Objective With the vigorous development of nuclear reactors and controlled thermonuclear fusion research, the release of tritium, the predominant radionuclide in nuclear wastewater, into the environment has attracted widespread attention. Its impact on human health has also become a hot topic of research. This article presents a visual analysis of the literature on the biological effects of tritium ingestion by organisms over the past 70 years, with the aim of elucidating the biological effects of tritiated water and identifying current research hotspots and emerging trends. Methods We retrieved articles on the biological effects of tritium radiation published in the China National Knowledge Infrastructure (CNKI) and Web of Science (WOS) over the past 70 years. CiteSpace software was used to generate visual maps, including annual number of publications, countries of publication, keyword clustering, keyword timeline, keyword burst, and literature co-citation. Results A total of 437 articles were included. The cumulative number of annual publications exhibited a linear growth trend. Research hotspots focused on low-radioactivity tritiated water, dose rate effect, DNA double-strand break damage, genetic effect, and cancer mortality. Emerging research frontiers included human lymphocyte immune injury, oxidase activity, comparison of marine organisms in different living environments, comparison of tritium and ionizing radiation effects, changes in mitochondrial ATP content, and the hormetic effect of low-dose radiation. Conclusion In cellular and animal models, high doses of tritium exposure induce negative biological effects. However, whether low doses of tritium esposure elicit beneficial biological effects remains to be further explored. It is suggested that domestic and foreign teams enhance academic collaboration and discussions, focusing on current hotspots and frontiers to deepen our understanding of the biological effects induced by tritium radiation. This will provide scientific solutions for disease treatment and establish a scientific basis for the safe utilization of nuclear energy and the formulation of safety standards for nuclear wastewater discharge.

This study assessed the role and mechanism of the recombinant Bacillus Calmette-Gue?rin vaccine(rBCG)with c-di-AMP adjuvant in regulating metabolism and immunity in epididymal white adipose(eWAT)in mice.Male C57BL/6 mice were intravenously immunized with BCG and rBCG,and their body weights were monitored.eWAT was isolated from the mice,and the stromal vascular fractions(SVFs)cell number was counted with a hemocytometer.Sections of mouse adipose tissue were prepared,and the size,number,and morphology of eWAT adipocytes and crown-like structure(CLS)formation were compared under a microscope after HE staining.The transcription levels of lipid metabolism-associated factors,cytokines and aging-associated genes in each group were determined with qRT-PCR.The body weights of mice gradually increased after immunization with BCG and rBCG.The proportions of eWAT increased,and the SVFs cell number decreased,in rBCG immunized mice.HE staining indicated that BCG immunization promoted hyperplasia,whereas rBCG immunization promoted hypertrophy of eWAT adipocytes;moreover,both BCG and rBCG immunization induced CLS formation in eWAT.The qRT-PCR results indicated that rBCG immunization inhibited the expression of genes associated with lipolysis and energy expenditure in eWAT.BCG immunization had little effect on cytokine transcription,whereas rBCG significantly induced the transcription of IFN-γ and IL-1Ra,and inhibited that of IL-15 and IL-2,but did not induce the expression of aging-associated genes.Thus,rBCG immunization induced eWAT adipocyte hypertrophy,which was associated with the inhibition of eWAT lipolysis and the regulation of cytokine expression.

Aim To explore the neuroprotective effects of salidroside on Parkinson's disease(PD)through modulation of inflammatory responses and the underly-ing mechanisms.Methods Mice were divided into five groups:healthy control group,1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)disease group,low-dose Rhodioloside intervention group,medium-dose salidroside intervention group,and high-dose salidro-side intervention group.MPTP-induced PD mouse model was established,and salidroside intervention was administered.Behavioral changes,inflammatory cyto-kine levels,autophagy-related protein expression,and neurons were observed through histological analysis and immunohistochemical staining.Results After MPTP treatment,mice exhibited significant behavioral chan-ges,increased pro-inflammatory cytokines,decreased anti-inflammatory cytokines,reduced autophagy-related proteins,and evident pyroptosis.Salidroside interven-tion alleviated these changes in a dose-dependent man-ner.Conclusions Salidroside exerts neuroprotective effects on PD by alleviating inflammatory responses and promoting autophagy,thereby protecting neurons.

