ObjectiveTo observe the clinical efficacy of Gandou Fumu Granules （GDFMG） combined with sodium dimercaptosulphonate （DMPS） on liver fibrosis in Wilson disease （WD） patients with the syndrome of phlegm and blood stasis， evaluate its effect on cuproptosis-related indicators， and explore the possible mechanisms of cuproptosis in WD-related liver fibrosis. MethodsSixty WD patients diagnosed with the syndrome of phlegm and blood stasis between January 2023 and December 2023 were randomly divided into a control group and an observation group， with 30 patients in each group. The control group received the copper chelator DMPS for the first 6 days， followed by calcium gluconate injection for the next 2 days， completing an 8-day treatment cycle. The observation group received GDFMG in addition to the treatment regimen of the control group， with both groups treated for 21 cycles. A Beckman fully automated biochemical analyzer was used to detect levels of type Ⅳ collagen （CⅣ）， hyaluronic acid （HA）， laminin （LN）， N-terminal propeptide of type Ⅲ procollagen （PⅢ-NP）， and serum copper （SCu） before and after treatment in both groups. Enzyme-linked immunosorbent assay （ELISA） was used to measure levels of ferredoxin 1 （FDX1）， lipoic acid synthetase （LIAS）， and dihydrolipoamide S-acetyltransferase （DLAT）. Atomic absorption spectroscopy measured 24-hour urine copper levels before treatment and after the 7， 14， and 21 treatment cycles in both groups. An Fibro Touch （FT） non-invasive liver fibrosis diagnostic device was used to measure liver stiffness （LSM） in both groups before and after treatment. Traditional Chinese medicine syndrome score （TCMSS） was evaluated at the same intervals. Clinical efficacy， adverse events， and safety indicators were also compared. ResultsAfter treatment， levels of CⅣ， HA， LN， and PⅢNP significantly decreased in both groups compared to pre-treatment levels （P<0.01）. The observation group showed a more pronounced reduction compared to the control group （P<0.05）. There were no statistically significant differences in SCu levels in both groups before and after treatment. After treatment， levels of FDX1，LIAS and DLAT significantly increased in both groups（P<0.01）. The observation group showed more notable improvements in these indicators than the control group （P<0.05）. After the 7， 14， 21 treatment cycles， 24-hour urine copper levels significantly increased in both groups compared to pre-treatment levels （P<0.01）. The observation group had a greater increase in 24-hour urine copper levels than the control group after treatment （P<0.05，P<0.01）， and although 24-hour urine copper levels increased after 7 cycles， a gradual decline was observed in subsequent cycles. After treatment， LSM levels significantly decreased in both groups compared to pre-treatment levels （P<0.01）， with the observation group showing a greater reduction than the control group （P<0.05）. Clinical efficacy was significantly better in the observation group than the control group （P<0.05）. No significant differences in the incidence of adverse events or safety indicators were observed between the two groups after treatment. ConclusionGDFMG combined with DMPS can reduce LSM in WD patients with liver fibrosis and the syndrome of phlegm and blood stasis， inhibit cuproptosis， and improve clinical efficacy.

Objective To obtain the protective performance parameters of barium sulfate mortar against positron nuclide γ-rays, provide reference data for precise shielding calculations, and guide the design, evaluation, and construction of radiation shielding. Methods The FLUKA program was used to build a model for simulating the dose equivalent rate variation around points of interest under the irradiation of the most commonly used positron nuclide ¹⁸F with changes in the thicknesses of lead and barium sulfate mortar. The transmission curves of lead and barium sulfate mortar were fitted, and the half-value layer (HVL) and lead equivalence of barium sulfate mortar were calculated based on the fitted curves. Results The ambient dose equivalent rate coefficient of positron nuclide ¹⁸F was 1.339 4×10⁻¹ μSv·m²/MBq·h and the HVL for lead was 4.037 mm, with deviations of 0.043% and 1.53% compared to the values provided in the AAPM Report No. 108, respectively. The HVLs for γ-rays produced by ¹⁸F, using barium sulfate mortar with apparent densities of 4.20, 4.00, and 3.90 g/cm³ mixed with 35.2-grade cement in a 4∶1 mass ratio, were 2.914, 2.969, and 3.079 cm, respectively. The lead equivalences were 0.1385, 0.1360, and 0.1311 mmPb/mm, respectively. Conclusion The three types of barium sulfate mortar can provide good protection against γ-rays in positron imaging locations. As the apparent density of barium sulfate increases, its protective effect improves slightly but remains significantly better than common construction materials like concrete and solid bricks.

