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 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

Objective To investigate the expression levels of class Ⅰ histone deacetylases(HDAC)in the serum of patients with newly diagnosed psoriatic arthritis(PsA)and screen out serological indicators that are of significance for early diagnosis and assessment of disease activity.Methods A total of 49 PsA patients newly diagnosed in Shanxi Provincial People's Hospital from August 2022 to February 2024 and 30 healthy individuals(control group)were enrolled in this study.Demographic data were collected,and disease severity was assessed.Serum samples were collected,and the expression levels of class Ⅰ HDAC(HDAC1,HDAC2,HDAC3,and HDAC8)in the serum of each group were determined by ELISA.The correlations between the expression levels of class Ⅰ HDAC and clinical assessment indicators in each group were evaluated.Multivariate Logistic regression was adopted to analyze the risk factors affecting the disease activity of PsA patients.The receiver operating characteristic curve was used to evaluate the diagnostic efficacy of the risk factors affecting the disease activity of PsA patients.Results Compared with the control group,PsA patients showed up-regulated expression levels of HDAC1(P=0.003),HDAC2(P=0.010),HDAC3(P=0.003),and HDAC8(P=0.018)in the serum.The serum HDAC1 level of PsA patients was positively correlated with erythrocyte sedimentation rate(r=0.344,P=0.028).The serum HDAC2 level was positively correlated with the overall assessment of disease activity(r=0.468,P=0.001),the disease activity index of arthritis(r=0.401,P=0.007),the number of swollen joints(r=0.308,P=0.042),hospital anxiety and depression scale(HADS)score of anxiety(r=0.360,P=0.018),and HADS score of depression(r=0.302,P=0.047).The serum HDAC3 level was correlated with erythrocyte sedimentation rate(r=0.542,P<0.001),C-reactive protein(CRP)level(r=0.440,P<0.001),HADS score of anxiety(r=0.420,P=0.005),interleukin-6 level(r=0.397,P=0.004),the overall assessment of disease activity(r=0.318,P=0.036),and the course of psoriatic arthritis(r=0.330,P=0.028).The serum HDAC8 level was positively correlated with HADS score of anxiety(r=0.477,P=0.008)and erythrocyte sedimentation rate(r=0.385,P=0.039).Compared with the patients with low disease activity,those with moderate to high disease activity presented up-regulated expression of HDAC3(P=0.041).HDAC2(P=0.028)and CRP(P=0.034)were risk factors for moderate to high disease activity in PsA patients.HDAC2(area under the curve=0.802,P=0.003)and CRP(area under the curve=0.718,P=0.033)had diagnostic value for the progression of PsA.Conclusions The expression levels of class Ⅰ HDAC in the serum of patients with newly diagnosed PsA were significantly different.The serum levels of HDAC2 and CRP are expected to become serological indicators for the early diagnosis and disease activity assessment of PsA.
Humans ; Histone Deacetylases/blood* ; Arthritis, Psoriatic/diagnosis* ; Male ; Female ; Histone Deacetylase 1/blood* ; Histone Deacetylase 2/blood* ; Adult ; Middle Aged ; Clinical Relevance ; Repressor Proteins

