Objective To investigate the effects of obesity-related indexes on cardiovascular autonomic nervous function in type 2 diabetes mellitus(T2DM)patients.Methods A total of 421 T2DM patients treated in the Department of Endocrinology of Gansu Provincial People's Hospital were enrolled in this study from October 2020 to October 2023.All the patients were divided into simple T2DM group with VFA<100 cm2(n=193)and obese group with VFA≥100 cm2(OB,n=228)according to visceral fat area(VFA).BMI,waist-to-height ratio(WHtR),waist-to-hip ratio(WHR),lipid accumulation index(LAP),visceral fat index(VAI),Chinese visceral fat index(CVAI),tapeness index(CI),body shape index(ABSI),and body roundness index(BRI)were calculated.Time domain parameters of heart rate variability(HRV)in 24 h holter electrocardiogram were recorded,including the global standard deviation(SDNN)of normal sinus RR interval,standard deviation of mean value of sinus RR interval(SDANN),root mean square difference(RMSSD)of normal continuous sinus RR interval.The percentage of adjacent RR interval difference>50 ms in total interval(PNN50),the HRV triangle index,the standard deviation of the difference of the entire adjacent NN interval length(SDSD).Results Compared with T2DM group,the OB group showed an increase in age,weight,BMI,WC,hip circumference(HC),neck circumference(NC),SBP,HbA1c,TG,SUA,CI,WHtR,WHR,VFA,SFA,VAI,LAP,CVAI,and BRI(P<0.05 or P<0.01),while a decrease in HDL-C(P<0.05).The SDNN,SDANN,SDSD,RMSSD,HRV trigonometric index,and PNN50 were lower in OB group than in T2DM group(P<0.05 or P<0.01).Spearman correlation analysis showed that SDNN and HRV trigonometric index was negatively correlated with age,DM duration,HR,SBP,PWV,WHtR,TG,SUA,VAI,LAP,BRI,VFA,LAP,and CVAI(P<0.05 or P<0.01).Logistic regression analysis shows that age,VFA,and LAP are influencing factors for cardiac autonomic dysfunction.The analysis of the working characteristic curve of the subjects showed that the area under the curve of VFA,age,and LAP in predicting cardiovascular autonomic dysfunction was 0.680,0.614,and 0.577,with sensitivity of 87.5%,41.7%,and 61.8%,and specificity of 47.3%,73.6%,and 55.6%respectively.Conclusions BMI,HC,NC,WC,TG,SFA,CI,WHtR,WHR,LAP,BRI,VAI,CVAI and VFA are closely related to cardiovascular autonomic nervous function in T2DM patients.As VFA,Ageand LAP increase,the risk of cardiovascular autonomic dysfunction increases.

Cytotoxicity, usually represented by cell viability, is a crucial parameter for evaluating drug safety in vitro. Accurate prediction of cell viability/cytotoxicity could accelerate drug development in the early stage. In this study, by integrating cellular transcriptome and cell viability data using four machine learning algorithms (support vector machine (SVM), random forest (RF), extreme gradient boosting (XGBoost), and light gradient boosting machine (LightGBM)) and two ensemble algorithms (voting and stacking), highly accurate prediction models of 50% and 80% cell viability were developed with area under the receiver operating characteristic curve (AUROC) of 0.90 and 0.84, respectively; these models also showed good performance when utilized for diverse cell lines. Concerning the characterization of the employed Feature Genes, the models were interpreted, and the mechanisms of bioactive compounds with a narrow therapeutic index (NTI) can also be analyzed. In summary, the models established in this research exhibit superior capacity to those of previous studies; these models enable accurate high-safety substance screening via cytotoxicity prediction across cell lines. Moreover, for the first time, Cytotoxicity Signature (CTS) genes were identified, which could provide additional clues for further study of mechanisms of action (MOA), especially for NTI compounds.