ObjectiveTo explore the role of cuproptosis and identify cuproptosis-related genes in Wilson disease （WD） through bioinformatics analysis and clinical validation，providing implications and directions for the diagnosis and treatment of WD. Methods（1） Screening of target genes： The differentially expressed genes （DEGs） between WD and healthy control were obtained from GeneCards，and the cuproptosis-related genes were obtained from Gene Expression Omnibus （GEO） and published literature.The cuproptosis-related genes in WD were obtained by intersection.Through gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses，the specific biological process，functions or metabolic pathways of cuproptosis-related genes in WD were predicted.Molecular docking and PyMOL visualization were then performed to analyze and verify the potential regulatory mechanism of Gandou Fumu Decoction for cuproptosis.（2）Validation of target genes： The blood samples of 15 WD patients treated in the department of encephalopathy and 15 healthy volunteers undergoing physical examinations in the health management center were randomly collected from the First Affiliated Hospital of Anhui University of Chinese Medicine.The expression levels of target genes were determined by Western blot and real-time PCR. Results（1） A total of 3 607 DEGs in WD were obtained from GSE107323 in GEO，and 68 cuproptosis-related genes were obtained from GeneCards and published literature.Twelve common target genes were obtained by intersection，including three up-related genes（SQSTM1，MIF1，and TAX1BP1） and nine down-regulated genes（CP，SERPINE1，AOC3，GPX4，SLC27A5，VEGF-A，PDHB，PDK1，and ATP7B）.The common target genes were mainly enriched in monocarboxylic acid metabolism，oxidoreductase activity，negative regulation of molecular functions，which mainly involved HIF-1，ferroptosis and other signaling pathways.Molecular docking and PyMOL visualization results showed Gandou Fumu Decoction had good binding ability with the cuproptosis-related genes PDK1，SERPINE1，VEGFA，and AOC3 in WD.（2）A total of 30 blood samples were collected，including 15 WD patients and 15 health volunteers.Western blot results showed that expression levels of target genes were consistent with the results obtained by bioinformatics analysis.RT-qPCR results showed that compared with healthy volunteers，WD patients had down-regulated mRNA levels of SERPINE1，GPX4，SLC27A5，and VEGF-A and up-regulated mRNA levels of SQSTM1 and MIF1（P<0.05）. ConclusionThe expression levels of cuproptosis-related genes in WD patients are consistent with the results predicted by bioinformatics analysis.The characteristic preparation Gandou Fumu Decoction of Xin'an Medicine showed good binding abilities with the cuproptosis-related genes in WD.Cuproptosis may play a key role in the pathophysiological mechanism of WD，which can provide a new target for the diagnosis and treatment of WD.