Aim To investigate the effect of tetrameth-ylpyrazine(TMP)on neuroinflammation after cerebral ischemia and hypoxia via mannose-binding lectin(MBL).Methods Patients diagnosed with ischaemic stroke at Shanxi Provincial People's Hospital were in-cluded in the study,and their clinicopathological data,as well as blood and urine samples,were collected with the consent of the patients and their families.Using these biological samples,differential proteins and tar-gets were identified by proteomic analysis and subse-quently verified with animal experiments.The mice were divided into the sham,dMCAO,and TMP(10,20,40 mg·kg-1)treatment groups.After seven days of drug administration,the modified neurological sever-ity score(mNSS)was used to assess the neurological function.TTC staining was used to detect the volume of cerebral infarction.Motor function was evaluated be-haviourally,and ELISA was used to detect MASP1,sC5b-9,TNF-α,IL-6,and IL-1β.Western blot was used to determine the expression of relevant proteins,such as MBL2,MASP2,and C3.Results Compared with the sham group,the dMCAO group exhibited in-creased neurological impairment,which was signifi-cantly ameliorated by TMP treatment.The expression levels of MBL2,C3 and MASP2 were elevated in the dMCAO group and were reduced following TMP treat-ment.Additionally,the dMCAO group showed elevat-ed expression of inflammatory factors IL-1 β,IL-6 and TNF-α,which were then suppressed by TMP treat-ment.Conclusion TMP inhibits the inflammatory re-sponse after ischemia and hypoxia by regulating MBL,thus attenuating brain injury.

Objective:To investigate the risk factors,clinical characteristics,and bacterial resistance of bloodstream infections caused by Streptococcus mitis in children with hematological disease,so as to provide a reference for infection control.Methods:The clinical information and laboratory findings of pediatric patients complicated with blood cultures positive for Streptococcus mitis from January 2018 to December 2020 in the Institute of Hematology & Blood Diseases Hospital were searched and collected.The clinical characteristics,susceptibility factors,and antibiotic resistance of the children were retrospectively analyzed.Results:Data analysis from 2018 to 2020 showed that the proportion of Streptococcus mitis isolated from bloodstream infections in children(≤14 years old)with hematological diseases was the highest(19.91％)and significantly higher than other bacteria,accounting for 38.64％of Gram-positive cocci,and presented as an increasing trend year by year.A total of 427 children tested positive blood cultures,including 85 children with bloodstream infections caused by Streptococcus mitis who tested after fever.Most children experienced a recurrent high fever in the early and middle stages(≤6 d)of neutropenia and persistent fever for more than 3 days.After adjusting the antibiotics according to the preliminary drug susceptibility results,the body temperature of most children(63.5％)returned to normal within 4 days.The 85 children were mainly diagnosed with acute myeloid leukemia(AML),accounting for 84.7％.The proportion of children in the neutropenia stage was 97.7％.The incidence of oral mucosal damage,lung infection,and gastrointestinal injury symptoms was 40％,31.8％,and 27.1％,respectively.The ratio of elevated C-reactive protein(CRP)and procalcitonin was 65.9％and 9.4％,respectively.All isolated strains of Streptococcus mitis were not resistant to vancomycin and linezolid,and the resistance rate to penicillin,cefotaxime,levofloxacin,and quinupristin-dalfopristin was 10.6％,8.2％,9.4％,and 14.1％,respectively.None of children died due to bloodstream infection caused by Streptococcus mitis.Conclusion:The infection rate of Streptococcus mitis is increasing year by year in children with hematological diseases,especially in children with AML.Among them,neutropenia and oral mucosal damage after chemotherapy are high-risk infection factors.The common clinical symptoms include persistent high fever,oral mucosal damage,and elevated CRP.Penicillin and cephalosporins have good sensitivity.Linezolid,as a highly sensitive antibiotic,can effectively control infection and shorten the course of disease.

