ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Objective: To investigate the emotional and behavioral problems among preschool children and the correlations with maternal parenting competence and family rearing environment, so as to provide a scientific basis and practical guidance for the physical and mental health development of preschool children. Methods: In June 2025, 660 preschool children aged 3-6 years old were selected from 10 kindergartens in Hefei, Anqing, and Tongling in Anhui Province by using a stratified cluster random sampling method. A questionnaire survey was conducted among all parents of preschool children using the Parent version of the Strengths and Difficulties Questionnaire, the Child Family Rearing Environment Scale, and the Chinese version of the Parenting Sense of Competence Scale. Pearson correlation analysis and multiple linear regression analysis were used to analyze the related factors of emotional and behavioral problems among preschool children. SPSS macro program Process 4.1 and Bootstrap method were used to test the mediating effect of family parenting environment between emotional and behavioral problems among preschool children and maternal parenting competence. Results: The detection rate of emotional and behavioral problems among preschool children was 20.15%. The total scores of family rearing environment and maternal parenting competence were negatively correlated with emotional and behavioral problems among preschool children ( r =-0.45,-0.79), and the total score of family rearing environment was positively correlated with the total score of maternal parenting competence ( r =0.43) (all P <0.01). Multiple linear regression showed that, after controlling whether being only child, parents educational level, registered residence location and other variables, family rearing environment, self efficacy and satisfaction were all negative predictors of emotional and behavioral problems among preschool children ( B =-0.07, -0.42, -0.42, all P <0.01). The mediation effect results showed that maternal parenting competence could positively predict the family rearing environment ( B =0.75), while maternal parenting competence and family rearing environment could both negatively predict emotional and behavioral problems among preschool children ( B =-0.49, -0.06 ) (all P <0.05). The Bootstrap sampling method test results showed that the effect value of the indirect effect of maternal parenting competence on emotional and behavioral problems through the family rearing environment was -0.04, and the effect proportion was 8.21 %. Conclusion Preschool children with a better family rearing environment and stronger maternal parenting competence are less likely to have emotional and behavioral problems, among which the family rearing environment has a mediating effect.

Objective: To investigate the relationship between pubertal timing and depressive symptoms among high school students in Suzhou, so as to provide scientific evidence for promoting adolescents mental health. Methods: From October 2023 to January 2024, 3 369 students were selected from 20 high schools in Suzhou using stratified cluster random sampling method. Physical examinations and questionnaire surveys were conducted. The Preece & Baines growth Model 1 was used to calculate the age at take off of height velocity (ATO) and age at peak height velocity (APHV), categorizing students into three groups: early pubertal timing group (< P 15 ), ontime group ( P 15 - P 85 ), and delayed group (> P 85 ). Binary Logistic regression was used to analyze its association with depressive symptoms. Results: The ATO for male and female high school students in Suzhou was (9.35±1.23) and ( 8.12 ±1.52) years old, respectively. The mean APHV was (12.35±0.74) years old for boys and (10.91±0.82) years old for girls. The overall prevalence of depressive symptoms was 34.22%, with no statistically significant gender difference ( χ 2=0.42, P =0.52). Significant differences in depressive symptom prevalence were observed across grade levels, breakfast frequency, weekly days of moderate to vigorous physical activity, daily sleep duration, history of school bullying, and the presence of Internet addiction ( χ 2=5.03-69.21, all P < 0.05 ). After adjusting for age, body mass index, region, boarding status, breakfast frequency, weekly moderate to vigorous physical activity days, sleep duration, campus bullying, and presence of Internet addiction, Logistic regression analysis revealed that when ATO was used to evaluate pubertal timing, the risk of depressive symptoms in the delayed group of boys was 1.65 times that of the on time group (95% CI =1.24-2.19); when APHV was used to evaluate pubertal timing, the risks of depressive symptoms in the early pubertal timing group and delayed group of boys were 1.43 times (95% CI =1.07-1.91) and 1.41 times (95% CI =1.05-1.88) of that of the on time group, respectively (all P <0.05). No statistically significant associations were found among females (all P > 0.05 ). Conclusion The prevalence of depressive symptoms among high school students in Suzhou is relatively high, and both early and delayed puberty timing in boys are associated with depressive symptoms.