OBJECTIVE To investigate the role and mechanism of paeonol in inhibiting the migration of bladder cancer T24 cells by regulating nuclear factor κB （NF-κB）/hypoxia-inducible factor-1α （HIF-1α）-mediated aerobic glycolysis. METHODS T24 cells were divided into control group， cisplatin group （positive control， 3.001 μg/mL）， and paeonol low-， medium- and high-dose groups （100， 200， 400 μg/mL）， respectively. After 24 h of administration intervention， the effect of paeonol on the migration ability of T24 cells was detected （expressed by the cell scratch wound healing rate）. The effect of paeonol on the mitochondrial membrane potential of T24 cells was detected （expressed by the ratio of red/green fluorescence intensity）. Cellular adenosine triphosphate （ATP） levels and lactate content in T24 cells were measured. The levels of NF-κB/HIF-1α signaling pathway， the expression of migration-related proteins， and key enzymes involved in aerobic glycolysis in the cells were all determined. RESULTS Compared with the control group， the cell scratch wound healing rates in the paeonol medium- and high-dose groups and the cisplatin group were decreased significantly （P＜0.01）； in the paeonol groups， the expression levels of NF-κB/HIF-1α signaling pathway-related proteins such as NF- κB and HIF-1α， migration-related proteins such as matrix metalloproteinase 2 （MMP2）， MMP9， and vascular endothelial growth factor， as well as key enzymes involved in aerobic glycolysis such as glucose transporter 1， hexokinase 2 and pyruvate kinase isozyme type M2， were all reduced to varying degrees in the cells， most of these reductions showed statistically significant differences （P＜0.05 or P＜0.01）； the ratio of red/green fluorescence intensity in mitochondria of cells in the medium- and high-dose paeonol groups were significantly decreased （P＜0.01）； the ATP concentration in cells of the paeonol high-dose group， and the lactate content in cells across all paeonol groups were significantly decreased （P＜0.05 or P＜0.01）. CONCLUSIONS Paeonol significantly inhibits the migration of bladder cancer T24 cells， and its mechanism of action may be related to the inhibition of the NF-κB/HIF-1α signaling pathway， and the down-regulation of key enzyme activities involved in aerobic glycolysis.

Hepatocellular carcinoma (HCC) is one of the fastest growing cancers in the world, ranking fourth among the causes of cancer-induced death in the world. At present, the field of HCC treatment is developing rapidly, and immunotherapy has been recognized as a promising treatment method, in which T cells play a key role in HCC immunotherapy. However, in the case of virus infection or in tumor microenvironment (TME), T cells will be continuously stimulated by antigens and then fall into the state of T cell exhaustion (Tex). This state will not only reduce the immunity of patients but also lead to poor efficacy of immunotherapy. Therefore, to deeply analyze the mechanism of Tex and to explore effective strategies to reverse Tex is the key point in the immunotherapy for HCC. This review aims to summarize the mechanism of Tex in HCC patients, and the current situation and shortcomings of drug research and development to reverse Tex at this stage, in order to provide theoretical basis for the optimization of immunotherapy regimen for HCC patients.
Humans ; Carcinoma, Hepatocellular/therapy* ; Liver Neoplasms/therapy* ; Immunotherapy/methods* ; T-Lymphocytes/immunology* ; Tumor Microenvironment/immunology* ; Animals ; T-Cell Exhaustion

Humans ; Gastrointestinal Microbiome ; Constipation/therapy* ; Probiotics/therapeutic use* ; Patients

