OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

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

OBJECTIVES: To study genotype-phenotype correlations in children with FGFR3 variants and to improve clinical recognition of related disorders. METHODS: Clinical data of 95 patients aged 0-18 years harboring FGFR3 variants, confirmed by whole‑exome sequencing at Shanghai Children's Medical Center from January 2012 to December 2023, were retrospectively reviewed. Detailed phenotypic characterization was performed for 22 patients with achondroplasia (ACH) and 10 with hypochondroplasia (HCH). RESULTS: Among the 95 patients, 52 (55%) had ACH, 24 (25%) had HCH, 9 (9%) had thanatophoric dysplasia, 3 (3%) had syndromic skeletal dysplasia, 2 (2%) had severe achondroplasia with developmental delay and acanthosis nigricans, and 5 (5%) remained unclassified. A previously unreported FGFR3 variant, c.1663G>T, was identified. All 22 ACH patients presented with disproportionate short stature accompanied by limb dysplasia, commonly with macrocephaly, a depressed nasal bridge, bowed legs, and frontal bossing; complications were present in 17 (77%). The 10 HCH patients predominantly exhibited disproportionate short stature with limb dysplasia and depressed nasal bridge. CONCLUSIONS ACH is the most frequent phenotype associated with FGFR3 variants, and missense variants constitute the predominant variant type. The degree of FGFR3 activation appears to correlate with the clinical severity of skeletal dysplasia.
Humans ; Receptor, Fibroblast Growth Factor, Type 3/genetics* ; Child ; Male ; Child, Preschool ; Female ; Infant ; Adolescent ; Dwarfism/genetics* ; Achondroplasia/genetics* ; Lordosis/genetics* ; Infant, Newborn ; Retrospective Studies ; Genetic Association Studies ; Bone and Bones/abnormalities* ; Phenotype ; Limb Deformities, Congenital

OBJECTIVE: The present study evaluated the effects of deep acupuncture at Weizhong acupoint (BL40) on bladder function and brain activity in a rat model of overactive bladder (OAB), and investigated the possible mechanisms around the acupuncture area that initiate the effects of acupuncture. METHODS: Adult female Sprague-Dawley rats were randomly divided into six groups, comprising a control group, model group, group treated with deep acupuncture at BL40, group treated with shallow acupuncture at BL40, group treated with acupuncture at non-acupoint next to BL40, and group treated with acupuncture at Xuanzhong (GB39). Urodynamic evaluation was used to observe the urination, and functional magnetic resonance imaging was used to observe the brain activation. The mechanism of acupuncture at BL40 in regulating bladder function was explored by toluidine blue staining and enzyme-linked immunosorbent assay, and the mechanism was verified by stabilizing mast cells (MCs) or blocking tibial nerve. RESULTS: Deep acupuncture at BL40 significantly increased the intercontraction interval in OAB rats and enhanced the mean amplitude of low frequency fluctuation of primary motor cortex (M1), periaquaductal gray matter (PAG), and pontine micturition center (PMC). It also increased the zero-lag functional connectivity between M1 and PAG and between PAG and PMC. Shallow acupuncture at BL40 and acupuncture at non-acupoint or GB39 had no effect on these indexes. Further studies suggested that deep acupuncture at BL40 increased the number and degranulation rate of MCs as well as the contents of 5-hydroxytryptamine, substance P, and histamine in the tissues around BL40. Blocking the tibial nerve by lidocaine injection or inhibiting MC degranulation by sodium cromoglycate injection obstructed the effects of acupuncture on restoring urinary function and modulating brain activation in OAB rats. CONCLUSION Deep acupuncture at BL40 may be more effective for inhibiting OAB by promoting degranulation of MCs around the acupoint and stimulating tibial nerve, thereby regulating the activation of the brain area that controls the lower urinary tract. Please cite this article as: Liu X, Zhang CY, Du XY, Li SS, Wang YQ, Zheng Y, Deng HZ, Fang XQ, Li JY, Wang ZQ, Xu SF, Mi YQ. Acupuncture at Weizhong (BL40) attenuates acetic acid-induced overactive bladder in rats by regulating brain neural activity through the modulation of mast cells and tibial nerves. J Integr Med. 2025; 23(1): 46-55.
Animals ; Urinary Bladder, Overactive/physiopathology* ; Mast Cells/physiology* ; Rats, Sprague-Dawley ; Female ; Acupuncture Therapy ; Acupuncture Points ; Rats ; Brain/physiopathology* ; Tibial Nerve/physiopathology* ; Acetic Acid ; Urinary Bladder/physiopathology*

