⁶³Ni is predominantly generated through neutron activation in nuclear reactors and is classified as a pure beta-emitting radionuclide with a half-life of 101.1 a. During decay, ⁶³Ni emits a beta ray with an energy of 65.87 keV. ⁶³Ni can be used in the manufacture of beta radiation sources, which are utilized as reference and working sources for beta activity measurement and beta energy response calibration. Additionally, it is used in electron capture detectors for chromatography, ionization sources in electron tubes, and electron capture probes in gas chromatography. These instruments have extensive applications in food safety, public health and epidemic prevention, soil pollution monitoring, and security. ⁶³Ni is an artificial radionuclide not commonly found in the natural environment under normal conditions. However, the ⁶³Ni generated during routine operations of nuclear power plants, as well as residual materials and wastes contaminated with ⁶³Ni during plant decommissioning, may be released into the environment through liquid effluents or solid wastes. This can pose potential radiation risks to both the public and the environment. Hence, it is necessary to monitor the activity concentration of ⁶³Ni. Currently, reports on this subject are limited in China, and there is a lack of established standards for the determination of ⁶³Ni in nuclear power plants. This article reviews the global literature on the pretreatment and purification measurement processes of ⁶³Ni. The merits and demerits are summarized for pretreatment methods such as acid leaching, mixed acid digestion, ashing acid leaching/dissolution, and alkali fusion, and for separation and purification methods like solvent extraction, precipitation, and extraction chromatography. The article also highlights the advantages of measurement using liquid scintillation counters. This review provides a reference for the establishment of the determination method of ⁶³Ni in liquid effluents and solid wastes from nuclear power plants.

OBJECTIVE To evaluate the cost-effectiveness of finerenone combined with standard of care （SoC） in the treatment of heart failure with mildly reduced ejection fraction （HFmrEF） or preserved ejection fraction （HFpEF）. METHODS Based on a phase Ⅲ clinical trial， a Markov model was constructed from the perspective of China’s healthcare system to compare the treatment outcomes of finerenone combined with SoC regimen versus SoC regimen alone in the treatment of different cardiac functional statuses of HFmrEF/HFpEF. Using quality-adjusted life year （QALY） as the health output index， 3 times China’s per capita GDP in 2023 as the willingness-to-pay （WTP） threshold， a simulation was conducted with a 3-month cycle length and a 10- year time horizon， incorporating an annual discount rate of 5%. The dynamic changes across various stages of HFmrEF/HFpEF treated with finerenone combined with SoC versus SoC alone were simulated to evaluate the long-term effectiveness and costs of the two treatment strategies. Additionally， one-way sensitivity analysis and probabilistic sensitivity analysis were performed， to test the robustness of the results. RESULTS The incremental cost-effectiveness ratio （ICER） of the finerenone combined with SoC regimen versus SoC regimen alone was 179 504.75 yuan/QALY， which was below the WTP threshold set in this study， indicating that the finerenone combined with SoC regimen possessed certain economic advantages. The results of one-way sensitivity analysis showed that the utility value of NYHA Ⅱ status， the drug price of finerenone， the discount rate， and the probability of hospital transfer for both groups had a great influence on ICER， but did not affect the robustness of the model. The probabilistic sensitivity analysis also confirmed the robustness of the model. CONCLUSIONS Under the WTP threshold set in this study， finerenone combined with SoC is cost-effective in the treatment of HFmrEF/HFpEF， compared with the SoC regimen.

