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 compare the efficacy of endoscopic bougie/balloon dilation(EBD),endoscopic radial incision(ERI),and ERI combined with esophageal stent placement(ESP)for the treatment of benign esophageal stenosis,and evaluate the feasibility and safety of ERI combined with ESP for the treatment of benign esophageal stenosis.Methods 48 Patients with benign esophageal stenosis from January 2019 to January 2023 were recruited,and divided into EBD group(n=24),ERI group(n=17)and ERI+ESP group(n=7).The differences in operating success,restenosis and complications among the three groups were compared.Results The number of previous endoscopic treatment in ERI+ESP group was more than that in EBD group and ERI group,and the differences were statistically significant(P＜0.05).Technical success was achieved in 23 cases and clinical remission in 23 cases in EBD group,technical success in 16 cases and clinical remission in 15 cases in ERI group,technical success in 7 cases and clinical remission in 7 cases in ERI+ESP group.There was no significant difference in technical success rate and clinical remission rate among the three groups(P＞0.05).After 3 months of follow-up,there were 15,9 and 1 cases of esophageal restenosis in the EBD group,ERI group and ERI+ESP group,respectively.There was no significant difference in the rate of esophageal restenosis among the 3 groups(P＞0.05).After 6 months of follow-up,there were 20 cases of esophageal restenosis in the EBD group,13 cases in the ERI group and 1 case in the ERI+ESP group.The rate of esophageal restenosis in the ERI+ESP group was significantly lower than that in the EBD group and the ERI group(P＜0.05).However,there was no statistically significant difference in the esophageal restenosis rate between the EBD group and the ERI group(P＞0.05).The time to the first postoperative restenosis was 74.00(48.75,159.00)days in the EBD group,84.00(54.50,195.00)days in the ERI group,and 250.00(206.00,289.00)days in the ERI+ESP group.The time to the first postoperative restenosis was longer in the ERI+ESP group than that in the EBD and ERI groups.The differences were statistically significant(P＜0.05),but there was no significant difference in restenosis time between EBD group and ERI group(P＞0.05).There were 5,5 and 3 cases of complications in the EBD group,ERI group and ERI+ESP group,respectively,and there was no significant difference in the incidence of complications among the three groups(P＞0.05).Conclusion ERI+ESP is comparable to EBD and ERI in terms of technical success and short-term clinical remission rate for the treatment of benign esophageal stenosis,and is superior to EBD and ERI in terms of long-term restenosis rate and restenosis time,with no influence on the occurrence of complications.

