Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB⁺ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg ^-/- Rag2 ^-/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.

Objective:To explore the clinical efficacy of 125I seeds implantation combined with transcatheter arterial chemoembolization (TACE) in the treatment of primary liver cancer. Methods:A retrospective analysis of data from 40 patients with primary liver cancer at the Northern Theater General Hospital from January 2018 to December 2020 (26 males, 14 females, age 41 to 82 years) was performed. Among them, 21 patients were in treatment group and underwent 125I seeds implantation combined with TACE treatment, while 19 patients were in control group and received TACE treatment. Alpha-fetoprotein (AFP) levels between the two groups were compared, effective rate and disease control rate (DCR) of the two groups were analyzed, and overall survival (OS) and progression-free survival (PFS) were observed. Data were analyzed by using Mann-Whitney U test, χ2 test, Kaplan-Meier method and log-rank test. Results:Two months after 125I seeds implantation, the effective rates of treatment group and control group were 76.19%(16/21) and 8/19, respectively ( χ2=4.83, P=0.028); the DCRs were 90.48%(19/21) and 11/19, respectively ( χ2=4.21, P=0.040). AFP levels in both groups decreased significantly, with treatment group showing a greater decrease rate (0.87(0.84, 0.90) and 0.66(0.65, 0.67); z=5.42, P<0.001). No serious adverse reaction was observed in either group. The median OS of treatment group and control group were 18.2 and 10.6 months, respectively ( χ2=10.98, P=0.037); the median PFS of the two groups were 8.4 and 6.1 months, respectively ( χ2=7.54, P=0.041). Conclusion:125I seeds implantation combined with TACE treatment can exert a synergistic and enhancing effect in the treatment of primary liver cancer.

Phytoremediation plays an important role in the treatment of heavy metal pollution in soil. In order to elucidate the mechanism of salicylic acid (SA) on copper absorption, seedlings from Xuzhou (with strong Cu-tolerance) and Weifang Helianthus tuberosus cultivars (with weak Cu-tolerance) were selected for pot culture experiments. 1 mmol/L SA was sprayed upon 300 mg/kg soil copper stress, and the photosynthesis, leaf antioxidant system, several essential mineral nutrients and the changes of root upon copper stress were analyzed to explore the mechanism of copper resistance. The results showed that Pn, Tr, Gs and Ci upon copper stress decreased significantly compared to the control group. Meanwhile, chlorophyll a, chlorophyll b and carotenoid decreased with significant increase in initial fluorescence (F₀), maximum photochemical quantum yield of PSⅡ (Fv/Fm), electron transfer rate (ETR) and photochemical quenching coefficient (qP) content all decreased. The ascorbic acid (AsA) content was decreased, the glutathione (GSH) value was increased, the superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) activity in the leaves were decreased, and the peroxidase (POD) activity was significantly increased. SA increased the Cu content in the ground and root system, and weakened the nutrient uptake capacity of K, Ca, Mg, and Zn in the root stem and leaves. Spray of exogenous SA can maintain the opening of leaf stomata, improve the adverse effect of copper on photosynthetic pigment and PSⅡ reaction center. Mediating the SOD and APX activity started the AsA-GSH cycle process, effectively regulated the antioxidant enzyme system in chrysanthemum taro, significantly reduced the copper content of all parts of the plant, and improved the ion exchange capacity in the body. External SA increased the content of the negative electric group on the root by changing the proportion of components in the root, promoted the absorption of mineral nutrient elements and the accumulation of osmoregulatory substances, strengthened the fixation effect of the root on metal copper, and avoided its massive accumulation in the H. tuberosus body, so as to alleviate the inhibitory effect of copper on plant growth. The study revealed the physiological regulation of SA upon copper stress, and provided a theoretical basis for planting H. tuberosus to repair soil copper pollution.
Antioxidants ; Copper ; Helianthus/metabolism* ; Salicylic Acid/pharmacology* ; Chlorophyll A/pharmacology* ; Spectroscopy, Fourier Transform Infrared ; Chlorophyll/pharmacology* ; Ascorbic Acid ; Superoxide Dismutase/metabolism* ; Photosynthesis ; Glutathione ; Plant Leaves ; Stress, Physiological ; Seedlings

