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

Many triterpenoid compounds have been successfully heterologously synthesized in Saccharomyces cerevisiae. To increase the yield of triterpenoids, various metabolic engineering strategies have been developed. One commonly applied strategy is to enhance the supply of precursors, which has been widely used by researchers. Squalene, as a precursor to triterpenoid biosynthesis, plays a crucial role in the synthesis of these compounds. This study primarily investigates the effect of different squalene levels in chassis strains on the synthesis of triterpenoids(oleanolic acid and ursolic acid), and the underlying mechanisms are further explored using real-time quantitative PCR(qPCR) analysis. The results demonstrate that the chassis strain CB-9-5, which produces high levels of squalene, inhibits the synthesis of oleanolic acid and ursolic acid. In contrast, chassis strains with moderate to low squalene production, such as Y8-1 and CNPK, are more conducive to the synthesis of oleanolic acid and ursolic acid. The qPCR analysis reveals that the expression levels of ERG1, βAS, and CrCYP716A154 in the oleanolic acid-producing strain CB-OA are significantly lower than those in the control strains C-OA and Y-OA, suggesting that high squalene production in the chassis strains suppresses the transcription of certain genes, leading to a reduced yield of triterpenoids. Our findings indicate that when constructing S. cerevisiae strains for triterpenoid production, chassis strains with high squalene content may suppress the expression of certain genes, ultimately lowering their production, whereas chassis strains with moderate squalene levels are more favorable for triterpenoid biosynthesis.
Squalene/analysis* ; Saccharomyces cerevisiae/genetics* ; Triterpenes/metabolism* ; Metabolic Engineering ; Oleanolic Acid/biosynthesis* ; Ursolic Acid

This study explored the potential therapeutic targets and mechanisms of Danggui Shaoyao San(DSS) in the prevention and treatment of Alzheimer's disease(AD) through transcriptomics and metabolomics, combined with animal experiments. Fifty male C57BL/6J mice, aged seven weeks, were randomly divided into the following five groups: control, model, positive drug, low-dose DSS, and high-dose DSS groups. After the intervention, the Morris water maze was used to assess learning and memory abilities of mice, and Nissl staining and hematoxylin-eosin(HE) staining were performed to observe pathological changes in the hippocampal tissue. Transcriptomics and metabolomics were employed to sequence brain tissue and identify differential metabolites, analyzing key genes and metabolites related to disease progression. Reverse transcription-quantitative polymerase chain reaction(RT-qPCR) was employed to validate the expression of key genes. The Morris water maze results indicated that DSS significantly improved learning and cognitive function in scopolamine(SCOP)-induced model mice, with the high-dose DSS group showing the best results. Pathological staining showed that DSS effectively reduced hippocampal neuronal damage, increased Nissl body numbers, and reduced nuclear pyknosis and neuronal loss. Transcriptomics identified seven key genes, including neurexin 1(Nrxn1) and sodium voltage-gated channel α subunit 1(Scn1a), and metabolomics revealed 113 differential metabolites, all of which were closely associated with synaptic function, oxidative stress, and metabolic regulation. RT-qPCR experiments confirmed that the expression of these seven key genes was consistent with the transcriptomics results. This study suggests that DSS significantly improves learning and memory in SCOP model mice and alleviates hippocampal neuronal pathological damage. The mechanisms likely involve the modulation of synaptic function, reduction of oxidative stress, and metabolic balance, with these seven key genes serving as important targets for DSS in the treatment of AD.
Animals ; Alzheimer Disease/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Mice, Inbred C57BL ; Metabolomics ; Transcriptome/drug effects* ; Maze Learning/drug effects* ; Hippocampus/metabolism* ; Humans ; Disease Models, Animal ; Memory/drug effects*