Pain modulation encompasses a complex neurobiological process, in which the lateral habenula (LHb) plays a crucial role in integrating, regulating and modulating pain signals. It is also involved in pain-related memory functions associated with perception, transmission and regulation of pain. Furthermore, the LHb collaborates with structures such as the spinal dorsal horn, forebrain, and amygdala to form an essential neural circuit that contributes to sensitization, development of tolerance, and adaptation processes related to pain. However, there remains limited understanding regarding the specific roles and interactions among different neuron subtypes within the LHb concerning pain regulation. Additionally, further investigation is warranted to explore functional changes and plasticity within both the LHb and its associated neural circuits in chronic pain models. Future research endeavors should utilize advanced neuroimaging techniques alongside optogenetics and gene editing technologies to elucidate intricate neural circuits, cellular architecture, and molecular mechanisms governing LHb function in pain regulation. In conclusion, this paper aims to comprehensively review existing literature on the involvement of the LHb and its neural circuits in modulating pain, thereby enhancing our understanding of their neurobiological mechanisms while providing novel targets for precise therapeutic strategies aimed at alleviating pain.

Objective Based on nuclear factor E2 associated factor 2(NRF2)/PTEN induced hypothesized kinase 1(PINK1)pathway,explored the ameliorating effect of rutaecarpine on chronic obstructive pulmonary disease(COPD)rats and its repairing effect on airway epithelial barrier.Methods COPD rat model were established by smoke combined with airway infusion of lipopolysaccharide;and were randomly divided into model group,control group,and experimental-L group,experimental-M group,experimental-H group,10 rats per group.Another 10 normal rats were selected as the normal group.Experimental-L,-M,-H groups were intraperitoneally injected 15,30 and 60 mg·mL-1 rutaecarpine at the dose of 10 mL·kg-1,respectively.The control group was received 4.05 x 10-2 mg·mL-1 prednisone acetate at the dose of 10 mL·kg-1 by gavage.The normal and model groups were given 0.9％NaCl by intraperitoneal injection.Six groups were treated for 28 days with once a day.The first second forced expiratory volume(FEV1)and forced vital capacity(FVC)of rats were measured by minor animal lung function tester.The levels of interleukin(IL)and interferon-γ(INF-γ)in alveolar lavage fluid were determined by enzyme-linked immunosorbent assay method.The expression levels of PINK1 and NRF2 proteins in the lung tissue were determined by Western blot.Results The levels of FEV1 in the experimental-M group,experimental-H group,control group,model group and normal group were(5.17±0.16),(6.36±0.12),(5.06±0.07),(2.24±0.20)and(6.84±0.11)mL;the levels of FVC were(6.71±0.13),(7.56±0.12),(6.81±0.07),(4.46±0.14)and(7.92±0.11)mL;the levels of IL-12 in alveolar lavage fluid were(7.08±0.51),(9.03±0.54),(7.92±0.79),(3.61±1.01)and(10.15±0.82)pg·mL-1;the levels of IL-9 in alveolar lavage fluid were(22.49±2.27),(15.02±1.41),(17.47±1.84),(38.72±1.28)and(11.78±0.94)pg·mL-1;the levels of INF-γ in alveolar lavage fluid were(13.18±0.54),(16.25±0.60),(15.23±0.43),(6.97±0.89)and(17.22±1.15)pg·mL-1;the relative expression levels of PINK1 protein were 1.10±0.06,1.30±0.09,1.18±0.15,0.42±0.03 and 1.61±0.05;the relative expression levels of NRF2 protein were 0.91±0.05,1.46±0.03,1.35±0.07,0.53±0.07 and 1.64±0.11,respectively.The differences of above indexes were statistically significant between the experimental-M group,experimental-H group,control group and the model group(all P＜0.05).Conclusion Rutaecarpine can inhibit inflammation,improve lung function and repair airway epithelial barrier in COPD rats,and its mechanism may be related to regulating NRF2/PINK1 pathway.

Hypertensive nephropathy is one of the common chronic kidney diseases in China,the morbidity and mortality are increasing year by year,which seriously endangers the physical and mental health of patients.Traditional Chinese medicine believes that human is an organic whole,the five viscera and six organs are closely related in physiology and pathology,based on the theory of"holistic concept",the application of Chinese medicine in the treatment of hypertensive nephropathy can effectively improve kidney function and reduce the occurrence of adverse reactions.Therefore,based on the theory of"five viscera in one",this paper summarizes the etiology and pathogenesis of hypertensive nephropathy and the treatment of hypertensive nephropathy from the five aspects of liver,heart,spleen,lung and kidney,aiming to provide new ideas for the prevention and treatment of kidney disease by traditional Chinese medicine.