Objective:To explore the clinical effects of sterilization of vas deferens by irrigation in clinic.Methods:Eighty-six male patients with voluntary sterilization were divided into control group(usual vasectomy,n=50)and observation group(sterilization of vas deferens by irrigation,n=36).The age,testicular volume,preoperative average concentration of spern,serum testosterone level,recovery duration evaluated by Artificial Obstruction Azoospermia(AOA)and degree of satisfaction were compared between the two groups of patients.Results:There were significant differences in recovery duration,degree of satisfaction between the two groups(P＜0.05).And there was no significant difference in age([32.0±5.5]years vs[31.0±6.3]years),testicular volume([16.0±4.8]mL vs[17.0±4.4]mL),preopera-tive average concentration of sperm([39.6±20.2]× 106/mL vs[40.2±22.6]× 106/mL)and levels of blood testosterone([4.3±0.8]ng/mL vs[4.4±0.8]ng/mL).There was significant difference in patency rate between the two sides of testicular ducts(91.7％vs 83.3％,P＜0.05).Conclusion:The method of sterilization of vas deferens by irrigation is worth popularizing in clinic.

Objective:To investigate the effects of tetramethylpyrazine(TMP)on spinal cord inflammation and phosphatidylinositol 3-kinase/serine-threonine kinase/nuclear factor-κB(PI3K/Akt/NF-κB)signaling pathway in rats with lumbar disc herniation(LDH).Methods:The rats were divided into Control group,lumbar disc herniation group(LDH group),TMP low-dose,high-dose group(TMP-L,TMP-H group),TMP high-dose+PI3K inhibitor group(TMP-H+LY294002 group)by random number table method.LDH rat model was established by autologous nucleus pulposus transplantation and treated with corresponding drugs.After administration,the pain threshold of rats in each group was measured by paw tactile tester and plantar thermal stimulation tester.Hematoxylin-eosin(HE)staining was used to observe the histomorphological changes of dorsal root ganglion.Enzyme linked immunosorbent assay(ELISA)was used to measure the levels of tumor necrosis factor α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)in the spinal dorsal horn.Immunohistochemistry was used to detect the expression of ionized calcium binding adapter molecule 1(Iba-1)and c-Fos in the spinal dorsal horn.Western blot was used to detect the expression of PI3K/Akt/NF-κB signaling pathway related proteins,and the ratios of p-PI3K/PI3K,p-Akt/Akt and p-NF-κB p65/NF-κB p65 were calculated.Results:At 24h before intervention,the paw withdrawal mechanical threshold(PWMT)and paw withdrawal thermal latency(PWTL)in the LDH group were lower than those in the Control group(P<0.05).At 24h after intervention,compared with Control group,the LDH group had severe nucleus deviation,blurred nucleoli,large amount of inflammatory cell infiltration and obvious cell swelling,decreased PWMT,PWTL,p-PI3K/PI3K and p-Akt/Akt,and increased levels of TNF-α,IL-1β,IL-6 and Iba-1,c-Fos and p-NF-κB p65/NF-κB p65(P<0.05).Com-pared with the LDH group,the neurons had less nuclear deviation,clearer nucleoli,less cell swelling and inflammatory cell infiltration in the TMP-L group and TMP-H group,and the PWMT,PWTL,p-PI3K/PI3K and p-Akt/Akt were in-creased in turn,while the levels of TNF-α,IL-1β,IL-6 and Iba-1,c-Fos,p-NF-κB p65/NF-κB p65 were decreased in turn(P<0.05).Compared with the TMP-H group,the TMP-H+LY294002 group had more severe pathological dam-age of neurons,obvious nuclear deviation,blurred nucleoli,cell swelling and inflammatory cell infiltration,decreased PWMT,PWTL,p-PI3K/PI3K and p-Akt/Akt,and increased levels of TNF-α,IL-1β,IL-6 and Iba-1,c-Fos and p-NF-κB p65/NF-κB p65(P<0.05).Conclusion:TMP can inhibit the activation of microglia and the expression of Iba-1 and c-Fos,and improve spinal cord inflammation in LDH rats,and its mechanism may be related to the regulation of PI3K/Akt/NF-κB signaling pathway.

