Diabetes,a metabolic disease stemming from impaired or defective insulin secretion,ranks among the most severe chronic illnesses globally.While several approved drugs exist for its treatment,they often come with multiple side effects.Therefore,there is a pressing need for safe and effective anti-diabetic medications.Traditional Chinese medicine has recognized Lycium barbarum(LB;goji berry)plant,commonly known as"wolfberry fruit"in China,for over 2,000 years.Natural compounds derived from LB show promise in reducing diabetes levels.Although research on the impact of LB on diabetes is still limited,our review aims to explore the potential of LB in reducing the risk of diabetes and examine the underlying mechanisms involved.LB can modulate diabetes through various pathways,such as inhibitingα-amylase and α-glucosidase activities,promoting β-cell proliferation,stimulating insulin secretion,inhibiting glucagon secretion,improving insulin resistance and glucose tolerance,and enhancing anti-oxidant and anti-inflammatory activities.Additionally,LB improves gut flora and immunomodulation,further aiding diabetes management.These findings highlight the potential clinical utility of LB in managing diabetes and its complications within the framework of evidence-based modern medicine.

Objective To explore the impact of deep learning image reconstruction(DLIR)algorithms on image quality of chest CT,detection rate of lung nodule and reproducibility of lung nodule radiomics feature data compared with adaptive statistical iterative reconstruction V(ASIR-V)algorithms.Methods Seventy-five patients with 211 lung nodules who underwent both ultra-low-dose CT(ULD-CT)and standard-dose CT(SDCT)were prospectively enrolled.ULD-CT images were reconstructed using different algorithms,namely high-level DLIR(DLIR-H),medium-level DLIR(DLIR-M)and 50％ASIR-V(50％ASIR-V),while SDCT images were reconstructed by 50％ASIR-V.Image noise was represented by the standard deviation(SD)of lung parenchyma CT values within identical ROI in both ULD-CT and SDCT images,and signal-to-noise ratio(SNR)were calculated.The detection rate of lung nodule were obtained and compared among different images.Radiomics features of lung nodules in chest 50％ASIR-V SDCT and each ULD-CT were extracted based on automatic segmentation methods,and intra-class correlation coefficients(ICC)of each ULD-CT and 50％ASIR-V SDCT were calculated respectively,and then compared among different ULD-CT algorithms.Results Compared with SDCT images reconstructed with 50％ASIR-V algorithm,all ULD-CT images reconstructed by different algorithms showed higher SD and lower SNR(all P＜0.05).ULD-CT images reconstructed by DLIR-H,DLIR-M and 50％ASIR-V exhibited progressively increasing SD and decreasing SNR(all adjusted P＜0.05).Taken 50％ASIR-V SDCT images as standards,ULD-CT by DLIR-H,DLIR-M and 50％ASIR-V each detected 207 lung nodules(207/211,98.10％),respectively.In chest ULD-CT images,the reproducibility with 50％ASIR-V SDCT for texture feature data of lung nodules on ULD-CT reconstructed by 50％ASIR-V algorithm was lower than that by DLIR-H and DLIR-M(both adjusted P＜0.05),while no significant difference was found between the latter two with 50％ASIR-V SDCT(adjusted P＞0.05).The first order and shape feature data of lung nodules on ULD-CT reconstructed by all 3 algorithms showed good reproducibility with 50％ASIR-V SDCT(median ICC＞0.75),and no significant difference was detected among them(all P＞0.05).Conclusion Compared with 50％ASIR-V ULD-CT,both DLIR-H and DLIR-M ULD-CT could significantly reduce image noise and improve image quality,as well as maintain reproducibility of radiomics features in lung nodules in a certain degree,especially DLIR-H.

