Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

The study aims to elucidate the existence forms(original constituents and metabolites) of Notoginseng Radix et Rhizoma in rats and reveal its metabolic pathways. After Notoginseng Radix et Rhizoma was administered orally once a day for seven consecutive days to rats, all urine and feces samples were collected for seven days, while the blood samples were obtained 6 h after the last administration. Using the ultra high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technique, this study identified 6, 73, and 156 existence forms of Notoginseng Radix et Rhizoma in the rat plasma, urine, and feces samples, respectively. Among them, 101 compounds were identified as new existence forms, and 13 original constituents were identified by comparing with reference compounds. The metabolic reactions of constituents from Notoginseng Radix et Rhizoma were mainly deglycosylation, dehydration, hydroxylation, hydrogenation, dehydrogenation, acetylation, and amino acid conjugation. Furthermore, the possible in vivo metabolic pathways of protopanaxatriol(PPT) in rats were proposed. Through comprehensive analysis of the liquid chromatography-mass spectrometry(LC-MS) data, isomeric compounds were discriminated, and the planar chemical structures of 32 metabolites were clearly identified. According to the literature, 48 original constituents possess antitumor and cardiovascular protective bioactivities. Additionally, 32 metabolites were predicted to have similar bioactivities by SuperPred. This research lays the foundation for further exploring the in vivo effective forms of Notoginseng Radix et Rhizoma.
Animals ; Rats ; Drugs, Chinese Herbal/pharmacokinetics* ; Rhizome/metabolism* ; Male ; Rats, Sprague-Dawley ; Chromatography, High Pressure Liquid ; Panax notoginseng/chemistry* ; Tandem Mass Spectrometry ; Feces/chemistry*

OBJECTIVE: Huachansu injection (HCSI), a promising anti-cancer Chinese medicine injection, has been reported to have the potential for reducing the toxicity of chemotherapy and improving the quality of life for colorectal cancer (CRC) patients. The objective of this study is to explore the synergistic and detoxifying effects of HCSI when used in combination with irinotecan (CPT-11). METHODS: To investigate the effect of HCSI on anti-CRC efficacy and intestinal toxicity of CPT-11, we measured changes in the biological behavior of LoVo cells in vitro, and anti-tumor effects in LoVo cell xenograft nude mice models in vivo. Meanwhile, the effect of HCSI on intestinal toxicity and the uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) expression was investigated in the CPT-11-induced colitis mouse model. Subsequently, we measured the effect of HCSI and its 13 constituent bufadienolides on the expression of UGT1A1 and organic anion transporting polypeptides 1B3 (OATP1B3) in HepG2 cells. RESULTS: The combination index (CI) results showed that the combination of HCSI and CPT-11 exhibited a synergistic effect (CI < 1), which significantly suppressing the LoVo cell migration, enhancing G2/M and S phase arrest, and inhibiting tumor growth in vivo. Additionally, the damage to intestinal tissues was attenuated by HCSI in CPT-11-induced colitis model, while the increased expression of UGT1A1 in HepG2 cells and in mouse was observed. CONCLUSION The co-therapy with HCSI alleviated the intestinal toxicity induced by CPT-11 and exerted an enhanced anti-CRC effect. The detoxifying mechanism may be related to the increased expression of UGT1A1 and OATP1B3 by HCSI and its bufadienolides components. The findings of this study may serve as a theoretical insights and strategies to improve CRC patient outcomes. Please cite this article as: Jiang B, Meng ZY, Hu YJ, Chen JJ, Zong L, Xu LY, Zhang XQ, Zhang JX, Han YL. Huachansu injection enhances anti-colorectal cancer efficacy of irinotecan and alleviates its induced intestinal toxicity through upregulating UGT1A1-OATP1B3 expression in vitro and in vivo. J Integr Med. 2025; 23(5):576-590.
Irinotecan/therapeutic use* ; Animals ; Glucuronosyltransferase/genetics* ; Humans ; Colorectal Neoplasms/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Nude ; Mice ; Up-Regulation/drug effects* ; Male ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Hep G2 Cells ; Cell Line, Tumor ; Intestines/drug effects* ; Amphibian Venoms

