ObjectiveTo improve the therapeutic effect of Buyang Huanwutang（BYHW） on diabetic kidney disease （DKD） and explore new methods for developing new Chinese medicine decoctions，we utilized 5-hydroxymethylcytosine （5hmC）-Seal sequencing technology and network pharmacology to modify BYHW. MethodsWe selected 14 diabetes mellitus （DM） patients and 15 DKD patients hospitalized in the Department of Endocrinology of Peking University Third Hospital in 2021. Circulating free DNA （cfDNA） in the patients’ plasma was sequenced. After data processing and screening， we performed temporal clustering analysis to select a DKD 5hmC gene set， which was then cross-validated with a DKD database gene set to obtain the DKD gene set. We retrieved target genes of the seven herbal components of BYHW from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Encyclopedia of Traditional Chinese Medicine （ETCM）， and performed cross-analysis with the DKD gene set to identify common genes shared by the disease and the Chinese medicines. A protein-protein interaction （PPI） network was constructed for the common genes to screen out the key genes. Chinese medicines targeting these key genes were searched against ETCM to identify removable Chinese medicines. Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed on non-common DKD genes， and key genes in DKD-related pathways were selected based on machine learning. The GSE30529 dataset was used to verify the expression trends of 5hmC-modified genes and the feasibility of target genes as drug targets. TCMBank was used to search for target genes and obtain compounds targeting these genes and the corresponding Chinese medicines to construct a "key target-compound-Chinese medicine" network. Molecular docking was employed to verify the binding affinity of compounds with key targets. TCMSP and ETCM were used to search and count the candidate Chinese medicines targeting DKD-related genes， and a new decoction was formed by adding the selected Chinese medicines. A mouse model of DKD was established to examine the efficacy of the new decoction based on the mouse body mass， random blood glucose， urinary microalbumin （mALB）， serum creatinine （Scr）， and blood urea nitrogen （BUN） and by hematoxylin-eosin staining， periodic acid-Schiff staining， Masson staining， immunofluorescence assay， and Real-time PCR. ResultsThe cross-analysis results showed that the DKD gene set included 507 genes， of which 30 were target genes of BYHW. The PPI analysis indicated that the top 15% target genes regarding the degree were interleukin-6 （IL-6）， Toll-like receptor 4 （TLR4）， lactotransferrin （LTF）， lipoprotein lipase （LPL）， and sterol regulatory element-binding transcription factor 1 （SREBF1）. Persicae Semen and Pheretima in BYHW were unrelated to key genes and removed. Machine learning identified 10 potential target genes， among which TBC1 domain family member 5 （TBC1D5）， RAD51 paralog B （RAD51B）， and proteasome 20S subunit alpha 6 （PSMA6） had expression trends consistent with the GSE30529 dataset and could serve as drug targets. The "key target-compound-Chinese medicine" network and molecular docking results indicated that the compounds with good binding affinity to target proteins were arginine， glycine， myristicin， serine， and tyrosine， corresponding to 121 Chinese medicines. The top 10 Chinese medicines targeting DKD-related genes were Lycii Fructus， Ginseng Radix et Rhizoma， Dioscoreae Rhizoma， Rehmanniae Radix Praeparata， Isatidis Radix， Glehniae Radix， Ophiopogonis Radix， Allii Sativi Bulbus， Isatidis Folium， and Bolbostemmatis Rhizoma. Based on traditional Chinese medicine theory， the new decoction was obtained after removal of Persicae Semen and Pheretima and addition of Rehmanniae Radix Praeparata and Dioscoreae Rhizoma. Animal experiment results indicated that the modified BYHW improved the kidney function and inhibited renal fibrosis in DKD mice， with better effects than the original decoction. ConclusionThe BYHW modified based on 5hmC-Seal sequencing demonstrates better performance in inhibiting fibrosis and ameliorating DKD than the original decoction. This elucidates the biomedical theory behind the epigenetic modification of traditional Chinese medicine prescriptions， potentially offering new perspectives for the exploration of these prescriptions