Objective:To investigate the efficacy of lightroom therapy on depressive mood and sleep problems in patients with depression, and the potential effects on physiological indices related to circadian rhythms.Methods:From October 2021 to July 2023, 54 patients with acute-phase depression hospitalized in the Mental Health Center of the First Hospital of Hebei Medical University were recruited. The participants were randomly assigned to either medication combined with the bright light therapy group (bright light group, n=36) or medication combined with the dim light therapy group (dim light group, n=18). Both groups received light therapy for 2 weeks, at 10 000 lx in the bright light group and 300 lx in the dim light group. Both groups received 30 minutes of light therapy from 7:30-8:00 a.m daily over two weeks, followed up for 1 week post-treatment. The Hamilton Depression Rating Scale (HAMD 17) was used to assess patients′ depressive symptoms, and the Pittsburgh Sleep Quality Index (PSQI) was used to assess patients′ sleep quality at baseline, at the end of every week. The 32-Item Hypomania Checklist (HCL-32) was used at the end of week 2 to assess the risk of manic switching after treatment. Daily measurements of body temperature, heart rate, and blood pressure were taken before and after light therapy, along with recording adverse events related to the therapy. Paired t- tests were used to compare changes in physiological indicators before and after treatment, and repeated measures ANOVA was applied to compare clinical symptom changes between the two groups. Results:Thirty-one and fifteen patients completed this study in the bright light and dim light groups, respectively, with no statistically significant difference in dropout rates( P>0.05). There were significant interaction effects between the time and group for HAMD 17 and PSQI score( F=5.51,4.11, both P<0.05). Both groups showed significant reductions in HAMD 17 and PSQI scores at baseline, week 1, week 2, and week 3 ( P<0.001). In the bright light group, body temperature increased significantly post-treatment on days 1-4, day 7, and day 12 (all P<0.05). Heart rate elevated on day 5 ( P<0.05).Systolic blood pressure decreased on days 4, 5, 11, and 12 compared to the pre-treatment baseline(all P<0.05). In the dim light group, systolic blood pressure increased on day 11 ( P<0.05). Diastolic blood pressure in the bright light group decreased on days 1, 5, and 6( P<0.05). No serious adverse events, vision loss, ocular structural changes occurred in either group. No hypomania or mania episodes were observed. The incidence of adverse events did not differ significantly ( P>0.05). Conclusion:Medication combined with indoor bright light is more effective than the combination of dim light for depressive symptoms and sleep problems in patients with depression. Patients receiving bright light also may exhibit a higher body temperature, accelerated heart rate, and reduced blood pressure.

Objective To investigate the effects of obesity-related indexes on cardiovascular autonomic nervous function in type 2 diabetes mellitus(T2DM)patients.Methods A total of 421 T2DM patients treated in the Department of Endocrinology of Gansu Provincial People's Hospital were enrolled in this study from October 2020 to October 2023.All the patients were divided into simple T2DM group with VFA<100 cm2(n=193)and obese group with VFA≥100 cm2(OB,n=228)according to visceral fat area(VFA).BMI,waist-to-height ratio(WHtR),waist-to-hip ratio(WHR),lipid accumulation index(LAP),visceral fat index(VAI),Chinese visceral fat index(CVAI),tapeness index(CI),body shape index(ABSI),and body roundness index(BRI)were calculated.Time domain parameters of heart rate variability(HRV)in 24 h holter electrocardiogram were recorded,including the global standard deviation(SDNN)of normal sinus RR interval,standard deviation of mean value of sinus RR interval(SDANN),root mean square difference(RMSSD)of normal continuous sinus RR interval.The percentage of adjacent RR interval difference>50 ms in total interval(PNN50),the HRV triangle index,the standard deviation of the difference of the entire adjacent NN interval length(SDSD).Results Compared with T2DM group,the OB group showed an increase in age,weight,BMI,WC,hip circumference(HC),neck circumference(NC),SBP,HbA1c,TG,SUA,CI,WHtR,WHR,VFA,SFA,VAI,LAP,CVAI,and BRI(P<0.05 or P<0.01),while a decrease in HDL-C(P<0.05).The SDNN,SDANN,SDSD,RMSSD,HRV trigonometric index,and PNN50 were lower in OB group than in T2DM group(P<0.05 or P<0.01).Spearman correlation analysis showed that SDNN and HRV trigonometric index was negatively correlated with age,DM duration,HR,SBP,PWV,WHtR,TG,SUA,VAI,LAP,BRI,VFA,LAP,and CVAI(P<0.05 or P<0.01).Logistic regression analysis shows that age,VFA,and LAP are influencing factors for cardiac autonomic dysfunction.The analysis of the working characteristic curve of the subjects showed that the area under the curve of VFA,age,and LAP in predicting cardiovascular autonomic dysfunction was 0.680,0.614,and 0.577,with sensitivity of 87.5%,41.7%,and 61.8%,and specificity of 47.3%,73.6%,and 55.6%respectively.Conclusions BMI,HC,NC,WC,TG,SFA,CI,WHtR,WHR,LAP,BRI,VAI,CVAI and VFA are closely related to cardiovascular autonomic nervous function in T2DM patients.As VFA,Ageand LAP increase,the risk of cardiovascular autonomic dysfunction increases.

