphate coatings is hydroxyapatite, whereas the concentrated 5 x SBF simulated body fluid, which is in the absence of Mg2+ and HCO3- crystal growth inhibitors, apparently accelerates the growth rate of hydroxyapatite coatings.
Biomimetic Materials ; Body Fluids ; Calcium Phosphates ; chemistry ; Coated Materials, Biocompatible ; chemical synthesis ; Computer Simulation ; Durapatite ; chemical synthesis ; Humans ; Nickel ; Titanium