ObjectiveThis paper aims to systematically reveal the effect difference and mechanisms of Zishenwan against chronic prostatitis （CP） before and after salt-processing of Anemarrhenae rhizoma and Phellodendri chinensis cortex based on an integrated strategy of ultra-high performance liquid chromatography-quadrupole-orbitrap mass spectrometry （UPLC-Q-Orbitrap-MS/MS）， network pharmacology， and serum metabolomics. MethodsZishenwan samples before and after salt-processing of Anemarrhenae rhizoma and Phellodendri chinensis cortex were extracted by alcohol-water dual extraction. The chemical components of each sample were detected by UPLC-Q-Orbitrap-MS/MS， and differential components were screened by multivariate statistical analysis. Network pharmacology analysis was performed based on the identified chemical components of Zishenwan to construct a protein-protein interaction （PPI） network of "component， target， and pathway"， and the core components， targets， and pathways of Zishenwan against CP were screened. Forty-two male Sprague-Dawley （SD） rats were randomly divided into a blank group， a model group， a Qianliekang group （1.54 g·kg^-1）， low- and high-dose raw Zishenwan groups （1.8， 5.4 g·kg^-1）， and low- and high-dose salt-processed Zishenwan groups （1.8， 5.4 g·kg^-1）. The CP rat model was established by intraprostatic injection of carrageenan. After one week of recovery， the rats were administered the corresponding drugs for 21 days， while those in the blank group and model group received the same volume of normal saline. After the experiment， serum and tissue samples were collected to evaluate pharmacodynamic indicators including organ indices， histopathology， and inflammatory factors in serum. Subsequently， untargeted serum metabolomics technology was used to analyze metabolite changes and perform pathway enrichment analysis. The network pharmacology was used to construct a network of "differential metabolite， reaction， enzyme， and gene". ResultsA total of 76 components were identified in raw and salt-processed Zishenwan， and 34 differential components were screened by multivariate statistical analysis. Among them， the contents of 14 components， including berberine， berberrubine， and phellodendrine， increased after salt-processing， while the contents of 20 components， such as neomangiferin， decreased. The 28 active components and 185 potential targets were screened out by network pharmacology. The core components included berberine， phellodendrine， magnoflorine， and jatrorrhizine， and the core targets included signal transducer and activator of transcription 3 （STAT3）， protein kinase B1 （Akt1）， and transcription factor AP-1 （JUN）. These targets were significantly enriched in pro-inflammatory signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） and mitogen-activated protein kinase （MAPK）. Compared with the model group， all Zishenwan administration groups showed decreased prostate index， reduced levels of interleukin （IL）-1β， IL-18， and B-cell lymphoma-2 （Bcl-2） in serum （P<0.05， P<0.01）， as well as varying degrees of alleviation in histopathological damage. At the same dose， compared with the raw Zishenwan groups， the salt-processed Zishenwan groups showed lower prostate index， pathological scores， and IL-1β， IL-18， and Bcl-2 levels in serum， but the differences were not statistically significant. Metabolomics reveals that 38 differential metabolites were reversed after salt-processed Zishenwan administration. Both raw and salt-processed Zishenwan regulated pathways such as β-alanine metabolism and tryptophan metabolism. In addition to the common regulated pathways， the salt-processed group specifically regulated pantothenate and coenzyme A biosynthesis， pyrimidine metabolism， and arginine and proline metabolism. The intersecting pathways between network pharmacology and metabolomics were tryptophan metabolism and arginine and proline metabolism， with overlapping targets including monoamine oxidase A （MAOA） and arginase 1 （ARG1）. ConclusionThe increased contents of components such as berberine and phellodendrine in salt-processed Zishenwan may enhance its therapeutic effect on CP by inhibiting the PI3K/Akt and MAPK signaling pathways， along with multi-target regulation of tryptophan， arginine， and pantothenate metabolism pathways to comprehensively regulate inflammatory and immune responses.