Objective:To investigate the efficacy of lightroom therapy on depressive mood and sleep problems in patients with depression, and the potential effects on physiological indices related to circadian rhythms.Methods:From October 2021 to July 2023, 54 patients with acute-phase depression hospitalized in the Mental Health Center of the First Hospital of Hebei Medical University were recruited. The participants were randomly assigned to either medication combined with the bright light therapy group (bright light group, n=36) or medication combined with the dim light therapy group (dim light group, n=18). Both groups received light therapy for 2 weeks, at 10 000 lx in the bright light group and 300 lx in the dim light group. Both groups received 30 minutes of light therapy from 7:30-8:00 a.m daily over two weeks, followed up for 1 week post-treatment. The Hamilton Depression Rating Scale (HAMD 17) was used to assess patients′ depressive symptoms, and the Pittsburgh Sleep Quality Index (PSQI) was used to assess patients′ sleep quality at baseline, at the end of every week. The 32-Item Hypomania Checklist (HCL-32) was used at the end of week 2 to assess the risk of manic switching after treatment. Daily measurements of body temperature, heart rate, and blood pressure were taken before and after light therapy, along with recording adverse events related to the therapy. Paired t- tests were used to compare changes in physiological indicators before and after treatment, and repeated measures ANOVA was applied to compare clinical symptom changes between the two groups. Results:Thirty-one and fifteen patients completed this study in the bright light and dim light groups, respectively, with no statistically significant difference in dropout rates( P>0.05). There were significant interaction effects between the time and group for HAMD 17 and PSQI score( F=5.51,4.11, both P<0.05). Both groups showed significant reductions in HAMD 17 and PSQI scores at baseline, week 1, week 2, and week 3 ( P<0.001). In the bright light group, body temperature increased significantly post-treatment on days 1-4, day 7, and day 12 (all P<0.05). Heart rate elevated on day 5 ( P<0.05).Systolic blood pressure decreased on days 4, 5, 11, and 12 compared to the pre-treatment baseline(all P<0.05). In the dim light group, systolic blood pressure increased on day 11 ( P<0.05). Diastolic blood pressure in the bright light group decreased on days 1, 5, and 6( P<0.05). No serious adverse events, vision loss, ocular structural changes occurred in either group. No hypomania or mania episodes were observed. The incidence of adverse events did not differ significantly ( P>0.05). Conclusion:Medication combined with indoor bright light is more effective than the combination of dim light for depressive symptoms and sleep problems in patients with depression. Patients receiving bright light also may exhibit a higher body temperature, accelerated heart rate, and reduced blood pressure.

From the Confucian perspective,different roles have different ethical considerations for physician-assisted suicide(PAS).From the perspective of patients,Confucianism does not support suicide as a right.For family members,Confucianism does not believe that PAS is more conducive to maintaining the dignity of patients.From a doctor's perspective,supporting PAS not only goes against the original intention of medicine,but may also lead to serious social consequences.In conclusion,Confucianism generally tends to adopt a negative attitude towards PAS.