ObjectiveTo improve the therapeutic effect of Buyang Huanwutang（BYHW） on diabetic kidney disease （DKD） and explore new methods for developing new Chinese medicine decoctions，we utilized 5-hydroxymethylcytosine （5hmC）-Seal sequencing technology and network pharmacology to modify BYHW. MethodsWe selected 14 diabetes mellitus （DM） patients and 15 DKD patients hospitalized in the Department of Endocrinology of Peking University Third Hospital in 2021. Circulating free DNA （cfDNA） in the patients’ plasma was sequenced. After data processing and screening， we performed temporal clustering analysis to select a DKD 5hmC gene set， which was then cross-validated with a DKD database gene set to obtain the DKD gene set. We retrieved target genes of the seven herbal components of BYHW from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Encyclopedia of Traditional Chinese Medicine （ETCM）， and performed cross-analysis with the DKD gene set to identify common genes shared by the disease and the Chinese medicines. A protein-protein interaction （PPI） network was constructed for the common genes to screen out the key genes. Chinese medicines targeting these key genes were searched against ETCM to identify removable Chinese medicines. Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed on non-common DKD genes， and key genes in DKD-related pathways were selected based on machine learning. The GSE30529 dataset was used to verify the expression trends of 5hmC-modified genes and the feasibility of target genes as drug targets. TCMBank was used to search for target genes and obtain compounds targeting these genes and the corresponding Chinese medicines to construct a "key target-compound-Chinese medicine" network. Molecular docking was employed to verify the binding affinity of compounds with key targets. TCMSP and ETCM were used to search and count the candidate Chinese medicines targeting DKD-related genes， and a new decoction was formed by adding the selected Chinese medicines. A mouse model of DKD was established to examine the efficacy of the new decoction based on the mouse body mass， random blood glucose， urinary microalbumin （mALB）， serum creatinine （Scr）， and blood urea nitrogen （BUN） and by hematoxylin-eosin staining， periodic acid-Schiff staining， Masson staining， immunofluorescence assay， and Real-time PCR. ResultsThe cross-analysis results showed that the DKD gene set included 507 genes， of which 30 were target genes of BYHW. The PPI analysis indicated that the top 15% target genes regarding the degree were interleukin-6 （IL-6）， Toll-like receptor 4 （TLR4）， lactotransferrin （LTF）， lipoprotein lipase （LPL）， and sterol regulatory element-binding transcription factor 1 （SREBF1）. Persicae Semen and Pheretima in BYHW were unrelated to key genes and removed. Machine learning identified 10 potential target genes， among which TBC1 domain family member 5 （TBC1D5）， RAD51 paralog B （RAD51B）， and proteasome 20S subunit alpha 6 （PSMA6） had expression trends consistent with the GSE30529 dataset and could serve as drug targets. The "key target-compound-Chinese medicine" network and molecular docking results indicated that the compounds with good binding affinity to target proteins were arginine， glycine， myristicin， serine， and tyrosine， corresponding to 121 Chinese medicines. The top 10 Chinese medicines targeting DKD-related genes were Lycii Fructus， Ginseng Radix et Rhizoma， Dioscoreae Rhizoma， Rehmanniae Radix Praeparata， Isatidis Radix， Glehniae Radix， Ophiopogonis Radix， Allii Sativi Bulbus， Isatidis Folium， and Bolbostemmatis Rhizoma. Based on traditional Chinese medicine theory， the new decoction was obtained after removal of Persicae Semen and Pheretima and addition of Rehmanniae Radix Praeparata and Dioscoreae Rhizoma. Animal experiment results indicated that the modified BYHW improved the kidney function and inhibited renal fibrosis in DKD mice， with better effects than the original decoction. ConclusionThe BYHW modified based on 5hmC-Seal sequencing demonstrates better performance in inhibiting fibrosis and ameliorating DKD than the original decoction. This elucidates the biomedical theory behind the epigenetic modification of traditional Chinese medicine prescriptions， potentially offering new perspectives for the exploration of these prescriptions