Objective:To describe the body mass index (BMI) level and long-term trends of Chinese older adults aged 65 and above.Methods:Older adults aged 65 and above from six waves (2002-2018) of the China Longitudinal Healthy Longevity Survey were selected as the study population. Multiple cross-sectional design with six survey waves conducted in 2002, 2005, 2008, 2011, 2014, and 2018 was adopted, enrolling 15 647, 15 358, 15 622, 9 166, 6 302, and 12 417 participants, respectively. Additionally, a total of 13, 755 participants were included in the cohort study design. Relevant information was collected through questionnaires and physical examinations. The χ2 trend test was used to compare the changes in the rates of underweight and overweight/obesity over the years, and the linear mixed-e?ects model (LMM) was used to fit trajectory curves of BMI changes with advancing age in older adults. Results:The baseline ages of the participants included in 2002, 2005, 2008, 2011, 2014, and 2018 were (85.16±11.26), (84.23±11.83), (84.99±12.16), (81.10±11.86), (78.89±11.30), and (83.08±12.42) years, respectively, with a relatively high proportion of females and rural residents. In the cohort study, the 13 755 participants had a median ( Q1, Q3) follow-up time of 6.5 (5.2, 10.0) years, with a cumulative follow-up duration of 109 041 person-years. In each wave, males had higher BMI than females, urban residents had higher BMI than rural residents, and BMI gradually decreased with increasing age (all P<0.001). The mean BMI of older adults in China increased from (19.37±3.80) kg/m2 in 2002 to (22.04±4.01) kg/m2 in 2018 ( P<0.001). Across all survey years, the prevalence of underweight was consistently higher in women than in men and in rural areas than in urban areas, with an upward trend as age increased (all P<0.001). In 2018, the underweight rates in the 65-79, 80-89, 90-99, and ≥100-year-old age groups were 8.0%, 16.7%, 26.2%, and 35.5%, respectively. Meanwhile, the prevalence of overweight/obesity was higher in men than in women and in urban areas than in rural areas, showing a declining trend with advancing age (all P<0.001). The prevalence of underweight among the older adults decreased significantly from 45.2% in 2002 to 18.9% in 2018 ( P<0.001), while the prevalence of overweight/obesity increased from 11.0% in 1998 to 29.6% in 2018 ( P<0.001). The trajectory curves fitted by the LMM model showed that individuals born in later decades had higher BMI levels at the same age compared to earlier cohorts. Conclusion:From 2002 to 2018, the BMI level among Chinese older adults showed an increasing trend. The prevalence of underweight showed a declining trend, while the rates of obesity and overweight increased. However, the underweight rate remained notably high among the oldest old.

Objective:To explore the relationships between physical activity and cognitive impairment in older adults aged ≥65 years in longevity areas in China.Methods:A total of 6 081 older adults aged ≥65 years from the Healthy Ageing and Biomarkers Cohort Study in China in 2021 were included in this study. Information about their demographic characteristics, lifestyles, and chronic disease histories were collected, the intensity of physical activity was evaluated by using Physical Activity Scale for the Elderly, and the cognitive function was evaluated by using Mini-Mental State Examination Scale (Chinese version). Multifactorial logistic regression model was used to analyze the associations between different levels and types of physical activity and cognitive impairment in older adults.Results:In the 6 081 older adults, 1 829 (30.1%) had cognitive impairment. After adjusting for confounders, older adults with T2 and T3 levels of physical activity had lower risks for cognitive impairment compared with those with T1 levels of physical activity, with ORs of 0.47 (95% CI: 0.40-0.55) and 0.22 (95% CI: 0.18-0.28). The results of different types of physical activities showed that the ORs in leisure activity T2 and T3 groups were 0.52 (95% CI: 0.44-0.63) and 0.49 (95% CI: 0.41-0.58), and the ORs in housework activity T2 and T3 groups were 0.36 (95% CI: 0.30-0.42) and 0.19 (95% CI: 0.16-0.24). There was no significant association between work-related activity and cognitive impairment. Conclusion:There is a negative association between the intensity level of physical activity and cognitive impairment, and active leisure and household activities might reduce the risk for cognitive impairment.

With population aging worldwide,Alzheimer's disease(AD)has become a serious human health issue.Owing in part to the complexity of the pathogenesis of AD,effective therapeutic options are lacking.Mesenchymal stem cell-derived exosomes(MSC-Exos)have powerful regenerative properties and repair functions,providing a new direction for treatment.They are donor-derived,easily stored,natural carriers,with low immunogenicity and a low risk of tumor formation.They have shown great potential in the treatment of AD and post-treatment rehabilitation.This article introduces the pathological mechanisms of AD and characteristics of MSC-Exos,provides a detailed review of the roles of MSC-Exos in the treatment of AD,including anti-inflammatory effects,immunomodulatory effects,and related signaling pathway modulation,and summarizes recent research progress,with the aim of providing a basis for the development of novel therapeutic approaches to AD.

With population aging worldwide,Alzheimer's disease(AD)has become a serious human health issue.Owing in part to the complexity of the pathogenesis of AD,effective therapeutic options are lacking.Mesenchymal stem cell-derived exosomes(MSC-Exos)have powerful regenerative properties and repair functions,providing a new direction for treatment.They are donor-derived,easily stored,natural carriers,with low immunogenicity and a low risk of tumor formation.They have shown great potential in the treatment of AD and post-treatment rehabilitation.This article introduces the pathological mechanisms of AD and characteristics of MSC-Exos,provides a detailed review of the roles of MSC-Exos in the treatment of AD,including anti-inflammatory effects,immunomodulatory effects,and related signaling pathway modulation,and summarizes recent research progress,with the aim of providing a basis for the development of novel therapeutic approaches to AD.

Objective:To describe the body mass index (BMI) level and long-term trends of Chinese older adults aged 65 and above.Methods:Older adults aged 65 and above from six waves (2002-2018) of the China Longitudinal Healthy Longevity Survey were selected as the study population. Multiple cross-sectional design with six survey waves conducted in 2002, 2005, 2008, 2011, 2014, and 2018 was adopted, enrolling 15 647, 15 358, 15 622, 9 166, 6 302, and 12 417 participants, respectively. Additionally, a total of 13, 755 participants were included in the cohort study design. Relevant information was collected through questionnaires and physical examinations. The χ2 trend test was used to compare the changes in the rates of underweight and overweight/obesity over the years, and the linear mixed-e?ects model (LMM) was used to fit trajectory curves of BMI changes with advancing age in older adults. Results:The baseline ages of the participants included in 2002, 2005, 2008, 2011, 2014, and 2018 were (85.16±11.26), (84.23±11.83), (84.99±12.16), (81.10±11.86), (78.89±11.30), and (83.08±12.42) years, respectively, with a relatively high proportion of females and rural residents. In the cohort study, the 13 755 participants had a median ( Q1, Q3) follow-up time of 6.5 (5.2, 10.0) years, with a cumulative follow-up duration of 109 041 person-years. In each wave, males had higher BMI than females, urban residents had higher BMI than rural residents, and BMI gradually decreased with increasing age (all P<0.001). The mean BMI of older adults in China increased from (19.37±3.80) kg/m2 in 2002 to (22.04±4.01) kg/m2 in 2018 ( P<0.001). Across all survey years, the prevalence of underweight was consistently higher in women than in men and in rural areas than in urban areas, with an upward trend as age increased (all P<0.001). In 2018, the underweight rates in the 65-79, 80-89, 90-99, and ≥100-year-old age groups were 8.0%, 16.7%, 26.2%, and 35.5%, respectively. Meanwhile, the prevalence of overweight/obesity was higher in men than in women and in urban areas than in rural areas, showing a declining trend with advancing age (all P<0.001). The prevalence of underweight among the older adults decreased significantly from 45.2% in 2002 to 18.9% in 2018 ( P<0.001), while the prevalence of overweight/obesity increased from 11.0% in 1998 to 29.6% in 2018 ( P<0.001). The trajectory curves fitted by the LMM model showed that individuals born in later decades had higher BMI levels at the same age compared to earlier cohorts. Conclusion:From 2002 to 2018, the BMI level among Chinese older adults showed an increasing trend. The prevalence of underweight showed a declining trend, while the rates of obesity and overweight increased. However, the underweight rate remained notably high among the oldest old.

Objective:To explore the relationships between physical activity and cognitive impairment in older adults aged ≥65 years in longevity areas in China.Methods:A total of 6 081 older adults aged ≥65 years from the Healthy Ageing and Biomarkers Cohort Study in China in 2021 were included in this study. Information about their demographic characteristics, lifestyles, and chronic disease histories were collected, the intensity of physical activity was evaluated by using Physical Activity Scale for the Elderly, and the cognitive function was evaluated by using Mini-Mental State Examination Scale (Chinese version). Multifactorial logistic regression model was used to analyze the associations between different levels and types of physical activity and cognitive impairment in older adults.Results:In the 6 081 older adults, 1 829 (30.1%) had cognitive impairment. After adjusting for confounders, older adults with T2 and T3 levels of physical activity had lower risks for cognitive impairment compared with those with T1 levels of physical activity, with ORs of 0.47 (95% CI: 0.40-0.55) and 0.22 (95% CI: 0.18-0.28). The results of different types of physical activities showed that the ORs in leisure activity T2 and T3 groups were 0.52 (95% CI: 0.44-0.63) and 0.49 (95% CI: 0.41-0.58), and the ORs in housework activity T2 and T3 groups were 0.36 (95% CI: 0.30-0.42) and 0.19 (95% CI: 0.16-0.24). There was no significant association between work-related activity and cognitive impairment. Conclusion:There is a negative association between the intensity level of physical activity and cognitive impairment, and active leisure and household activities might reduce the risk for cognitive impairment.

Background and Aims:Papillary thyroid carcinoma (PTC) generally has a good prognosis,leading to relatively limited research on the psychological status of PTC patients. However,animal studies have shown that PTC is associated with negative emotions,which may adversely affect the prognosis of the disease. Therefore,this study was performed to explore the relationship between PTC and negative emotions,focusing on anxiety and depression,to understand their association and provide information for clinical practice and research.Methods:Patients diagnosed with PTC after surgery in the Department of Thyroid Surgery at the Second Affiliated Hospital of Nanchang University from June 2021 to April 2022 were selected as the observation group. Healthy volunteers without a history of thyroid disease or thyroid surgery during the same period were selected as the control group. The emotional status of the subjects in the past year was assessed using a general questionnaire,the self-rating anxiety scale (SAS),and the self-rating depression scale (SDS). Multivariable Logistic regression was used to analyze the connection of anxiety and depression to the risk of developing PTC. Results:Comparing the four components of SAS,there was no significant difference in the motor tension scores between the observation group and the control group (P=0.496). However,the observation group had significantly higher scores in psychological emotions,neurofunctional disorders,somatic symptoms,and the total SAS score compared to the control group (all P<0.05). Comparing the four components of SDS,there were no significant differences in psychological emotions and psychomotor scores between the two groups (both P>0.05). However,the observation group had significantly higher scores in somatic disorders,psychological disorders,and the total SDS score compared to the control group (all P<0.05). Multivariable Logistic regression analysis of the 20 items of SAS showed that anxiety,panic,insanity,tremors,somatic pain,numbness in hands and feet,palpitations,nightmares,and sleep disturbances were associated with the risk of PTC. Multivariable Logistic regression analysis of the 20 items of SDS indicated that somatic and psychological disorder scores were related to the risk of PTC. Conclusion:Negative emotions are associated with the occurrence and development of PTC,and there may be mutual influences between them. Therefore,attention should be given to the psychological well-being of both healthy individuals and PTC patients. The mechanisms underlying the association between negative emotions and PTC require further exploration.