OBJECTIVE: Several epidemiological observational studies have related particulate matter (PM) exposure to Inflammatory bowel disease (IBD), but many confounding factors make it difficult to draw causal links from observational studies. The objective of this study was to explore the causal association between PM _2.5 exposure, its absorbance, and IBD. METHODS: We assessed the association of PM _2.5 and PM _2.5 absorbance with the two primary forms of IBD (Crohn's disease [CD] and ulcerative colitis [UC]) using Mendelian randomization (MR) to explore the causal relationship. We conducted two-sample MR analyses with aggregated data from the UK Biobank genome-wide association study. Single-nucleotide polymorphisms linked with PM _2.5 concentrations or their absorbance were used as instrumental variables (IVs). We used inverse variance weighting (IVW) as the primary analytical approach and four other standard methods as supplementary analyses for quality control. RESULTS: The results of MR demonstrated that PM _2.5 had an adverse influence on UC risk (odds ratio [ OR] = 1.010; 95% confidence interval [ CI] = 1.001-1.019, P = 0.020). Meanwhile, the results of IVW showed that PM _2.5 absorbance was also causally associated with UC ( OR = 1.012; 95% CI = 1.004-1.019, P = 0.002). We observed no causal relationship between PM _2.5, PM _2.5 absorbance, and CD. The results of sensitivity analysis indicated the absence of heterogeneity or pleiotropy, ensuring the reliability of MR results. CONCLUSION Based on two-sample MR analyses, there are potential positive causal relationships between PM _2.5, PM _2.5 absorbance, and UC.
Humans ; Mendelian Randomization Analysis ; Particulate Matter/analysis* ; Polymorphism, Single Nucleotide ; Inflammatory Bowel Diseases/genetics* ; Air Pollutants/analysis* ; Crohn Disease/genetics* ; Colitis, Ulcerative/genetics* ; Genome-Wide Association Study ; Risk Factors ; Environmental Exposure

OBJECTIVE: Cigarette smoking exacerbates the progression of pulmonary tuberculosis (TB). The role of tertiary lymphoid structures (TLS) in chronic lung diseases has gained attention; however, it remains unclear whether smoking-exacerbated lung damage in TB is associated with TLS. This study aimed to analyze the characteristics of pulmonary TLS in smokers with TB and to explore the possible role of TLS in smoking-related lung injury in TB. METHODS: Lung tissues from 36 male patients (18 smokers and 18 non-smokers) who underwent surgical resection for pulmonary TB were included in this study. Pathological and immunohistological analyses were conducted to evaluate the quantity of TLS, and chest computed tomography (CT) was used to assess the severity of lung lesions. The correlation between the TLS quantity and TB lesion severity scores was analyzed. The immune cells and chemokines involved in TLS formation were also evaluated and compared between smokers and non-smokers. RESULTS: Smoker patients with TB had significantly higher TLS than non-smokers ( P < 0.001). The TLS quantity in both the lung parenchyma and peribronchial regions correlated with TB lesion severity on chest CT (parenchyma: r = 0.5767; peribronchial: r = 0.7373; both P < 0.001). Immunohistochemical analysis showed increased B cells, T cells, and C-X-C motif chemokine ligand 13 (CXCL13) expression in smoker patients with TB ( P < 0.001). CONCLUSION Smoker TB patients exhibited increased pulmonary TLS, which was associated with exacerbated lung lesions on chest CT, suggesting that cigarette smoking may exacerbate lung damage by promoting TLS formation.
Humans ; Male ; Tuberculosis, Pulmonary/immunology* ; Middle Aged ; Tertiary Lymphoid Structures/pathology* ; Adult ; Lung/pathology* ; Smoking/adverse effects* ; Smokers ; Aged ; Tomography, X-Ray Computed