This paper aimed to investigate the therapeutic effect and mechanism of action of the Yiqi Fumai Formula(YQFM), a kind of traditional Chinese medicine(TCM), on mice with experimental heart failure based on the "heart-gut axis" theory. Based on the network pharmacology integrated with the group collaboration algorithm, the active ingredients were screened, a "component-target-disease" network was constructed, and the potential pathways regulated by the formula were predicted and analyzed. Next, the model of experimental heart failure was established by intraperitoneal injection of adriamycin at a single high dose(15 mg·kg~(-1)) in BALB/c mice. After intraperitoneal injection of YQFM(lyophilized) at 7.90, 15.80, and 31.55 mg·d~(-1) for 7 d, the protective effects of the formula on cardiac function were evaluated using indicators such as ultrasonic electrocardiography and myocardial injury markers. Combined with inflammatory factors in the cardiac and colorectal tissue, as well as targeted assays, the relevant indicators of potential pathways were verified. Meanwhile, 16S rDNA sequencing was performed on mouse fecal samples using the Illumina platform to detect changes in gut flora and analyze differential metabolic pathways. The results show that the administration of injectable YQFM(lyophilized) for 7 d significantly increased the left ventricular end-systolic internal diameter, fractional shortening, and ejection fraction of cardiac tissue of mice with experimental heart failure(P<0.05). Moreover, markers of myocardial injury were significantly decreased(P<0.05), indicating improved cardiac function, along with significantly suppressed inflammatory responses in cardiac and intestinal tissue(P<0.05). Additionally, the species of causative organisms was decreased, and the homeostasis of gut flora was improved, involving a modulatory effect on PI3K-Akt signaling pathway-related inflammation in cardiac and colorectal tissue. In conclusion, YQFM can affect the "heart-gut axis" immunity through the homeostasis of the gut flora, thereby exerting a therapeutic effect on heart failure. This finding provides a reference for the combination of TCM and western medicine to prevent and treat heart failure based on the "heart-gut axis" theory.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Heart Failure/microbiology* ; Mice ; Mice, Inbred BALB C ; Male ; Disease Models, Animal ; Gastrointestinal Microbiome/drug effects* ; Heart/physiopathology* ; Humans ; Signal Transduction/drug effects*

Wumei Pills, a classic traditional Chinese medicine(TCM) formula, are widely used in the treatment of biliary ascariasis and diarrhea. In recent years, studies have shown that Wumei Pills have advantages in the treatment of type 2 diabetes mellitus(T2DM), while there are no relevant reports that systematically evaluate the efficacy of Wumei Pills in the treatment of T2DM. This study addresses this issue by systematically evaluating the efficacy and safety of Wumei Pills, aiming to provide an evidence-based basis for clinical practice. PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, and VIP were researched for the randomized controlled trial(RCT) involving Wumei Pills for the treatment of T2DM that were published from inception to September 2024. RevMan 5.3 was used for the Meta-analysis of the data. A total of 18 RCTs were included, with a total of 1 437 patients. Meta-analysis produced the following results.(1)Treatment group outperformed control group in terms of overall response rate(RR=1.28, 95%CI[1.14, 1.43], P<0.000 1), fasting blood glucose(FPG)(WMD=-0.69, 95%CI[-0.93,-0.46], P<0.000 01), two-hour postprandial plasma glucose(2hPG)(WMD=-0.74, 95%CI[-1.17,-0.31], P<0.000 7), glycated hemoglobin(HbA1c)(WMD=-0.39, 95%CI[-0.60,-0.18], P=0.000 3), high-density lipoprotein(HDL)(WMD=0.38, 95%CI[0.28, 0.48], P<0.000 01), and body mass index(BMI)(WMD=-1.41, 95%CI[-2.40,-0.42], P=0.005).(2)The two groups had comparable effects regarding total cholesterol(TC)(WMD=-0.53, 95%CI[-1.13, 0.08], P=0.09) and low-density lipoprotein(LDL)(WMD=-0.25, 95%CI[-0.56, 0.06], P=0.12).(3)Triglycerides(TG)(WMD=-0.28,95%CI [-0.59,0.03],P=0.08), sensitivity analysis showed potential reduction effect(WMD=-0.20,95%CI[-0.36,-0.04],P=0.01). Occurrence of adverse drug reaction(RR=0.43,95%CI [0.23,0.80],P=0.007), sensitivity analysis showed significant disappearance(RR=0.56,95%CI[0.26,1.22],P=0.14), suggesting that the efficacy of treatment group was not better than that of control group. The results indicate that the treatment of T2DM with Wumei Pills is greatly related to the improvement of glucose metabolism, lipid metabolism, and clinical efficacy. The findings provide a basis for clinical application of Wumei Pills in treating T2DM, while the conclusion remains to be verified by clinical studies with higher quality.
Humans ; Diabetes Mellitus, Type 2/blood* ; Drugs, Chinese Herbal/administration & dosage* ; Randomized Controlled Trials as Topic ; Blood Glucose/metabolism* ; Hypoglycemic Agents/therapeutic use* ; Treatment Outcome ; Glycated Hemoglobin/metabolism* ; Female

