Baihuasheshecao(Hedyotis diffusa) is a commonly used traditional Chinese medicine derived from the whole herb of H. diffusa and has been widely utilized in folk medicine. It possesses anti-tumor, antibacterial, and anti-inflammatory properties, making it one of the frequently used herbs in TCM clinical practice. However, Shuixiancao(H. corymbosa) and Xianhuaercao(H. tenelliflora), species of the same genus, are often used as substitutes for Baihuasheshecao. To substantiate the medicinal basis of Baihuasheshecao, this study systematically reviewed classical herbal texts and modern literature, examining its nomenclature, botanical origin, harvesting, processing, properties, meridian tropism, pharmacological effects, and clinical applications. The results indicate that Baihuasheshecao was initially recorded as "Shuixiancao" in Preface to the Indexes to the Great Chinese Botany(Zhi Wu Ming Shi Tu Kao). Based on its morphological characteristics and habitat description, it was identified as H. diffusa in the Rubiaceae family. Subsequent records predominantly refer to it as Baihuasheshecao as its official name. In most regions, Baihuasheshecao is recognized as the authentic medicinal material, distinct from Shuixiancao and Xianhuaercao. Baihuasheshecao is harvested in late summer and early autumn, and the dried whole plant, including its roots, is used medicinally. The standard processing method involves cutting. It is known for its effects in clearing heat, removing toxins, reducing swelling and pain, and promoting diuresis to resolve abscesses. Initially, it was mainly used for treating appendicitis, intestinal abscesses, and venomous snake bites, and later, it became a treatment for cancer. The excavation of its clinical value followed a process in which overseas Chinese introduced the herb from Chinese folk medicine to other countries. After its unique anti-cancer effects were recognized abroad, it was reintroduced to China and gradually became a crucial TCM for cancer treatment. The findings of this study help clarify the historical and contemporary uses of Baihuasheshecao, providing literature support and a scientific basis for its rational development and precise clinical application.
Humans ; China ; Drugs, Chinese Herbal/chemistry* ; Hedyotis/classification* ; Medicine, Chinese Traditional/history*

BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

The PA-PB1 interface of the influenza polymerase is an attractive site for antiviral drug design. In this study, we designed and synthesized a mini-library of indazole-containing compounds based on rational structure-based design to target the PB1-binding interface on PA. Biological evaluation of these compounds through a viral yield reduction assay revealed that compounds 27 and 31 both had a low micromolar range of the half maximal effective concentration (EC₅₀) values against A/WSN/33 (H1N1) (8.03 μmol/L for 27; 14.6 μmol/L for 31), while the most potent candidate 24 had an EC₅₀ value of 690 nM. Compound 24 was effective against different influenza strains including a pandemic H1N1 strain and an influenza B strain. Mechanistic studies confirmed that compound 24 bound PA with a K _d which equals to 1.88 μmol/L and disrupted the binding of PB1 to PA. The compound also decreased the lung viral titre in mice. In summary, we have identified a potent anti-influenza candidate with potency comparable to existing drugs and is effective against different viral strains. The therapeutic options for influenza infection have been limited by the occurrence of antiviral resistance, owing to the high mutation rate of viral proteins targeted by available drugs. To alleviate the public health burden of this issue, novel anti-influenza drugs are desired. In this study, we present our discovery of a novel class of indazole-containing compounds which exhibited favourable potency against both influenza A and B viruses. The EC₅₀ of the most potent compounds were within low micromolar to nanomolar concentrations. Furthermore, we show that the mouse lung viral titre decreased due to treatment with compound 24. Thus our findings identify promising candidates for further development of anti-influenza drugs suitable for clinical use.