OBJECTIVE To research the effect and mechanism of fermentation of Astragalus membranaceus on endogenous metabolites in hyperuricemia model rats using serum UHPLC-HRMS. METHODS The SD rats were randomly divided into different groups, including blank group, model group, benzbromarone group(20 mg·kg-1), as well as fermentation of Astragalus membranaceus high-dose(3 g·kg-1) and low-dose group(1.5 g·kg-1). Model group and each treatment group were disposed with 300 mg·kg-1 oxonic acid potassium to establish hyperuricemia models. At the time of 1 h after modeling, rats in each treatment group were given corresponding drugs for intervention. Collected rat serum after 14 d. The serum of different groups were collected for endogenous metabolites research using UHPLC-HRMS. After multivariate statistical analysis, the different metabolites and metabolic pathways were selected. RESULTS The hyperuricemia rat modes were successfully established by oxonic acid potassium 14 d, and fermentation of Astragalus membranaceus showed good uric acid reducing effect. Compared with the blank group, 17 potential biomarkers associated with hyperuricemia were found in the model group. Among them, 9 potential biomarkers were significantly recalled by fermentation of Astragalus membranaceus. It mainly involved sphingolipid metabolism, pyrimidine metabolism, tryptophan metabolism, pantothenic acid and CoA biosynthesis, glycine, serine and threonine metabolism and other pathway. CONCLUSION This study can provide a basis for revealing the mechanism of reducing uric acid by fermentation of Astragalus membranaceus, and lay a foundation for the further development and utilization of Astragalus.

Objective To explore the effects of ginsenoside Rg1 on blood-brain barrier, neuroinflammation and behavioral function of traumatic brain injury (TBI) mouse model.MethodsThe experiment was divided into two parts. In the first part, 27 SPF male BALB/c mice were randomly divided into blank group, sham operation group and TBI model group, with 9 mice in each group. TBI model group was made by controlled cortical impact (CCI) after craniotomy, while sham operation group was only performed craniotomy without any treatment, and the blank group was not treated at all. The effect of modeling was evaluated after operation. In the second part, 50 male BALB/c mice were randomly divided into sham operation group, three different drug dosage groups and solvent (DMSO) control group, with 8 mice in each group. The drug treatment groups were injected with ginsenoside Rg1 at the doses of 10, 20 and 40 mg/kg respectively 6 hours after TBI model had been successfully established, while the DMSO control group was given the same amount of 1% DMSO for one week, twice a day. Modified neurological severity scores (mNSS) were performed on the 1st, 3rd, 7th and 14th day after modeling, and the blood-brain barrier leakage was detected by Western blotting on the 3rd day after modeling. On the 14th and 16th day, the elevated cross maze test and water maze test were used to detect the neurobehavioral function. On the 28th day after anesthesia and perfusion, the brains were taken out, and the neuroinflammation such as activation of microglia and astrocytes was observed by immunofluorescence staining.ResultsThe expression level of MMP-9, a marker of blood-brain barrier, decreased in ginsenoside Rg1 treatment group (P<0.01). The number of microglia （Iba-1 positive) and astrocyte (GFAP positive) cells decreased significantly (P<0.05), which indicated that neuroinflammation was inhibited, and the best effect was achieved at the dosage of 20 mg/kg (P<0.01). The mNSS of mice in ginsenoside Rg1 treatment group were significantly lower than those in DMSO control group (P < 0.01), and the proportion of times they entered the open arm was significantly higher than that in DMSO control group (P < 0.05). The time ratio in the quadrant where the water maze experimental platform was located and the times of crossing the platform were significantly higher than those in control group (P < 0.05), and the dosage of 20 mg/kg had the best effect.ConclusionThe TBI mouse model was successfully constructed and applied to the study of ginsenoside Rg1 repair of mouse traumatic brain injury. Ginsenoside Rg1 can significantly improve blood-brain barrier, alleviate neuroinflammation and improve neurobehavioral function in TBI model mice, and the effect is the most significant at the dose of 20 mg/kg.

