Objective To provide technical support for the formulation of scientific and reasonable supervision measures for enterprises engaged in the exploitation and utilization of ores with associated radionuclides in Guangxi Province, China. Methods A radionuclide analysis was performed on solid materials generated during production processes such as zirconium-titanium ore dressing and processing in multiple enterprises in Guangxi Province. The radiation levels of effluents was measured. Measurement and analysis were performed on the environmental air radon concentration levels and environmental γ-radiation dose rates at the factory boundaries of these enterprises and the surrounding environmental protection targets. Results The air absorption dose rate of γ radiation, the concentrations of radon and its daughters, and the radiation levels of surface water and aerosols at the factory boundaries and in the surrounding environment were all at normal levels. The specific activities of nuclides ²³⁸U, ²³²Th, and ²²⁶Ra in the raw ore, zirconium products, rutile products, and monazite products within the factory area were relatively high. The γ radiation air absorption dose rates in the corresponding workshops were also relatively high, with the zirconium-rutile workshop being the area with the highest values. Materials such as zirconium products, rutile, and monazite all showed a certain amount of radon exhalation. Conclusion The radiation level of tailings met the criteria of monitoring exemption, and the enterprises did not generate radioactive solid waste. Attention should be paid to the personal dose of the staff in areas with high radiation dose rates.

Objective:To investigate the impact of limonin(LIM)on the necrotic apoptosis of myocardial cells in rats with myocardial infarction(MI)by regulating the receptor-interacting protein 1(RIP1)/receptor-interacting protein 3(RIP3)/mixed-lineage kinase domain-like protein(MLKL)signaling pathway.Methods:A total of 60 Sprague-Dawley rats were randomly divided into sham-operation group(Sham group),MI model group(Model group),low-dose LIM group(LIM-L group,25 mg/kg LIM),high-dose LIM group(LIM-H group,50 mg/kg LIM),and high-dose LIM+RIP1 inhibitor Nec-1 group(LIM-H+Nec-1 group,50 mg/kg LIM+0.6 mg/kg Nec-1),with 12 rats in each group.A rat model of MI was established by ligation of the coronary artery.The changes of cardiac func-tion were examined for each group;HE staining was used to observe the pathological changes of myocardial tissue;the 2,3,5-triphen-yltetrazolium chloride-Evans blue method was used to measure myocardial infarct area;the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method was used to observe the necrotic apoptosis of myocardial cells;quantitative real-time PCR and Western blot were used to measure the expression levels of mRNAs and proteins associated with the RIP1/RIP3/MLKL signaling pathway and the expression of apoptosis-related proteins.Results:Compared with the Sham group,the Model group had significant re-ductions in left ventricular ejection fraction,left ventricular systolic pressure,and the expression level of B-cell lymphoma-2(Bcl-2)in myocardial tissue(all P<0.001)and significant increases in left ventricular end-systolic volume,left ventricular end-diastolic pres-sure,left ventricular end-diastolic volume,myocardial infarct area,cell apoptosis rate,the mRNA and protein expression levels of RIP1,RIP3,and MLKL in myocardial tissue,and the protein expression levels of Bcl-2 associated X protein and cysteinyl aspartate-specific proteinase 3 in myocardial tissue(all P<0.001),as well as swelling and disordered arrangement of myocardial cells with ne-crosis and massive inflammatory cell infiltration on HE pathological sections.Compared with the Model group,the LIM-H group showed reverse changes in the above indicators(RIP1 mRNA:P=0.002,RIP3 mRNA:P=0.008,and the other indexes P were all<0.001),with alleviations of myocardial histopathological injury and inflammatory cell infiltration.Nec-1 promoted the effect of LIM in alleviating the necrotic apoptosis of myocardial cells in MI rats.Conclusion:LIM may alleviate the necrotic apoptosis of myocardial cells in MI rats by downregulating the RIP1/RIP3/MLKL signaling pathway.

Traumatic brain injury(TBI)is mostly caused by motor vehicle traffic accidents or competitive sports,with high mortality and disability.TBI mainly includes primary injury and secondary injury.Primary injuries were caused directly by external forces.Secondary injuries include brain edema,excitotoxic effect of neuron cells,oxidative stress and neuroinflammation,etc.Effective intervention of secondary injury not only helps to improve the prognosis of patients with TBI,but also reduces the risk of Parkinson's disease and other neurodegenerative diseases related to TBI.Autophagy is one of approaches to regulate homeostasis in cells,and autophagy dysfunction has been found in several neurodegenerative diseases and TBI.It is speculated that autophagy dysfunction may play an important role in TBI and explain why patients with TBI have higher risk of neurodegenerative disease.Discovering the role of autophagy in the pathological mechanism of TBI may provide new targets for TBI clinical treatment and cognitive impairment prevention in patients with TBI.