This study selected 6 529 plant-based Chinese materia medica(PCMM) from Chinese Materia Medica as research subjects and applied a random permutation test to explore the overall correlation characteristics between nature and flavor, as well as the correlation characteristics after distinguishing different medicinal parts and harvest seasons. The results showed that the overall correlation characteristics between nature and flavor in PCMM were significantly associated in the following pairs: cold and bitter, cool and bitter, cool and astringent, cool and light, neutral and sweet, neutral and astringent, neutral and light, neutral and sour, hot and pungent, and warm and pungent. When analyzing the data by distinguishing medicinal parts and/or harvest seasons, new correlation patterns emerged, characterized by the disappearance of some significant correlations and the emergence of new ones. When analyzing by medicinal parts alone, significant correlations were found in the following cases: cold and light in leaves, cold and salty in barks, cool and sweet in fruits and seeds, neutral and pungent in whole herbs, neutral and salty in stems, and warm and salty in flowers. However, no significant correlations were found between cool and bitter in stems and other types of herbs, cool and astringent in fruits, seeds, flowers, and other types of herbs, cool and light in leaves, fruits, seeds, barks, flowers and other types of herbs, neutral and sweet in barks, neutral and astringent in whole herbs and stems, neutral and light in leaves, fruits, seeds, and flowers, neutral and sour in whole herbs, stems, barks, flowers, and other types of herbs, and hot and pungent in whole herbs, stems, flowers, and other types of herbs. When analyzing by harvest season alone, significant correlations were found in the following cases: cold and salty, and cool and sour in herbs harvested in winter, and neutral and salty in herbs harvested year-round. However, no significant correlation was found between cool and light in herbs harvested in winter. When considering both medicinal parts and harvest seasons, compared to the independent influence of medicinal parts, 14 new significant correlations emerged(e.g., the correlation between cool and bitter in stems harvested in spring), while 53 previously significant correlations disappeared(e.g., the correlation between cool and bitter in barks harvested in summer). Compared to the independent influence of harvest seasons, 11 new significant correlations appeared(e.g., the correlation between cold and light in barks harvested in autumn), while 50 previously significant correlations disappeared(e.g., the correlation between hot and pungent in leaves harvested in winter). This study is the first to reveal the influence of medicinal parts and harvest seasons on the correlation between nature and flavor in PCMM, which highlights that these two factors can interact and jointly affect nature-flavor correlations. Further research is needed to explore the underlying mechanisms. This study provides a deeper understanding of the inherent scientific connotations of herbal properties and offers a theoretical foundation for the cultivation and harvesting of PCMM.
Seasons ; Plants, Medicinal/growth & development* ; Drugs, Chinese Herbal/chemistry* ; Taste

The auxin/indole-3-acetic acid (Aux/IAA) gene family is an important regulator for plant growth hormone signaling, involved in plant growth, development, as well as response to environmental stresses. In the present study, we identified SmIAA7 which is potentially associated with Salvia miltiorrhiza leaf development through comparatively analyzed the transcriptome data from different pinnate leaves. SmIAA7 was successfully isolated from S. miltiorrhiza using the specific primers. Then subsequent bioinformatic analysis, prokaryotic expression and purification, subcellular localization, and induction expression analysis under auxin and abiotic stress were performed. The full-length of SmIAA7 contained an ORF of 684 bp encoding a protein of 227 amino acid with a molecular weight of 25.3 kD. Conserved domain analysis showed that SmIAA7 contains the conserved Aux_IAA domain (pfam02309). Sequence analysis and phylogenetic tree analysis results indicated SmIAA7 was phylogenetically close to IAA7 and IAA14 from other plants, suggesting SmIAA7 involved in plant growth and development as well as response to environmental stresses. The prokaryotic expression vector pET28a-SmIAA7 was constructed and SmIAA7 recombinant protein was successfully expressed in E. coli Rosetta (DE3) strain. Subcellular localization experiment demonstrated that SmIAA7 localized in the nucleus of plant cells. Real-time fluorescence quantitative PCR results showed that the expression level of SmIAA7 was upregulated in response to auxin. Drought, low temperature, and salt stress significantly increased the transcript level of SmIAA7 gene. This study lays a foundation for further elucidating the role of SmIAA7 in leaf development, signal transduction, and stress defense in S. miltiorrhiza.

Objective:To explore the relationship between urinary cadmium levels and thyroid hormone levels in people aged 40-89 years old in selected areas of China.Methods:Based on the "Investigation of the Impact of Soil Quality of Agricultural Land on Human Health in Typical Areas" project from October 2019 to August 2020, a multi-stage stratified random sampling method was used to include 6 588 middle-aged and older adults aged 40-89. Demographic characteristics, dietary frequency and disease status were collected through the questionnaire and physical examination. Urinary cadmium and urinary creatinine were detected by random midstream urine. Fasting venous blood was collected for the detection of Triiodothyronine (T3) and Thyroxine (T4). The linear mixed effects model was used to explore the association of urine cadmium levels with thyroid hormone levels. Its dose-response relationship was explored by using the restricted cubic spline.Results:The age of the subjects was (63.48±12.18) years, with males accounting for 51.28%. The M ( Q 1,Q 3) of urinary cadmium level, T3 and T4 was 2.48 (1.36, 4.42) μg/g·creatinine, (1.96±0.51) nmol/L and (113.75±29.11) nmol/L, respectively. The linear mixed effects model showed that the changes of T3 and T4 were 0.027 (0.009, 0.044) nmol/L and 2.019 (1.084, 2.953) nmol/L for each one-unit increase (natural logarithm transformed) of urinary cadmium. The restricted cubic spline showed that there was a positive nonlinear association between urinary cadmium and T3 as well as T4 (all Pnonlinear<0.05). Conclusion:In selected areas of China, the urinary cadmium level of middle-aged and older adults aged 40-89 years is positively associated with T3 and T4.