Objective To explore whether indoor light-assisted therapy can rapidly improve depression and anxiety symptoms in patients with depression,as well as the safety of indoor-light-assisted therapy.Methods From September 2021 to December 2022,patients with depression were recruited from the Mental Health Center of the First Hospital of Hebei Medical University.According to the random number table method,patients were divided into test group and control group.The test group was treated with light therapy 30 minutes from 7:30 am to 8:00 am daily for 2 weeks in addition to antidepressant therapy.Antidepressant therapy was continued after completion of light therapy and patients were followed up for 2 weeks.The control group was treated with regular antidepressants throughout the four-week trial.Hamilton depression scale(HAMD17)and the Hamilton anxiety scale(HAMA)were used to assess the clinical symptoms at the baseline and the end of every week of treatment.Safety was evaluated using patient adverse events,anterior segment photography and visual testing.Results A total of 80 patients were enrolled,including 40 in the test group and 40 in the control group.The data of dropped were processed for missing values and then included in the statistical analysis.At the 1st(20.0％vs.0.0％)and 2nd(45.0％vs.17.5％)weekend of treatment,the response rate in the test group was significantly higher than that in the control group.There was an interaction between the time point and the group in HAMD17 total score(F=9.66,P<0.01).The scores of HAMD17 at the end of every week in the test group were significantly lower than that in the control group(P<0.05).There were significant differences in the reduction rate of total score in HAMD17[33.3％(25.0％,43.3％)vs.13.9％(9.9％,19.8％)]and HAMA[22.4％(16.5％,35.3％)vs.14.2％(4.4％,26.9％)]between the two groups(P<0.05).Incidences of adverse effect were not significantly different between the two groups(12.5％vs.10.0％,P=1.00).There were no severe adverse events or mania was reported in the test group and the eye examination showed no abnormality.Conclusion Compared with antidepressant therapy alone,indoor light therapy combined with antidepressant can quickly improve depression and anxiety symptoms in patients with depression,shorten the duration of depression treatment,and has good safety.

Objective:To analyze the rash characteristics and diagnosis and treatment process of measles infection in patients with diabetes mellitus and psoriasis, to reduce the clinical diagnosis and treatment delay of such patients.Methods:The clinical data of a patient with diabetes combined with psoriasis and measles infection who was diagnosed and treated in The First Hospital of Yulin in April 2015 were analyzed.Results:The patient was admitted to hospital due to polydipsia and polyuria for 3 years and fever for 3 days. Hypoglycemic and anti-inflammatory treatment after admission was not good. On the third day after hospitalization, rash on the trunk and the extremities was seen. The patient had a history of measles infection. Based on clinical practice, Measles morbillivirus infection was not excluded, and Measles morbillivirus infection was confirmed by pathogen inspection. Measles reinfection was considered to be caused by variation of Measles morbillivirus. The atypical rash formed because of the patient's need for long-term treatment with Acitretin capsule and capotriol for psoriasis. After adjusting the antibiotic treatment, hypoglycemia and antiviral therapy were given, the body temperature was normal and the rash gradually subsided.Conclusion:For patients with type 2 diabetes mellitus and psoriasis, if they have a fever, they should be considered comprehensively to guard against re-infection caused by measles virus mutation. Timely etiological diagnosis is performed to avoid missed diagnosis and delayed treatment.

