Rubi Fructus has a long history of medicinal and edible use in China. It contains chemical components such as terpenes, flavonoids, phenolic acids, fatty acids, and alkaloids, and possesses various pharmacological activities, including antioxidant, anti-inflammatory, hypoglycemic, anti-tumor, anti-osteoporosis, and liver-protective effects. Rubi Fructus is widely applied in medical, health, and food fields. The quality of Rubi Fructus can directly affect the safety and effectiveness of clinical medication. Therefore, this article reviews the research progress on the chemical constituents and pharmacological effects of Rubi Fructus. Based on the concept of traditional Chinese medicine(TCM) quality markers(Q-markers), the article explores the screening and determination of Q-markers for Rubi Fructus from various aspects, including plant kinship, traditional efficacy, medicinal properties, measurability of chemical composition, different processing methods, producing areas, harvesting periods, and planting conditions. The components ellagic acid, kaempferol, quercetin, kaempferol-3-O-rutinoside, rutin, astragalin, tiliroside, and hyperoside are preliminarily proposed as Q-markers for Rubi Fructus, providing a reference for the quality control of Rubi Fructus.
Drugs, Chinese Herbal/pharmacology* ; Humans ; Rubus/chemistry* ; Fruit/chemistry* ; Quality Control ; Animals

OBJECTIVES: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations. METHODS: A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022. RESULTS: A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05). CONCLUSIONS Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Mutation ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Child ; Infant ; GTP Phosphohydrolases/genetics* ; Membrane Proteins/genetics* ; Adolescent ; Hematopoietic Stem Cell Transplantation ; Proportional Hazards Models ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis

OBJECTIVES: To explore the underlying pharmacological mechanisms and its potential effects of Chinese medicine herbal formula Sini Powder (SNP) on hepatocellular carcinoma (HCC). METHODS: The active components of SNP and their in vivo distribution were identified using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Construction of component-target-disease networks, protein-protein interaction network, Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and molecular docking were employed to analyze the active components and anti-HCC mechanisms of SNP. Cell viability assay and wound healing assay were utilized to confirm the effect of SNP-containing serum (2.5%, 5.0%, 10%, 20%, and 40%), isoprenaline or propranolol (both 10, 100, and 1,000 µ mol/L) on proliferation and migration of HepG 2 or Huh7 cells. Meanwhile, the effect of isoprenaline or propranolol on the β 2 adrenergic receptor (ADRB2) mRNA expression on HepG2 cells were measured by real-time quantitative reverse transcription (RT-qPCR). Mice with subcutaneous tumors were either subjected to chronic restraint stress (CRS) followed by SNP administration (364 mg/mL) or directly treated with SNP (364 mg/mL). These two parallel experiments were performed to validate the effects of SNP on stress responses. Stress-related proteins and hormones were quantified using RT-qPCR, enzyme-linked immunosorbent assay, and immunohistochemistry. Metagenomic sequencing was performed to confirm the influence of SNP on the gut microbiota in the tumor-bearing CRS mice. RESULTS: The distribution of the 12 active components of SNP was confirmed in various tissues and feces. Network pharmacology analysis confirmed the anti-HCC effects of the 5 active components. The potential anti-HCC mechanisms of SNP may involve the epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase Src (SRC) and signal transducer and activator of transcription 3 (STAT3) pathways. SNP-containing serum inhibited the proliferation of HepG2 and Huh7 cells at concentrations of 2.5% and 5.0%, respectively, after 24 h of treatment. Furthermore, SNP suppressed tumor progression in tumor-bearing mice exposed to CRS. SNP treatment also downregulated the expressions of stress-related proteins and pro-inflammatory cytokines, primarily by modulating the gut microbiota. Specifically, the abundance of Alistipes and Prevotella, which belong to the phylum Bacteroidetes, increased in the SNP-treated group, whereas Lachnospira, in the phylum Firmicutes, decreased. CONCLUSION SNP can combat HCC by alleviating stress responses through the regulation of gut microbiota.
Animals ; Gastrointestinal Microbiome/drug effects* ; Liver Neoplasms/microbiology* ; Carcinoma, Hepatocellular/microbiology* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Powders ; Cell Proliferation/drug effects* ; Mice ; Molecular Docking Simulation ; Cell Line, Tumor ; Hep G2 Cells ; Receptors, Adrenergic, beta-2/genetics* ; Stress, Physiological/drug effects* ; Cell Movement/drug effects* ; Male ; Protein Interaction Maps/drug effects* ; Cell Survival/drug effects* ; Proto-Oncogene Mas