Objective The high post-surgery recurrence rate of endometriosis(EMs)has emerged as a challenge in the long-term manaagement of the condition.This study is aimed at investigating the mechanisms of Neiyiting(NYT)decoction in preventing postoperative recurrence of EMs.Methods An animal model of EMs postoperative recurrence and a model of endometrial stromal cells(hEM15A)cocultured with macrophages(RAW 264.7 cell line)were established for both in vivo and in vitro experiments.An autotransplantation method was used to establish a rat model of EMs.The rats were divided into 4 groups(6 rats per group)and received the corresponding treatments:a Model group receiving distilled water,a Gestrinone group receiving gestrinone at 0.325 mg/kg,a low-dose NYT(NYT-L)group receiving NYT decoction at 5.04 g/(kg-d),and a high-dose NYT(NYT-H)group receiving NYT decoction at 10.08 g/(kg-d).The treatment was administered for 3 weeks via intragastric gavage.In addition,6 SD rats were randomly selected for the control group(Control group),and were given distilled water for 3 weeks via intragastric gavage.The sizes and pathological changes of recurrent lesions in EMs rats were observed.Immunohistochemistry and qRT-PCR were performed to assess the expression of M1 macrophage marker CD86 protein and mRNA in vivo.Additionally,immunohistochemistry and qRT-PCR were used to assess the expression of indicator proteins related to the triggering receptor expressed on myeloid cells 1(TREM1)/Toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling pathway and mRNA.The proliferation of hEM15A cells in the coculture experiment was observed.Flow cytometry was performed to determine the polarization of RAW264.7 macrophages,and qRT-PCR was used to determine the expression levels of inducible nitric oxide synthase(iNOS)and interleukin 1β(IL-1β)mRNA.Western blot was performed to determine the expression of signaling pathway-related indicator proteins in vitro.ELISA was performed to determine the levels of inflammatory factors in vitro.Results Compared with the Model group,the volume of recurrent lesions in the NYT-H group was reduced(P＜0.01).Findings from the macrophage M1 polarization assessment showed that the expression levels of CD86 protein and mRNA in the recurrent lesions of the Model group were higher than those in the control group(P＜0.01).The expression levels of CD86 protein and mRNA in the recurrent lesions of the NYT-H group were lower than those of the Model group(P＜0.01).In addition,the RAW 264.7 cell experiment further verified that NYT decoction could reduce the number of CD86-positive macrophages induced by plasmids overexpressing TREM1 and reduce the expression of IL-1β and iNOS mRNA(P＜0.01).The results of the hEM15A cell proliferation assay showed that NYT decoction down-regulated KI-67 protein expression in hEM15A cells induced by macrophage M1 polarization(P＜0.01).The results of TREM1/TLR4/NF-κB signaling pathway showed that the protein and mRNA expression levels of TREM1,TLR4,and NF-κB in the recurrent lesions of the Model group were higher than those of the control group(P＜0.01).Compared with those in the Model group,the protein and mRNA expression levels of TREM1,TLR4,and NF-κB in the recurrent lesions of the NYT-H group were lower(P＜0.01).In addition,the coculture experiment of RAW264.7 and hEM15A cells further confirmed that NYT decoction reduced the expression of TREM1,TLR4,and P-P65 proteins(P＜0.01).Conclusion NYT decoction can inhibit macrophage M1 polarization through the TREM1/TLR4/NF-κB signaling pathway,improve the inflammation level,and inhibit the formation of ectopic endometrial lesions,thereby preventing postoperative recurrence of EMs.

Objective To screen metabolic core genes in colon cancer based on machine learning algorithms and analyze their functional mechanisms.Methods Data were obtained from The Cancer Genome Atlas(TCGA)database and the Gene Expression Omnibus(GEO)database.The TCGA co-hort included 375 tumor samples and 32 adjacent normal tissue samples,while the GSE39582 cohort comprised 419 tumor samples.Univariate Cox regression analysis combined with random forest,sup-port vector machine recursive feature elimination(SVM-RFE),and least absolute shrinkage and selec-tion operator(LASSO)regression algorithms were employed to screen for metabolic core genes.Re-ceiver operating characteristic(ROC)curves were plotted,and the area under the curve(AUC)was used to evaluate the predictive efficacy of the core genes.Real-time fluorescent quantitative polymerase chain reaction(qRT-PCR)and immunohistochemistry(IHC)methods were adopted to detect the ex-pression of the core genes.The core genes were knocked down to explore their roles in colon cancer.Results Three core genes,namely CPT2,SCP2 and NR3C2,were screened based on machine learning algorithms.According to the comparison results of the AUCs of the ROC curves,NR3C2 exhibited the best predictive efficacy.qRT-PCR detection results showed that NR3C2 mRNA was lowly ex-pressed in colon cancer cell lines;IHC detection results revealed that NR3C2 was lowly expressed in colon cancer tissues.Knocking down NR3C2 significantly promoted the proliferation and migration of colon cancer cells.Conclusion NR3C2 is identified as a core metabolic inhibitory gene in colon cancer by cross-applying three machine learning algorithms,which may provide a new strategy for metabolic targeted therapy.

