Aim To perform high-throughput screen-ing of immunomodulatory traditional Chinese medicine(TCMs)based on an in vitro B cell differentiation-antibody secretion model,identifying active herbal candidates with immune-enhancing properties to pro-vide novel therapeutic options and theoretical support for influenza virus treatment in immunocompromised in-dividuals.Methods B cells were stimulated with dif-ferent concentrations of cytosine-phosphate-guanine oli-godeoxynucleotide 2006(CpG)and nterleukin-2(IL-2)to promote proliferation,differentiation,and anti-body secretion,and the effects of varying concentra-tions of the solvent DMSO were also evaluated.The op-timal conditions for the B cell differentiation-anti-body secretion model were determined based on the se-cretion levels of three antibody isotypes.The feasibility of the model was further validated using rapamycin,a known B cell function inhibitor.On this basis,a high-throughput screening platform for immunomodulatory a-gents was optimized and established.Subsequently,the immune-enhancing activity of 465 polarity extract from TCMs was evaluated.Results The optimal con-ditions for the model were determined as 2 mg·L-1 CpG,1.67 × 106 nkat·L-1 IL-2,and DMSO with a volume fraction of 0.1％.Rapamycin effectively inhib-ited B cell differentiation into plasmablast and signifi-cantly reduced antibody production,indicating the reli-ability of the model.Multiple rounds of screening re-vealed that the dichloromethane extract of licorice,the dichloromethane extract of Vinegar-processed Curcumae Rhizoma,the cyclohexane extract of Honey-prepared Radix Asteris,and the aqueous extract of Siphonostegia chinensis Benth were identified to significantly promote both B cell proliferation and differentiation and anti-body secretion at a concentration of 600 μg·L-1.Conclusion This study successfully optimizes an in vitro B cell differentiation-antibody secretion model and identifies several TCM extracts,including licorice,with potential immune-enhancing activity.

OBJECTIVE: This study aimed to investigate possible serum 25-hydroxyvitamin D [25(OH)D] cutoffs for the associations between 25(OH)D and Bone turnover markers (BTMs), and how GC gene variation influences such cutoffs in Chinese women of childbearing age. METHODS: In total, 1,505 non-pregnant or non-lactating women (18-45 years) were recruited from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance. Serum 25(OH)D, osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), β-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (β-CTX), and single nucleotide polymorphisms were determined. Locally weighted regression and smoothing scatterplot and segmented regression were performed to estimate the 25(OH)D thresholds. RESULTS: The median serum 25(OH)D was 16.63 (11.96-22.55) ng/mL and the prevalence of low serum 25(OH)D (< 12 ng/mL) was 25.2%. Women with the lowest 25(OH)D had the highest β-CTX. After adjustment for the confounders, 25(OH)D cutoffs for OC [14.04 (12.84-15.23) ng/mL], β-CTX [13.94 (12.49-15.39) ng/mL], and P1NP [13.87 (12.37-15.37) ng/mL] in the whole population, cutoffs for OC [12.30 (10.68-13.91) ng/mL], β-CTX [12.23 (10.22-14.23) ng/mL], and P1NP [11.85 (10.40-13.31) ng/mL] in women with the GC rs2282679 G allele, and cutoffs for OC [12.75 (11.81-13.68) ng/mL], β-CTX [13.05 (11.78-14.32) ng/mL], and P1NP [12.81 (11.57-14.06) ng/mL] in women with the GC rs2282679 T allele, were observed. Below these cutoffs, BTMs were negatively associated with 25(OH)D, while above these cutoffs, BTMs plateaued. CONCLUSION In Chinese women of childbearing age, there were thresholds effect of serum 25(OH)D concentrations on BTMs. The results indicated that serum 25(OH)D concentrations < 13.87 ng/mL in this population had adverse influences on maintaining bone remodeling. BTMs were suppressed at a relatively lower serum 25(OH)D in women with the GC rs2282679 G allele compared with those with the T allele.
Humans ; Female ; Vitamin D/blood* ; Adult ; Middle Aged ; Polymorphism, Single Nucleotide ; Adolescent ; Young Adult ; China ; Biomarkers/blood* ; Bone Remodeling/genetics* ; Vitamin D-Binding Protein/genetics* ; Procollagen/blood* ; Osteocalcin/blood* ; Peptide Fragments/blood* ; East Asian People