Following the core outcome set standards for development(COS-STAD), this study aims to construct core outcome set(COS) for clinical research on traditional Chinese medicine(TCM) treatment of simple obesity. Firstly, a comprehensive review was conducted on the randomized controlled trial(RCT) and systematic review(SR) about TCM treatment of simple obesity that were published in Chinese and English databases to collect reported outcomes. Additional outcomes were obtained through semi-structured interviews with patients and open-ended questionnaire surveys for clinicians. All the collected outcomes were then merged and organized as an initial outcome pool, and then a preliminary list of outcomes was formed after discussion by the working group. Subsequently, two rounds of Delphi surveys were conducted with clinicians, methodology experts, and patients to score the importance of outcomes in the list. Finally, a consensus meeting was held to establish the COS for clinical research on TCM treatment of simple obesity. A total of 221 RCTs and 12 SRs were included, and after integration of supplementary outcomes, an initial outcome pool of 141 outcomes were formed. Following discussions in the steering advisory group meeting, a preliminary list of 33 outcomes was finalized, encompassing 9 domains. Through two rounds of Delphi surveys and a consensus meeting, the final COS for clinical research on TCM treatment of simple obesity was determined to include 8 outcomes: TCM symptom scores, body mass index(BMI), waist-hip ratio, waist circumference, visceral fat index, body fat rate, quality of life, and safety, which were classified into 4 domains: TCM-related outcomes, anthropometric measurements, quality of life, and safety. This study has preliminarily established a COS for clinical research on TCM treatment of simple obesity. It helps reduce the heterogeneity in the selection and reporting of outcomes in similar clinical studies, thereby improving the comparability of research results and the feasibility of meta-analysis and providing higher-level evidence support for clinical practice.
Humans ; Obesity/therapy* ; Medicine, Chinese Traditional ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Drugs, Chinese Herbal/therapeutic use*

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

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

Rapid and ultrasensitive detection of pathogen-associated biomarkers is vital for the early diagnosis and therapy of bacterial infections. Herein, we developed a close-packed and ordered Au@AgPt array coupled with a cascade triggering strategy for surface-enhanced Raman scattering (SERS) and colorimetric identification of the Staphylococcus aureus biomarker micrococcal nuclease (MNase) in serum samples. The trimetallic Au@AgPt nanozymes can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) molecules to SERS-enhanced oxidized TMB (oxTMB), accompanied by the color change from colorless to blue. In the presence of S. aureus, the secreted MNase preferentially cut the nucleobase AT-rich regions of DNA sequences on magnetic beads (MBs) to release alkaline phosphatase (ALP), which subsequently mediated the oxTMB reduction for inducing the colorimetric/SERS signal fade away. Using this "on-to-off" triggering strategy, the target S. aureus can be recorded in a wide linear range with a limit of detection of 38 CFU/mL in the colorimetric mode and 6 CFU/mL in the SERS mode. Meanwhile, the MNase-mediated strategy characterized by high specificity and sensitivity successfully discriminated between patients with sepsis (n = 7) and healthy participants (n = 3), as well as monitored the prognostic progression of the disease (n = 2). Overall, benefiting from highly active and dense "hot spot" substrate, MNase-mediated cascade response strategy, and colorimetric/SERS dual-signal output, this methodology will offer a promising avenue for the early diagnosis of S. aureus infection.