Objective:To investigate the mechanism by which microRNA-183 (miR-183) regulates the progression of diabetic nephropathy (DN) through targeting phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and modulating the AKT signaling pathway, and to identify potential therapeutic targets for DN.Methods:(1) Bioinformatic analysis of miRNA expression: MiRNA expression datasets from diabetic nephropathy (DN) and control samples were obtained from the Gene Expression Omnibus database. Differential expression analysis was performed, and differentially expressed miRNAs (DEmiRNAs) were identified using thresholds of an absolute log 2 (fold changes) >1 and an adjusted P-value<0.05. The results were visualized in a volcano plot and a heatmap. (2) Animal model establishment and in vivo interventional studies: A DN rat model was induced by administration of a high-fat/high-sucrose diet combined with an intraperitoneal injection of streptozotocin. Rats were randomly assigned into four groups ( n=10 per group) using a random number table: control group, DN model group, miR-183 inhibitor negative control (NC) group, and miR-183 inhibitor group. The latter two groups received tail vein injections of the miR-183 inhibitor NC or the miR-183 inhibitor, respectively, for eight consecutive weeks. Parameters including fasting blood glucose, 24-hour urinary protein excretion, urinary albumin excretion rate (UAER), serum creatinine, and blood urea nitrogen (BUN) were measured. Renal histopathological changes were assessed by HE and PAS staining. Furthermore, the expression of candidate miRNAs from patient data was validated, and the mechanism of action of miR-183 was investigated using quantitative real-time PCR and Western blotting. (3) In vitro mechanistic investigations in cultured podocytes: Mouse podocyte clone-5 (MPC5) cells were cultured in vitro and subjected to the following conditions: normal glucose (5.3 mmol/L glucose), high glucose (30 mmol/L glucose), and osmotic control (5.3 mmol/L glucose+19.5 mmol/L mannitol). Cells in the logarithmic growth phase were transfected with the miR-183 inhibitor (100 nmol/L), miR-183 mimic (50 nmol/L), or their corresponding negative controls. A dual-luciferase reporter assay was conducted to validate the binding interaction between miR-183 and the 3'-untranslated region (3'UTR) of PTEN. The effects of miR-183 on the AKT signaling pathway, apoptosis-related proteins, and cell viability were evaluated by quantitative real-time PCR, Western blotting, and the cell counting kit-8 assay, respectively. Results:MiR-183 expression was markedly upregulated in renal tissues from DN patients and DN model rats (both P<0.05). Inhibition of miR-183 significantly reduced renal miR-183 levels by 90.2% ( P<0.01), decreased fasting blood glucose by 65.3% ( P<0.01), and improved renal function parameters, including reductions in urinary protein (40.3%), blood urea nitrogen (32.1%), urinary albumin excretion rate (22.5%), and serum creatinine (40.2%) (all P<0.01). Histological analyses showed attenuation of glomerular lesions and glycogen accumulation. Bioinformatic prediction and experimental validation identified PTEN as a direct target of miR-183, confirmed by dual-luciferase assays. In vitro, miR-183 inhibition increased PTEN expression, reduced AKT phosphorylation, promoted podocyte proliferation, and suppressed apoptosis (upregulation of Bcl-2 and downregulation of cleaved-caspase-3). These effects were abolished upon PTEN knockdown. Conclusions:miR-183 aggravates DN by targeting PTEN and activating the AKT signaling pathway. Inhibition of miR-183 improves renal function and reduces podocyte apoptosis, suggesting miR-183 as a potential therapeutic target for DN.

Objective:To evaluate the levels and source of cadmium exposure by dietary pathway among middle-aged and elderly people ≥40 in cadmium-contaminated areas of China.Methods:A total of 7 193 people aged 40-89 years from four typical cadmium-contaminated areas in China were selected as the study subjects. Food Frequency Questionnaire (FFQ), Total Diet Study (TDS) and a 3-day-24-hour dietary recall survey were conducted. Dietary cadmium intake and food sources through dietary pathways were assessed based on cadmium content in foods, consumption amounts and intake frequencies.Results:The mean age of the participants was 63.39±12.21 years, with 50.05% being males. The average monthly dietary cadmium intake was 7.39 μg/(kg·BW). Staple foods and vegetables were the primary sources of dietary cadmium intake, accounting for 57.51% and 32.48%, respectively. The monthly dietary cadmium intake in all surveyed regions did not exceed the Provisional Tolerable Monthly Intake (PTMI) recommended by the Joint FAO/WHO Expert Committee on Food Additives (JECFA).Conclusion:The monthly dietary cadmium intake among middle-aged and elderly people in cadmium-contaminated areas of China is relatively low, with the risk remaining at an acceptable level. Staple foods and vegetables are the most significant contributors to dietary cadmium intake.