Objective To investigate the effect of isorhyncophylline on cognitive impairment in rats with acute cerebral infarction and its corresponding mechanism.Methods SD rats were separated into acute cerebral infarction group,sham operation group,low-dose isorhyncophylline group,high-dose isorhyncophylline group,nimodipine group,and high-dose isorhyncophylline+ADU-S100 group,with 24 rates for each group.Except the sham operation group,the rats in other groups were treated with filament model to construct the model of acute cerebral infarction.In the sham operation group,only the right external carotid artery,common carotid artery and internal carotid artery were exposed,and the filament was not inserted.After successful modeling,the medication was administered once a day for 2 weeks.After the modeling was successful,the rats in the low dose group and the high dose group were given 5 mg/kg and 20 mg/kg respectively,and the same amount of isotonic saline was injected intraperitoneally.Nimodipine group rats were given 30 mg/kg nimodipine by intragastric administration,and the same amount of isotonic saline was also injected intraperitoneally.The rats in high dose isorhyncophylline+ADU-S 100 group were given 20 mg/kg isorhyncophylline by intragastric administration and 20 mg/kg ADU-S 100 intraperitoneally.Rats in sham operation group and acute cerebral infarction group were injected with 10 ml/kg isotonic saline by intragastric administration and intraperitoneal injection.The medication was administered once a day for 2 weeks.The Zela-Longa neurological function score was evaluated in all the rats 24 h after the final medication,and then Morris water maze test was conducted and their escape latency and the number of stays in the original platform quadrant were recorded.The levels of interleukin 6(IL-6)and tumor necrosis factor(TNF)α in serum were detected by enzyme-linked immunosorbent assay(ELISA).The water content of brain tissue was detected in each group.The volume of cerebral infarction was measured by 2,3,5-triphenyltetrazolium chloride(TTC)staining.Evans blue was applied to detect blood-brain barrier permeability.Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the expression of ZO-1 and occludin messenger RNA(mRNA)in brain tissue of each group.The expression of STING,phosphorylated tank-bound kinase 1(p-TBK1)and phosphorylated interferon regulatory factor 3(p-IRF3)in rat brain tissues was detected by western blot and compared between groups.Results Compared with sham operation group,the neurological function score([2.96±0.32]vs.0),brain tissue water content([86.9±3.2]％vs.[71.8±3.1]％),serum TNF-a([86.7±3.5]ng/L vs.[35.6±1.7]ng/L)and IL-6([167.8±6.1]ng/L vs.[50.2±2.2]ng/L)levels,cerebral infarction volume([28.6±1.3]mm3 vs.0 mm3),evans blue content([1.57±0.13]g/Lvs.[0.96±0.08]g/L),STING([1.83±0.16]vs.[0.86±0.08]),p-TBK1([0.89±0.07]vs.[0.41±0.03]),and p-IRF3([0.67±0.05]vs.[0.13±0.01])protein expression in brain tissue were increased,expression of ZO-1([0.45±0.04]vs.[1.00±0.00])and occludin mRNA([0.23±0.02]vs.[1.00±0.00])in brain tissue were decreased,the escape latency was prolonged([33.6±1.6]s vs.[12.3±0.5]s),and the number of stays in the original platform quadrant([5.9±0.2]times vs.[15.7±0.4]times)was decreased in the acute cerebral infarction group 24 h after last medication administration(all P＜0.05).(2)Compared with acute cerebral infarction group,the neurological function score([2.37±0.21],[1.14±0.17],[1.18±0.13]vs.[2.96±0.32]),brain tissue water content([81.8±3.0]％,[74.9±3.0]％,[74.3±2.9]％vs.[86.9±3.2]％),serum TNF-α([71.1±1.4]ng/L,[43.4±2.0]ng/L,[41.5±1.9]ng/L vs.[86.7±3.5]ng/L)and IL-6([129.8±5.4]ng/L,[81.2±3.8]ng/L,[80.0±3.6]ng/L vs.[167.8±6.1]ng/L)levels,cerebral infarction volume([21.7±1.0]mm3,[10.5±0.5]mm3,[10.7±0.5]mm3 vs.[28.6±1.3]mm3),evans blue content([1.39±0.12]g/L,[1.16±0.10]g/L,[1.18±0.19]g/L vs.[1.57±0.13]g/L),STING([1.50±0.14],[1.02±0.11],[1.01±0.09]vs.[1.83±0.16]),p-TBK1([0.75±0.05],[0.54±0.04],[0.52±0.05]vs.[0.89±0.07]),and p-IRF3([0.51±0.05],[0.25±0.02],[0.27±0.02]vs.[0.67±0.05])protein expression in brain tissue were decreased,expression of ZO-1([0.58±0.05],[0.87±0.07],[0.89±0.09]vs.[0.45±0.04])and occludin mRNA([0.36±0.03],[0.71±0.06],[0.69±0.05]vs.[0.23±0.02])in brain tissue were increased,the escape latency were shortened([28.6±1.0]s,[16.5±0.7]s,[16.4±0.7]s vs.[33.6±1.6]s),and the number of stays in the original platform quadrant([8.2±0.3]times,[12.8±0.5]times,[12.9±0.5]times vs.[5.9±0.2]times)were increased in the low-dose isorhyncophylline group,high-dose isorhyncophylline group,and nimodipine group(all P＜0.05).(3)Compared with high-dose isorhyncophylline group,the neurological function score([2.12±0.14]vs.[1.14±0.17]),brain tissue water content([78.7±3.2]％vs.[74.9±3.0]％),serum TNF-a([59.7±2.1]ng/L vs.[43.4±2.0]ng/L)and IL-6([118.9±4.6]ng/L vs.[81.2±3.8]ng/L)levels,cerebral infarction volume([16.6±0.4]mm3 vs.[10.5±0.5]mm3),evans blue content([1.36±0.10]g/L vs.[1.16±0.10]g/L),and STING([1.37±0.12]vs.[1.02±0.11]),p-TBK1([0.67±0.05]vs.[0.54±0.04]),and p-IRF3([0.39±0.03]vs.[0.25±0.02])protein expression in brain tissue were increased,expression of ZO-1([0.63±0.05]vs.[0.87±0.07])and occludin mRNA([0.46±0.05]vs.[0.71±0.06])in brain tissue were decreased,the escape latency was prolonged([23.4±1.0]svs.[16.5±0.7]s),and the number of stays in the original platform quadrant([9.6±0.3]times vs.[12.8±0.5]times)was decreased in the isorhyncophylline high-dose+ADU-S100 group(all P＜0.05).Conclusion Isorhyncophylline can inhibit inflammation,reduce blood-brain barrier damage,reduce cerebral edema,and improve cognitive impairment in rats with acute cerebral infarction,and the mechanism of which may be related to the inhibition of STING/TBK1/IRF3 pathway.

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 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.