Objective:To explore the effects of hydroxychloroquine(HCQ)on immune mediators dysregulation in severe infection after chemotherapy in acute myeloid leukemia(AML)and its molecular mechanism.Methods:Bone marrow or peripheral blood samples of 36 AML patients with severe infection(AML-SI)and 29 AML patients without infection(AML-NI)after chemotherapy were collected from the First Affiliated Hospital of Gannan Medical University from August 2022 to June 2023.In addition,the peripheral blood of 21 healthy subjects from the same period in our hospital was selected as the control group.The mRNA expressions of CXCL12,CXCR4 and CXCR7 were detected by RT-qPCR technology,and the levels of IL-6,IL-8 and TNF-α were detected by ELISA.Leukemia-derived THP-1 cells were selected and constructed as AML disease model.At the same time,bone marrow mesenchymal stem cells(BM-MSCs)from AML-SI patients were co-cultured with THP-1 cells and divided into Mono group and Co-culture group.THP-1 cells were treated with different concentration gradients of HCQ.The cell proliferation activity was subsequently detected by CCK-8 method and apoptosis was detected by Annexin V/PI double staining flow cytometry.ELISA was used to detect the changes of IL-6,IL-8 and TNF-α levels in the supernatant of the cell co-culture system,RT-qPCR was used to detect the mRNA expression changes of the core members of the CXCL12-CXCR4/7 regulatory axis,and Western blot was used to detect the expressions of apoptosis regulatory molecules and related signaling pathway proteins.Results:CXCL12,CXCR4,CXCR7,as well as IL-6,IL-8,and TNF-α were all abnormally increased in AML patients,and the increases were more significant in AML-SI patients(P＜0.01).Furthermore,there were statistically significant differences between AML-NI patients and AML-SI patients(all P＜0.05).HCQ could inhibit the proliferation and induce the apoptosis of THP-1 cells,but the low concentration of HCQ had no significant effect on the killing of THP-1 cells.When THP-1 cells were co-cultured with BM-MSCs of AML patients,the levels of IL-6,IL-8 and TNF-α in the supernatance of Co-culture group were significantly higher than those of Mono group(all P＜0.01).After HCQ intervention,the levels of IL-6,IL-8 and TNF-α in cell culture supernatant of Mono group were significantly decreased compared with those before intervention(all P＜0.01).Similarly,those of Co-culture group were also significantly decreased(all P＜0.001).However,the expression of the core members of the CXCL12-CXCR4/7 regulatory axis was weakly affected by HCQ.HCQ could up-regulate the expression of pro-apoptotic protein Bax,down-regulate the expression of anti-apoptotic protein Bcl-2,as well as simultaneously promote the hydrolytic activation of Caspase-3 when inhibiting the activation level of TLR4/NF-κ B pathway,then induce the programmed death of THP-1 cells after intervention.Conclusion:The core members of CXCL12-CXCR4/7 axis and related cytokines may be important mediators of severe infectious immune disorders in AML patients.HCQ can inhibit cytokine levels to reverse immune mediators dysregulation and suppress malignant biological characteristics of leukemia cells.The mechanisms may be related to regulating the expression of Bcl-2 family proteins,hydrolytically activating Caspase-3 and inhibiting the activation of TLR4/NF-κ B signaling pathway.

Objective To explore the relationship between cognitive function changes and leukoaraiosis(LA)and cerebrovascular reserve(CVR)in elderly patients with rheumatoid arthritis(RA).Methods A total of 160 elderly patients with RA were selected and their cognitive function were also evaluated.Based on the scoring results of Montreal cognitive assessment(MoCA),all patients were categorized into normal cognitive function group[non cognitive impairment(CI)group]and CI group,respectively.The general clinical information of the patients were recorded,LA via head MRI were evaluated,and CVR through breath holding index(BHI)were assessed,respectively.The relevant risk factors of the two groups of RA patients were analyzed,and univariate and multivariate logistic regression analyses were used to screen the independent risk factors for cognitive decline in elderly patients with RA,and the predictive efficacy of LA score and BHI in the two groups of patients were compared,respectively.Results There were significant differences in education level,coronary heart disease,diabetes,disease activity score(DAS28 score),BHI and LA score between the two groups(P＜0.05).Multivariate logistic regression results displayed that BHI and LA score were independent risk factors for cognitive decline.The receiver operating characteristic(ROC)curve suggested that BHI had a higher predictive value for cognitive decline in elderly RA patients.Conclusion The LA score of elderly RA patients with CI increases while BHI significantly decreases.BHI has a high diagnostic value in predicting cognitive decline in elderly RA patients.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.