This study investigated the chemical constituents of Rhododendri Mollis Flos. The n-butanol fraction of 95% ethanol extract of Rhododendri Mollis Flos was separated and purified using chromatographic techniques, including normal-phase silica gel, ODS, and Sephadex LH-20 column chromatography. The structures of the isolated compounds were identified by spectroscopic techniques. Seven compounds were isolated and identified as rhodomollein LXⅦ(1), rhodomollein X(2), nivalenol(3),(3S,6S)-cis-linalool-3,7-oxide-β-D-glucopyranoside(4), thymidine(5), cyclo(Ala-Tyr)(6), and(S)-5-hydroxypyrrolidin-2-one(7). Among them, compound 1 was identified as a new compound, and compound 3 was isolated from this plant for the first time. The analgesic activity of compound 1 was evaluated using the acetic acid-induced writhing test. At a dose of 5.0 mg·kg~(-1), compound 1 showed a 75.4% inhibition rate in the writhing test, indicating significant analgesic activity.
Drugs, Chinese Herbal/isolation & purification* ; Rhododendron/chemistry* ; Animals ; Flowers/chemistry* ; Mice ; Male ; Analgesics/isolation & purification* ; Molecular Structure

OBJECTIVE: Objective To investigate the relationship between cervical disc herniation and C₀-C₂ Cobb angle. METHODS: The clinical data of 301 patients with cervical disc herniation from 2020 to 2024 were retrospectively analyzed. The median value of C₀-C₂ Cobb angle measurements from 301 patients was used as the boundary, cervical disc herniation patients were divided into two groups, C₀-C₂ Cobb angle <28.50 group and 151 patients with C₀-C₂ Cobb angle≥28.50 group. Among them, 150 patients in C₀-C₂ Cobb angle <28.50 group included 53 males and 97 females, aged 23 to 76 (57.32±12.55) years, with a disease duration of 7 to 19 (13.81±5.32) months;the othor 151 patients with C₀-C₂ Cobb angle≥28.50 group including 61 males and 90 females, aged 25 to 74 (56.86±12.51) years, with a disease duration of 8 to 18 (14.13±5.56) months. The cervical lordosis angle (C₀-C₂ Cobb angle and C₂-C₇ Cobb angle), T₁ inclination slope (T₁S) and cervical sagittal axial distance (C₂-C₇ SVA) were measured on the lateral cervical radiographs. The correlation between C₀-C₂ Cobb angle and cervical disc herniation range, protrusion position, average protrusion size and other parameters was analyzed. RESULTS: When the C₀-C₂ Cobb angle<28.50°, the average protrusion size was (2.21±0.56) mm, the C₂-C₇ Cobb angle was (19.92±12.06)° and the C₂-C₇ SVA was (1.10±1.20) mm. When the C₀-C₂ Cobb angle≥28.50°, the average protrusion size was (2.38±0.60) mm, the C₂-C₇ Cobb angle was (12.01±13.09 )°, the C₂-C₇ SVA was (1.53±1.36) mm, and the difference was statistically significant (P<0.05). Between the two groups of patients with C₀-C₂ Cobb angle < 28.50° and C₀-C₂ Cobb angle≥28.50°, there were significant differences in the size of C_3,4, C_4,5, C_5,6, C_6,7, C₇, T₁ disc herniation in single segment (P<0.05 ). C₀-C₂ Cobb angle was correlated with age(r=-0.135, P<0.05 ), C₂-C₇ Cobb angle (r=-0.382, P<0.01 ), C₂-C₇ SVA (r=0.293, P<0.01), average protrusion size (r=0.139, P<0.05), and the size of C_3,4 (r=0.215, P<0.01 ), C_4,5 (r=0.176, P<0.01 ), C_5,6 (r=0.144, P<0.05 ), C_6,7 (r=0.158, P<0.05 ), C₇T₁ (r=0.535, P<0.05) disc herniation. CONCLUSION There is a positive correlation between C₀-C₂ Cobb angle and the size of cervical disc herniation. C₀-C₂ Cobb angle can reflect the degree of cervical disc herniation. Previous studies have shown that the biomechanical changes between C₀-C₂ Cobb angle, C₂-C₇ Cobb angle, C₂-C₇ SVA and cervical extensor muscle group may be risk factors for accelerating cervical disc herniation and this may be one of the mechanisms that C₀-C₂ Cobb angle is positively correlated with the size of cervical disc herniation.
Humans ; Male ; Female ; Middle Aged ; Intervertebral Disc Displacement/physiopathology* ; Adult ; Cervical Vertebrae/diagnostic imaging* ; Aged ; Retrospective Studies ; Young Adult