Objective To comparatively analyze the clinical characteristics of primary bilateral macronodular adrenal hyperplasia(PBMAH)and adrenal cortisol-producing Adenoma(CPA),and enhance the understanding of two diseases.Methods The clinical data of 85 PBMAH patients(PBMAH group)and 195 CPA patients(CPA group)diagnosed at Department of Endocrinology,the First Medical Center of Chinese PLA General Hospital,from September 2014 to August 2024 were retrospectively analyzed.The demographic characteristics,comorbidities,biochemical indicators,adrenocorticotropic hormone-cortisol(ACTH-F)levels,and adrenal imaging features and treatment conditions were compared between the two groups.Results(1)General characteristics:Compared with CPA group,PBMAH group had older age at diagnosis and a higher proportion of male patients.(2)Clinical characteristics:Compared with CPA group,PBMAH group had a longer disease duration,a higher proportion of subclinical Cushing's syndrome(CS),and a higher proportion of hypertension,impaired glucose tolerance/diabetes,bone mass reduction or osteoporosis,with higher serum potassium levels,and the differences were statistically significant(P<0.01).(3)Hormone levels:Both PBMAH and CPA groups showed ACTH-F rhythm disorder,significantly increased cortisol levels and suppressed ACTH.Compared with PBMAH group,CPA group had stronger autonomous cortisol secretion ability,manifested by increased midnight serum cortisol(F0:00),16:00 serum cortisol(F16:00),24-hour urinary free cortisol(24 h UFC)levels and lower 8:00 serum ACTH(ACTH8:00)and 16:00 serum ACTH(ACTH16:00)(P<0.01).After low-dose dexamethasone suppression test(LDDST),CPA group showed lower suppression rates of ACTH and cortisol,and higher proportions of paradoxical elevation in serum cortisol and 24 h UFC compared with PBMAH(P<0.01).Conclusions PBMAH has a longer disease course and higher proportions of comorbid metabolic disorders than CPA,mostly manifested as subclinical Cushing's syndrome.CPA has stronger autonomous cortisol secretion ability,with cortisol less likely to be suppressed after LDDST and more obvious paradoxical elevation of cortisol and 24 h UFC.

Objective To investigate the clinical and pathological characteristics of adrenal cortical carcinoma(ACC),compare differences between hypercortisolism and non-functional ACC,and assess the diagnostic value of indicators such as Ki-67 index.Methods The clinical data of 57 ACC patients admitted to the First Medical Center of Chinese PLA General Hospital from January 2015 to March 2025 were retrospectively analyzed.According to the results of endocrine function assessment,47 of these patients were divided into hypercortisolism group(n=19)and non-functional group(n=28).The differences in clinical and pathological characteristics between the two groups were compared,and non-parametric tests and Spearman correlation analysis were used to explore the relationship between Ki-67 index and tumor stage as well as imaging features.Results Among the 57 patients,there were 20 males and 37 females,with a male-to-female ratio of 1:1.85.The age ranged from 16 to 76 years,and the age at diagnosis was(48.7±13.3)years.The tumor diameter was(10.53±4.14)cm.The tumors were located on the right side in 12 cases(21.1%),on the left side in 34 cases(59.6%),and bilaterally in 11 cases(19.3%).Among them,16 cases(28.1%)were complicated with glucose metabolism disorders,31 cases(54.3%)had hypertension,and 20 cases(35.1%)had hypokalemia.According to ENSAT staging,there were 0 cases in stage Ⅰ,15 cases(26.3%)in stage Ⅱ,24 cases(42.1%)in stage Ⅲ,and 18 cases(31.6%)in stage Ⅳ.Endocrine function assessment was completed in 47 of the 57 patients,including 28 cases(59.6%)of non-functional ACC and 19 cases(40.4%)of hypercortisolism(including 1 case of hypercortisolism combined with increased sex hormone secretion).Compared with non-functional group,hypercortisolism group had a significantly higher prevalence of hypertension(P=0.014),later ENSAT stage(P=0.010),and a higher proportion of hypervascularization(P=0.048).The median Ki-67 index was 20%(10%-40%),showing no significant correlation with either the maximum tumor diameter or SUVmax value,but it was related to ENSAT staging,with Ki-67 index in stageⅣ patients being significantly higher than that in stage Ⅱ(P=0.032).Immunohistochemistry results showed that the positive rate of Inhibin-α was 84.8%,and the positive rate of Melan-A was 40.9%.Conclusions ACC is a rare malignant endocrine tumor.ACC patients with hypercortisolism are more likely to be complicated with hypertension,have later staging,and more common hypervascular manifestations.Clinically,their endocrine function should be prioritized for assessment,and more active treatment strategies should be adopted.Diagnosis should be combined with imaging characteristics(such as hypervascularization)and immunohistochemical indicators(Ki-67,Inhibin-α,Melan-A).The significant increase in Ki-67 is in the advanced stage can serve as an important prognostic indicator to guide individualized treatment.