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

Background::Erosive esophagitis (EE) is a gastroesophageal reflux disease characterized by mucosal breaks in the esophagus. Proton pump inhibitors are widely used as maintenance therapy for EE, but many patients still relapse. In this trial, we evaluated the noninferiority of vonoprazan vs. lansoprazole as maintenance therapy in patients with healed EE. Methods::We performed a double-blind, double-dummy, multicenter, phase 3 clinical trial among non-Japanese Asian adults with endoscopically confirmed healed EE from April 2015 to February 2019. Patients from China, South Korea, and Malaysia were randomized to vonoprazan 10 mg or 20 mg once daily or lansoprazole 15 mg once daily for 24 weeks. The primary endpoint was endoscopically confirmed EE recurrence rate over 24 weeks with a noninferiority margin of 10% using a two-sided 95% confidence interval (CI). Treatment-emergent adverse events (TEAEs) were recorded.Results::Among 703 patients, EE recurrence was observed in 24/181 (13.3%) and 21/171 (12.3%) patients receiving vonoprazan 10 mg or 20 mg, respectively, and 47/184 (25.5%) patients receiving lansoprazole (differences: -12.3% [95% CI, -20.3% to-4.3%] and -13.3% [95% CI, -21.3% to -5.3%], respectively), meeting the primary endpoint of noninferiority to lansoprazole in preventing EE recurrence at 24 weeks. Evidence of superiority (upper bound of 95% CI <0%) was also observed. At 12 weeks, endoscopically confirmed EE recurrence was observed in 5/18, 2/20, and 7/20 of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. TEAEs were experienced by 66.8% (157/235), 69.0% (156/226), and 65.3% (158/242) of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. The most common TEAE was upper respiratory tract infection in 12.8% (30/235) and 12.8% (29/226) patients in vonoprazan 10 mg and 20 mg groups, respectively and 8.7% (21/242) patients in lansoprazole group.Conclusion::Vonoprazan maintenance therapy was well-tolerated and noninferior to lansoprazole for preventing EE recurrence in Asian patients with healed EE.Trial Registration::https://clinicaltrials.gov; NCT02388737.

Objective: For patients with atrial fibrillation (AF) complicated with acute coronary syndrome (ACS), both anticoagulant and antiplatelet therapy should be applied, but the use of anticoagulation therapy is still poor in these patients in China. The purpose of this study was to explore the status and adherence of antithrombotic therapy in AF patients with ACS and the impact on 1 year clinical outcomes. Methods: Patients with AF hospitalized for ACS were retrospectively included from 6 tertiary hospitals in China between July 2015 and December 2020. According to the use of anticoagulant drugs at discharge, patients were divided into two groups: anticoagulant treatment group and non-anticoagulant treatment group. Logistic regression model was used to analyze the main factors influencing the use of anticoagulant drugs in patients with atrial fibrillation complicated with ACS. Major adverse cardiac events (MACEs) were defined as all-cause death, non-fatal myocardial infarction or coronary revascularization, and ischemic stroke and Bleeding Academic Research Consortium (BARC) 3 bleeding events were also collected at 1 year after discharge. After propensity score matching, Cox proportional hazards models and Kaplan-Meier analysis were used to evaluate the effect of anticoagulant treatment and non-anticoagulant treatment on 1-year prognosis. The patients were divided into different groups according to whether anticoagulation was performed at discharge and follow-up, and the sensitivity of the results was analyzed. Results: A total of 664 patients were enrolled, and 273 (41.1%) were treated with anticoagulant therapy, of whom 84 (30.8%) received triple antithrombotic therapy, 91 (33.3%) received double antithrombotic therapy (single antiplatelet combined with anticoagulant), and 98 (35.9%) received single anticoagulant therapy. Three hundred and ninety-one (58.9%) patients were treated with antiplatelet therapy, including 253 (64.7%) with dual antiplatelet therapy and 138 (35.3%) with single antiplatelet therapy. After 1∶1 propensity score matching between the anticoagulant group and the non-anticoagulant group, a total of 218 pairs were matched. Multivariate logistic regression analysis showed that history of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention were predictors of the absence of anticoagulant therapy, while history of ischemic stroke and persistent atrial fibrillation were predictors of anticoagulant therapy. At 1-year follow-up, 218 patients (79.9%) in the anticoagulant group continued to receive anticoagulant therapy, and 333 patients (85.2%) in the antiplatelet group continued to receive antiplatelet therapy. At 1-year follow-up, 36 MACEs events (13.2%) occurred in the anticoagulant group, and 81 MACEs events (20.7%) in the non-anticoagulant group. HR values and confidence intervals were calculated by Cox proportional risk model. Patients in the non-anticoagulant group faced a higher risk of MACEs (HR=1.802, 95%CI 1.112-2.921, P=0.017), and the risk of bleeding events was similar between the two group (HR=0.825,95%CI 0.397-1.715, P=0.607). Conclusions: History of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention are independent factors for the absence of anticoagulant therapy in patients with AF complicated with ACS. The incidence of MACEs, death and myocardial infarction is lower in the anticoagulant group, and the incidence of bleeding events is similar between the two groups. The risk of bleeding and ischemia/thrombosis should be dynamically assessed during follow-up and antithrombotic regiments should be adjusted accordingly.
Humans ; Atrial Fibrillation/drug therapy* ; Platelet Aggregation Inhibitors/adverse effects* ; Acute Coronary Syndrome/drug therapy* ; Fibrinolytic Agents/therapeutic use* ; Retrospective Studies ; Treatment Outcome ; Anticoagulants ; Myocardial Infarction/complications* ; Hemorrhage ; Percutaneous Coronary Intervention ; Ischemic Stroke/drug therapy* ; Stroke