Aim To establish and evaluate an alternative meth-od for detecting skin sensitization of cosmetics based on local lymph node assay using bromodeoxyuridine(BrdU)with flow cytometry(FCM).Methods(1)25％hexyl cinnamic alde-hyde(HCA)was chosen as a positive control with an acetone:olive oil(4∶1,V/V,AOO)mixture as a vehicle control for the experiment.The dorsal sides of both ears of mice were treated with test solutions on day 1,day 2,and day 3.Brdu solution was injected inter-peritoneally on day 5.On day 6,the bilateral ears and mandibular lymph nodes were excised,and the number of Brdu positive cells was measured by flow cytometry.The stim-ulation index(SI)was calculated to identify whether it was ≥3,in order to establish the method of LLNA:Brdu-FCM.(2)BrdU-FCM test was conducted using a blind method with the fif-teen reference substances listed in OECD TG429 whose skin sensitization potentials were known.The test substances were dissolved in AOO,N,N-dimethylformamide(DMF)or dimeth-yl sulfoxide(DMSO)at three different concentrations.Tests were performed the same as above.SI and EC2.7 were calculat-ed to evaluate whether the test substance was categorized as a skin sensitizer.The reliability and accuracy of the method were validated by comparing the classification of test substances with that in OECD TG429.Results The SI for 25％HCA was 3.9,showing positive in the skin sensitization test.It demonstrated that the LLNA:Brdu-FCM test method was properly implemen-ted.Nine test substances(2,4-dinitrochlorobenzene,4-pheny-lenediamine,cobalt chloride,2-mercaptobenzothiazole,hexyl-cinnamaldehyde,eugenol,phenyl benzoate,cinnamic alcohol,imidazolidinyl urea)were positive,and six test substances(methyl methacrylate,chlorobenzene,isopropanol,lactic acid,methyl salicylate,salicylic acid)were negative.The method was evaluated with sensitivity of 90％,specificity of 100％,positive prediction rate of 100％,negative prediction rate of 83％,false positive rate of 0％,false negative rate of 17％and accuracy of 93％.The LLNA:BrdU-FCM assay could correctly categorize the test substances that were skin sensitizers or non-sensitizers.Conclusion The LLNA:BrdU-FCM assay appears to be a relia-ble predictor of skin sensitization protential of chemicals,and it is expected to an alternative method for identifying skin sensitization as a supplementary in safety evaluation of cosmetic ingredient.

OBJECTIVE: To analyze the Epstein-Barr virus (EBV) load in different lymphocyte subsets, as well as clinical characteristics and outcomes in patients with hematologic malignancies experiencing EBV reactivation. METHODS: Peripheral blood samples from patients were collected. B, T, and NK cells were isolated sorting with magnetic beads by flow cytometry. The EBV load in each subset was quantitated by real-time quantitative polymerase chain reaction (RT-qPCR). Clinical data were colleted from electronic medical records. Survival status was followed up through outpatient visits and telephone calls. Statistical analyses were performed using SPSS 25.0. RESULTS: A total of 39 patients with hematologic malignancies were included, among whom 35 patients had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median time to EBV reactivation was 4.8 months (range: 1.7-57.1 months) after allo-HSCT. EBV was detected in B, T, and NK cells in 20 patients, in B and T cells in 11 patients, and only in B cells in 4 patients. In the 35 patients, the median EBV load in B cells was 2.19×10⁴ copies/ml, significantly higher than that in T cells (4.00×10³ copies/ml, P <0.01) and NK cells (2.85×10² copies/ml, P <0.01). Rituximab (RTX) was administered for 32 patients, resulting in EBV negativity in 32 patients with a median time of 8 days (range: 2-39 days). Post-treatment analysis of 13 patients showed EBV were all negative in B, T, and NK cells. In the four non-transplant patients, the median time to EBV reactivation was 35 days (range: 1-328 days) after diagnosis of the primary disease. EBV was detected in one or two subsets of B, T, or NK cells, but not simultaneously in all three subsets. These patients received a combination chemotherapy targeting at the primary disease, with 3 patients achieving EBV negativity, and the median time to be negative was 40 days (range: 13-75 days). CONCLUSION In hematologic malignancy patients after allo-HSCT, EBV reactivation commonly involves B, T, and NK cells, with a significantly higher viral load in B cells compared to T and NK cells. Rituximab is effective for EBV clearance. In non-transplant patients, EBV reactivation is restricted to one or two lymphocyte subsets, and clearance is slower, highlighting the need for prompt anti-tumor therapy.
Humans ; Hematologic Neoplasms/virology* ; Herpesvirus 4, Human/physiology* ; Epstein-Barr Virus Infections ; Hematopoietic Stem Cell Transplantation ; Virus Activation ; Lymphocyte Subsets/virology* ; Flow Cytometry ; Killer Cells, Natural/virology* ; Male ; Female ; B-Lymphocytes/virology* ; Viral Load ; Adult ; T-Lymphocytes/virology* ; Middle Aged