This article reviews the concept, current status and the commonly used assessment methods of self-compassion in cancer patients. This article also summarizes the intervention methods for improving self-compassion in cancer patients, so as to provide a reference for effectively exerting the positive role of self-compassion on cancer patients.

Objective:To evaluate the efficacy and safety of 125I seeds implantation for lymph nodes metastasis (LNM) from radioactive iodine-refractory differentiated thyroid carcinoma (RAIR-DTC), and to verify the computer three-dimensional treatment planning system (TPS) from the dosimetry accuracy in assisting seeds implantation to treat LNM. Methods:Retrospective analysis was performed on 17 RAIR-DTC patients with LNM admitted to the General Hospital of Northern Theater Command from December 2016 to January 2019 (8 males, 9 females, median age 58 years). All patients underwent preoperative TPS planning design, CT-guided puncture and 125I seeds implantation (seed activity 14.8-25.9 MBq). The dosimetric results of postoperative validation were compared with those of preoperative planning, including the dosimetric parameters such as target volume before and after surgery and the dose received by 90% and 100% gross tumor volume (GTV) ( D90, D100), the percentage received by 100% and 150% of the prescription dose ( V100, V150), homogeneity index (HI). All patients underwent CT after 6 months to compare the LNM size, serum thyroglobulin (Tg) level, and the improvement of complications before and after treatment. Efficacies were divided into complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD). Paired t test or Wilcoxon signed rank test were used to analyze the data. Results:Among 17 patients, a total of 226 125I radioactive seeds were implanted. Among them, 1 achieved CR, 10 achieved PR, 4 were with SD, and 2 were with PD. The diameter of LNM was 1.40(0.65, 3.05) cm before treatment and was 0.40(0.21, 0.91) cm 6 months after treatment ( z=-3.95, P<0.05). The Tg before treatment was 23.50(20.94, 72.92) μg/L and was 8.90(3.20, 40.22) μg/L 6 months after treatment ( z=-5.009, P<0.001). Tg antibody were all negative. There were 90.90% (20/22) of patients had slightly lower D90 than the prescribed dose ((12 378.8±3 182.0) vs (12 497.8±1 686.4) cGy; t=0.251, P>0.05). The postoperative dose parameters D100 and V150 ((6 881.5±1 381.8) cGy, (58.5±18.4)%) were both lower than those of preoperative plan ((8 085.8±2 330.0) cGy, (66.5±17.7)%; t values: 8.913, 3.032, both P<0.05), and the remaining indicators were not significantly different from those of the preoperative plan ( t values: 0.251, 1.493, z values: from -1.604 to -0.593, all P>0.05). Conclusions:According to the TPS preoperative plan, 125I seeds implantation for treating RAIR-DTC LNM can achieve the expected dose distribution, and the short-term tumor local control is effective. It is a safe and effective treatment method.

OBJECTIVES: Lung cancer is one of the most common malignant tumors in the world, and its lethality ranks the first among many malignant tumors. For non-small cell lung cancer (NSCLC) patients, due to the high mortality rate, the overall 5-year survival rate is less than 15%. When NSCLC undergoes local invasion, the 5-year survival rate is only 20%, and it is even lower when distant metastasis occurs up to 4%. Almonertinib is an innovative drug independently researched and developed by China with independent intellectual property rights. As an epidermal growth factor receptor tyrosine kinase inhibitor, almonertinib is mainly used for locally advanced or metastatic NSCLC patients with epidermal growth factor receptor (EGFR) T790M mutation. This study aims to investigate the effects of almonertinib on the proliferation, invasion and migration of NSCLC cells in vitro. METHODS: NSCLC cells H1975 and PC-9 were cultured in vitro. The effects of almonertinib on the proliferation, apoptosis, invasion, and migration of H1975 and PC-9 cells were detected by CCK-8 assay, apoptotic assay and Transwell assay. The expression of invasion and migration related proteins was detected by Western blotting. RESULTS: The CCK-8 experiment showed that almonertinib inhibited the proliferation of H1975 and PC-9 cells in a time- and dose-dependent manner. The IC CONCLUSIONS Almonertinib can inhibit the proliferation, invasion, and migration of NSCLCH1975 and PC-9 cells in vitro and vivo, and promote the apoptosis of H1975 and PC-9 cells. The underlying mechanism may be related to the inhibition of tumor cell epithelial mesenchymal transformation and metalloproteinase expression.
Acrylamides ; Animals ; Apoptosis ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Cell Line, Tumor ; Cell Proliferation ; Drug Resistance, Neoplasm ; ErbB Receptors/genetics* ; Humans ; Indoles ; Lung Neoplasms ; Mice ; Mice, Nude ; Mutation ; Protein Kinase Inhibitors/pharmacology* ; Pyrimidines