Objective To explore the effect and preliminary mechanism of the plant-derived immunostimulatory molecule,ophiopogonin,on enhancing the immune response of a subunit vaccine with the receptor-binding domain(RBD)of coronavirus spike protein as the antigen.Methods CCK-8 assay was used to determine the cytotoxicity of ophiopogonin D'(OPD')on bone marrow-derived dendritic cells(BMDCs).Female Balb/c mice were randomly divided into RBD,RBD/OPD',RBD/Alum,and control groups.The immunization dose was 5 μg of antigen per mouse and 100 μg of adjuvant per mouse,and immunization was carried out according to the intramuscular injection immunization procedure on days 0,21,and 42.The titers of specific IgG and its subtype antibodies were detected by ELISA.The cytokine levels in the supernatant of splenocytes were detected using ELISA.The number of splenocytes secreting IFN-γ was detected by ELISpot.Laser confocal microscopy was employed to observe the uptake of antigen by BMDCs.The phagocytic ability of BMDCs for antigen was quantitatively analyzed by flow cytometry.The mechanism of its enhanced immune effect was preliminarily explored using transcriptomics technology combined with bioinformatics research.Results When the concentration of OPD'was less than 5 μg/mL,the survival rate of BMDCs was 100%.After a single intramuscular injection in mice,except for a slight decrease in body weight,the other biochemical indicators were within corresponding normal ranges.After intramuscular injection immunization of the vaccine,the titers of serum-specific IgG,IgG1,and IgG2a in the RBD/OPD'group were significantly higher than those in the RBD group(P<0.05).Compared with the RBD group,the RBD/OPD'group induced a high-level Th1 cell immune response of IL-1β,TNF-α,and IFN-γ(P<0.01)and had more lymphocytes secreting IFN-γ(P<0.001).Laser confocal microscopy displayed that BMDCs took up more antigens after OPD'treatment,which was further confirmed with flow cytometry in quantitative analysis on antigen uptake rate(P<0.01).Transcriptomics results indicated that there was more significant enrichment of the PPAR signaling pathway in the RBD/OPD'group than the RBD group,suggesting that OPD'may activate the PPAR signaling pathway to exert its adjuvant effect.Conclusion OPD'effectively enhances the immune response of the RBD subunit vaccine,and its action mechanism may be related to the activation of the PPAR signaling pathway.

Objective To establish a mouse model of infection with the minimum lethal dose of Vibrio vulnificus(V.vulnificus)and to evaluate the protective efficacy of inactivated whole-cell(IWC)vaccine using this model.Methods A mouse model of lethal-dose infection was established by intraperitoneal injection of different doses of V.vulnificus.Bacterial colonization in the organs was detected with tissue homogenate plating,and pathological changes in the organs were observed after tissue section staining.Flow cytometry was used to detect immune cell responses after liver tissues were digested into single-cell suspension.IWC vaccine of V.vulnificus was prepared,and the mice were immunized through different routes to observe the protective efficacy of the vaccine.Results A mouse model of infection with the minimum lethal dose at 1×106 CFU of V.vulnificus was successfully established.After infection,the bacteria were mainly colonized in the liver of mice and caused severe pathological damages.Compared with the uninfected mice,the proportion of neutrophils in the liver was significantly increased in the infected mice,whereas the proportions of B cells and T cells were correspondingly decreased(P<0.05).A single intramuscular or intraperitoneal injection of the IWC vaccine could protect the mice effectively against lethal infection of V.vulnificus in 7 d later(P<0.01),although the level of serum IgG having no significant increase.Conclusion A mouse model of lethal-dose infection with V.vulnificus is successfully established,with histopathological characteristics.The IWC vaccine of V.vulnificus rapidly mediates immune protection in this model probably independent of IgG.

Objective To prepare tubeimoside Ⅲ nanoemulsion(TBMⅢ-NE)and evaluate its adjuvant effect in vaccines.Methods TBMⅢ-NE was prepared using low-energy emulsification.Dynamic light scattering was used to characterize the particle size and polydispersity index of the obtained TBMⅢ-NE,and transmission electron microscopy(TEM)was employed to observe the morphology.CCK-8 assay was utilized to determine the cytotoxicity of TBMⅢ-NE on bone marrow-derived dendritic cells(BMDCs).The in vitro safety of TBMⅢ-NE was evaluated using a hemolysis assay.The ability of TBMⅢ-NE to promote the phagocytosis of antigens by DC2.4 cells was observed using confocal laser microscopy.After co-incubation of TBMⅢ-NE with BMDCs,the expression levels of CD40,CD86,MHC-Ⅰ,and CCR7 on the surface of BMDCs were detected using flow cytometry,and the levels of cytokines in the supernatant of BMDCs were measured using enzyme-linked immunosorbent assay(ELISA).After female BALB/c mice were immunized with the SARS-CoV-2 antigen RBD in combination with TBMⅢ-NE,ELISA was conducted to determine the serum levels of specific IgG,IgG2a,and IgG1 antibodies.The number of specific IFN-γ-secreting cells in mouse splenocytes was detected using enzyme-linked immunospot(ELISpot)assay.Results The prepared blank nanoemulsion(BNE)and TBMⅢ-NE were in a particle size of 25.46 and 25.89 nm,and a polydispersity index of 0.214 and 0.125,respectively.TEM displayed that TBMⅢ-NE was in uniform sphere and well dispersed.When the TBMⅢ-NE adjuvant was diluted by 400-fold,the survival rate of BMDCs was approximately 86%.Compared with free TBMⅢ,the hemolytic toxicity of TBMⅢ-NE was significantly reduced(P<0.01).TBMⅢ-NE promoted the phagocytosis of antigens by DC2.4 cells and significantly increased the expression of CCR7 on the surface of BMDCs(P<0.05),indicating its potential to promote more dendritic cells to effectively migrate to lymph nodes.TBMⅢ-NE also promoted the expression of IL-6 and IL-1β in the supernatant of BMDCs(P<0.05).When combined with RBD,TBMⅢ-NE significantly increased the levels of specific IgG,IgG2a,and IgG1 antibodies in mouse serum(P<0.01)and promoted the secretion of specific IFN-γ in splenocytes(P<0.01),indicating that TBM Ⅲ-NE could enhance specific cellular immune responses.Conclusion A stable and highly effective TBMⅢ-NE that can induce humoral and cellular immune responses is successfully prepared.