Obesity is a worldwide health problem. An imbalance in energy metabolism is an important cause of obesity and related metabolic diseases. Our previous studies showed that inhibition of miR-429 increased the protein level of uncoupling protein 1 (UCP1) in beige adipocytes; however, whether local inhibition of miR-429 in subcutaneous adipose tissue affects diet-induced obesity and related metabolic disorders remains unclear. The aim of this study was to investigate the effect of local overexpression of miR-429 sponge in subcutaneous adipose tissue on obesity and related metabolic disorders. The control adeno-associated virus (AAV) or AAV expressing the miR-429 sponge was injected into mouse inguinal white adipose tissue. Seven days later, the mice were fed a high-fat diet for 10 weeks to induce obesity. The effects of the miR-429 sponge on body weight, adipose tissue weight, plasma glucose and lipid levels, and hepatic lipid content were explored. The results showed that the overexpression of miR-429 sponge in subcutaneous white adipose tissue reduced body weight and fat mass, decreased fasting blood glucose and plasma cholesterol levels, improved glucose tolerance, and alleviated hepatic lipid deposition in mice. Mechanistic investigation showed that the inhibition of miR-429 significantly upregulated the expression of UCP1 in adipocytes and adipose tissue. These results suggest that local inhibition of miR-429 in subcutaneous white adipose tissue ameliorates obesity and related metabolic disorders potentially by upregulating UCP1, and miR-429 is a potential therapeutic target for the treatment of obesity and related metabolic disorders.
Animals ; MicroRNAs/physiology* ; Obesity/metabolism* ; Mice ; Adipose Tissue, White/metabolism* ; Metabolic Diseases ; Subcutaneous Fat/metabolism* ; Male ; Uncoupling Protein 1/metabolism* ; Diet, High-Fat ; Mice, Inbred C57BL

Bacillus mycoides JA20-1 was screened and identified as a biocontrol bacterium with a high capacity for producing volatile organic compounds(VOCs) in the laboratory. This strain had significant inhibitory effects on various postharvest disease pathogens in crops, such as Botrytis cinerea, as well as soil-borne disease pathogens in ginseng, such as Sclerotinia ginseng. In order to accelerate its industrialization process, in this study, single-factor experiments and response surface optimization methods were used. The fermentation medium and fermentation conditions in the shake flask of strain JA20-1 were systematically optimized by using cell production volume as the response variable. Meanwhile, the biocontrol effect of JA20-1 on B. cinerea of ginseng during the storage period was evaluated by using the method of fumigation in a dry dish in vitro. The results indicated that the optimal fermentation medium formulation for strain JA20-1 was as follows: 1% yeast paste, 1% soluble starch, 0.25% K_2HPO_4·3H_2O, and 0.2% NaCl. The optimal fermentation conditions in the shake flask were vaccination size of 3%, culture volume of 50 mL in a 250 mL Erlenmeyer flask, pH of 6.2, fermentation temperature of 34 ℃, shaking speed of 180 r·min~(-1), and incubation time of 18 hours. The bacteria count in the fermentation broth under these conditions reached 2.17 × 10~8 CFU·mL~(-1), which was 6.58 times higher than before. The average control efficacy of the fermentation broth on Botrytis cinerea of ginseng under in vitro fumigation reached 61.70% and 84.04% respectively, when 20 mL and 30 mL per dish were used. The research provided theoretical support and technical foundation for the development and utilization of Bacillus mycoides JA20-1 and the biocontrol of soil-borne diseases in ginseng and postharvest diseases in crops.
Botrytis/drug effects* ; Fermentation ; Panax/microbiology* ; Plant Diseases/prevention & control* ; Volatile Organic Compounds/metabolism* ; Bacillus/physiology* ; Pest Control, Biological/methods* ; Biological Control Agents/metabolism* ; Culture Media/chemistry*

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