OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2 , and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
Humans ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Disorder of Sex Development, 46,XY/blood* ; Male ; Membrane Proteins/genetics* ; Child, Preschool ; Child ; Retrospective Studies ; Adolescent ; Female ; Mutation ; Testosterone/blood* ; Infant ; Dihydrotestosterone/blood*

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.

An 81-year-old female patient was treated with anti-infective therapy of omadacycline for a soft-tissue skin infection,and developed acute kidney injury(AKI)6 d after the administration of omadacycline.Laboratory tests showed that the urea was 6.11 mmol·L-1,the creatinine was 236.40 μmol·L-1,and the glomerular filtration rate was 18.18 mL·min-1·(1.73m2)-1,which led to the definitive diagnosis of AKI.The association score of the suspected drug using Naranjo's Assessment Scale suggests that the patient's adverse reaction of AKI was suspected to be caused by omadacycline.After stopping omadacycline,the patient's renal function indicators gradually recovered after symptomatic treatment with renal protection and continuous blood purification.This paper discussed the occurrence mechanism and treatment prognosis of AKI caused by omadacycline.It suggestd that clinical use of omadacycline should be alert to the adverse effects of renal injury,and timely medication analysis and symptomatic treatment should be carried out to ensure the safety and effectiveness of treatment.

BACKGROUND:Marine traditional Chinese medicine offers a potentially effective and less adverse treatment for osteoporosis.OBJECTIVE:To explore the pharmacological regulations and procedures of traditional Chinese medicine in treating osteoporosis through data mining and network pharmacology techniques.METHODS:Data mining and network pharmacology methods were used to study the medication pattern and mechanism of marine Chinese medicine patented prescriptions approved by China National Intellectual Property Administration for the treatment of osteoporosis,and special attention was paid to the core Chinese medicine constituents of these prescriptions.The core constituents of the compound drug group composed of oyster-Dipsacus asper-epimedium were comprehensively identified and analyzed by using ultra-high-performance liquid chromatography tandem mass spectrometry.RESULTS AND CONCLUSION:(1)We collected 381 authorized compound patents for the treatment of osteoporosis from the database inception to April 1,2024.Among these,48 patent groups utilized marine traditional Chinese medicine.These prescriptions contained 183 Chinese herbal medicines,of which 13 marine traditional Chinese medicines were used 574 times in total,and the number of flavors used in a single patented formula ranged from 2 to 41.(2)Oyster was the most frequently used marine ingredient,while Dipsacus asper,epimedium,Rehmannia glutinosa,Eucommia ulmoides Oliv.were the most frequent non-marine components.Association rule analysis identified oyster,Dipsacus asper,and epimedium as the core drug group.Network pharmacology analysis revealed that the core targets of this group for the treatment of osteoporosis included ALB,AKT1,TP53,PPARG,and SRC.Sitosterol,liquiritigenin,japonine,luteolin,and kaempferol were identified as the core components within the marine traditional Chinese medicine prescriptions.(3)The GO and KEGFG enrichment analyses suggested a potential association between the mechanism of the core drug group and the rap1/mapk signaling pathway in the treatment of osteoporosis.(4)The molecular docking verified the beneficial interactions between core components and core targets.(5)The ultra-high-performance liquid chromatography tandem mass spectrometry analysis of the compound medicine confirmed the presence of luteolin,sitosterol,kaempferol,and other components,aligning with the drug components identified by network pharmacology.Quantitative analysis indicated that flavonoids,terpenes,and alkaloids constituted a significant proportion of the compound medicine's components.

An 81-year-old female patient was treated with anti-infective therapy of omadacycline for a soft-tissue skin infection,and developed acute kidney injury(AKI)6 d after the administration of omadacycline.Laboratory tests showed that the urea was 6.11 mmol·L-1,the creatinine was 236.40 μmol·L-1,and the glomerular filtration rate was 18.18 mL·min-1·(1.73m2)-1,which led to the definitive diagnosis of AKI.The association score of the suspected drug using Naranjo's Assessment Scale suggests that the patient's adverse reaction of AKI was suspected to be caused by omadacycline.After stopping omadacycline,the patient's renal function indicators gradually recovered after symptomatic treatment with renal protection and continuous blood purification.This paper discussed the occurrence mechanism and treatment prognosis of AKI caused by omadacycline.It suggestd that clinical use of omadacycline should be alert to the adverse effects of renal injury,and timely medication analysis and symptomatic treatment should be carried out to ensure the safety and effectiveness of treatment.

BACKGROUND:Marine traditional Chinese medicine offers a potentially effective and less adverse treatment for osteoporosis.OBJECTIVE:To explore the pharmacological regulations and procedures of traditional Chinese medicine in treating osteoporosis through data mining and network pharmacology techniques.METHODS:Data mining and network pharmacology methods were used to study the medication pattern and mechanism of marine Chinese medicine patented prescriptions approved by China National Intellectual Property Administration for the treatment of osteoporosis,and special attention was paid to the core Chinese medicine constituents of these prescriptions.The core constituents of the compound drug group composed of oyster-Dipsacus asper-epimedium were comprehensively identified and analyzed by using ultra-high-performance liquid chromatography tandem mass spectrometry.RESULTS AND CONCLUSION:(1)We collected 381 authorized compound patents for the treatment of osteoporosis from the database inception to April 1,2024.Among these,48 patent groups utilized marine traditional Chinese medicine.These prescriptions contained 183 Chinese herbal medicines,of which 13 marine traditional Chinese medicines were used 574 times in total,and the number of flavors used in a single patented formula ranged from 2 to 41.(2)Oyster was the most frequently used marine ingredient,while Dipsacus asper,epimedium,Rehmannia glutinosa,Eucommia ulmoides Oliv.were the most frequent non-marine components.Association rule analysis identified oyster,Dipsacus asper,and epimedium as the core drug group.Network pharmacology analysis revealed that the core targets of this group for the treatment of osteoporosis included ALB,AKT1,TP53,PPARG,and SRC.Sitosterol,liquiritigenin,japonine,luteolin,and kaempferol were identified as the core components within the marine traditional Chinese medicine prescriptions.(3)The GO and KEGFG enrichment analyses suggested a potential association between the mechanism of the core drug group and the rap1/mapk signaling pathway in the treatment of osteoporosis.(4)The molecular docking verified the beneficial interactions between core components and core targets.(5)The ultra-high-performance liquid chromatography tandem mass spectrometry analysis of the compound medicine confirmed the presence of luteolin,sitosterol,kaempferol,and other components,aligning with the drug components identified by network pharmacology.Quantitative analysis indicated that flavonoids,terpenes,and alkaloids constituted a significant proportion of the compound medicine's components.

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 observe the clinical efficacy of"hegu needling"combined with"joint needling"in the treatment of chronic lumbar muscle strain.Methods A total of 64 patients with chronic lumbar muscle strain were randomly divided into observation group and control group,32 cases in each group.The control group was treated with routine acupuncture,and the observation group was treated with"hegu needling"combined with"joint needling"on the basis of the control group.One week for a course of treatment,a total of two courses of treatment.After two weeks of treatment,the clinical efficacy of the two groups was evaluated,and the changes of Visual Analogue Scale(VAS)of pain score and simplified Oswestry Dysfunction Index questionnaire(simplified ODI)score were observed before and after treatment.The changes of spinal mobility were compared before and after treatment between the two groups.Results(1)The total effective rate was 93.75%(30/32)in the observation group and 78.13%(25/32)in the control group.The curative effect of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the simplified ODI score and spinal activity score of the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the simplified ODI score and spinal activity score,the differences were statistically significant(P＜0.05).(3)After two weeks of treatment,the VAS scores of the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the VAS score,the difference was statistically significant(P＜0.05).After one month of treatment,there was no significant difference in VAS score of the observation group when compared with that after two weeks of treatment(P＞0.05).Conclusion"Hegu needling"combined with"joint needling"in the treatment of chronic lumbar muscle strain can significantly improve the patients'pain symptoms,enhance the patient's waist function,and improve the patients'spinal mobility.