Objective To investigate the clinical application of three-dimensional intracavitary/free-hand interstitial brachytherapy technique in radical radiotherapy for cervical cancer. Methods A retrospective study was conducted on the clinical data of patients with cervical cancer who underwent radical radiotherapy using CT-guided three-dimensional intracavitary/free-hand interstitial brachytherapy technique in The Affiliated Cancer Hospital of Nanjing Medical University from April 2019 to September 2021. The short-term efficacy and adverse reactions were analyzed, and the independent predictors affecting short-term efficacy were evaluated by logistic risk regression model. Results A total of 182 patients were included, and all patients successfully completed the treatment. Clinical efficacy assessment performed 3 months after treatment revealed an overall response rate of 90.65%; the incidence of grade 3 and 4 adverse reactions in the lower gastrointestinal tract was 4.4% during treatment. After reclassifying stage IIIC patients according to the International Federation of Gynecology and Obstetrics (FIGO) 2009 staging system and including factors affecting the stage, it was found that the tumor volume before brachytherapy was the main factor affecting the clinical efficacy of patients at this stage (P = 0.004). Conclusion As a key method in radical radiotherapy for cervical cancer, three-dimensional intracavitary/free-hand interstitial brachytherapy technique is safe and effective and can be quickly popularized in primary hospitals beyond regional cancer centers for cervical cancer brachytherapy.

Objective To investigate the key physical and chemical properties of nintedanib liposomes prepared by 4 different methods in order to screen out the best preparation method of nintedanib liposomes.Methods Firstly,nintedanib liposomes were prepared by thin film dispersion,reverse evaporation,ethanol injection and modified ethanol injection,respectively.The entrapment efficiency of nintedanib liposomes was then determined by dialysis and characterized for particle size,dispersibility,surface potential,and morphology.Their stability was evaluated after being placed at room temperature for 7 d.Results Circular nintedanib liposomes were respectively prepared by thin film dispersion,reverse evaporation,ethanol injection and modified ethanol injection,with a particle size of(285.1±12.3),(271.4±5.9),(226.3±14.8)and(197.2±11.2)nm,an encapsulation rate of(15.82±1.26)％,(16.71±1.35)％,(25.12±3.21)％and(32.5±3.61)％,respectively.The nintedanib liposomes prepared by modified ethanol injection had significantly smallest particle size and highest encapsulation efficiency than the liposomes by the other 3 methods(P＜0.05).In 7 d after being placed at room temperature,the particle sizes of the liposomes prepared by film dispersion and reverse evaporation were increased notably(P＜0.01),but no such change was observed in the liposomes prepared by ethanol injection and modified ethanol injection(P＞0.05).Conclusion Nintedanib liposomes prepared by modified ethanol injection have excellent key physical and chemical properties,and this method is an optical one for preparing nintedanib liposomes.

Objective·To examine the expression level of protein arginine methyltransferase 6(PRMT6)in breast carcinoma tissues and to assess its impact on the proliferative and migratory behaviors of breast cancer cells.Methods·The PRMT6 transcriptome sequencing data between 33 tumor tissues and normal tissues from The Cancer Genome Atlas(TCGA)database was analyzed through the R language.The gene expression profile interactive analysis(GEPIA2)online database was used to analyze the difference of PRMT6 expression in normal breast tissues and breast cancer tissues.By using the immunohistochemistry(IHC)data of human normal breast tissues and breast cancer tissues from Human Protein Atlas(HPA)database to analyze the protein expression of PRMT6.IHC was used to detect the expression of PRMT6 in breast cancer tissues and paired para-tumor tissues from 27 clinical samples.After PRMT6 was knocked down with small interfering RNA(siRNA)in MDA-MB-231 and MCF-7 cells,the expression of PRMT6 was detected by qRT-PCR and Western blotting.The proliferation ability of breast cancer cells was measured with cell counting kit-8(CCK-8)assay and colony formation assay.The effect of PRMT6 on the migration ability of breast cancer cells was detected by wound healing assay and Transwell assay.By using the RNA-sequence data from GSE210948 of Gene Expression Omnibus(GEO)database,differentially expressed genes were analyzed in control and low expression groups of PRMT6.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was performed to reveal the signaling pathways associated with PRMT6.Cell cycle analysis was detected by flow cytometry.The expressions of cyclin D1 and EMT-related proteins(E-cadherin,N-cadherin and Vimentin)were detected by Western blotting after knocking down PRMT6.Results·Bioinformatics analysis and IHC results showed that PRMT6 was highly expressed in breast cancer tissues compared with normal tissues(P=0.000)and para-tumor tissues(P=0.001).qRT-PCR and Western blotting results verified that the siRNA significantly reduced the expression level of PRMT6 in MDA-MB-231 and MCF-7 cell lines compared with the control group(mRNA:P=0.006,P=0.004;P=0.001,P=0.043.Protein:P=0.035,P=0.001;P=0.003,P=0.002).After knocking down PRMT6,the proliferation(P=0.014,P=0.000;P=0.003,P=0.003)and migration(P=0.000,P=0.000;P=0.000,P=0.002)ability of breast cancer cells were inhibited significantly.The KEGG pathway enrichment analysis showed that the expression of PRMT6 affected the cell cycle pathway.After knocking down PRMT6,the expression of cyclin D1 decreased in protein level(P=0.021,P=0.000;P=0.034,P=0.014)and transcription level(P=0.036,P=0.001;P=0.044,P=0.000).Knock down of PRMT6 increased the number of cells in G0/G1 phase(P=0.000;P=0.003)and decreased the number of cells in G2/M phase of the cell cycle.The expression level of E-cadherin increased(P=0.002,P=0.012;P=0.043,P=0.003),while the expression levels of N-cadherin(P=0.004,P=0.041;P=0.032,P=0.034)and Vimentin(P=0.028,P=0.005;P=0.024,P=0.001)decreased in PRMT6 knockdown cells.Conclusion·PRMT6 is highly expressed in breast cancer,which can promote the proliferation and migration of breast cancer cells.