Objective To simulate and analyze the dose distribution from external exposure and its influencing factors of induced radioactivity in proton therapy site. Methods Referencing a domestically under-construction proton therapy facility, a geometric model of the proton therapy site was constructed, and the FLUKA program was used to simulate the distribution of the induced radioactive dose of the proton therapy site under the conditions of different energies, beam angles, irradiation time, cooling time and medium of the treatment site. Results For a 230 MeV proton beam with a current of 3.0 nA, directed along the negative Z-axis and irradiating a phantom for two minutes, at the shutdown moment, the ambient dose equivalent rates in air and vacuum 5, 30, and 50 cm away from the phantom surface were (1 039.02±5.82)-(127.86±1.20) and (1 037.96±4.38)~(127.35±0.93) μSv/h, respectively. The mean difference was 0.51~1.06 μSv/h, and the air-immersed external irradiation accounted for <1% of the total irradiation, which rapidly decreased to 1/15 of the shutdown moment value after cooling for 10 minutes. Under the condition of 130~250 MeV, the ambient dose equivalent rates at the shutdown moments 5, 30 and 50 cm away from the surface of the phantom were (427.49±3.12)-(1 058.41±4.66), (100.36±0.92)-(259.70±1.69) and (50.15±0.68)-(131.93±1.11) μSv/h, respectively. Irradiation for one-five minutes, and at the moment of shutdown at 5, 30, and 50 cm from the surface of the phantom were (688.19±3.33)-(1 594.04±8.08), (167.60±1.35)-(388.24±2.96) and (84.73±0.69)-(195.94±1.56) μSv/h. The peripheral dose-equivalent rate of the sensed radioactivity decreases with the irradiation time, the energy of the beam, and the distance from the model. The peak dose equivalent rate around the induced radioactivity exists in the beam direction, which is significantly larger than that in the non-beam direction. Conclusion Proton therapy sites are characterized by relatively large levels of induced peripheral radioactive dose equivalent rates, mainly originating from patients. In actual practice, a suitable working position can be chosen according to the direction of the beam current, especially the direction of the final irradiation field beam current, in the non-beam current direction and as far away from the patient as possible. Within 10 minutes after the end of treatment, staff should try to avoid close contact with the patients.

Objective To assess the sweat secretion of Yin-deficient ovariectomized rats and investigate the changes in biochemical indexes.Methods Eighteen SD female rats were randomly divided into a sham operation group,model group,and positive control group of six rats each.The rats in the sham operation group underwent a sham operation,and those in the model group and positive control group underwent bilateral ovariectomy.L-Thyroxine(92 mg/kg)was given once a day for 7 consecutive days starting on the 7th postoperative day to establish a Yin-deficient ovariectomized model.The rats in the positive control group were orally administered Qinggu San Tang(7.3 g/kg)once a day,while those in the sham operation group and model group were orally administered an equal amount of distilled water once a day for a total of 14 days.Sweat secretion from the plantar region of the foot was measured using the Wada-Takagaki reagent coloring method.At the end of the experiment,blood was taken from the abdominal aorta and the tissue of the paw pads was separated.The serum levels cyclic adenosine monophosphate(cAMP),cyclic guanosine monophosphate(cGMP),luteinizing hormone(LH),gonadotropin-releasing hormone(GnRH),and estradiol(E2)were measured by enzyme-linked immunosorbent assay.Western Blot was used to determine the expression levels of M3 R,β2 AR,and aquaporin-5(AQP5)in the paw pad.Results The three main findings of this study were as follows.(1)Compared with the rats in the sham operation group,those in the model group were more irritable and aggressive,and their body weights decreased while their average temperature and sweat secretion significantly increased.(2)Serum cAMP level and cAMP/cGMP ratio increased,the LH and GnRH levels significantly increased,and the E2 level decreased.(3)M3 R expression was down-regulated and β2 AR and AQP5 expression was up-regulated in the paw pads of the rats.After 2 weeks of positive control treatment,the serum cAMP level and cAMP/cGMP ratio significantly decreased and the LH and GnRH levels decreased;however,no statistically significant difference was observed in the serum E2 level.The expression levels of M3 R were increased-regulated in paw pads of the rats,and reduced expression of β2 AR and AQP5.Conclusions Sweat secretion significantly increased in this"combined disease and evidence"model of perimenopausal syndrome kidney yin deficiency established by desiccation combined with thyroxine.The underlying mechanism may be related to the changes in cGMP,cAMP,and key proteins M3 R,β2 AR,and AQP5 in sweat glands that regulate sweat secretion.