Objective To investigate the impact of enterovirus 71(EV71)on skeletal muscle injury and explore its mechanism in relation to the caspase-1/interleukin(IL)-1 β signaling pathway in EV71-induced skeletal muscle damage.Methods One-day-old BALB/c suckling mice were divided randomly into three groups:normal control(NC)(n=60),EV71 infection model(n=60),and caspase-1 inhibitor(EV71+VX765)(n=15)groups.The NC and EV71 model groups were further subdivided into four subgroups(5,7,10,and 14 days)(n=5 mice per group).An EV71-infected model was established by intraperitoneal injection of 25 × 103 μL/kg EV71 viral solution for 3 consecutive days.Mice in the caspase-1 inhibitor group received VX765(20 mg/kg)intraperitoneally 6 hours post-viral inoculation,continued daily for 10 days until sample collection.Mice in the NC group received an equivalent volume of saline containing 5％dimethylsulfoxide and 10％PEG300,followed by 2％cell maintenance solution after 6 hours.Post-modeling body weight and clinical disease scores were recorded.Pathological skeletal muscle damage was observed by hematoxylin-eosin(HE)staining,and expression levels of EV71 VP-1(viral capsid protein),pro-caspase-1,cleaved-caspase-1,IL-1 β,α-smooth muscle actin(SMA),and Collagen Ⅰ were detected by Western blot and immunofluorescence.Results Compared with the NC group at the same time points,mice in the EV71 model group exhibited reduced body weight,elevated disease scores,and skeletal muscle pathology characterized by inflammatory cell infiltration,myofiber dissolution,and decreased cross-sectional area(HE staining).Western blot showed significantly increased levels of EV71 VP-1,IL-1β,α-SMA,and Collagen Ⅰ in skeletal muscle homogenate from EV71 mice at 5,7,and 10 days post-infection(P＜0.001).In contrast,mice in the VX765 group showed improved body weight,reduced clinical scores(P＜0.01),and significant downregulation of EV71 VP-1(P＜0.01),pro-caspase-1,cleaved-caspase-1,IL-1β,and Collagen Ⅰ compared with the EV71 model group(P＜0.01).These findings were confirmed by immunofluorescence,indicating that inhibition of caspase-1 alleviated EV71-induced skeletal muscle injury.Conclusions EV71 may induce skeletal muscle injury by activating the caspase-1/IL-1β signaling pathway.

Objective:To investigate the association between social jetlag and depressive symptoms among college students, as well as its potential influencing factors.Methods:A cross-sectional study was conducted through an online questionnaire platform (Wenjuanxing) from March to April 2023, collecting data on social jetlag, depressive symptoms, and other factors from students at Shantou University. Social jetlag time was defined as the absolute difference between the midpoint of sleep time on weekends and weekdays, with a cutoff at the 75th percentile. The presence of social jetlag was defined as social jetlag time≥1 hour. Depressive symptoms were assessed using the Beck Depression Inventory (BDI), with a score of≥10 indicating the presence of depressive symptoms. Participants were divided into depressive symptom group (BDI≥10) and non-depressive symptom group (BDI<10). Linear regression and logistic regression models were used to analyze the relationship between social jetlag and depressive symptoms, with interaction terms and subgroup analyses to explore potential influencing factors.Results:A total of 1 323 college students were included. The social jetlag time (median 0.71 hour vs. 0.50 hour, Z=-3.36, P<0.001) and prevalence of social jetlag (37.64% vs. 30.57%, χ2=7.03, P=0.008) were both higher in the depressive symptom group than in the non-depressive symptom group. The linear regression model showed that each additional hour of social jetlag was associated with an increase of 0.67 points in BDI score (95% CI=0.16-1.18, β=0.06, P=0.010), after adjusting for age, gender, body mass index, being a medical student, smoking, drinking, caffeine intake, physical exercise, anxiety symptoms, insomnia symptoms, and sleep duration. The logistic regression model indicated that social jetlag was a risk factor for depressive symptoms (O R=1.34, 95% CI=1.02-1.76, P=0.036), which was moderated by physical exercise (interaction P=0.033). Among participants without physical exercise, social jetlag was associated with depressive symptoms ( OR=1.71, 95% CI=1.18-2.48, P=0.005), while no such association was found among those with physical exercise ( OR=0.97, 95% CI=0.64-1.47, P=0.892). Conclusion:Social jetlag may be associated with depressive symptoms in college students. This adverse relationship may be improved by enhancing physical exercise.