BACKGROUND: The association of systemic inflammatory response index (SIRI) with prognosis of coronary artery disease (CAD) patients has never been investigated in a large sample with long-term follow-up. This study aimed to explore the association of SIRI with all-cause and cause-specific mortality in a nationally representative sample of CAD patients from United States. METHODS: A total of 3386 participants with CAD from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included in this study. Cox proportional hazards model, restricted cubic spline (RCS), and receiver operating characteristic curve (ROC) were performed to investigate the association of SIRI with all-cause and cause-specific mortality. Piece-wise linear regression and sensitivity analyses were also performed. RESULTS: During a median follow-up of 7.7 years, 1454 all-cause mortality occurred. After adjusting for confounding factors, higher lnSIRI was significantly associated with higher risk of all-cause (HR = 1.16, 95% CI: 1.09-1.23) and CVD mortality (HR = 1.17, 95% CI: 1.05-1.30) but not cancer mortality (HR = 1.17, 95% CI: 0.99-1.38). The associations of SIRI with all-cause and CVD mortality were detected as J-shaped with threshold values of 1.05935 and 1.122946 for SIRI, respectively. ROC curves showed that lnSIRI had robust predictive effect both in short and long terms. CONCLUSIONS SIRI was independently associated with all-cause and CVD mortality, and the dose-response relationship was J-shaped. SIRI might serve as a valid predictor for all-cause and CVD mortality both in the short and long terms.

OBJECTIVE: To explore the effect of bear bile powder (BBP) on acute lung injury (ALI) and the underlying mechanism. METHODS: The chemical constituents of BBP were analyzed by ultra-high-pressure liquid chromatography-mass spectrometry (UPLC-MS). After 7 days of adaptive feeding, 50 mice were randomly divided into 5 groups by a random number table (n=10): normal control (NC), lipopolysaccharide (LPS), dexamethasone (Dex), low-, and high-dose BBP groups. The dosing cycle was 9 days. On the 12th and 14th days, 20 µL of Staphylococcus aureus solution (bacterial concentration of 1 × 10^-7 CFU/mL) was given by nasal drip after 1 h of intragastric administration, and the mice in the NC group was given the same dose of phosphated buffered saline (PBS) solution. On the 16th day, after 1 h intragastric administration, 100 µL of LPS solution (1 mg/mL) was given by tracheal intubation, and the same dose of PBS solution was given to the NC group. Lung tissue was obtained to measure the myeloperoxidase (MPO) activity, the lung wet/dry weight ratio and expressions of CD14 and other related proteins. The lower lobe of the right lung was obtained for pathological examination. The concentrations of inflammatory cytokines including interleukin (IL)-6, tumour necrosis factor α (TNF-α ) and IL-1β in the bronchoalveolar lavage fluid (BALF) were detected by enzyme linked immunosorbent assay, and the number of neutrophils was counted. The colonic contents of the mice were analyzed by 16 sRNA technique and the contents of short-chain fatty acids (SCFAs) were measured by gas chromatograph-mass spectrometer (GC-MS). RESULTS: UPLC-MS revealed that the chemical components of BBP samples were mainly tauroursodeoxycholic acid and taurochenodeoxycholic acid sodium salt. BBP reduced the activity of MPO, concentrations of inflammatory cytokines, and inhibited the expression of CD14 protein, thus suppressing the activation of NF-κB pathway (P<0.05). The lung histopathological results indicated that BBP significantly reduced the degree of neutrophil infiltration, cell shedding, necrosis, and alveolar cavity depression. Moreover, BBP effectively regulated the composition of the intestinal microflora and increased the production of SCFAs, which contributed to its treatment effect (P<0.05). CONCLUSIONS BBP alleviates lung injury in ALI mouse through inhibiting activation of NF-κB pathway and decreasing expression of CD14 protein. BBP may promote recovery of ALI by improving the structure of intestinal flora and enhancing metabolic function of intestinal flora.
Animals ; Acute Lung Injury/pathology* ; Lipopolysaccharides ; Ursidae ; Gastrointestinal Microbiome/drug effects* ; Bile/chemistry* ; Lipopolysaccharide Receptors/metabolism* ; Powders ; Male ; Lung/drug effects* ; Mice ; Peroxidase/metabolism* ; Signal Transduction/drug effects* ; Cytokines/metabolism*