OBJECTIVE: By analyzing the differential miRNA in seminal plasma between individuals with normal and abnormal sperm DNA fragmentation index（DFI）, we aim to identify miRNA that may impact sperm DNA integrity and target genes, and attempt to analyze their potential mechanisms of action. METHODS: A total of 161 study subjects were collected and divided into normal control group, DFI-medium group and DFI-abnormal group based on the DFI detection values. Differential miRNA were identified through miRNA chip analysis. Through bioinformatics analysis and target gene prediction, miRNA related to DFI and specific target genes were identified. The relative expression levels of differential miRNA and target genes in each group were compared to explore the impact of their differential expression on DFI. RESULTS: Through miRNA chip analysis, a total of 11 differential miRNA were detected. Bioinformatics analysis suggested that miR-26a-5p may be associated with reduced sperm DNA integrity. And gene prediction indicated that PTEN was a specific target gene of miR-26a-5p. Compared to the normal control group, the relative expression levels of miR-26a-5p in both the DFI-medium group and the DFI-abnormal group showed a decrease, while the relative expression levels of PTEN showed an increase. The relative expression levels of miR-26a-5p in all groups were negatively correlated with DFI values, while the relative expression levels of PTEN showed a positive correlation with DFI values in the DFI-medium group and the DFI-abnormal group. The AUC of miR-26a-5p in the DFI-medium group was 0.740 (P<0.05), with a sensitivity of 73.6% and a specificity of 71.5%; the AUC of PTEN was 0.797 (P<0.05), with a sensitivity of 76.5% and a specificity of 78.4%. In the DFI-abnormal group, the AUC of miR-26a-5p was 0.848 (P<0.05), with a sensitivity of 81.3% and a specificity of 78.1%. While the AUC of PTEN was 0.763 (P<0.05), with a sensitivity of 77.2% and a specificity of 80.2%. CONCLUSION miR-26a-5p affects the integrity of sperm DNA by regulating the expression of PTEN negatively. The relative expression levels of seminal plasma miR-26a-5p and PTEN have good diagnostic value for sperm DNA integrity damage, which can help in the etiological diagnosis and prognosis analysis of abnormal DFI. This provides a diagnostic and treatment approach for the study and diagnosis of DFI abnormalities without clear etiology.
Male ; Humans ; MicroRNAs/genetics* ; PTEN Phosphohydrolase/genetics* ; Spermatozoa ; Semen/metabolism* ; DNA Fragmentation

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Microglial functions are linked to Ca²⁺ signaling, with endoplasmic reticulum (ER) calcium stores playing a crucial role. Microglial abnormality is a hallmark of Alzheimer's disease (AD), but how ER Ca²⁺ receptors regulate microglial functions under physiological and AD conditions remains unclear. We found reduced ryanodine receptor 2 (Ryr2) expression in microglia from an AD mouse model. Modulation of RyR2 using S107, a RyR-Calstabin stabilizer, blunted spontaneous Ca²⁺ transients in controls and normalized Ca²⁺ transients in AD mice. S107 enhanced ATP-induced migration and phagocytosis while reducing ramification in control microglia; however, these effects were absent in AD microglia. Our findings indicate that RyR2 stabilization promotes an activation state shift in control microglia, a mechanism impaired in AD. These results highlight the role of ER Ca²⁺ receptors in both homeostatic and AD microglia, providing insights into microglial Ca²⁺ malfunctions in AD.
Animals ; Microglia/pathology* ; Alzheimer Disease/pathology* ; Phagocytosis/drug effects* ; Ryanodine Receptor Calcium Release Channel/metabolism* ; Disease Models, Animal ; Mice ; Cell Movement/drug effects* ; Mice, Transgenic ; Calcium Signaling/physiology* ; Calcium/metabolism* ; Mice, Inbred C57BL ; Male ; Endoplasmic Reticulum/metabolism*