Objective: To investigate the effects and mechanisms of Xuebijing injection (XBJ) on Chimeric antigen receptor-T (CAR-T) cell function and its therapeutic potential against CAR-T therapy-associated cytokine storms (CRS). Methods: Anti-CD19 CAR-T cells were established based on FMC63 antibodies. Different doses of XBJ (1 and 10 mg/mL) were added to the culture system. Untreated anti-CD19 CAR-T cells served as negative controls. After 48-h co-culture, the effects of XBJ on CAR-T cell function were assessed. Carboxyfluorescein diacetate succinimidyl ester staining was used to assess the effect of XBJ on CAR-T cell proliferation. Flow cytometry, luciferase reporter gene assays, and real time cellular analysis were employed to evaluate the effects of XBJ on CAR-T cell cytotoxicity in vitro. RNA-sequencing was performed to analyze the effects of XBJ on CAR-T cell gene expression. Network pharmacology predicted potential XBJ therapeutic targets for CRS, which were verified in a THP-1 macrophage inflammation model. Results: XBJ enhanced both the proliferation and tumor killing capacities of CAR-T cells. Transcriptome analysis showed that XBJ treatment affects multiple genes and pathways in CAR-T cells, with differential gene enrichment in multiple cell proliferation and growth factor pathways. Potential targets for CRS control by XBJ were predicted using network pharmacology, and the inhibitory effect of XBJ on the expression of relevant genes was verified using a macrophage model. Conclusion The results of this study indicate that XBJ can enhance the killing effect of CAR-T cells on tumor cells and that the mechanism is related to the regulation of T cell proliferation and activation. Moreover, XBJ inhibited excessive inflammation associated with CAR-T therapy. However, the current findings remain to be further validated through in vivo experiments.

Craniocerebral injury with seawater immersion is a special kind of compound injury, with low temperature, high permeability, high alkali, high salt content, and bacterial infection being the main causes. The injury is also characterized with complex damage mechanisms, difficulty to treat, and poor prognosis. At present, the damage mechanisms of craniocerebral injury with seawater immersion are mainly studied by establishing the experimental animal models at the levels of tissue, cell, organelle, molecule, etc. However, the craniocerebral injury with seawater immersion is more complex than the simple onshore craniocerebral injury, therefore, a stable disease model is not easy to construct. Most researches on the specific injury mechanisms are relatively single and one-sided, with many different views in existence, and the damage mechanisms of craniocerebral injury with seawater immersion have hitherto not been clear. The authors reviewed the research progress in the damage mechanisms of craniocerebral injury with seawater immersion, in order to promote the in-depth study of the mechanism of craniocerebral injury with seawater immersion and provide reference for its clinical treatment.