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

Objective:To discuss the effect of exosomes(Exos)loaded with microRNA-520a-5p(miR-520a-5p)on the pregnancy outcomes in fetal mice with intrauterine growth restriction(FGR),and to clarify its mechanism.Methods:The mouse placental mesenchymal stem cells(MSCs)were cultured in vitro and transfected with miR-520a-5p adenovirus vector(Ad-miR-520a-5p)to obtain the Exos with high miR-520a-5p load(miR-520a-5p-MSCs-Exos),which were then identified.The C57BL/6 mice were mated in cages at a female∶male ratio of 2∶1 to achieve successful pregnancy.Forty pregnant mice were divided into control group,FGR group,NC-MSCs-Exos group,and miR-520a-5p-MSCs-Exos group,with 10 mice in each group.Except for control group,the mice in other groups were exposed to excessive dexamethasone(DEX)during pregnancy to induce FGR models in the pregnant mice.The body weights of the fetal mice at birth and at 1,2,3,and 4 weeks after birth were detected;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of miR-520a-5p,DNA methyltransferase 3b(DNMT3b),and vascular endothelial growth factor(VEGF)mRNA in placenta tissue of the mice in various groups;Western blotting method was used to detect the expression levels of DNMT3b and VEGF proteins in placenta tissue of the mice in various groups;methylation-specific PCR(MSP)was used to analyze the methylation rates of VEGF promoter in placenta tissue of the mice in various groups;dual-luciferase reporter gene assay was used to verify the targeting relationship between miR-520a-5p and DNMT3b.Results:The results of transmission electron microscope(TEM)and nanoparticle tracking analysis(NTA)showed that the Exos were spherical with particle size concentrated near 100 nm;the Western blotting method results showed that the surface biomarkers CD63 and CD81 of Exos were positively expressed.The RT-qPCR results showed that compared with NC-MSCs-Exos and Ad-NC-MSCs-Exos,the expression level of miR-520a-5p in Ad-miR-520a-5p-MSCs-Exos was increased(P＜0.001).The differences in birth body weight and the body weights at 1,2,and 3 weeks after birth of the fetal mice among four groups were statistically significant(F=36.084,F=19.851,F=77.755,F=103.223;P＜0.001).Compared with control group,the birth body weight and the body weights at 1,2,and 3 weeks after birth of the fetal mice in FGR group were decreased(P＜0.05);compared with FGR group and NC-MSCs-Exos group,the birth body weight and the body weights at 1,2,and 3 weeks after birth of the fetal mice in miR-520a-5p-MSCs-Exos group were increased(P＜0.05).The One-way ANOVA results showed that the differences in the expression levels of miR-520a-5p,DNMT3b,and VEGF mRNA in placenta tissue of the mice among four groups were statistically significant(F=103.224,F=856.460,F=214.563;P＜0.001).The pairwise comparison between groups showed that compared with control group,the expression levels of miR-520a-5p and VEGF mRNA in placenta tissue of the mice in FGR group were decreased(P＜0.05),and the expression level of DNMT3b mRNA was increased(P＜0.05);compared with FGR group and NC-MSCs-Exos group,the expression levels of miR-520a-5p and VEGF mRNA in placenta tissue of the mice in miR-520a-5p-MSCs-Exos group were increased(P＜0.05),and the expression level of DNMT3b mRNA was decreased(P＜0.05).The One-way ANOVA results showed that the differences in the expression levels of DNMT3b and VEGF proteins in placenta tissue of the mice among four groups were statistically significant(F=245.601,F=149.360;P＜0.001).The pairwise comparison between groups showed that compared with control group,the expression level of DNMT3b protein in placenta tissue of the mice in FGR group was increased(P＜0.05),and the expression level of VEGF protein was decreased(P＜0.05);compared with FGR group and NC-MSCs-Exos group,the expression level of DNMT3b protein in placenta tissue of the mice in miR-520a-5p-MSCs-Exos group was decreased(P＜0.05),and the expression level of VEGF protein was increased(P＜0.05).The One-way ANOVA results showed that the difference in the methylation rate of VEGF promoter in placenta tissue of the mice among four groups was statistically significant(F=687.096,P＜0.001).The pairwise comparison between groups showed that compared with control group,the methylation rate of VEGF promoter in placenta tissue of the mice in FGR group was increased(P＜0.05);compared with FGR group and NC-MSCs-Exos group,the methylation rate of VEGF promoter in placenta tissue of the mice in miR-520a-5p-MSCs-Exos group was decreased(P＜0.05).Dual-luciferase reporter gene assay results showed that compared with miR-NC group,the luciferase activity in the cells containing DNMT3b-WT reporter vector in miR-520a-5p group was decreased(P＜0.05);compared with miR-NC group,the luciferase activity in the cells containing DNMT3b-MUT reporter vector in miR-520a-5p group had no change,no significant difference was observed(P＞0.05).Conclusion:The MSCs-derived Exos highly loaded with miR-520a-5p may improve the pregnancy outcomes of FGR fetal mice by targeting and down-regulating the expression of DNMT3b,inhibiting VEGF methylation,and promoting VEGF expression.

OBJECTIVE: To analyze the origin and influencing factors the titer of ABO blood group antibody in neonates. METHODS: A total of 303 newborn blood samples collected in our hospital from August 2023 to March 2024 were selected for the detection of ABO blood group settings and the determination of the total titers of IgG and IgM blood group antibodies in plasma. IgM antibodies were treated with dithithreitol (DTT) to determine the titers of IgG antibodies. The total titer of the blood group antibody was compared with that of the IgG antibody. The clinical data of mothers and newborns were collected, and the correlation between the antibody titer and these clinical data was analyzed. RESULTS: Among the 303 newborn specimens, 14 cases (4.62%) were identified to possess blood group antibodies. The influence of the maternal ABO blood group on the generation of high-potency blood group antibodies in newborns was observed to follow the order of O>B>A>AB, with a significant statistical difference ( P < 0.01). Of the 123 (40.59%) newborns born to mothers of type O, 121 (98.37%) had blood group antibody titers > 2. Of the 20 (6.60%) newborns born to mothers of type AB, all 20 (100.00%) had blood group antibody titers < 2. Among 89 (29.37%) mothers of type A and 71 (23.43%) mothers of type B, the titer of 100% newborn blood group antibody was less than 2, when the newborn blood group was incompatible with the mother's blood group; the titer of the newborn blood type antibody was higher or lower, when the newborn blood type was compatible with the mother's blood type. The titer of the newborn blood group antibodies is related to the number of pregnancies of the mothers and has no association with other clinical data (such as the mother's number of obortions), the number of production, fetal gestation age. CONCLUSION The majority of ABO blood group antibodies in neonates are IgG antibodies from the mothers, and few are produced by the neonates themselves. In some neonates, IgG anti-A and/or anti-B can agglutinate with anti-stereotyped cells at room temperature. The maternal ABO blood type is the primary factor influencing the titer of the newborn blood type. The number of maternal pregnancies is a factor affecting the high titer ABO blood group antibodies in newborns.
Humans ; Infant, Newborn ; ABO Blood-Group System/immunology* ; Female ; Immunoglobulin G/blood* ; Immunoglobulin M/blood* ; Pregnancy ; Blood Grouping and Crossmatching

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies