ObjectiveThis study aims to analyze the pharmacodynamic material basis and multi-target mechanism of action of Banxia Baizhu Tianmatang combined with Danggui Shaoyaosan in the treatment of Meniere's disease（MD）. MethodsUltra-performance liquid chromatography-high resolution mass spectrometry （UPLC-HRMS） （mobile phase： gradient elution with 0.1% formic acid aqueous solution-acetonitrile. Mass spectrometry scanning range： m/z 90-1 300） was used to identify the chemical components of the compound recipe and components absorbed into blood. The core mechanism was predicted by combining network pharmacology （target screening via SwissTargetPrediction and GeneCards databases， and construction of protein-protein interaction （PPI） network by STRING） and molecular docking （evaluated by Autodock， with binding energy ≤ -5.0 kcal·mol^-1）. For animal experiment validation， 36 Sprague Dawley （SD） rats were divided into a blank group， a model group （postauricular injection of lipopolysaccharide （LPS） at 1 mg·kg^-1）， low/medium/high-dose Chinese medicine groups （5.94， 11.88， and 23.76 g·kg^-1·d^-1， respectively）， and Western medicine group （betahistine at 0.1 mg·kg^-1·d^-1）. After eight weeks of intervention， the gene and protein expressions in cochlear tissue were detected. Results①A total of 2 831 chemical components and 173 components absorbed into blood were identified， with terpenoids showing the highest absorption rate into blood（10.28%）. ②60 common drug-disease targets were screened， with core targets including tumor necrosis factor-α（TNF-α），interleukin-6（IL-6）， Toll-like receptor 4（TLR4）， angiotensin-converting enzyme（ACE）， and endothelial nitric oxide synthase 3（NOS3）.These targets were enriched in the nuclear factor-κB（NF-κB） signaling pathway and renin-angiotensin system（P<0.05）. Molecular docking showed that the active component YC-1 had a strong binding ability to TNF（binding energy-9.66 kcal·mol^-1）. ③In animal experiments， the high-dose Chinese medicine group significantly down-regulated the expression of pro-inflammatory factors TNF mRNA（P<0.01）and up-regulated vascular regulatory factors NOS3 protein（P<0.01）， and alleviated cochlear pathological damage［hematoxylin eosin （HE） score： from 4 to 2］. ConclusionThis compound recipe synergistically regulates the TNF/NF-κB inflammatory pathway and ACE/NOS3 vascular homeostasis pathway through flavonoids， triterpenoids， and other components， thereby inhibiting endolymphatic hydrops and cochlear damage. It provides a scientific basis for the theory of "simultaneous treatment of phlegm and blood stasis" in traditional Chinese medicine.

ObjectiveTo investigate the protective effect of the extract of Liuwei Dihuangwan （LW） on mitochondrial damage in the Alzheimer's disease （AD） model of Caenorhabditis elegans （C. elegans）. MethodC. elegans transfected with human β-amyloid protein （Aβ） _1-42 gene was used as an AD model. The rats were divided into blank group， model group， metformin group （50 mmol·L^-1）， and low， medium， and high dose （1.04， 2.08， 4.16 g·kg^-1） LW groups. Behavioral methods were used to observe the sensitivity of 5-hydroxytryptamine （5-HT） in nematodes. Western blot was used to detect the expression of Aβ in nematodes. Total ATP content in nematodes was detected by the adenine nucleoside triphosphate （ATP） kit， and mitochondrial membrane potential was detected by the JC-1 method. In addition， the mRNA expression of Aβ expression gene （Amy-1）， superoxide dismutase-1 （SOD-1）， mitochondrial transcription factor A homologous gene-5 （HMG-5）， mitochondrial power-associated protein 1 （DRP1）， and mitochondrial mitoprotein 1 （FIS1） was detected by real-time fluorescence quantitative polymerase chain reaction （RT-PCR）. ResultThe extract of LW could reduce the hypersensitivity of the AD model of nematodes to exogenous 5-HT （P<0.05） and delay the AD-like pathological characteristics of hypersensitivity to exogenous 5-HT caused by toxicity from overexpression of Aβ in neurons of the AD model of nematodes. Compared with the blank group， in the model group， the mRNA expression of Aβ protein and Amy-1 increased （P<0.01）， and the mRNA expression of SOD-1 and HMG-5 decreased （P<0.01）. The mRNA expression of DRP1 and FIS1 increased （P<0.01）， and the level of mitochondrial membrane potential decreased （P<0.05）. The content of ATP decreased （P<0.01）. Compared with the model group， in the positive medicine group and medium and high dose LW groups， the mRNA expression of Aβ protein and Amy-1 decreased （P<0.05，P<0.01）， and the mRNA expression of SOD-1 and HMG-5 increased （P<0.01）. The mRNA expression of DRP1 decreased （P<0.05，P<0.01）， and that of FIS1 decreased （P<0.01）. The level of mitochondrial membrane potential increased （P<0.01）， and the content of ATP increased （P<0.05，P<0.01）. ConclusionThe extract of LW may enhance the antioxidant ability of mitochondria， protect mitochondrial DNA， reduce the fragmentation of mitochondrial division， repair the damaged mitochondria， adjust the mitochondrial membrane potential， restore the level of neuronal ATP， and reduce the neuronal damage caused by Aβ deposition.

Diabetic peripheral neuropathy is a common diabetic complication.Presently,our understanding of its pathogenesis is incomplete,and there are no effective treatment options.In-depth research requires the use of animal experiments.The criteria for modeling success and the evaluation method for peripheral nerve function recovery are critical for carrying out animal experiments into type 2 diabetic peripheral neuropathy.However,but there has been a lack of systematic interrogation and analysis of the evaluation method used with type 2 diabetic peripheral neuropathy models.Therefore,the author reviewed the recent data,summarized and analyzed the evaluation method used for animal models of type 2 diabetic peripheral neuropathy of small and large nerve fibers,and proposed future directions for development,providing a reference for related research.

Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

Objective:To establish high performance liquid chromatography (HPLC) wavelength switching method to simultaneously determine the contents of chlorogenic acid, hydroxysafflor yellow A, ferulic acid, Nicotiflorin, Osthole and columbianadin in Tongluo Zhibi Prescription.Methods:The column was XBridge C18 column (250 mm × 4.6 mm, 5 μm); the mobile phase was acetonitrile (A)-0.1% phosphate water (B); gradient eluted, with flow rate: 1 ml/min, column temperature: 30 °C, detection wavelength 330 nm (0-14 min detection of chlorogenic acid, 15-80 min detection of ferulic acid, Nicotiflorin, Osthole, and columbianadin), 403 nm (14-15 min detection of hydroxysafflower yellow pigment A).Results:Chlorogenic acid, hydroxyrhodopsin A, ferulic acid, kaempferol 3-O-rutinoside, serpentin, and dihydroeurobicarpus angelicus acid ester showed good linearity ( R2 ≥ 0.999 8) within 0.029 7-1.485 0, 0.030 0-1.500 0, 0.009 9-0.495 0, 0.017 5-0.875 0, 0.028 4-1.420 0, 0.013 7-0.685 0 μg, respectively. The precision, stability (24 h), repeatability relative standard deviation ( RSD) were all <2%. The average spiked recoveries were all in the range of 95%-105%, and the RSDs were all in the range of 0.32%-1.67%. In 10 batches of test samples of Tongluo Zhibi Prescription, the content of the above six components, including chlorogenic acid, was determined to be 0.221 60, 0.314 30, 0.085 10, 0.032 95, 0.043 87, 0.026 21 mg/g in the following order. Conclusion:The established HPLC wavelength switching method is fast, simple and accurate, which can be used for simultaneous determination of the content of the above six components in Tongluo Zhibi Prescription, which provides reference for quality monitoring and new dosage form research of Tongluo Zhibi Prescription.

As a normal physiological substance,D-galactose can induce a process similar to natural brain aging in vivo and in vitro when administered excessively,and thus it is widely used to induce brain aging models in China and abroad.The model of brain failure induced by D-galactose has the advantages of a short modeling time,low cost,and significant effect.However,the induction mechanisms are complex and diverse,and the relationships between the mechanisms are unclear,which limit the practical applications of the model.This article reviews the in vivo metabolism of D-galactose and the various mechanisms involved in the induction of brain aging,as well as the links between the mechanisms,to provide a reference for the application and development of this model and the in-depth study of brain aging.

BackgroundAt least 77.0% of breast cancer patients will experience cancer-related fatigue. Hope level and resilience play as two important factors that have influence on cancer-related fatigue. Currently， most studies involve one single factor， either the level of hope or resilience， and explore its relationship with the cancer-related fatigue. Only limited studies explore the action mechanism behind with all three factors put together. ObjectiveTo investigate the mediating role of resilience between hope and cancer-related fatigue in patients with breast cancer， and to provide references for finding intervention targets for cancer-related fatigue in breast cancer patients. MethodsFrom March to October 2022， this study was conducted on the sample size of 324 hospitalized patients from three Grade-A tertiary hospitals in Shaanxi Province. These patients were over 18 years old and pathologically diagnosed as breast cancer. Hope level， resilience and cancer-related fatigue were assessed， respectively， using Adult Dispositional Hope Scale （ADHS）， Connor-Davidson Resilience Scale （CD-RISC-10） and Cancer Fatigue Scale （CFS）. Pearson Correlation Analysis was used to analyze the relationship between ADHS score， CD-RISC-10 score and CFS score. AMOS 22.0 was used to analyze the mediating effect of resilience between hope level and cancer-related fatigue in breast cancer patients. ResultsThe detection rate of cancer-related fatigue in patients with breast cancer was 88.58%. Scores of ADHS and CD-RISC-10 were negatively correlated with CFS score （r=-0.750， -0.809， P<0.01）. ADHS score was positively correlated with CD-RISC-10 score （r=0.901， P<0.01）. Resilience had a mediating effect between the hope level and cancer-related fatigue. The mediating effect value was -0.676（95% CI： -1.005~-0.347）， accounting for 81.90% of the total effect. ConclusionThe hope level of breast cancer patients can affect cancer-related fatigue directly as well as indirectly through resilience. Resilience plays a partial mediating role between hope level and cancer-related fatigue .