Objective To investigate the effect of varying blood pressure stratification on renal function in the diabetic population.Methods A prospective cohort study was conducted,enrolling 9 489 diabetic patients from a total of 101 510 Kailuan Group employees who underwent health examinations between July 2006 and October 2007.The follow-up period was(8.6±4.0)years.Participants were categorized into four groups based on their baseline blood pressure levels:normal blood pressure(systolic blood pressure<120 mmHg and diastolic blood pressure<80 mmHg),elevated blood pressure(systolic blood pressure 120-130 mmHg and diastolic blood pressure<80 mmHg),stage 1 hypertension(systolic blood pressure 130-140 mmHg and/or diastolic blood pressure 80-90 mmHg),and stage 2 hypertension(systolic blood pressure≥140 mmHg and/or diastolic blood pressure≥90 mmHg).The incidence density of chronic kidney disease(CKD)was compared among these groups.A multivariate Cox proportional hazards regression model was employed to assess the effects of different blood pressure levels on renal function in diabetic patients,with the stability of the results confirmed using a multivariate time-dependent Cox proportional hazards model.Sensitivity analysis was conducted after excluding cases of cardiovascular disease(CVD)during follow-up,and cases using antihypertensive and antidiabetic medications at baseline.Results(1)At baseline,stage 1 hypertension patients demonstrated statistically significant higher differences with age and body mass index(BMI)compared to normal blood pressure group(P<0.05).(2)By the end of the follow-up,2 294 cases of CKD were identified,including 1 117 cases of estimated glomerular filtration rate(eGFR)decline and 1 575 cases of urinary protein.The incidences density of CKD,eGFR decline and urinary protein for stage 1 hypertension group were 39.4,16.3 and 25.5 per thousand person-years,respectively,all of which were statistically significant different from normal blood pressure group(log-rank test,P<0.01).(3)Multivariate Cox regression analysis revealed that,compared to the normal blood pressure group,stage 1 hypertension was associated with a 29%increased risk of CKD(HR=1.29,95%CI 1.09-1.52)and a 40%increased risk of eGFR decline(HR=1.40,95%CI 1.08-1.80)in diabetic individuals.Conclusion Stage 1 hypertension significantly increases the risk of CKD and eGFR decline in diabetic individuals,with a particularly notable effect on the risk of eGFR decline.

Objective To observe the changes of cervical sagittal parameters of digital radiography(DR)at bilateral oblique position of cervical spine in patients with neck type cervical spondylopathy(NTCS)after cervical rotation and lifting manipulations,and to evaluate the clinical significance of cervical sagittal parameters in assessing the efficacy of NTCS by combining the pain score of visual analogue scale(VAS).Methods A retrospective analysis was carried out in 36 NTCS patients admitted to the outpatient clinic of the Tuina Department of Foshan Hospital of Traditional Chinese Medicine from November 2020 to May 2021.According to the treatment method,the patients were divided into the trial group and the control group,with 18 patients in each group.The trial group was treated with cervical rotation and lifting manipulations,and the control group was treated with cervical vertebra traction.The two groups were treated once every other day for 2 continuous weeks.The changes of VAS pain score and sagittal parameters of DR such as sagittal vertical axis of cervical vertebra 2-7(C2-7 SVA),the T1 slope(T1S),neck tilt(NT),and thoracic inlet angle(TIA)in the two groups were observed before and after treatment.Spearman correlation analysis was used to explore the correlation between VAS scores of pain level and cervical sagittal parameters.Results(1)Before treatment,there was no statistically significant difference in the VAS pain scores between the two groups(P＞0.05).After treatment,the VAS pain scores in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease of the scores in the trial group was significantly superior to that in the control group(P＜0.01).(2)Before treatment,there was no statistically significant difference in the values of cervical sagittal parameters of C2-7 SVA,T1S,NT,and TIA between the two groups(P＞0.05).After treatment,the C2-7 SVA,T1S,and TIA of the trial group were significantly improved compared with those before treatment(P＜0.05),but the improvement of NT was not obvious(P＞0.05);the cervical sagittal parameters of the control group were not significantly improved compared with those before treatment(P＞0.05).The intergroup comparison showed that the improvement of C2-7 SVA,T1S,and TIA in the trial group was significantly superior to that in the control group(P＜0.05 or P＜0.01),while the difference in NT between the two groups after treatment was not statistically significant(P＞0.05).(3)The results of Spearman correlation analysis showed that before treatment,VAS pain score had no correlation with C2-7 SVA,T1S,NT,and TIA(P＞0.05),C2-7 SVA was negatively correlated with NT(r=-0.502,P＜0.05),and T1S was positively correlated with NT(r=0.601,P＜0.05).After treatment,VAS pain score was negatively correlated with C2-7 SVA(r=-0.362,P＜0.05)and positively correlated with TIA(r=0.476,P＜0.05),C2-7 SVA was positively correlated with NT(r=0.928,P＜0.05),and T1S was positively correlated with TIA(r=0.623,P＜0.05).Conclusion Both cervical rotation and lifting manipulations and cervical traction can relieve the pain and adjust cervical sagittal parameters in the patients with NTCS,but cervical rotation and lifting manipulations are more effective in treating NTCS.And there may be a correlation between the VAS scores of pain level and cervical sagittal parameters in patients with NTCS.