Objective:To explore the evaluation and relationship of hepatitis B virus(HBV)surface antigen(HBsAg)in clinical laboratory in different detection systems,further scientifically and reasonably to explain the test results for serving clinical practices.Methods:During the period from June 2021 to July 2022,100 425 specimens of patients with screened,suspected and confirmed HBV infections were collected from the clinical departments(mainly infectious hepatology)of Nanyang Central Hospital.Detection methodology included quantitative(electrochemiluminescence and chemiluminescence),qualitative(gold standard),semi-quantita-tive(ELISA),and highly sensitive HBV-DNA(RT-PCR)methods,and then analyzed the strengths and weaknesses and closeness be-tween each methodology.The relationship between the two Roche HBsAg detection systems was analyzed by correlation analysis.The HBsAg efficacy analysis was validated using Cut/Off value setting and detection limit,which in turn analyzed the distribution of false-positive and false-negative reporting models.Results:Detection results for low-and medium-concentration HBsAg showed a correla-tion between the electrochemical luminescence semi-quantitative method and ELISA method.ELISA method still had advantages in terms of sensitivity and specificity when detecting HBsAg,and there were no significant differences compared to domestic and interna-tional HBsAg quantitative detection systems.Performance validation conducted in accordance with the CNAS-GL038 document showed that the minimum detection limit for HBsAg calculated using the ELISA method in this laboratory was 0.1 U/ml.When the ROC curve Cut/Off value was set to 0.105,the area under the curve was the largest(AUC=0.986).Based on Roche's semi-quantitative electroche-miluminescence detection and patient medical history,in the common reporting model for hepatitis B five-item detection using ELISA method,HBsAg false positives occurred most frequently when HBsAg was positive alone,and HBsAg occurred most frequently in the false positive range when the OD value was less than 0.5.In ELISA method for detecting HBsAg,as the OD value increased from 0.01 to 0.10,the number of false-negative results also increased.Roche Elecsys HBsAg Ⅱ Quant Ⅱ and Elecsys HBsAg Ⅱ testing systems exhibited good linearity under certain conditions,with a ratio of approximately 1/0.18.In Elecsys HBsAg Ⅱ Quant Ⅱ detection sys-tem,the test results of HBsAg samples diluted 400 times were highly consistent with the original test results with a coefficient of deter-mination R2=0.993 8.Conclusion:There was a certain relationship between various detection systems of HBsAg at a suitable concen-tration.The detection of HBsAg by ELISA can meet the needs of clinical detection.

Lysosomes represent a promising target for cancer therapy and reducing drug resistance. However, the short treatment time and low efficiency of lysosomal targeting have limited the application in lysosome-targeting anticancer drugs. In this study, we proposed an adhesive-bandage approach and synthesized a new lysosomal targeting drug, namely long-term lysosome-targeting anticancer drug (LLAD). It contains a SLC38A9-targeting covalently bound moiety and an alkaline component both to prolong the inhibition of SLC38A9 in lysosomes and alkalinize lysosomes. Upon short term and low-dose treatment of HeLa cells, at passage 0, with LLAD, it rapidly alkalinized lysosomes and also can be detected in lysosomes even at passage 15. LLAD induced apoptosis in HeLa cells through long-term lysosomal damage, and showed better long-term anticancer effect than cisplatin in vivo. Overall, our study paves the way for developing long-term lysosomal targeting drugs to treat cancer and overcome the drug resistance of cancer cells, and also provides a candidate drug, LLAD, for treating cancer.

Diabetes, a metabolic disease stemming from impaired or defective insulin secretion, ranks among the most severe chronic illnesses globally. While several approved drugs exist for its treatment, they often come with multiple side effects. Therefore, there is a pressing need for safe and effective anti-diabetic medications. Traditional Chinese medicine has recognized Lycium barbarum (LB; goji berry) plant, commonly known as "wolfberry fruit" in China, for over 2,000 years. Natural compounds derived from LB show promise in reducing diabetes levels. Although research on the impact of LB on diabetes is still limited, our review aims to explore the potential of LB in reducing the risk of diabetes and examine the underlying mechanisms involved. LB can modulate diabetes through various pathways, such as inhibiting α-amylase and α-glucosidase activities, promoting β-cell proliferation, stimulating insulin secretion, inhibiting glucagon secretion, improving insulin resistance and glucose tolerance, and enhancing antioxidant and anti-inflammatory activities. Additionally, LB improves gut flora and immunomodulation, further aiding diabetes management. These findings highlight the potential clinical utility of LB in managing diabetes and its complications within the framework of evidence-based modern medicine.

Objective To explore the traditional Chinese medicine(TCM)syndrome character-istics and medication patterns of cerebral small vessel disease(CSVD)using data mining techniques.Methods Clinical research literature on TCM treatment of CSVD,published from the establishment of the database to September 1,2024,was retrieved from the China National Knowledge Infrastructure(CNKI),Wanfang,and VIP databases.Analyses were conducted on syndromes,drug frequencies,properties,flavors,and meridian tropisms.Data mining was performed using R4.4.1 software to ex-plore associations,correlations,and clustering of TCM herbs,aiming to elucidate medication patterns in CSVD treatment.Results A total of 60 prescription formulas for treating CSVD were screened,involving 142 TCM herbs with a total usage frequency of 1,312 times.The top five most frequently used herbs were Chuanxiong,Danggui,Dilong,Huangqi,and Chishao.Herb properties were pre-dominantly warm and cold;flavors were mainly pungent,bitter,and sweet;and meridian tropisms were primarily to the liver,spleen,and heart meridians.Twenty-nine strong association rules were identified,and association analysis revealed core herbal combinations centered around Chuanxiong,Chishao,and Danggui.Clustering analysis yielded five herbal combinations.Conclusion CSVD is characterized by a deficiency in essence and excess in superficiality.Treatment should focus on tonify-ing deficiencies and eliminating excesses,combining both tonification and purgation methods.Medication patterns predominantly involve herbs for promoting blood circulation and removing blood stasis,often combined with herbs for nourishing the kidney and marrow,calming the liver and suppressing wind,and awakening the mind and opening the orifices.

Background With the large-scale production and application of carbon black nanoparticles (CBNPs), occupational and general exposure is obviously increasing. Related studies have shown that exposure to CBNPs can induce oxidative stress, inflammation, and DNA damage. Objective To establish a CBNPs-induced malignant transformation (C-BEAS-2B) model of human lung epithelial cells (BEAS-2B) and explore the role and mechanism of circCCDC138 in the malignant transformation process. Methods At 0, 10, 20, 40 and 80 μg·mL⁻¹ CBNPs concentrations, cell viability was detected by CCK8 assay. BEAS-2B cells were exposed to 20 mg·mL⁻¹ CBNPs for three months, and a malignant transformation model of BEAS-2B induced by CBNPs was constructed. The migration and invasion abilities of the cells were detected by cell scratch and Transwell assays. The expressions of circ-CCDC138 in BEAS-2B and C-BEAS-2B were detected by qRT-PCR, and its stability was verified by a digestive resistance test. A cell model with interference or overexpression of circCCDC138 was constructed, and the expression of circCCDC138 in the cells was detected by quantitative reverse transcription-PCR. The cell cycle and apoptosis were determined by flow cytometry. Western blot was used to analyze the expression of p53 protein. Results The CBNPs used in the experiment were spherical particles with a chain-like structure. In the 20 μg·mL⁻¹ CBNPs group, the reduction in the viability of BEAS-2B cells was relatively small (10%). Compared with the control cells, the 20 μg·mL⁻¹ CBNPs group showed more obvious cell migration and invasion at 24 h and 48 h, indicating that the exposure to CBNPs induced early malignant transformation of BEAS-2B cells (P<0.01). The circCCDC138 expression in C-BEAS-2B was upregulated in a time-dependent manner after exposure to CBNPs. Compared with the C-BEAS-2B cells, the C-BEAS-2B cells over-expressing circCCDC138 exhibited arrested S phase progression (36.9%) and apoptosis resistance (P<0.01), along with down regulation of p53 protein expression in the cells (P<0.01), while the C-BEAS-2B cells interfering with circCCDC138 showed the opposite results (P<0.01). Conclusion BEAS-2B cells exposed to CBNPs (20 μg·mL⁻¹) have significantly enhanced migration and invasion abilities, showing early malignant transformation characteristics. In addition, circCCDC138 is highly expressed in C-BEAS-2B cells with RNase R digestive resistance and increases in a time-dependent manner with CBNPs exposure. More importantly, circCCDC138 may promote the induction of malignant transformation of cells by inhibiting p53 protein expression.