Objectives:To establish a risk prediction model for gastrointestinal bleeding after cardiopulmonary bypass heart surgery,and to verify the prediction efficacy. Methods:A total of 1 002 patients who underwent cardiopulmonary bypass heart surgery in the department of cardiac great vascular surgery of our hospital from January 2019 to November 2023 were collected by convenient sampling method.They were divided into gastrointestinal bleeding group(n=47)and non-gastrointestinal bleeding group(n=955).Logistic regression analysis was used to establish the risk prediction model,and the area under ROC curve test and Hosmer-Lemeshow χ2 test were used to compare the two groups of data Model prediction effect.Bootstrap method was used for internal validation. Results:The risk prediction model of gastrointestinal bleeding after cardiopulmonary bypass heart surgery included four predictors:time of aortic occlusion(OR=1.021,95%CI:1.012-1.030),history of digestive disease(OR=5.710,95%CI:1.697-19.212),use of intra-aortic balloon counterpulsation(OR=22.180,95%CI:5.870-83.808),and continuous kidney replacement therapy(OR=12.159,95%CI:5.066-29.181).Model formula:Logit(P)=-5.821+0.021×time of aortic occlusion+1.742×history of digestive disease+3.099×whether intra-aortic balloon counterpulsation was used+2.498×whether continuous renal replacement therapy was used.The area under ROC curve was 0.812(95%CI:0.746-0.877),sensitivity was 64.6%,specificity was 85.7%,and Youden index was 0.503.After internal validation by Bootstrap method,the consistency index after correction is 0.813. Conclusions:The risk prediction model constructed in this study cohort has a good auxiliary prediction performance for the occurrence of gastrointestinal bleeding after cardiopulmonary bypass surgery,which is helpful for risk stratification for gastrointestinal bleeding after cardiopulmonary bypass surgery and facilitate clinical decision-making in daily clinical work.

Objective:To observe the effect of fractional flow reserve derived from computed tomography(FFRcT)measurement system based on iterative algorithm in diagnosing survival prognosis of patients with acute ST-segment elevation myocardial infarction(STEMI)after they underwent emergency percutaneous coronary intervention(PCI).Methods:A total of 98 patients with acute STEMI complicated with multi vessel disease(MVD)were prospectively selected from the Affiliated Hospital of Inner Mongolia Medical University during October 2022 and February 2024.All patients were divided into two groups according to random double-blind method:FFRCT guidance group(49cases)and coronary angiography(CAG)guidance group(49cases).The FFRCT guidance group used FFRCT as the diagnostic basis,which carried out complete revascularization strategy according to FFRCT examination results.CAG guidance group handled infarct-related vessels as the CAG guidance.The basic clinical data,operation details of PCI surgery/technical indicators and utilization indicators of related resource of the two groups were observed,and angina pectoris attack and major adverse cardiovascular events(MACE)and other prognosis indicators of related survival of the two groups were observed and followed up.The primarily observed endpoints were all-cause death,heart failure,stroke,MACE,and composite endpoint event of stroke and revascularization again within 24 months follow-up.Results:The proportion of undergoing PCI on non-infarct-related vessel was 55.10％(27/49)in FFRCT group.In the comparison of operation detail of surgery/technique indicator after PCI surgery between two groups,the operation time of FFRCT guidance group was(65±10)min,which was longer than that[(60±8)min]of CAG guidance group,and the total length of stent was(31±10)mm,which was shorter than that[(36±10)mm]of CAG guidance group.There were statistically significant differences in the above two indicators between the two groups(t=-4.062,-6.710,P＜0.05),respectively.There were no statistically significant differences in the amount of contrast agent,average diameter of stent and length of stay between the two groups(P＞0.05).Compared with the CAG group,the incidences of non-lethal myocardial infarction,primary endpoint events,recurrent angina pectoris,and revascularization of FFRCT group significantly reduced within 24 months follow-up,and the differences of them between two groups were statistically significant(x2=4.926,5.273,6.091,5.804,P＜0.05),respectively.Conclusion:Using FFRCT measurement system based on iterative algorithm in PCI process of emergency for patients with acute STEMI complicated with MVD to examine and guide revascularization is safe and effective,which is worthy of recognition.It has obvious advantages over CAG guidance in reducing the risk of cardiovascular and cerebrovascular events,and in improving prognosis after PCI.