AIM:To evaluate the macular microstructural changes in patients with rhegmatogenous retinal detachment(RRD)after silicone oil tamponade by spectral-domain optical coherence tomography(SD-OCT).METHODS:From November 2019 to July 2021, 27 patients with 27 eyes in RRD who underwent vitrectomy combined with silicone oil tamponade in Cangzhou Aier Eye Hospital were enrolled in this study as the observation group, other 30 healthy volunteers with 30 eyes were included in the control group. The best corrected visual acuity(BCVA)of patients before and after operation were observed, and quantified evaluation of the postoperative macular microstructural changes were performed by SD-OCT.RESULTS: The BCVA(LogMAR)of the observation group at 1wk and 3mo after operation(0.61±0.23, 0.69±0.34)were improved compared with those before operation(1.43±0.77)(all P<0.01). The cube volume and average cube thickness in the macular area at 3mo after operation in the observation group were lower than those at 1wk and 1mo after operation in the control group(all P<0.05). There were no differences in the average ganglion cell-inner plexiform layer(GCIPL)thickness, minimum GCIPL thickness, average macular retinal nerve fiber layer(mRNFL)thickness and minimum mRNFL thickness at 1wk, 1 and 3mo after operation in the observation group, but all decreased compared with the control group(all P<0.01). There were 9 eyes with subretinal fluid(SRF)in the observation group during postoperative follow-up, SRF had a tendency to be gradually absorbed, but 1 eye had a secondary macular hole; 3 eyes had ellipsoid zone disruption, which had a tendency to be gradually repaired; 2 eyes had submacular perfluorocarbon liquid; 2 eyes had macular edema.CONCLUSION: SD-OCT can show the microstructure and morphological changes very well in macular area in patients with RRD after silicone oil tamponade, and has important clinical value for the preoperative and postoperative follow-up evaluation of RRD.