Objective:To investigate serum vitamin A and vitamin D status in children aged 2-<7 years in 20 cities in China.Methods:A cross-sectional study was conducted. A total of 2 924 healthy children aged 2-<7 years were recruited from September 2018 to September 2019 from 20 cities in China, categorized by age groups of 2-<3 years, 3-<5 years, and 5-<7 years. The demographic and economic characteristics and health-related information of the enrolled children were investigated. Body weight and height were measured by professional staff members. The serum vitamin A and vitamin D levels were detected by high-performance liquid chromatography-tandem mass spectrometry. Chi-square test and Logistic regression were applied to analyze the association between vitamin A and vitamin D deficiency and insufficiency as well as their underlying impact factors.Results:The age of the 2 924 enrolled children was 4.33 (3.42, 5.17) years. There were 1 726 males (59.03%) and 1 198 females (40.97%). The prevalences of vitamin A and vitamin D deficiency in enrolled children were 2.19% (64/2 924) and 3.52% (103/2 924), respectively, and the insufficiency rates were 29.27% (856/2 924) and 22.20% (649/2 924), respectively. Children with both vitamin A and vitamin D deficiencies or insufficiencies were found in 10.50% (307/2 924) of cases. Both vitamin A ( χ2=7.91 and 8.06, both P=0.005) and vitamin D ( χ2=71.35 and 115.10, both P<0.001) insufficiency rates were higher in children aged 3-<5 and 5-<7 years than those in children aged 2-<3 years. Vitamin A and vitamin D supplementation in the last 3 months was a protective factor for vitamin A and D deficiency and insufficiency, respectively ( OR=0.68 and 0.22, 95% CI 0.49-0.95 and 0.13-0.40, both P<0.05). The rates of vitamin A and D insufficiency was higher in children with annual household incomes <60 000 RMB than in those with annual household incomes ≥60 000 RMB ( χ2=34.11 and 10.43, both P<0.01). Northwest and Southwest had the highest rates of vitamin A and vitamin D insufficiency in children aged 2-<7 yeas, respectively ( χ2=93.22 and 202.54, both P<0.001). Conclusions:Among 20 cities in China, children aged 2-<7 years experience high rates of vitamin A and vitamin D insufficiency, which are affected by age, family economic level, vitamin A and vitamin D supplementation, and regional economic level. The current results suggest that high level of attention should be paid to vitamin A and vitamin D nutritional status of preschool children.

Objective:To analyze the genetic variations and clinical phenotypic characteristics of epilepsy associated with CSNK2B gene mutations. Methods:A case series summary study.Clinical data of 15 epileptic children with CSNK2B gene mutations diagnosed and treated at the Third Affiliated Hospital of Zhengzhou University and the Peking University First Hospital from February 2016 to October 2023 were retrospectively analyzed.The clinical manifestations, genotypes, and electroencephalography (EEG) results were summarized. Results:Among the 15 children (8 boys and 7 girls), 14 cases had de novo mutations in the CSNK2B gene, and 1 case had hereditary variations.There were 5 missense variants, 4 splice-site variants, 3 frameshift variants, and 3 nonsense variants.Ten mutation sites had not been previously reported (c.326G>A/p.Cys109Tyr, c.485A>G/p.His162Arg, c.368-1G>A, c.464A>C/p.Asp155Ala, c.301T>G/p.Tyr101Asp, c.342T>A/p.Cys114*, c.198del/p.Asn67Thrfs*5, c.292-10T>G, c.573-574del/p.Lys191Asnfs*54, and c. 11C>G/p.Ser4*).The age of onset of seizures ranged from 14 days to 6 years, with 13 cases starting within 2 years old.The types of seizures included focal seizures in 9 cases, generalized tonic-clonic seizure (GTCS) in 5 cases, myoclonic seizures in 1 case, atonic seizures in 1 case, atypical absence seizures in 1 case, and epileptic seizures in 1 case.Three cases had multiple seizures, and 4 cases had cluster seizures.The EEG showed slow background activity in 1 case.Epileptiform discharges were observed in 13 cases during the interictal phase, including generalized discharges in 6 cases, multifocal discharges in 3 cases, and focal discharges in 5 cases.Two cases had normal EEG findings.Brain magnetic resonance imaging results were normal in 10 cases.The age of the last follow-up ranged from 1 year and 1 month to 13 years and 10 months.Seizures were controlled in 12 cases treated with 1 or 2 antiepileptic drugs, while seizures persisted in 2 cases treated with multiple antiepileptic drugs, and 1 case suffered no seizures for 1 year and 3 months, without antiepileptic drug treatment.Oxcarbazepine was effective in 5 cases (5/7), Valproate sodium was effective in 6 cases (6/8), and Levetiracetam was effective in 3 cases (3/9). Conclusions:CSNK2B gene mutations are mainly de novo mutations, and epilepsy triggered by them typically starts within 2 years of age.GTCS and focal seizures are the most common types.The seizures of most children are easily controlled with the effective treatment of Oxcarbazepine, Valproate sodium, and Levetiracetam.

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.