Objective To evaluate the clinical value of 125I seeds implantation (RSI) for treatment of lymph nodes metastases (LNM) in patients with 131I refractory differentiated thyroid carcinoma (RAIR-DTC).Methods A total of 42 RAIR-DTC patients with LNM (14 males,28 females,median age 49 years) who underwent RSI guided by CT from January 2015 to June 2016 were retrospectively analyzed.All patients underwent CT and their serum thyroglobulin (Tg) levels were measured 2,4 and 6 months post-treatment.The LNM size and serum Tg levels before and after treatment were compared,and the curative effect of RSI for complications was observed.Paired t test,x2 test,repeated measurement analysis of variance,Spearman correlation analysis were used to analyze the data.Results Two patients (4.76％) achieved complete remission,9(21.43％) achieved partial remission,29(69.05％) had no change,2(4.76％) were with progressive disease in all 42 patients.Thetotal effective rate was 95.24％ (40/42).The LNM diameter post-treatment was (1.39±0.75) cm,significantly lower than that before treatment ((1.99±0.38) cm;t=5.557,P＜0.01).The Tg level 2,4 and 6 months posttreatment was (53.24± 14.05),(33.17±7.61) and (25.93± 10.91) μg/L,respectively,which was significantly lower than that before treatment ((57.72± 15.23) μg/L;F =23.612,all P＜0.05).The age,sex,metastatic site,and the number of seeds implanted in each lesion were not the influencing factors on RSI (x2 values:0.569-15.884,rs =0.277,all P＞0.05).The LNM size was the influencing factor on RSI (x2=4.524,P＜0.05).Conclusions 125I RSI can significantly alleviate the clinical symptoms of RAIR-DTC patients with LNM,and the LNM size has relevance for the treatment effect.The clinical follow-up time of serum Tg level can be extended to 6 months or even longer.

Objective To investigate the character and location of a novel gene R049 and its expressed protein in uropathogenic Escherichia coli(UPEC) strain 132 isolated in China. MethodsThe chromosome library of UPEC132 was constructed by a shotgun strategy and the sequence analysis was carried out by a high-throughput pyrophosphate sequencing. Sequence reads were assembled with the Newbler program.The characters of R049-associated specific fragment were analyzed using the bioinformatics methods. Outer and inner membrane proteins of UPEC132 were extracted and then detected by SDS-PAGE and Western blot analysis together with the whole-cell lysates. ResultsThe 169 022 bp contig containing gene R049 was obtained and its sequence was very similar to the chromosome associated sequence of UPEC strain 536. It showed that a 20 773 bp fragment including R049 replaced the pathogenicity island PAI Ⅲ536 of UPEC536 in above 169 022 bp contig. The fragment had a lower GC content (46.97％) and 16 bp direct repeats in two ends. Significantly it also was adjacented to thrW tRNA, insertion element and genes coding integrase. Thus the 20 773 bp fragment was named R049 genome island(R049-GI). There were 25 ORFs in R049-GI, and gene R049 was located in the thirteenth ORF. The results of SDS-PAGE and Western blot revealed gene R049 encoded an outer membrane protein in the size of 47.0× 103. ConclusionGene R049, encoding an outer membrane protein, was a component part of the genome island in UPEC 132 chromosome acquired by horizontal gene transfer.