Objective:To investigate the efficacy and safety of deep transcranial magnetic stimulation (dTMS) as an adjunctive treatment for depression.Methods:From May 2021 to June 2022, 56 patients aged 18-60 who met the diagnostic criteria in the International Classification of Diseases (ICD-10) for depression were recruited from the Mental Health Center of the First Hospital of Hebei Medical University.According to the random number table method, they were divided into dTMS combined with the drug treatment group (dTMS group, n=28), and the repetitive transcranial magnetic stimulation(rTMS) combined with the drug treatment group (rTMS group, n=28). Both groups received dTMS or rTMS based on drug therapy, 5 times weekly for 2 weeks in total. At the baseline and the end of 2nd week of treatment, the Hamilton Depression Rating Scale (HAMD 17) and Hamilton Anxiety Rating Scale (HAMA) were used to assess patients′ depression and anxiety symptoms, and the 32-Item Hypomania Checklist (HCL-32) was used to assess the risk of mania after treatment.The reductions on HAMD 17 and HAMA were the primary assessment, and the treatment response rate in HAMD 17, adverse events and the risk of switching to mania were also assessed. The efficacy was compared between the two groups by using independent samples t-test and chi-square test. Results:There was no significant difference in baseline HAMD 17 and HAMA scores between the two groups ( P>0.05). At the end of 2nd week of the treatment, The HAMD 17 reduction and the reduction rate were higher in the dTMS group than in the rTMS group( t=3.27, P=0.02; t=2.11, P=0.04). The HAMA reduction and the reduction rate showed a trend favouring the dTMS group, but the difference was insignificant ( t=1.03, P=0.31; t=0.76, P=0.45). The treatment response rates on the HAMD 17 assessment were 52.2%(12/23) and 38.5% (10/26) in the dTMS and rTMS groups, respectively. However, the difference was not statistically significant (χ 2=0.93, P=0.34). The overall incidence of adverse events was 14.3% (4/28) in the dTMS group and 7.1% (2/28) in the rTMS group, with no significant differences between the two groups (χ 2=0.19, P=0.67). All subjective discomforts during the treatment automatically resolved within three days, and no mania was reported. Conclusion:As the adjunctive treatment, both TMS protocols are safe and effective in relieving the depressive and anxious symptoms of depressive disorder, and the adjunctive dTMS seems better in treating depressive symptoms than rTMS.

Objective:To investigate the efficacy and safety of deep transcranial magnetic stimulation (dTMS) as an adjunctive treatment for depression.Methods:From May 2021 to June 2022, 56 patients aged 18-60 who met the diagnostic criteria in the International Classification of Diseases (ICD-10) for depression were recruited from the Mental Health Center of the First Hospital of Hebei Medical University.According to the random number table method, they were divided into dTMS combined with the drug treatment group (dTMS group, n=28), and the repetitive transcranial magnetic stimulation(rTMS) combined with the drug treatment group (rTMS group, n=28). Both groups received dTMS or rTMS based on drug therapy, 5 times weekly for 2 weeks in total. At the baseline and the end of 2nd week of treatment, the Hamilton Depression Rating Scale (HAMD 17) and Hamilton Anxiety Rating Scale (HAMA) were used to assess patients′ depression and anxiety symptoms, and the 32-Item Hypomania Checklist (HCL-32) was used to assess the risk of mania after treatment.The reductions on HAMD 17 and HAMA were the primary assessment, and the treatment response rate in HAMD 17, adverse events and the risk of switching to mania were also assessed. The efficacy was compared between the two groups by using independent samples t-test and chi-square test. Results:There was no significant difference in baseline HAMD 17 and HAMA scores between the two groups ( P>0.05). At the end of 2nd week of the treatment, The HAMD 17 reduction and the reduction rate were higher in the dTMS group than in the rTMS group( t=3.27, P=0.02; t=2.11, P=0.04). The HAMA reduction and the reduction rate showed a trend favouring the dTMS group, but the difference was insignificant ( t=1.03, P=0.31; t=0.76, P=0.45). The treatment response rates on the HAMD 17 assessment were 52.2%(12/23) and 38.5% (10/26) in the dTMS and rTMS groups, respectively. However, the difference was not statistically significant (χ 2=0.93, P=0.34). The overall incidence of adverse events was 14.3% (4/28) in the dTMS group and 7.1% (2/28) in the rTMS group, with no significant differences between the two groups (χ 2=0.19, P=0.67). All subjective discomforts during the treatment automatically resolved within three days, and no mania was reported. Conclusion:As the adjunctive treatment, both TMS protocols are safe and effective in relieving the depressive and anxious symptoms of depressive disorder, and the adjunctive dTMS seems better in treating depressive symptoms than rTMS.