Aim To explore the mechanism of baicalin combined with heat stimulation in treating acute lym-phoblastic leukemia(ALL)based on network pharma-cology and in vitro experiments.Methods The CCK-8 assay was used to screen the suitable conditions for heat stimulation to interfere ALL cell lines Jurkat,CCRF-CEM,Hut-78 and a normal lymphocyte HMy2.CIR,and the effects of baicalin combined with heat stimulation on the proliferation of three ALL cell lines and a normal lymphocyte were tested.The key targets of baicalin combined with fever stimulation for the treatment of ALL were obtained based on network phar-macological analysis,and the potential mechanisms were predicted by gene ontology(GO)annotation and kyoto encyclopedia of genes and genomes(KEGG)en-richment.The expression levels of TNF-α,AKT1,TYMS and CASP3 mRNA in ALL cell lines Jurkat and CCRF-CEM were examined by RT-qPCR with baicalin alone and baicalin combined with heat stimulation.Results The optimal conditions for heat stimulation to intervene ALL cells were 41 ℃ for 24 h,and heat stimulation combined with baicalin synergistically inhibited the growth of ALL cell lines and effectively reduced the cy-totoxicity of baicalin.Based on the network pharmaco-logical analysis,55 intersecting targets of baicalin with ALL diseases and 77 intersecting targets of baicalin with fever were obtained.The results of GO annotation and KEGG enrichment suggested that baicalin com-bined with fever stimulation to intervene ALL might be associated with influencing intracellular reactive oxygen species metabolism,DNA transcription and apoptotic processes involved in cysteine enzymes.Apoptosis,TNF and IL-17 signaling pathways were the key pathways for baicalin combined with heat stimulation in treating ALL.Under heat stimulation at 41 ℃ using SDHA gene as housekeeping gene,in vitro experiments showed that baicalin significantly up-regulated the expression of TNF-α and CASP3,and down-regulated the expression of TYMS in ALL cells.Conclusions Based on net-work pharmacologic analyses and in vitro experiments,baicalin combined with heat stimulation can regulate TNF-α and CASP3 gene levels in ALL cells and de-stroy cellular structure to promote cell apoptosis,thus synergistically treating ALL.

Objective:This study aims to investigate the risk factors of venous thromboembolism(VTE)in patients with chronic heart failure(CHF),and establish a model for predicting the risk of VTE.Methods:A nested case-control study was conducted on CHF patients admitted in Pengzhou People's Hospital between June 2022 and June 2023.A total of 66 patients were diagnosed with VTE among the 960 CHF patients.Then another 66 patients paired by age and gender to those with VTE were selected from the remaining non-VTE patients as control group.Gener-al data,D dimer(D-D),thrombin-antithrombin complex(TAT),plasmin-α2-antiplasmin complex(PIC),tissue plasminogen activator-inhibitor complex(t-PAIC),thrombomodulin(TM)and Padua score were compared between two groups.Multivariate Logistic regression analysis was used to screen the independent risk factors of VTE in CHF patients.The receiver operating characteristic(ROC)curve analysis was applied to assess the efficacy of each indicator in predicting the risk of VTE in CHF patients.Results:Compared to patients in the non-VTE group,those in the VTE group had significantly higher D-D[3.26(1.87,6.19)mg/L vs.0.81(0.56,1.26)mg/L],TAT[5.60(4.90,8.80)ng/ml vs.2.60(1.70,3.30)ng/ml],TM[16.40(13.50,20.03)TU/ml vs.9.65(7.60,11.20)TU/ml],PIC[1.24(0.94,1.68)μg/ml vs.0.84(0.65,1.22)μg/ml],t-PAIC[12.60(9.38,17.05)ng/ml vs.7.70(5.53,9.70)ng/ml],proportion of atrial fibrillation/flutter(54.5％vs.22.7％)and Padua score[4(3,4)points vs.3(2,3)points](P＜0.001 all),and significantly lower lymphocyte count[0.99(0.60,1.38)×109/Lvs.1.20(0.76,1.67)×109/L,P=0.020].Multivariate Logistic regression analysis indicated that after adjusting confounders,TM(OR=2.456,95％CI 1.389～14.296,P=0.012)and Padua score(OR=3.257,95％CI 1.270～13.073,P=0.037)were independent risk factors for VTE in CHF patients.A predictive model was constructed using above-mentioned two indexes.The area under the ROC curve(AUC)of the combined prediction was 0.941(95％CI 0.901～0.980),which was significantly higher than those of TM(AUC=0.889,95％CI 0.833～0.945)and Padua score(AUC=0.801,95％CI 0.731～0.871)alone(Z=2.672,4.063,P=0.008,＜0.001).Conclusion:Padua score and TM were independent risk factors for VTE in CHF patients,and their combined detec-tion could better predict the risk of VTE in these patients.