Objective·To identify key genes that may be regulated by fatty acid alteration in pancreatic cancer through tumor transcriptome screening,and to explore the expression of zinc finger protein 143(ZNF143)in pancreatic cancer and its effect on the migration and invasion of pancreatic cancer cells.Methods·The R language was utilized to integrate transcriptome data,including the GSE164760 dataset from the Gene Expression Omnibus(GEO)database,179 pancreatic cancer tissue samples and 4 adjacent non-cancerous tissue samples from The Cancer Genome Atlas(TCGA)database,as well as 167 normal pancreatic tissue samples from the Genotype-Tissue Expression(GTEx)database.We conducted screening and analysis of potential differential genes that may be induced by dysregulation of fatty acid metabolism in pancreatic cancer.After treating pancreatic cancer cells with palmitic acid(PA)and oleic acid(OA)for 24 hours,the mRNA levels of candidate genes were detected by qRT-PCR.According to the median expression level of the screened gene,pancreatic cancer patients in the TCGA database were divided into two groups with high and low expression of ZNF143.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway and Gene Ontology(GO)enrichment analyses were performed for the differential genes of the two groups.siRNA was used to knock down the expression of ZNF143 in pancreatic cancer cells,and the effects on cell migration and invasion were examined by wound healing assay and invasion assay.Western blotting was used to explore the impact of ZNF143 on epithelial mesenchymal transition(EMT)-related proteins and the Wnt/β-catenin pathway.Results·The bioinformatics database was processed to analyze key genes associated with the up-regulation of genes in lipid metabolism disorders in pancreatic cancer and liver cancer.Among them,ZNF143 was a potential gene associated with fatty acid accumulation in pancreatic cancer.In vitro experiments confirmed that the mRNA level of ZNF143 was significantly up-regulated after treating pancreatic cancer cells with palmitic acid or oleic acid.Both KEGG and GO enrichment analyses demonstrated that the differentially expressed genes associated with ZNF143 were predominantly enriched in adhesion pathways.In functional experiments,the migration and invasion abilities of pancreatic cancer cells transfected with ZNF143 siRNA were reduced,and the expression of EMT-related proteins was also decreased,potentially related to the activation of the Wnt/β-catenin pathway.Conclusion·Fatty acid accumulation up-regulates the mRNA expression of ZNF143 in pancreatic cancer cells,and ZNF143 may enhance the migration and invasion of these cells by facilitating EMT through activation of the Wnt/β-catenin pathway.

