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

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.

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

Objective To investigate the effect of dietary intake on the childbirth outcomes of primipara women with full-term labor analgesia. Methods A total of 400 primipara women with full-term labor analgesia were randomly divided into observation group and control group. The observation group received intake management and individualized dietary guidance, while the control group ate and drank according to their own wishes. The childbirth quality, the incidence of vomiting, the use of oxytocin due to uterine atony, the rate of intrapartum fever, the rate of perineal incision, the rate of cesarean section, the rate of vaginal assisted delivery, and the rate of postpartum hemorrhage were compared between the two groups. The duration of the first stage of labor, the duration of the second stage of labor, the duration of labor analgesia, and the amount of postpartum hemorrhage within 2 hours were also compared. Neonatal Apgar score, random blood glucose, umbilical artery blood pH value, umbilical artery blood lactic acid (Lac) value, the incidence of neonatal asphyxia, the incidence of neonatal fever, and the incidence of neonatal hypoglycemia were compared between the two groups. Results The observation group had lower incidences of vomiting, oxytocin use rate due to uterine atony, intrapartum fever rate, perineal incision rate, transferring cesarean section rate, and vaginal assisted delivery compared to the control group(P < 0.05). The observation group had lower rates of postpartum hemorrhage, shorter duration of the first and second stages of labor, shorter duration of labor analgesia, and less postpartum hemorrhage within 2 hours compared to the control group, and the incidences of neonatal hyperglycemia and hypoglycemia in the observation group were lower than those in the control group (P < 0.05). There were no statistically significant differences in umbilical artery blood pH value, Lac value, neonatal Apgar score, random blood glucose, neonatal asphyxia rate, and neonatal fever rate between the two groups (P>0.05). Conclusion Intake management and individualized dietary guidance during labor can reduce the incidence of uterine atony, shorten the duration of labor, decrease the incidence of dystocia, reduce postpartum hemorrhage within 2 hours and decrease the incidence of neonatal glucose abnormality.

Objective To explore the effect of intermittent fasting combined with diversified management mode on weight loss of overweight and obese people. Methods A total of 120 overweight and obese patients were selected as research objects, and randomly divided into control group (n=60) and experimental group (n=60). The control group was given intermittent fasting, and the experimental group was given diversified management mode on the basis of the control group. Waist circumference, body mass, body mass index (BMI), waist-to-hip ratio and blood lipid level were compared between the two groups; the scores of hunger, satiety, satisfaction and the incidence of adverse reactions were compared between the two groups. Results After intervention, waist circumference, body mass, BMI, waist-to-hip ratio, total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) in the experimental group were significantly lower, and high-density lipoprotein cholesterol (HDL-C) was significantly higher than that in the control group (P < 0.05). After intervention, the hunger score of the experimental group was significantly lower, and the satiety score and satisfaction score were significantly higher than those of the control group (P < 0.05). The total incidence of adverse reactions in the experimental group was 6.67%, which was significantly lower than 20.00% in the control group (P < 0.05). Conclusion The application of intermittent fasting combined with diversified management mode in overweight and obese people is better, which can improve the relevant clinical indicators and blood lipid levels, and has high safety.

Objective:To systematically evaluate influencing factors of multi-drug resistant organisms (MDROs) infection in patients undergoing liver transplantation and to provide reference for infection prevention and control.Methods:The relevant literatures on the influencing factors of MDROs infection after liver transplantation included in PubMed, Medline, Embase, Wed of Science, China Biology Medicine disc, Wanfang Database, China National Knowledge Infrastructure and VIP were searched by computer, and the search time was from the establishment of databases to September 1, 2023. The languages were limited to Chinese and English. Two evaluators screened literature and extracted data, and used The Newcastle Ottawa Scale to evaluate the quality of the final included literature. Meta-analysis was performed using RevMan5.4 software.Results:Finally, a total of 17 literatures were included, including five case-control studies and 12 cohort studies. The results of Meta-analysis showed that ClassⅡ toⅣ hepatic encephalopathy, renal insufficiency, colonization of drug-resistant organisms before transplantation, performing tracheal intubation, tracheal intubation time greater than or equal to 48 h, tracheal intubation time greater than or equal to 72 h, length of ICU stay, use of antibiotics before transplantation, postoperative bile leakage, postoperative fungal culture of positivity, reoperation after transplantation and hemodialysis were risk factors for MDROs infection after liver transplantation ( P<0.05) . Conclusions:There are many influencing factors for multi-drug resistant organisms infection in liver transplant patients after surgery. Medical staff should be vigilant and identify relevant risk factors, conduct infection risk assessment and take preventive and control measures based on risk factors to improve the prognosis of liver transplant patients.