Objective To investigate the impact of enterovirus 71(EV71)on skeletal muscle injury and explore its mechanism in relation to the caspase-1/interleukin(IL)-1 β signaling pathway in EV71-induced skeletal muscle damage.Methods One-day-old BALB/c suckling mice were divided randomly into three groups:normal control(NC)(n=60),EV71 infection model(n=60),and caspase-1 inhibitor(EV71+VX765)(n=15)groups.The NC and EV71 model groups were further subdivided into four subgroups(5,7,10,and 14 days)(n=5 mice per group).An EV71-infected model was established by intraperitoneal injection of 25 × 103 μL/kg EV71 viral solution for 3 consecutive days.Mice in the caspase-1 inhibitor group received VX765(20 mg/kg)intraperitoneally 6 hours post-viral inoculation,continued daily for 10 days until sample collection.Mice in the NC group received an equivalent volume of saline containing 5％dimethylsulfoxide and 10％PEG300,followed by 2％cell maintenance solution after 6 hours.Post-modeling body weight and clinical disease scores were recorded.Pathological skeletal muscle damage was observed by hematoxylin-eosin(HE)staining,and expression levels of EV71 VP-1(viral capsid protein),pro-caspase-1,cleaved-caspase-1,IL-1 β,α-smooth muscle actin(SMA),and Collagen Ⅰ were detected by Western blot and immunofluorescence.Results Compared with the NC group at the same time points,mice in the EV71 model group exhibited reduced body weight,elevated disease scores,and skeletal muscle pathology characterized by inflammatory cell infiltration,myofiber dissolution,and decreased cross-sectional area(HE staining).Western blot showed significantly increased levels of EV71 VP-1,IL-1β,α-SMA,and Collagen Ⅰ in skeletal muscle homogenate from EV71 mice at 5,7,and 10 days post-infection(P＜0.001).In contrast,mice in the VX765 group showed improved body weight,reduced clinical scores(P＜0.01),and significant downregulation of EV71 VP-1(P＜0.01),pro-caspase-1,cleaved-caspase-1,IL-1β,and Collagen Ⅰ compared with the EV71 model group(P＜0.01).These findings were confirmed by immunofluorescence,indicating that inhibition of caspase-1 alleviated EV71-induced skeletal muscle injury.Conclusions EV71 may induce skeletal muscle injury by activating the caspase-1/IL-1β signaling pathway.