Aim To perform high-throughput screen-ing of immunomodulatory traditional Chinese medicine(TCMs)based on an in vitro B cell differentiation-antibody secretion model,identifying active herbal candidates with immune-enhancing properties to pro-vide novel therapeutic options and theoretical support for influenza virus treatment in immunocompromised in-dividuals.Methods B cells were stimulated with dif-ferent concentrations of cytosine-phosphate-guanine oli-godeoxynucleotide 2006(CpG)and nterleukin-2(IL-2)to promote proliferation,differentiation,and anti-body secretion,and the effects of varying concentra-tions of the solvent DMSO were also evaluated.The op-timal conditions for the B cell differentiation-anti-body secretion model were determined based on the se-cretion levels of three antibody isotypes.The feasibility of the model was further validated using rapamycin,a known B cell function inhibitor.On this basis,a high-throughput screening platform for immunomodulatory a-gents was optimized and established.Subsequently,the immune-enhancing activity of 465 polarity extract from TCMs was evaluated.Results The optimal con-ditions for the model were determined as 2 mg·L-1 CpG,1.67 × 106 nkat·L-1 IL-2,and DMSO with a volume fraction of 0.1％.Rapamycin effectively inhib-ited B cell differentiation into plasmablast and signifi-cantly reduced antibody production,indicating the reli-ability of the model.Multiple rounds of screening re-vealed that the dichloromethane extract of licorice,the dichloromethane extract of Vinegar-processed Curcumae Rhizoma,the cyclohexane extract of Honey-prepared Radix Asteris,and the aqueous extract of Siphonostegia chinensis Benth were identified to significantly promote both B cell proliferation and differentiation and anti-body secretion at a concentration of 600 μg·L-1.Conclusion This study successfully optimizes an in vitro B cell differentiation-antibody secretion model and identifies several TCM extracts,including licorice,with potential immune-enhancing activity.

Objective To compare the effects of different detector combinations of 320-row CT on the image quality and radiation dose of head CT to explore the feasibility of using a wide detector for head CT scanning.Methods Totally 100 patients underwent head CT scanning due to trauma or cerebrovascular disease at some hospital from June to August 2023 were collected prospectively and divided into group A and group B by using block randomization grouping method,with the length of the block group being 2 and 50 patients in each group.In group A,all the detectors had the widths at z-axis direction being 40×0.5 mm and head scanning was completed after multiple exposures;in group B,detector combinations with widths of 280×0.5 mm or 320×0.5 mm were chosen based on the patient's head size in the head-foot direction(z-axis direction),and head scanning was performed with a single-turn exposure.The remaining scanning and image reconstruction parameters in the two groups were kept completely consistent.The head image quality of the 2 groups was evaluated objectively and scored subjectively by 2 radiologists.The volume CT dose index(CTDIvol),dose length product(DLP)and exposure time of the 2 groups were recorded,and the effective dose(ED)was calculated.SPSS 22.0 software was used for statistical analysis.Results In terms of objective evaluation of image quality,at the level of the parietal skull group B had the CT value of gray matter,image noise and contrast to noise ratio(CNR)of the images higher than those of group A,and the differences were statistically significant(all P<0.05);at the level of the posterior skull group B had the CT values of gray and white matter,image noise and air noise lower while CNR higher than those of group A,and the differences were statistically significant(all P<0.05).In terms of subjective scoring of image quality,at the levels of parietal and posterior skull group A behaved better than group B,and the differences were statistically significant(all P<0.05).In group A 5 patients had obvious motion artifacts affecting the diagnosis and the image quality scores not higher than 2,and secondary scanning had to be carried out;In group B all the patients had no obvious motion artifacts and met the diagnosis requirements.When compared with group A Group B had the CTDIvol,DLP,ED and exposure time decreased by 17.44%,17.24%,17.48%and 85.53%,respectively,and the differences were statistically significant(all P<0.05).Conclusion A wide detector gains advantages over a 20 mm detector in image quality when 320-row CT is used for head CT scanning,with the diagnosis requirements satisfied.[Chinese Medical Equipment Journal,2025,46(4):57-62]