BACKGROUND: The use of inserted sham acupuncture as a placebo in randomized controlled trials (RCTs) is controversial, because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment. OBJECTIVE: This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects. SEARCH STRATEGY: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022. INCLUSION CRITERIA: RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment. DATA EXTRACTION AND ANALYSIS: The total effect measured for an acupuncture treatment group in RCTs were divided into three components, including the natural history and/or regression to the mean effect (controlled for no-treatment group), the placebo effect, and the specific effect of acupuncture. The first two constituted the contextual effect of acupuncture, which is mimicked by a sham acupuncture treatment group. The proportion of acupuncture total effect size was considered to be 1. The proportion of natural history and/or regression to the mean effect (PNE) and proportional contextual effect (PCE) of included RCTs were pooled using meta-analyses with a random-effect model. The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture. The proportion of insert-specific effect of sham acupuncture (PIES) was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture. The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies, and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES. RESULTS: This analysis included 32 studies with 5492 patients. The overall PNE was 0.335 (95% confidence interval [CI], 0.255-0.415) and the PCE of acupuncture was 0.639 (95% CI, 0.567-0.710) of acupuncture's total effect. The proportional contribution of the placebo effect to acupuncture's total effect was 0.191, and the PIES was 0.189. When we modeled the exclusion of the insert-specific effect of sham acupuncture, the acupuncture treatment effect changed from no difference to a significant difference in 45.45% of the included RCTs, and in 40.91% of the external validated RCTs. CONCLUSION The insert-specific effect of sham acupuncture in RCTs represents 18.90% of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect. More than 40% of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for. Considering the impact of the insert-specific effect of sham acupuncture, caution should be taken when using inserted sham acupuncture placebos in RCTs. Please cite this article as: Luo XC, Liu JL, Yao MH, Chen YM, Fan AY, Liang FR, Zhao JP, Zhao L, Zhou X, Zhong XY, Yang JH, Li B, Zhang Y, Sun X, Li L. Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey. J Integr Med. 2025; 23(6):630-640.
Acupuncture Therapy/methods* ; Humans ; Randomized Controlled Trials as Topic ; Placebo Effect ; Placebos ; Treatment Outcome

Objective:To explore the impact of different six-character qigong training modes on respiratory muscle function early after a stroke.Methods:Sixty-six stroke survivors in the early stage of recovery were randomly divided into a control group, a modified training group, and an ancient training group, each of 22. In addition to routine rehabilitation training, the control group received conventional respiratory training. The modified training and ancient training groups were trained in modified six-character qigong or ancient six-character qigong, respectively, for two weeks. Before the treatment, after the two weeks and one month later, maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP), forced expiratory volume in one second, forced vital capacity, peak expiratory flow, maximum mid-expiratory flow, and peak inspiratory flow were measured. Diaphragm mobility during quiet inspiration and maximum inspiration were also quantified.Results:After 2 weeks of treatment and at 1 and 3 months after the end of the treatment, all three groups showed significant improvement in MIP, MEP and the pulmonary ventilation indicators, but the average improvement in the modified training group was significantly greater than in the other two groups. Their average diaphragm mobility was also significantly greater.Conclusion:Modified six-character qigong respiratory training is more effective than its ancient counterpart in improving respiratory muscle function, pulmonary ventilation, and diaphragm mobility early after a stroke, with effects which persist for at least one month.

Objective:Analyze the medical reimbursement rate and influencing factors under the DIP payment method to refine the DIP payment policy,promote the optimization of internal operations in medical institutions,and ensure reasonable compensation.Methods:Based on the 2022 DIP fund settlement data from 196 medical institutions in City A,the study used multiple linear regression to analyze the factors affecting medical reimbursement rate and conducted a heterogeneity analysis for medical institutions of different levels.Results:The medical reimbursement rate for medical institutions in City A in 2022 was 103.32%.Medical institutions with lower CMI standardized inpatient costs,lower rates of deviation cases,tertiary care institutions,lower proportion of level-four surgeries,and lower ratios of resident to employee medical insurance cases have higher medical reimbursement rate(P<0.05).Heterogeneity analysis reveals that therates of deviation cases,the proportion of primary care diseases,the ratio of resident to employee medical insurance cases,and the low-standard admission rate have different impacts on medical institutions of different levels.Conclusion:Medical insurance departments should improve policies for primary care diseases,dynamically adjust disease catalogs and payment standards,optimize funding levels and institutional coefficients,and increase penalties for violations to ensure effective use of funds.Medical institutions need to strengthen their understanding of policies,focus on refined internal management,promote standardized and rational diagnosis and treatment through performance assessment transformation,and leverage their own advantages in medical services to reasonably increase the medical reimbursement rate.

Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients.Here,we demonstrated the antileukemia activity of a novel small molecular compound NL101,which is formed through the modification on bendamustine with a suberanilohydroxamic acid(SAHA)radical.NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells.It induces DNA damage and caspase 3-mediated apoptosis.A genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library screen revealed that phosphatase and tensin homologous(PTEN)gene is critical for the regulation of cell survival upon NL101 treatment.The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome(MDS)cells,accompanied by the activation of protein kinase B(AKT)signaling pathway.The inhibition of mammalian target of rapamycin(mTOR)by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death.These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.

Objective To investigate the therapeutic effect of transcutaneous auricular vagus nerve stimulation(taVNS)on overweight/obesity patients,and to explore its central mechanism.Methods Twenty-six overweight/obesity patients were randomly divided into two groups,12 cases in the taVNS test group(shortened as the taVNS group)and 14 cases in the lifestyle intervention control group(shortened as the control group).The patients in the control group were treated with online lifestyle intervention of calorie-restricted diet(CRD),and the patients in the taVNS group were treated with taVNS on the basis of the intervention for the control group.The taVNS was performed on unilateral acupoints of spleen and endocrine,twice(in the morning and at evening)per day,for five days a week.The treatment for the two groups covered four weeks.The obesity indicators such as body weight,body mass index(BMI)and waist circumference of the patients in the two groups were observed before and after treatment.Moreover,the resting-state cerebral functional magnetic resonance imaging(fMRI)data of the patients were collected after treatment,and then the regulatory effect of taVNS on the regional homogeneity(ReHo)of local cerebral area of the patients was observed.Results(1)During the trial,one case in each group dropped off,and a total of 24 patients(including 13 cases in the control group and 11 cases in the taVNS group)were finally included in the statistical analysis of the observation indicators.(2)After treatment,the body weight,BMI and waist circumference of patients in the taVNS group were decreased compared with those before treatment(P＜0.05),while the obesity indicators in the control group only showed a downward trend compared with those before treatment,the differences being not statistically significant(P＞0.05).The improvement of the obesity indicators of body weight,BMI,and waist circumference in the taVNS group was significantly superior to that in the control group,and there were statistically significant differences in the post-treatment indicators and in the pre-and post-treatment difference values of the indicators between the two groups(P＜0.05 or P＜0.01).(3)After treatment,the taVNS group had greater ReHo values in the left prefrontal lobe and medial frontal gyrus than the control group,and the control group had greater ReHo value in the right parietal lobe than the taVNS group,which indicated that compared with the control group,the ReHo of the left prefrontal lobe and medial frontal gyrus in the taVNS group was increased and the ReHo of the right parietal lobe was decreased(Pvoxel＜0.001,Pcluster＜0.05,corrected by FWE level).Conclusion As a non-invasive treatment method,taVNS exerts certain efficacy for the treatment of overweight/obesity patients.The central response mechanism for treatment of obesity is probably related with the modulation of taVNS on the functional areas of left prefrontal lobe,medial frontal gyrus,and right parietal lobe of the patients.

The successful development of messenger RNA (mRNA) vaccines provides a new strategy for mRNA-based therapies for the treatment of various diseases. Nanomaterials have attracted much attention in nanomedicine due to their unique physicochemical properties. Therefore, combining mRNA therapy with nanomaterial-based delivery systems to form a unique mRNA delivery system for the treatment of various central nervous system diseases is undoubtedly an innovative new therapeutic strategy. In this review paper, the advances in delivery strategies for mRNA, including lipid carriers, protein mRNA complexes, polymeric carriers, and mixed carriers, were summarized, and their applications in central nervous system diseases therapeutic such as mRNA vaccines and genome editing in combination with mRNA therapy were described.