Objective:To describe the prevalence of psychological distress and to analyze its influencing factors among Chinese children and adolescents aged 9-18 years in 2019.Methods:Data was from the 2019 Chinese National Survey on Students' Constitution and Health, and 148 892 children and adolescents were included. Psychological distress was measured using the Kessler Psychological Distress Scale (K10): scores ≤19 were defined as no psychological distress, scores between 20-24 were defined as mild psychological distress, scores between 25-29 were defined as moderate psychological distress, and scores ≥30 were defined as severe psychological distress (moderate to severe psychological distress were defined as high psychological distress). The ANOVA, t test, and χ2 test were used to compare the differences in K10 scores and high psychological distress rates among children and adolescents with different characteristics. The ANOVA and trend χ2 test were used to analyze the trends. Modified-Poisson regression models were used to determine influencing factors of high psychological distress. Results:The K10 scores for Chinese children and adolescents aged 9-18 years in 2019 was 21.5±9.2, and their rate of high psychological distress was 31.6%. The rates of high psychological distress among children and adolescents aged 9-12, 13-15, and 16-18 years were 22.3%, 35.9%, and 38.8%. K10 scores and rates of high psychological distress showed an increasing trend as age increased (trends test all P<0.001). K10 scores and rates of high psychological distress were higher among children and adolescents who were older, female, rural, in areas with medium to low GDP per capita level, and with lower parental education (all P<0.001). Multifactorial modified-Poisson regression analysis showed that children and adolescents aged 13-15 years, 16-18 years, female, rural, and in areas with low to moderate GDP per capita level were at higher risk of high psychological distress (all P<0.05), with a OR (95% CI) of 1.55 (1.52-1.58), 1.66 (1.63-1.69), 1.07 (1.05-1.09), 1.02 (1.01-1.04), 1.10 (1.07-1.12). Children and adolescents in areas with medium to high GDP per capita level, whose father had a secondary or high school degree, whose father had a college degree or above, whose mother had a secondary or high school degree, and whose mother had a college degree or above were at lower risk of high psychological distress (all P<0.05), with a OR (95% CI) of 0.96 (0.94-0.98), 0.92 (0.90-0.93), 0.84 (0.82-0.86), 0.95 (0.93-0.97), 0.86 (0.83-0.88). Conclusions:The prevalence of psychological distress was high among Chinese children and adolescents aged 9-18 years in 2019, which is a vital problem. Mental health interventions need to be implemented among children and adolescents that were older, girls, rural, live in areas with lower economic levels, and whose parents have a lower education level.

Objective:To analyze the association between the occurrence of spermarche and menarche and psychological distress among Chinese Han children and adolescents aged 9 to 18 years.Methods:Data were drawn from the 2019 Chinese National Survey on Students' Constitution and Health, and a total of 54 438 boys aged 11 to 18 years and 76 376 girls aged 9 to 18 years with psychological distress, spermarche/menarche records were included in the final analysis. The occurrence of spermarche/menarche was recorded by physicians, and psychological distress was classified according to the Kessler Psychological Distress Scale scores. The chi-square test was used to compare the difference between groups in the occurrence of spermarche/menarche, and the multinomial logistic regression model and stratification analysis was established to analyze the association between psychological distress and spermarche/menarche.Results:The incidence of spermarche/menarche in 2019 ranged from 6.3% to 96.5% for eight age groups of Chinese boys and 2.8% to 99.0% for ten age groups of girls. The rates of high psychological distress among boys and girls were 32.5% and 32.7%. Among boys aged 11 to 18 years, the rate of high psychological distress increased with age, with a trend test P<0.001, and the difference in the rate of high psychological distress between those who had and had not had their spermarche was not statistically significant in all age groups. Among girls aged 9 to 18 years, the rate of high psychological distress increased with age, with a trend P<0.001; the rate of high psychological distress was higher in the group with menarche at age 10 and 12 than in the group without menarche (all P<0.05). High psychological distress was positively correlated with spermarche among boys aged 13-15 years living in urban areas and hight level economic development areas ( OR=1.11, 95% CI: 1.02-1.21; OR=1.18, 95% CI: 1.06-1.32). Overall, high psychological distress was positively correlated with menarche in girls aged 9-12 and 13-15 years ( OR=1.33, 95% CI: 1.25-1.42; OR=1.22, 95% CI: 1.07-1.39). High psychological distress was positively correlated with menarche among girls aged 9-12 years living in different regions except for the Northeast region, in areas with different levels of economic development, and in urban and rural areas, in girls aged 13-15 years living in urban, central, and western regions, and in girls aged 16-18 years residing in the central region. Conclusions:This study found an association between the occurrence of spermarche/menarche and psychological distress among Chinese Han children and adolescents aged 9 to 18 years in 2019, which was particularly significant among girls aged 9 to 12 years and boys aged 13 to 15 years living in areas with higher levels of socioeconomic development.