Objective:This study aims to investigate the risk factors of venous thromboembolism(VTE)in patients with chronic heart failure(CHF),and establish a model for predicting the risk of VTE.Methods:A nested case-control study was conducted on CHF patients admitted in Pengzhou People's Hospital between June 2022 and June 2023.A total of 66 patients were diagnosed with VTE among the 960 CHF patients.Then another 66 patients paired by age and gender to those with VTE were selected from the remaining non-VTE patients as control group.Gener-al data,D dimer(D-D),thrombin-antithrombin complex(TAT),plasmin-α2-antiplasmin complex(PIC),tissue plasminogen activator-inhibitor complex(t-PAIC),thrombomodulin(TM)and Padua score were compared between two groups.Multivariate Logistic regression analysis was used to screen the independent risk factors of VTE in CHF patients.The receiver operating characteristic(ROC)curve analysis was applied to assess the efficacy of each indicator in predicting the risk of VTE in CHF patients.Results:Compared to patients in the non-VTE group,those in the VTE group had significantly higher D-D[3.26(1.87,6.19)mg/L vs.0.81(0.56,1.26)mg/L],TAT[5.60(4.90,8.80)ng/ml vs.2.60(1.70,3.30)ng/ml],TM[16.40(13.50,20.03)TU/ml vs.9.65(7.60,11.20)TU/ml],PIC[1.24(0.94,1.68)μg/ml vs.0.84(0.65,1.22)μg/ml],t-PAIC[12.60(9.38,17.05)ng/ml vs.7.70(5.53,9.70)ng/ml],proportion of atrial fibrillation/flutter(54.5％vs.22.7％)and Padua score[4(3,4)points vs.3(2,3)points](P＜0.001 all),and significantly lower lymphocyte count[0.99(0.60,1.38)×109/Lvs.1.20(0.76,1.67)×109/L,P=0.020].Multivariate Logistic regression analysis indicated that after adjusting confounders,TM(OR=2.456,95％CI 1.389～14.296,P=0.012)and Padua score(OR=3.257,95％CI 1.270～13.073,P=0.037)were independent risk factors for VTE in CHF patients.A predictive model was constructed using above-mentioned two indexes.The area under the ROC curve(AUC)of the combined prediction was 0.941(95％CI 0.901～0.980),which was significantly higher than those of TM(AUC=0.889,95％CI 0.833～0.945)and Padua score(AUC=0.801,95％CI 0.731～0.871)alone(Z=2.672,4.063,P=0.008,＜0.001).Conclusion:Padua score and TM were independent risk factors for VTE in CHF patients,and their combined detec-tion could better predict the risk of VTE in these patients.

Objective To compare the effects of different detector combinations of 320-row CT on the image quality and radiation dose of head CT to explore the feasibility of using a wide detector for head CT scanning.Methods Totally 100 patients underwent head CT scanning due to trauma or cerebrovascular disease at some hospital from June to August 2023 were collected prospectively and divided into group A and group B by using block randomization grouping method,with the length of the block group being 2 and 50 patients in each group.In group A,all the detectors had the widths at z-axis direction being 40×0.5 mm and head scanning was completed after multiple exposures;in group B,detector combinations with widths of 280×0.5 mm or 320×0.5 mm were chosen based on the patient's head size in the head-foot direction(z-axis direction),and head scanning was performed with a single-turn exposure.The remaining scanning and image reconstruction parameters in the two groups were kept completely consistent.The head image quality of the 2 groups was evaluated objectively and scored subjectively by 2 radiologists.The volume CT dose index(CTDIvol),dose length product(DLP)and exposure time of the 2 groups were recorded,and the effective dose(ED)was calculated.SPSS 22.0 software was used for statistical analysis.Results In terms of objective evaluation of image quality,at the level of the parietal skull group B had the CT value of gray matter,image noise and contrast to noise ratio(CNR)of the images higher than those of group A,and the differences were statistically significant(all P<0.05);at the level of the posterior skull group B had the CT values of gray and white matter,image noise and air noise lower while CNR higher than those of group A,and the differences were statistically significant(all P<0.05).In terms of subjective scoring of image quality,at the levels of parietal and posterior skull group A behaved better than group B,and the differences were statistically significant(all P<0.05).In group A 5 patients had obvious motion artifacts affecting the diagnosis and the image quality scores not higher than 2,and secondary scanning had to be carried out;In group B all the patients had no obvious motion artifacts and met the diagnosis requirements.When compared with group A Group B had the CTDIvol,DLP,ED and exposure time decreased by 17.44%,17.24%,17.48%and 85.53%,respectively,and the differences were statistically significant(all P<0.05).Conclusion A wide detector gains advantages over a 20 mm detector in image quality when 320-row CT is used for head CT scanning,with the diagnosis requirements satisfied.[Chinese Medical Equipment Journal,2025,46(4):57-62]