With prominent medicinal value, Gelsemium elegans has been overexploited, resulting in the reduction of the wild resource. As a result, artificial cultivation turns out to be a solution. However, this medicinal species is intolerant to low temperature, and thus genes responding to the low temperature are important for the cultivation of this species. Based on the transcriptome database of G. elegans at 4 ℃, 29 differentially expressed GeERF genes were identified. Bioinformatics analysis of 21 GeERF gene sequences with intact open reading frames showed that 12 and 9 of the GeERF proteins respectively clustered in DREB subgroup and ERF subgroup. GeDREB1 A-1-GeERF6 B-1, with molecular weight of 23.78-50.96 kDa and length of 212-459 aa, were all predicted to be hydrophilic and in nucleus. Furthermore, the full-length cDNA sequence of GeERF2B-1 was cloned from the leaves of G. elegans. Subcellular localization suggested that GeERF2B-1 was located in the nucleus. According to the quantitative reverse-transcription PCR(qRT-PCR), GeERF2B-1 showed constitutive expression in roots, stems, and leaves of G. elegans, and the expression was the highest in roots. In terms of the response to 4 ℃ treatment, the expression of GeERF2B-1 was significantly higher than that in the control and peaked at 12 h, suggesting a positive response to low temperature. This study lays a scientific basis for the functional study of GeERF transcription factors and provides gene resources for the improvement of stress resistance of G. elegans.
DNA, Complementary ; Gene Expression Regulation, Plant ; Phylogeny ; Plant Proteins/metabolism* ; Temperature ; Transcription Factors/metabolism*

BACKGROUND: Epigenetics, especially DNA methylation, plays an important role in the pathogenesis of primary Sjogren syndrome (pSS). Our study aimed to reveal the role of DNA methylation in peripheral monocytes of pSS patients. METHODS: A total of 11 pSS patients and five age-matched healthy controls (HCs) were included in this study. Monocytes were isolated from peripheral blood mononuclear cells using magnetic microbeads. DNA methylation profiles were generated using Human Methylation 850K BeadChips. RESULTS: In monocytes from pSS patients, we identified 2819 differentially methylated positions (DMPs), comprising 1977 hypomethylated- and 842 hypermethylated-DMPs, corresponding to 1313 unique genes when compared with HCs. IFI44L, MX1, PAARP9, and IFITM1, which influence the interferon (IFN) signaling pathway, were among the genes hypomethylated in pSS. Functional analysis of genes with a minimum of two DMPs showed involvement in antigen binding, transcriptional regulation, cell adhesion, IFN-γ pathway, type I IFN pathway, antigen presentation, Epstein-Barr virus infection, human T-lymphotropic virus type 1 virus infection, and metabolic disease-related pathways. In addition, patients with higher serum IgG levels exhibited enrichment in Notch signaling and metabolic-related pathways. Upon comparing monocytes with salivary gland epithelial cells, an important overlap was observed in the cell cycle, cell senescence, and interleukin-17 signaling pathways. The differentially methylated genes were more enriched in the ribosome- and AMP-activated protein kinase signaling pathway in anti-Ro/SSA and anti-La/SSB autoantibodies double-positive patients. CONCLUSION Genome-wide DNA methylation profiling revealed significant differences in DNA methylation in monocytes isolated from patients with pSS.
DNA Methylation/genetics* ; Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Humans ; Leukocytes, Mononuclear ; Monocytes ; Sjogren's Syndrome/genetics*

The molecular identification of Fritillaria taibaiensis and its relatives was studied by real-time PCR with a TaqMan-MGB probe. DNA was extracted from F. taibaiensis and its relatives. According to the sequence of ITS1 region, the mutation sites of F. taipaiensis and its related species were identified by MEGA7.0 software. The specific primers (a pair) and a TaqMan-MGB probe were designed by Primer Premier 6.0 software. In the Roche LightCycler 96 system, the lowest limit of detection for F. taipaiensis DNA template was 0.002 39 ng·μL^-1, and the optimal T_m value range was 60 and 61 ℃. Specificity identification showed that the method had good specificity for F. taipaiensis, as it could be distinguished from other 13 different Fritillaria species including F. unibracteata. Since this method could accurately identify F. taipaiensis and its related species, it provides technical support for rational development of F. taipaiensis resources, management of Chinese medicinal market and supervision of raw materials in Chinese medicine manufacturing enterprises.