Objective:To investigate the association between social jetlag and depressive symptoms among college students, as well as its potential influencing factors.Methods:A cross-sectional study was conducted through an online questionnaire platform (Wenjuanxing) from March to April 2023, collecting data on social jetlag, depressive symptoms, and other factors from students at Shantou University. Social jetlag time was defined as the absolute difference between the midpoint of sleep time on weekends and weekdays, with a cutoff at the 75th percentile. The presence of social jetlag was defined as social jetlag time≥1 hour. Depressive symptoms were assessed using the Beck Depression Inventory (BDI), with a score of≥10 indicating the presence of depressive symptoms. Participants were divided into depressive symptom group (BDI≥10) and non-depressive symptom group (BDI<10). Linear regression and logistic regression models were used to analyze the relationship between social jetlag and depressive symptoms, with interaction terms and subgroup analyses to explore potential influencing factors.Results:A total of 1 323 college students were included. The social jetlag time (median 0.71 hour vs. 0.50 hour, Z=-3.36, P<0.001) and prevalence of social jetlag (37.64% vs. 30.57%, χ2=7.03, P=0.008) were both higher in the depressive symptom group than in the non-depressive symptom group. The linear regression model showed that each additional hour of social jetlag was associated with an increase of 0.67 points in BDI score (95% CI=0.16-1.18, β=0.06, P=0.010), after adjusting for age, gender, body mass index, being a medical student, smoking, drinking, caffeine intake, physical exercise, anxiety symptoms, insomnia symptoms, and sleep duration. The logistic regression model indicated that social jetlag was a risk factor for depressive symptoms (O R=1.34, 95% CI=1.02-1.76, P=0.036), which was moderated by physical exercise (interaction P=0.033). Among participants without physical exercise, social jetlag was associated with depressive symptoms ( OR=1.71, 95% CI=1.18-2.48, P=0.005), while no such association was found among those with physical exercise ( OR=0.97, 95% CI=0.64-1.47, P=0.892). Conclusion:Social jetlag may be associated with depressive symptoms in college students. This adverse relationship may be improved by enhancing physical exercise.

Piezo1 is a mechanosensitive ion channel protein widely expressed in mammalian cells with the function of sensing mechanical stimuli and of mediating signaling,and is embedded in the membranes of erythrocytes,the major cellular component of blood.Piezo1 regulates the morphology and function of erythrocytes by mediating the in-flux of Ca2+into the cell in crosstalk with the Gardos channel(KCa3.1),constituting the"Piezo1-Ca2+-Gardos channel axis".However,when Piezo1 is abnormally expressed or over-activated by its specific agonist(Yoda1),it can also lead to abnormal erythrocyte morphology and dysfunction,and even cause the development of related he-reditary diseases.

BackgroundThe incidence of delirium in critically ill psychiatric patients is high， and there are many factors affecting delirium occurrence. At present， epidemiological studies on delirium among critically ill patients in psychiatric hospitals are limited. ObjectiveTo explore the risk factors for delirium in critically ill patients in a psychiatric hospital， so as to guide the clinical management of delirium in psychiatric hospitals. MethodsThis retrospective study included 427 critically ill patients who were admitted to Shenzhen Kangning Hospital from January 1， 2019 to May 31， 2021. The delirium situation， gender， age， pre-admission course of illness （duration from the onset of acute mental state changes to in-patient registration at a psychiatric hospital）， history of mental illness， history of cognitive dysfunction， history of using psychoactive substances， history of using sedative and hypnotic drugs， number of combined chronic diseases， number of combined drugs and type of disease were examined as potential risk factors for delirium. Single Logistic regression was used to analyze the potential risk factors for delirium， and the potential risk factors were incorporated into the multi-factor Logistic regression analysis model so as to gradually screen out the risk factors for delirium in critically ill psychiatric patients. ResultsDelirium was present in 33.49% （143/427） of critically ill patients. Multi-factor Logistic regression analysis demonstrated that the presence of delirium was associated with mental and behavioral disorders caused by psychoactive substances （OR=8.949， P<0.01）， absent history of mental illness （OR=4.202， P<0.01）， number of combined chronic diseases （OR=1.249， P<0.01）， age （OR=1.031， P<0.01） and pre-admission course of illness （OR=0.942， P<0.01） . ConclusionDelirium was present in nearly 1/3 critically ill patients in the psychiatric hospital. The risk factors for delirium included short course of illness before admission， age， more combined chronic diseases， absent history of mental illness， mental and behavioral disorders caused by psychoactive substances. ［Funded by Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties （number， SZGSP013）］