Aim To explore the mechanism of baicalin combined with heat stimulation in treating acute lym-phoblastic leukemia(ALL)based on network pharma-cology and in vitro experiments.Methods The CCK-8 assay was used to screen the suitable conditions for heat stimulation to interfere ALL cell lines Jurkat,CCRF-CEM,Hut-78 and a normal lymphocyte HMy2.CIR,and the effects of baicalin combined with heat stimulation on the proliferation of three ALL cell lines and a normal lymphocyte were tested.The key targets of baicalin combined with fever stimulation for the treatment of ALL were obtained based on network phar-macological analysis,and the potential mechanisms were predicted by gene ontology(GO)annotation and kyoto encyclopedia of genes and genomes(KEGG)en-richment.The expression levels of TNF-α,AKT1,TYMS and CASP3 mRNA in ALL cell lines Jurkat and CCRF-CEM were examined by RT-qPCR with baicalin alone and baicalin combined with heat stimulation.Results The optimal conditions for heat stimulation to intervene ALL cells were 41 ℃ for 24 h,and heat stimulation combined with baicalin synergistically inhibited the growth of ALL cell lines and effectively reduced the cy-totoxicity of baicalin.Based on the network pharmaco-logical analysis,55 intersecting targets of baicalin with ALL diseases and 77 intersecting targets of baicalin with fever were obtained.The results of GO annotation and KEGG enrichment suggested that baicalin com-bined with fever stimulation to intervene ALL might be associated with influencing intracellular reactive oxygen species metabolism,DNA transcription and apoptotic processes involved in cysteine enzymes.Apoptosis,TNF and IL-17 signaling pathways were the key pathways for baicalin combined with heat stimulation in treating ALL.Under heat stimulation at 41 ℃ using SDHA gene as housekeeping gene,in vitro experiments showed that baicalin significantly up-regulated the expression of TNF-α and CASP3,and down-regulated the expression of TYMS in ALL cells.Conclusions Based on net-work pharmacologic analyses and in vitro experiments,baicalin combined with heat stimulation can regulate TNF-α and CASP3 gene levels in ALL cells and de-stroy cellular structure to promote cell apoptosis,thus synergistically treating ALL.

OBJECTIVE: To investigate whether meranzin hydrate (MH) can alleviate depression-like behavior and hypomotility similar to Chaihu Shugan Powder (CSP), and further explore the potential common mechanisms. METHODS: Totally 120 Spraque-Dawley rats were randomly divided into 5-8 groups including sham, vehicle, fluoxetine (20 mg/kg), mosapride (10 mg/kg), CSP (30 g/kg), MH (9.18 mg/kg), [D-Lys3]-GHRP-6 (Dlys, 0.5 mg/kg), and MH+Dlys groups by a random number table, 8 rats in each group. And 32 mice were randomly divided into wild-type, MH (18 mg/kg), growth hormone secretagogue receptor-knockout (GHSR-KO), and GHSR+MH groups, 8 mice in each group. The forced swimming test (FST), open field test (OFT), tail suspension test (TST), gastric emptying (GE) test, and intestinal transit (IT) test were used to assess antidepressant and prokinetic (AP) effects after drug single administration for 30 min with absorbable identification in rats and mice, respectively. The protein expression levels of brain-derived neurotrophic factor (BDNF) and phosphorylated mammalian target of rapamycin (p-mTOR) in the hippocampus of rats were evaluated by Western blot. The differences in functional brain changes were determined via 7.0 T functional magnetic resonance imaging-blood oxygen level-dependent (fMRI-BOLD). RESULTS: MH treatment improved depression-like behavior (FST, OFT) and hypomotility (GE, IT) in the acute forced swimming (FS) rats (all P<0.05), and the effects are similar to the parent formula CSP. The ghrelin antagonist [D-Lys3]-GHRP-6 inhibited the effect of MH on FST and GE (P<0.05). Similarly, MH treatment also alleviated depression-like behavior (FST, TST) in the wild-type mice, however, no effects were found in the GHSR KO mice. Additionally, administration of MH significantly stimulated BDNF and p-mTOR protein expressions in the hippocampus (both P<0.01), which were also prevented by [D-Lys3]-GHRP-6 (P<0.01). Besides, 3 main BOLD foci following acute FS rats implicated activity in hippocampus-thalamus-basal ganglia (HTB) circuits. The [D-Lys3]-GHRP-6 synchronously inhibited BOLD HTB foci. As expected, prokinetic mosapride only had effects on the thalamus and basal ganglia, but not on the hippocampus. Within the HTB, the hippocampus is implicated in depression and FD. CONCLUSIONS MH accounts for part of AP effects of parent formula CSP in acute FS rats, mainly via ghrelin-related shared regulation coupled to BOLD signals in brain areas. This novel functionally connection of HTB following acute stress, treatment, and regulation highlights anti-depression unified theory.
Rats ; Mice ; Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; Ghrelin/metabolism* ; Antidepressive Agents/therapeutic use* ; Hippocampus ; Stress, Psychological ; Mammals/metabolism*