Objective To investigate the similarities and differences in the pathophysiological responses caused by different infection sites in sepsis patients and to evaluate the clinical significance of the source of infection on the prognosis of patients.Methods A total of 159 patients with a clear source of infection in Foshan Hospital of Traditional Chinese Medicine from January 1,2021 to January 1,2023 were selected and divided into survival group(n=98)and death group(n=61)based on their survival status within 28 days.The independent risk factors affecting the prognosis of sepsis patients were determined by multivariate Logistic regression analysis.The 28-day mortality rates of different infection source groups were compared,and the distribution differences of serum biomarkers in different infection source groups were explored by analysis of variance.Results Among the 159 patients,the frequency of infection source distribution was as follows in descending order:Respiratory tract(62.89％),urinary tract(13.84％),abdomen(13.21％),skin and soft tissue(10.06％).Multivariate Logistic regression analysis showed that age,procalcitonin,sepsis-related organ failure assessment score,and respiratory tract infection source were significant risk factors affecting the 28-day mortality of sepsis patients(P＜0.05).Different infection source groups showed different degrees of differences in inflammation,coagulation,and organ dysfunction,with heterogeneity.Conclusion The differences in the source of infection lead to significant differences in the pathophysiological features(inflammatory response,coagulation activation,and organ dysfunction)and short-term prognosis(28-day mortality)of sepsis.

Objectives: . The annual prevalence of chronic rhinosinusitis (CRS) is increasing, and the lack of effective treatments imposes a substantial burden on both patients and society. The formation of nasal polyps in patients with CRS is closely related to tissue remodeling, which is largely driven by the epithelial-mesenchymal transition (EMT). MicroRNA (miRNA) plays a pivotal role in the pathogenesis of numerous diseases through the miRNA-mRNA regulatory network; however, the specific mechanism of the miRNAs involved in the formation of nasal polyps remains unclear. Methods: . The expression of EMT markers and Smad3 were detected using western blots, quantitative real-time polymerase chain reaction, and immunohistochemical and immunofluorescence staining. Differentially expressed genes in nasal polyps and normal tissues were screened through the Gene Expression Omnibus database. To predict the target genes of miR-145-5p, three different miRNA target prediction databases were used. The migratory ability of cells was evaluated using cell migration assay and wound healing assays. Results: . miR-145-5p was associated with the EMT process and was significantly downregulated in nasal polyp tissues. In vitro experiments revealed that the downregulation of miR-145-5p promoted EMT. Conversely, increasing miR-145-5p levels reversed the EMT induced by transforming growth factor-β1. Bioinformatics analysis suggested that miR-145-5p targets Smad3. Subsequent experiments confirmed that miR-145-5p inhibits Smad3 expression. Conclusion . Overall, miR-145-5p is a promising target to inhibit nasal polyp formation, and the findings of this study provide a theoretical basis for nanoparticle-mediated miR-145-5p delivery for the treatment of nasal polyps.

