Single-cell analysis of phenotypic plasticity could improve the development of more effective therapeutics. Still, the development of tools to measure single-cell heterogeneity has lagged due to difficulties in manipulating and culturing single cells. Here, we describe a single-cell culture and phenotyping platform that employs a starburst microfluidic network and automatic liquid handling system to capture single cells for long-term culture and multi-dimensional analysis and quantify their clonal properties via their surface biomarker and secreted cytokine/growth factor profiles. Studies performed on this platform found that cells derived from single-cell cultures maintained phenotypic equilibria similar to their parental populations. Single-cell cultures exposed to chemotherapeutic drugs stochastically disrupted this balance to favor stem-like cells. They had enhanced expression of mRNAs and secreted factors associated with cell signaling, survival, and differentiation. This single-cell analysis approach can be extended to analyze more complex phenotypes and screen responses to therapeutic targets.

Objective To investigate the distribution of dense fine speckled(DFS)antinuclear antibody(ANA)in different ages,genders,and diseases,and to explore its clinical significance in the diagnosis of auto-immune disease(AID).Methods A retrospective summary was conducted on the clinical basic data of 53520 patients who visited the hospital from January 2022 to April 2024,as well as the results of indirect immunoflu-orescence(IIF)ANA fluorescence karyotype and titer,and immunoblotting ANA spectrum,and the relation-ship between DFS positivity and AID was analyzed.Results Of the 53 520 serum samples,the rate of ANA fluorescence positivity was 32.40％,with DFS-positive samples accounting for 1.18％of all ANA fluores-cence-positive samples.The male-to-female ratio of DFS positives was 1∶1.94,with the highest percentage of 51.9％in the 21-40 age group.Among DFS positive individuals,only 12.14％were clinically diagnosed with AID disease,significantly lower than other ANA fluorescent karyotype positive individuals(23.31％,P＜0.001).The overall positivity rate of ANA spectra using immunoblotting in DFS-positive individuals was 23.54％,which was significantly lower than that in other fluorescent karyotype positive ANA individuals(73.26％,P＜0.001).Moreover,DFS positive individuals were mainly accompanied by antibody positivity such as anti-Ro52 antibodies,which had no diagnostic specificity in AID diagnosis.When comparing DFS posi-tive individuals with similar fluorescence morphology to those with homogeneous nuclear granules and nuclei,at an ANA titer of 1∶100,the proportion of AID patients in homogeneous nuclear granules and nuclei was 20.04％,significantly higher than the proportion of AID patients in DFS positive individuals(9.44％,P=0.001).With the increase of ANA titer,the proportion of AID diseases significantly increased in both karyo-type samples.When the ANA titer of DFS positive samples was increased to ≥ 1∶320,the proportion of AID diseases significantly increased to 30.77％(P=0.002).Conclusion DFS is a rare ANA fluorescent karyo-type,and DFS positive individuals are mainly found in females aged 21-40,mostly non AID patients.Howev-er,high titers of DFS cannot rule out the possibility of AID.In clinical work,special attention should be paid to distinguishing it from the homogeneous nuclear granule type to avoid misdiagnosis.

Nuclear medicine plays an indispensable role in the diagnosis,treatment,and prognosis of a wide range of diseases.Nuclear medicine using radionuclides for diagnosis has the advantages of accuracy,speed,high sensitivity and high resolution.Currently,several radionuclides play pivotal roles in disease diagnosis.This article primarily examines the clinical application and research of diagnostic radionuclides,including 18 F,89 Zr,68 Ga,99m Tc,131 I,123 I,and 11 C.The objective is to offer valuable insights for disease diagnosis and staging of diseases.