Objective:To compare the diagnostic efficacy of 18F-prostate specific membrane antigen (PSMA)-1007 PET/CT, 18F-FDG PET/CT and multi-parameter MRI (mpMRI) in prostate cancer (PCa). Methods:Retrospective analysis was conducted on data from 22 patients ((72.6±6.2) years) with pathologically confirmed PCa in the Affiliated Taizhou People′s Hospital of Nanjing Medical University between April 2021 and September 2022. All patients underwent 18F-PSMA-1007 PET/CT, 18F-FDG PET/CT, and mpMRI examination within 30 d, and the imaging parameters were collected, including PSMA-SUV max, FDG-SUV max, minimum apparent diffusion coefficient (ADC min), mean apparent diffusion coefficient (ADC mean), PSMA-SUV max/ADC min, PSMA-SUV max/ADC mean, FDG-SUV max/ADC min, FDG-SUV max/ADC mean. Patients were divided into groups based on the International Society of Urological Pathology (ISUP) grading (≤3 vs >3) and serum total prostate specific antigen (TPSA; ≤20 μg/L vs >20 μg/L), and differences of imaging parameters between groups were compared (Mann-Whitney U test or independent-sample t test). ROC curves were generated to evaluate the diagnostic ability of each parameter for different levels of PCa. χ2 test and ROC curve analysis were used to compare the detection rate and diagnostic efficiency of three imaging methods for primary focus, lymph node metastasis, and bone metastasis in PCa. Results:Differences were found between ISUP≤3 ( n=6) and >3 ( n=16) groups in PSMA-SUV max/ADC min, PSMA-SUV max/ADC mean, PSMA-SUV max, and ADC min ( z values: from -2.65 to -2.36, t=3.60, P values: 0.002-0.018). But there was no significant difference found between TPSA≤20 μg/L ( n=5) and >20 μg/L ( n=17) groups in all indices ( z values: from -1.76 to -1.45, t values: -1.19 and 1.28, all P>0.05). The optimal cut-off value for PSMA-SUV max/ADC min in differentiating high-grade and low-grade PCa was determined to be 22.628×10 3. In the patient-based analysis, no statistical difference was found in the detection rate of PCa primary tumors among 18F-PSMA-1007 PET/CT, 18F-FDG PET/CT, and mpMRI ( χ2=1.91, P=0.767). However, the detection rates of lymph node and bone metastasis among three imaging methods were significantly different (72.73%(16/22), 59.09%(13/22), 36.36%(8/22) and 81.82%(18/22), 63.64%(14/22), 45.45%(10/22); χ2 values: 6.03, 6.29; P values: 0.049, 0.043). 18F-PSMA-1007 PET/CT resulted in a 36.36%(8/22) increase in N stage and the 40.91%(9/22) increase in M stage compared to mpMRI. Conclusions:PSMA-SUV max/ADC min is a valuable parameter for differentiating high-grade and low-grade PCa. 18F-PSMA-1007 PET/CT demonstrates superior detection rate of PCa lymph node and bone metastasis compared to 18F-FDG PET/CT and mpMRI, and exhibits higher diagnostic efficiency, so it can be recommended for NM staging in patients with PCa.

Objective:To explore the clinical and genetic characteristics of two children with Neurodevelopmental disorders (NDDs) due to variants of TANC2 gene. Methods:Clinical data of two children who were admitted to the Third Affiliated Hospital of Zhengzhou University respectively in April 2020 and April 2021 were retrospectively analyzed. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. By using " TANC2 gene", "Neurodevelopmental disorders", "Nervous system development disorders", " TANC2" as the key words, similar cases were searched from the CNKI, Wanfang database platform and PubMed database, with the search time set as from the establishment of the database to December 2023. This study was approved by Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No. 2020-57). Results:Case 1 was a 1-year-and-3-month-old girl who had developed convulsions at 1 year old and had three episodes of seizures. Her epilepsy had resolved with the treatment of oxcarbazepine, which was stopped at the age of 2-year-and-7-month. Her language, movement and intelligence development were all normal. Case 2 was a 1-year-and-10-month-old boy, who had developed convulsions at 1 year old. His seizure type was myoclonus, and the frequency was dozens of times a day. His epilepsy had resolved with the treatment of sodium valproate. His language, movement and intelligence development was delayed for about half a year. Genetic analysis showed that both children had harbored novel variants of the TANC2 gene (NM_025185.4), including c. 3398G>A (p.Gly1133Glu) and c.2829+ 1G>A, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the former was rated as likely pathogenic (PS2+ PM2_Supporting+ PP3) and the latter was rated as pathogenic (PVS1+ PS2+ PM2_Supporting). Two previous reports were retrieved, which had involved 17 cases and 16 variants. Common features had included autism spectrum disorder (70.6%, 12/17), intellectual disability (94.1%, 16/17), language and motor retardation (88.2%, 15/17; 58.8%, 10/17), facial dysmorphism, epilepsy, ataxia, and thoracic and spinal deformities. Conclusion:Variants of the TANC2 gene probably underlay the epilepsy and development delay in these children with NDDs.

Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients.Here,we demonstrated the antileukemia activity of a novel small molecular compound NL101,which is formed through the modification on bendamustine with a suberanilohydroxamic acid(SAHA)radical.NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells.It induces DNA damage and caspase 3-mediated apoptosis.A genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library screen revealed that phosphatase and tensin homologous(PTEN)gene is critical for the regulation of cell survival upon NL101 treatment.The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome(MDS)cells,accompanied by the activation of protein kinase B(AKT)signaling pathway.The inhibition of mammalian target of rapamycin(mTOR)by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death.These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.