Small-molecule phenolic substances widely exist in animals and plants, and have some shared biological activities. The metabolism of phenylalanine and tyrosine in the human body, and especially the metabolism of catecholamine neurotransmitters, produces endogenous small-molecule phenols. Endogenous small-molecule phenolic substances are functionally related to the important physiological processes and the occurrence of mental diseases in humans and some animals, which are systematically sorts and summarized in this review. Integrating the previous experimental research and literature analysis on natural small-molecule phenols by our research group, the understanding of the hypothesis that "small-molecule phenol are pharmacological signal carriers" was deepened. Based on above, the concept of "phenolomics" was further proposed, analyzed the research direction and research content which can bring into the knowledge framework of phenolomics. The induction of phenolomics will provide wider perspectives on explaining the pharmacological mechanism of drugs, discovering new drug targets, and finding biomarkers of mental diseases.

Objective To explore the clinical efficacy and safety of Beimu Zhizhu Prescription(derived from the modification of Zhizhu Pills)in the treatment of GERC by retrospectively analyzing the clinical data of 297 patients with gastroesophageal reflux cough(GERC).Methods A retrospective cohort study was conducted in a total of 297 patients with GERC of rebellious stomach qi type who were admitted to the Outpatient Department of Wangjing Hospital of China Academy of Chinese Medical Sciences from July 2021 to July 2023.The patients were divided into an exposure group(136 cases)and a non-exposure group(161 cases)according to the medication of Beimu Zhizhu Prescription or not.The exposure group was treated with Beimu Zhizhu Decoction,and the non-exposure group was treated with proton pump inhibitor of Esomeprazole Magnesium Enteric-coated Tablets.A total of 119 pairs of cases were obtained after propensity score matching(PSM)at the ratio of 1 to 1.The changes of salivary pepsin level before and after treatment in the two groups were observed.After two weeks and eight weeks of treatment,the cough response rate and the remission rates for reflux-related symptoms of acid reflux,heartburn,belching and gastric distension were compared between the two groups,and the incidence of adverse reactions was recorded.Results(1)After two weeks of treatment,the comparison of symptom remission rate after PSM showed that the cough response rate and the remission rates for reflux-related symptoms of acid reflux,heartburn,belching and gastric distension in the exposure group were 84.87％(101/119),80.77％(84/104),82.61％(76/92),82.5％(66/80),84.42％(65/77),respectively,and those in the non-exposure group were 73.95％(88/119),72.90％(78/107),70.41％(69/98),65.38％(51/78),64.38％(47/73),respectively.The intergroup comparison showed that the remission rates for all of the symptoms except for acid reflux in the exposure group was significantly superior to that in the non-exposure group(P＜0.05 or P＜0.01).After eight weeks of treatment,the cough response rate and the remission rates for reflux-related symptoms of acid reflux,heartburn,belching,and gastric distension in the exposure group were 94.74％(36/38),91.67％(33/36),91.43％(32/35),93.75％(30/32),94.12％(32/34),respectively,and those in the non-exposure group were 77.78％(35/45),74.42％(32/43),71.43％(30/42),68.42％(26/38),66.67％(24/36),respectively.The intergroup comparison showed that the remission rate of all of the symptoms in the exposure group was significantly superior to that in the non-exposure group(P＜0.05 or P＜0.01).(2)After two weeks of treatment,the comparison of salivary pepsin level after PSM showed that the salivary pepsin level of the exposure group was significantly lower than that before treatment(P＜0.01),while that of the non-exposure group was not significantly decreased(P＞0.05).The decrease of salivary pepsin level in the exposure group was significantly superior to that in the non-exposure group.Statistically significant differences were presented in the post-treatment salivary pepsin level after two weeks of treatment and in the pre-and post-treatment difference of salivary pepsin level between the two groups(P＜0.05 or P＜0.01).(3)There were four cases(2.48％)of adverse reactions in the non-exposure group,while no related adverse reactions occurred in the exposure group.There was no significant difference in the incidence of adverse reactions between the two groups(x2=1.180,P=0.178).Conclusion Beimu Zhizhu Decoction can effectively relieve cough and reflux-related symptoms of acid reflux,heartburn,belching,and gastric distension in patients with GERC of rebellious stomach qi type,reduce the level of salivary pepsin,and has high safety.