Objective:To explore the new mode of screening and intervention for obstructive sleep apnea (OSA) in civil servants and its influencing factors.Methods:From September to December 2017, 1 241 civil servants who underwent annual physical examination in the outpatient department of a civil servant unit in Guangdong province were enrolled. They were screened for high-risk patients with OSA by Berlin questionnaire, and then those high-risk patients would receive type 3 home sleep testing (HST). Patients diagnosed with OSA were given free continuous positive airway pressure (CPAP) intervention and follow-up. The HST acceptance of high-risk OSA patients, OSA prevalence, CPAP initial treatment response rate and adherence trend and influencing factors were analyzed among the civil servants.Results:A total of 1036 civil servants completed the Berlin Questionnaire screening, of which 22.0% (228/1 036) were positive for the Berlin Questionnaire and were considered to be at high risk for OSA. A total of 228 high-risk OSA patients underwent free HST screening, and 32.5% (74/228) refused sleep monitoring. 154 people received sleep monitoring, 103 people were eventually diagnosed with OSA, of which 41 were mild (40.2%), 35 were moderate (33.3%), and 27 were severe (26.5%). The estimated prevalence of OSA among civil servants was 9.9% (103/1 036). All OSA patients were provided with free auto-CPAP treatment, and only 55.3% (57/103) received initial CPAP treatment. Multivariate logistic regression analysis showed that the CPAP treatment response rate was positively correlated with the severity of OSA ( OR=5.65, 95% CI: 1.007―31.693); it was negatively correlated with the general health status score of the 36-Item Short Form of the Medical Outcomes Survey (SF-36, OR=0.968, 95% CI: 0.938―0.998).Self-determined behavioral interventions and self-perceptions that treatment not needed were the reasons for not receiving treatment.In the first week of initial CPAP treatment follow-up, 70.2% (40/57) patients had good adherence ≥4 h/night, and the median adherence was 5.0(4.0, 6.0) h/night. The adherence of 17 cases (29.8%) was less than 4 h/night, and the median adherence was 0 (0, 2.0) h/night. Univariate analysis showed that those with difficulty falling asleep, anxiety, depression, and adverse reactions to CPAP (nasal mask discomfort and suffocation) had worse adherence. The long-term adherence to CPAP treatment gradually declined, and by the 2-year follow-up period, only 22.0% of patients had good adherence. Conclusions:Even with free sleep screening and disease intervention mode, the acceptance of sleep monitoring and CPAP treatment is still low, and the short-term and long-term adherence to CPAP is poor. Epworth sleepiness Score, hypertension, and disease cognition affected the acceptance of sleep monitoring. Psycho psychological factors and adverse reactions to CPAP affect patient compliance.

ObjectiveTo investigate the prevenance rate and related factors of anxiety among the public before and after outbreak of COVID-19， and to provide scientific guidance for public health emergency response in psychological intervention field. MethodsBy using the convenient sampling method， residents in Chinese mainland participated in predesigned questionnaire survey from February 7^th to February 14^th， 2020， meantime， all the selected individuals were assessed using Self-rating Anxiety Scale （SAS）. The anxiety status was also retrospectively evaluated before January 20^th， prior to the outbreak. Thereafter， a before-and-after comparison was conducted on the anxiety status， and the related influencing factors were discussed. ResultsA total of 1 222 valid questionnaires were collected， with a valid rate of 93.8%. After the outbreak， the number of people with anxiety symptoms increased from 90 （7.4%） to 172 （14.1%）， with statistical difference （P<0.01）. The SAS score increased from （40.65±10.43） to （36.32±8.46）， with statistical difference （P<0.01）. For overall sample， the independent risk factors of anxiety aggravation included serious disruptions of daily life （P<0.01）， older age （P<0.01）， female （P<0.01）， poor education background （P=0.005）， occupied in medical staff （P=0.031） and lack of medical education （P=0.039）. For medical staff， the independent risk factors of anxiety aggravation included sense of being-alienated （P<0.01）， older age （P<0.01）， female （P=0.002） and serious disruptions of daily life （P=0.044）. ConclusionThe prevalence rate of anxiety is increased after the outbreak of COVID-19， especially among the general public with serious disruptions of daily life， older age， females， poor education background， and the lack of medical education， and among medical staff with sense of being-alienated， older age， females， and serious disruptions of daily life.