Objective:To explore the clinical feasibility of finger-pressing therapy based on the theory of treating impotence alone with Yang Ming to reduce incidence of ICU acquired weakness (ICU-AW) in critically ill children and provide a feasible nursing plan for ICU acquired asthenia in critically ill children.Methods:A quasi-experimental study was conducted. A total of 73 critically ill children were admitted to the PICU of Kunming Children′s Hospital from January 1 to April 30, 2021. According to the random number table, the subjects were divided into the observation group (37 cases) and the control group (36 cases). Children in the control group received routine PICU nursing. The children in the observation group were treated with PICU routine nursing and finger-pressing therapy based on the theory of treating impotence alone with Yang Ming. The two groups were compared in terms of limb muscle strength score (MRC-Score), incidence of ICU-AW, basic activities of life (Barthel Index, BI), limb muscle thickness.Results:After intervention, the MRC-Score of the observation group was 50 (46, 52) points, which was higher than 46 (40, 48) points of the control group, and the difference between the two groups was statistically significant ( Z=-3.70, P<0.05). The incidence of ICU-AW in the observation group was 32.43% (12/37), and the incidence of ICU-AW in the control group was 72.22% (26/36). The difference between the two groups was statistically significant ( χ2=11.58, P<0.05). The BI score of the observation group was 63 (50, 70), which was higher than 44 (40,60) of the control group, and the difference between the two groups was statistically significant ( Z=-3.94, P<0.05). The reduction degree of quadriceps femoris thickness in the observation group at D3-D1 was (-0.381 ± 0.131) cm, which was lower than (-0.762 ± 0.182) cm in the control group, and the difference between the two groups was statistically significant ( t=10.29, P<0.05). Conclusions:The application of finger-pressing therapy guided by theory of treating impotence alone with Yang Ming in the early rehabilitation of critically ill children can enhance muscle strength, prevent muscle atrophy and reduce the incidence of ICU-AW in critically ill children.

Cryoablation (CRA) and microwave ablation (MWA) are two main local treatments for hepatocellular carcinoma (HCC). However, which one is more curative and suitable for combining with immunotherapy is still controversial. Herein, CRA induced higher tumoral PD-L1 expression and more T cells infiltration, but less PD-L1^highCD11b⁺ myeloid cells infiltration than MWA in HCC. Furthermore, CRA had better curative effect than MWA for anti-PD-L1 combination therapy in mouse models. Mechanistically, anti-PD-L1 antibody facilitated infiltration of CD8⁺ T cells by enhancing the secretion of CXCL9 from cDC1 cells after CRA therapy. On the other hand, anti-PD-L1 antibody promoted the infiltration of NK cells to eliminate PD-L1^highCD11b⁺ myeloid cells by antibody-dependent cell-mediated cytotoxicity (ADCC) effect after CRA therapy. Both aspects relieved the immunosuppressive microenvironment after CRA therapy. Notably, the wild-type PD-L1 Avelumab (Bavencio), compared to the mutant PD-L1 atezolizumab (Tecentriq), was better at inducing the ADCC effect to target PD-L1^highCD11b⁺ myeloid cells. Collectively, our study uncovered the novel insights that CRA showed superior curative effect than MWA in combining with anti-PD-L1 antibody by strengthening CTL/NK cell immune responses, which provided a strong rationale for combining CRA and PD-L1 blockade in the clinical treatment for HCC.

DNA is a biological polymer that encodes and stores genetic information in all living organism. Particularly, the precise nucleobase pairing inside DNA is exploited for the self-assembling of nanostructures with defined size, shape and functionality. These DNA nanostructures are known as framework nucleic acids (FNAs) for their skeleton-like features. Recently, FNAs have been explored in various fields ranging from physics, chemistry to biology. In this review, we mainly focus on the recent progress of FNAs in a pharmaceutical perspective. We summarize the advantages and applications of FNAs for drug discovery, drug delivery and drug analysis. We further discuss the drawbacks of FNAs and provide an outlook on the pharmaceutical research direction of FNAs in the future.

Stimulator of interferon genes (STING) is a cytosolic DNA sensor which is regarded as a potential target for antitumor immunotherapy. However, clinical trials of STING agonists display limited anti-tumor effects and dose-dependent side-effects like inflammatory damage and cell toxicity. Here, we showed that tetrahedral DNA nanostructures (TDNs) actively enter macrophages to promote STING activation and M1 polarization in a size-dependent manner, and synergized with Mn²⁺ to enhance the expressions of IFN-β and iNOS, as well as the co-stimulatory molecules for antigen presentation. Moreover, to reduce the cytotoxicity of Mn²⁺, we constructed a TDN-MnO₂ complex and found that it displayed a much higher efficacy than TDN plus Mn²⁺ to initiate macrophage activation and anti-tumor response both in vitro and in vivo. Together, our studies explored a novel immune activation effect of TDN in cancer therapy and its synergistic therapeutic outcomes with MnO₂. These findings provide new therapeutic opportunities for cancer therapy.