Sleep disorder, migraine, cognitive and behavioral disorders, anxiety and depression are common comorbidities of epilepsy. The comorbidity rate of epilepsy patients is eight times that of the general population, which affects the prognosis and quality of life of epilepsy patients. Perampanel (PER), as a third-generation antiseizure medication, has shown promising clinical research and application in the treatment of comorbidities in epilepsy. PER can improve the total sleep time, sleep latency and sleep efficiency of patients with epilepsy comorbid sleep disorder. PER also shows good efficacy in reducing seizure and migraine attacks of patients with epilepsy comorbid migraine. Meanwhile, the impact of PER on overall cognitive characteristics is neutral, with no systematic cognitive deterioration or improvement, but behavioral changes are one of the most common adverse events related to PER. For patients with comorbid anxiety and depression, PER does not exacerbate the anxiety and depression of epilepsy patients, and the severity of anxiety and depression in some patients will improve. This article will review the mechanism of action and clinical treatment research progress of PER on comorbidities of epilepsy.

Objective:To investigate the mechanism of Yunshi Ganmao Heji against respiratory syncytial virus (RSV) infection based on network pharmacology and in vivo experiments. Methods:Network pharmacological prediction: Several databases including TCMSP and GeneCards were used to predict the active ingredients and targets of Yunshi Ganmao Heji in the intervention of RSV infection. Cytoscape 3.2.1 software was used to construct the traditional Chinese medicine component-disease target network diagram. The interactions between proteins were analyzed by STRING database. GO functional enrichment analysis and KEGG pathway enrichment analysis were performed using Metascape database. Molecular docking technology was used to verify the results of network pharmacology. Experimental verification of Yunshi Ganmao Heji for the intervention of RSV infection: A mouse model of RSV infection was established through intranasal infection. After the administration of Yunshi Ganmao Heji, blood routine test results, lung indexes and pathological changes in lung tissue were analyzed. Peripheral blood T cell subsets were detected by flow cytometry. The levels of TNF-α, IL-6 and IL-1β in serum were detected by ELISA. RT-PCR was used to detect the relative expression of TLR4, NF-κB and RSV-N gene at mRNA level in lung tissues.Results:A total of 41 active ingredients of Yunshi Ganmao Heji and 111 drug targets for RSV infection were obtained. Besides, 167 signaling pathways mainly including PI3K/AKT, MAPK and Toll-like receptor signaling pathways were obtained. Molecular docking results showed that the binding energies of luteotin, kaempferol and quercetin, three active ingredients of Yunshi Ganmao Heji, with RSV-G, RSV-F, PI3K, AKT1 and Bcl-2 were less than 0 kcal/mol. In vivo experiment results showed that compared with RSV group, the counts of white blood cells and lymphocytes increased and the lung index decreased in high-dose Yunshi Ganmao Heji group, with statistically significant difference ( P<0.05). HE staining showed pulmonary hyperplasia, thickened alveolar wall and inflammatory cell infiltration in interstitium in RSV group. Alveoli in ribavirin group as well as low-dose, medium-dose and high-dose Yunshi Ganmao Heji groups tended to be of uniform size, and the alveolar walls was roughly uniform in thickness. Compared with RSV group, the low-dose, medium-dose and high-dose Yunshi Ganmao Heji groups showed significantly increased numbers of CD3 +, CD4 + and CD8 + T lymphocytes, decreased CD4 + /CD8 + T cell ratio, lower levels of TNF-α, IL-6, IL-1β in serum, and reduced viral load and inhibited expression of TLR4 and NF-κB at mRNA level in lung tissues ( P<0.05). Conclusions:Yunshi Ganmao Heji can regulate RSV infection by targeting multiple targets and pathways with several active ingredients. Its main functions are to alleviate pathological injury in lung tissues and reduce inflammatory response, and the possible mechanism underlying the antiviral functions may be related to its inhibitory effect on the activation of TLR4/NF-κB pathway.