ObjectiveTo construct a quantitative differentiation model of traditional Chinese medicine （TCM） syndromes by taking primary osteoporosis （POP） with kidney yang deficiency syndrome as an example， and to provide methodological reference for the standardization of syndrome differentiation. MethodsHigh-frequency clinical features of POP were screened by descriptive statistical analysis， and strong association features of POP were obtained by association rule algorithm. On this basis， a latent structure （latent tree） model was established through latent structure analysis， and the implicit and explicit variables （features） related to POP with kidney yang deficiency syndrome were comprehensively clustered， and the clustering results were interpreted by the indexes of mutual information and cumulative information coverage， to explore the primary and secondary symptoms， and to deduce the categories of POP with kidney yang deficiency syndrome based on the probability of the features appearing in the various latent categories. Based on the categories， the clinical feature scores and identification thresholds were calculated， and the syndrome differentiation model of POP with kidney yang deficiency was initially constructed by combining the comprehensive judgment rules. Finally， the results of TCM professionals' judgment were used as the gold standard to further evaluate the effectiveness of the model in assisting the syndrome differentiation. ResultsThe 32 features strongly associated with POP were obtained， and the Bayes information critedon score of the further constructed latent tree model was -15291.93. Based on the mutual information and the cumulative information coverage， the main symptoms of POP with kidney yang deficiency syndrome were bone weakness， fatigue， pale tongue， clear urine， frequent nocturnal urination， cold limbs， thin pulse， white coating， and secondary symptoms were weakness， loss of libido， loose stool， frequent urination， lumbar and knee weakness， and fear of cold. From the probability of the occurrence of each clinical feature in different latent categories of POP with kidney yang deficiency syndrome， the state was introduced as S0 category （none/mild kidney yang syndrome）/ S1 category （moderate kidney yang syndrome）/ S2 category （severe kidney yang syndrome）. Optimizing the preliminary rules of state identification and refining the state of S1 category， the results showed that among 970 patients with POP， there were 520 patients having no/mild kidney yang deficiency syndrome， 224 patients with moderate to mild kidney yang deficiency syndrome， 81 patients with moderate to severe kidney yang deficiency syndrome， and 145 patients with severe kidney yang deficiency syndrome. During the evaluation and validation process， the correct rate of the model assessment index was 0.8835， while the sensitivity was 0.7181， and the specificity was 0.9437. ConclusionCombined with the latent structure analysis of the association rule， the syndrome differentiation model for POP with kidney yang deficiency could be constructed， and the model shows a good quantitative identification effect， which can provide methodological supports for clinicians to improve the efficiency and accuracy of TCM diagnosis.

ObjectiveTo investigate the identification of kidney Yang deficiency syndrome of patients with osteoporosis（OP）， and to form the clinical syndrome identification rules of traditional Chinese medicine（TCM）. MethodBasic information， etiology， clinical symptoms and other characteristics of 982 OP patients were included， and statistical tests were used to screen the variables associated with kidney Yang deficiency syndrome. Taking the decision tree as the base model， bootstrap aggregation algorithm（Bagging algorithm） was utilized to establish the classification model of kidney Yang deficiency syndrome in OP， generating numerous rules and removing redundancy. Combining least absolute shrinkage and selection operator（LASSO） regression to screen key rules and integrate them to construct an identification model， achieving the identification of kidney Yang deficiency syndrome in OP patients. ResultEighteen key identification rules were screened out， and of these， where 11 rules with regression coefficients>0 correlated positively with the kidney Yang deficiency syndrome， the rule with the highest coefficient was chilliness（present）&feverish sensation over the palm and sole（absent）. The other 7 rules with regression coefficients<0 correlated negatively with the syndrome， the rule with the lowest coefficient was reddish tongue（present）&diarrhea（absent）&deficiency of endowment（absent）. According to the regression coefficients of each key rule， variables with importance>0.2 were ranked as chilliness， reddish tongue， feverish sensation over the palm and sole， cold limbs， clear urine， diarrhea， deficiency of endowment， prolonged illness. The results of the partial dependence analysis of the identification model showed that compared to OP patients without chilliness， those with chilliness（present） had a 0.266 8 higher probability of being identified as having kidney Yang deficiency syndrome， indicating that this variable had the highest impact on identification of the syndrome. Similarly， compared to OP patients without reddish tongue， those with reddish tongue had a 0.141 9 lower probability of being identified as having kidney Yang deficiency syndrome， indicating that this variable had the highest impact on identifying non-kidney Yang deficiency syndrome. The accuracy， sensitivity， specificity and area under receiver operating characteristic curve（AUC） of the established kidney Yang deficiency syndrome identification model in the test set were 0.865 9， 0.853 7， 0.872 0 and 0.931 5， respectively. ConclusionA precise identification model of OP kidney Yang deficiency syndrome is conducted basing on the rule ensemble method of Bagging combining LASSO regression， and the screened key rules can explain the identification process of kidney Yang deficiency syndrome. In this research， according to the regression coefficients of rules， the importance and partial dependence of variables， combined with the thinking of TCM， the influence of patient characteristics on the identification of syndromes is described， so as to reveal the primary and secondary syndromes of identification and assist the clinical identification of kidney Yang deficiency syndrome.