Objective To explore the value of plasma Tau protein and resistin in early prediction of brain injury in premature infants caused by intrauterine infection. Method A total of 47 premature infants in NICU with early-onset sepsis were selected as infection group from January 2017 to October. According to the cranial MRI, the infection group was further divided into brain injury group (22 cases) and non-brain injury group (25 cases). In addition, 12 normal preterm infants were selected as the control group. Enzyme linked immunosorbent assay (ELISA) was used to detect plasma Tau protein and resistin levels on the first, third and seventh day after birth in three groups. Results The Tau protein in the brain injury group increased significantly on the first day, and then gradually decreased, while it was higher than that in the non-brain injury group and the control group at all time points, and there were statistical differences (P<0.05). At different time points, there was no difference in the level of Tau protein between the non-brain injury group and the control group (P>0.05). The level of resistin in the brain injury group increased significantly on the first day until the third day, and significantly decreased in the seventh day, and it was higher than that in the non-brain injury group and the control group at all time points, and there were statistical differences (P<0.05). Resistin increased on the first day, then gradually decreased, and returned to normal on the seventh day in the non-brain injury group. Conclusion Detection of plasma Tau protein and resistin levels within 3 days after birth may be helpful for early prediction of brain damage in premature infants with intrauterine infection.

Objective:To study the antimicrobial properties of CaO/ZnO core-shell nanoparticles.Methods:The CaO/ZnO core-shell nanoparticles were prepared via precipitation method.The pH and calcium ion release from the samples which composed of eugenol and nanoparticles were examined respectively.The form of the particles was observed under electron microscope,the ions were analysed by inductively coupled plasma(ICP).The antibacterial activities against Streptococcus mutans,Enterococcus faecalis,Escherichia coli and Staphylococcus aureus were evaluated by agar diffusion test (ADT).Results:CaO/ZnO core-shell nanoparticles were spherical with core-shell structure and with the diameter of 80-90 nm.The calcium ion release and pH were gradually increasing from the nanoparticles in PBS.The antibacterial activity of CaO/ZnO core-shell nanoparticles-eugenol was significantly greater than that of iRoot SP and zinc oxide-eugenol sealer(P<0.01).Conclusion:CaO/ZnO core-shell nanoparticles possess antibacterial activity.

Objective To explore the relationships of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) with growth of very low birth weight (VLBW) infants in the early postnatal stage. Methods According to the individual gestational age and birth weight, 32 cases of VLBW infants were divided into small for gestational age (SGA) group and appropriate for gestational age (AGA) group. After birth, all the infants were given the same nutritional intake. The body weight, body length, head circumference and body mass index (BMI) were monitored at different time points (d0, d7, d14 and d28 after birth). Serum IGF-1 and IGFBP-3 levels were measured by radiommunoassay, and IGF-1/IGFBP-3 molar ratio was calculated. Results There was no signiifcant difference of body weight, body length, head circumference and BMI between two groups at d0, d7, d14 after birth. Body weight and BMI in SGA group were less than those in AGA group at d28 after birth (P<0.05). The levels of IGF-1, IGFBP-3 and IGF-1/IGFBP-3 in SGA group and IGF-1/IGFBP-3 in AGA group did not change with age after birth. The levels of IGF-1 and IGFBP-3 were increased in AGA group after birth. The level of IGF-1 in AGA group at d14 and d28 after birth was higher than that in AGA group at d0 after birth (P<0.05). The level of IGFBP-3 in AGA group at d28 after birth was higher than that in AGA group at d0 after birth (P<0.05). The levels of IGF-1 and IGFBP-3 in SGA group at d28 after birth were lower than those in AGA group at d28 after birth (P<0.05). Conclusions Serum IGF-1 and IGFBP-3 levels in SGA group are lower than those in AGA group. Low levels of IGF-1 and IGFBP-3 may result in growth retardation.