1.Progress on antisense oligonucleotide in the field of antibacterial therapy
Jia LI ; Xiao-lu HAN ; Shi-yu SONG ; Jin-tao LIN ; Zhi-qiang TANG ; Zeng-ming WANG ; Liang XU ; Ai-ping ZHENG
Acta Pharmaceutica Sinica 2025;60(2):337-347
With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.
2.Association between sleep characteristics, physical activity patterns with depressive and anxiety symptoms in college students
Chinese Journal of School Health 2025;46(4):552-557
Objective:
To explore the relationship between sleep characteristics, physical activity patterns, with depressive and anxiety symptoms in college students, so as to provide reference for student mental health promotion.
Methods:
From September to November 2023, a convenience sampling method was used to select 7 954 college students aged 18-22 years from 9 universities in Shanghai, Hubei, and Jiangxi. Assessments were conducted using the International Physical Activity Questionnaire Short-Form (IPAQ-SF), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder Scale-7 (GAD-7), and Pittsburgh Sleep Quality Index (PSQI) to evaluate physical activity, depressive and anxiety symptoms, and sleep quality, respectively. Logistic regression analysis was employed to explore the impact of sleep characteristics and physical activity patterns on depressive and anxiety symptoms and their comorbidity among college students.
Results:
The detection rates for depressive symptoms, anxiety symptoms, and comorbid depression and anxiety symptoms were 25.67%, 35.39%, and 23.15%, respectively. Factors such as gender, grade, household registration, parental education level, annual family income, family structure, and dietary habits were all associated with the detection rates of depressive and anxiety symptoms and their comorbidity (χ2=4.41-118.39, P<0.05). Physical activity patterns, sleep duration, sleep quality, and sleepwake characteristics were also associated with the occurrence of depressive and anxiety symptoms and their comorbidity (χ2=9.66-627.70, P<0.05). Logistic regression analysis showed that college students who stayed up late and slept less than 7 had the highest risk of depressive and anxiety symptoms and their comorbidity (OR=1.93, 1.85, 1.88, P<0.05). Compared to regular physical activity patterns, insufficient physical activity patterns were associated with an increased risk of depressive and anxiety symptoms (all OR=1.18, P<0.05). Further stratified analysis results showed that the risk of depression, anxiety and their comorbidity increased in college students who stayed up late and slept less than 7 h, went to bed before midnight and slept less than 7 h, or went to bed before midnight and slept more than 7 h but did not have sufficient physical activity (P<0.05).
Conclusions
Sleep characteristics and physical activity patterns significantly affect depressive and anxiety symptoms in college students. Universities should strengthen sleep management and implement flexible physical activity interventions to help students establish healthy lifestyles.
6.The role of CYP2E1 in trichloroethylene-induced skin sensitization and liver damage in guinea pigs
Lijuan WU ; Xiangrong SONG ; Fengrong LU ; Hongling LI ; Jiaheng HE ; Xiao ZHANG ; Hailan WANG
China Occupational Medicine 2025;52(3):249-256
Objective To investigate the role of cytochrome P450 2E1 (CYP2E1) in trichloroethylene (TCE)-induced skin sensitization and liver damage in guinea pigs, using diallyl sulfide (DAS), a CYP2E1 inhibitor, as an intervention. Methods Specific pathogen-free female guinea pigs were randomly divided into blank control group, solvent control group, positive control (2,4-dinitrochlorobenzene) group, TCE-exposure group, and DAS-intervention group. Skin sensitization experiments were conducted using the guinea pig TCE maximal dose-skin sensitization test. Urinary trichloroacetic acid levels were determined following TCE induction and challenge. At 48 hours after the final challenge, serum liver function markers and inflammatory cytokines levels were detected. Histopathological examination on skin and liver tissues was performed, and hepatic CYP2E1 protein expression and oxidative stress indicators were assessed. Results The sensitization rates of guinea pigs were 100.0%, 75.0%, and 33.3% in the positive control, TCE-exposure, and DAS-intervention groups, respectively, while the blank control and solvent control groups were both 0.0%. Compared with the guinea pigs in TCE-exposure group, those in the DAS-intervention group had lower urinary trichloroacetic acid levels at intradermal induction, local induction, first challenge, and 24 hours after the final challenge time point (all P<0.05). Histopathology of guinea pigs showed dermal inflammatory infiltration and basal keratinocyte necrosis in the TCE-exposure group, whereas only mild dermal inflammation was observed in the DAS-intervention group. The guinea pigs in TCE-exposure group exhibited diffuse hepatocellular necrosis, while hepatic damage in the DAS-intervention group was alleviated, characterized by only mild hepatocellular steatosis and hepatocyte swelling around the central vein. The skin sensitization rate of guinea pigs in the TCE-exposure group increased (all P<0.01), the serum alanine aminotransferase (ALT )activity, the levels of interleukin (IL)-2, IL-17, and tumor necrosis factor-α (TNF- α) increased (all P<0.05), the relative expression of CYP2E1 protein, the activity of superoxide dismutase (SOD), and the level of malondialdehyde in liver tissue increased (all P<0.05), while the activity of catalase decreased (P<0.05), compared with the blank control and solvent control groups. The serum ALT activity and the levels of IL-2, IL-17, and TNF-α of guinea pigs in DAS-intervention group reduced (all P<0.05), as well as CYP2E1 protein expression, SOD activity, and malondialdehyde level in liver tissue reduced (all P<0.05), compared with the TCE-exposure group. Conclusion TCE can induce hepatic CYP2E1 expression, thereby promoting oxidative stress and inflammatory responses, which contributes to skin sensitization and liver damage. DAS alleviates TCE-induced toxic effects on skin and liver by inhibiting CYP2E1 expression.
7.Mechanism of action of energy metabolism in hepatic ischemia-reperfusion injury and related targeted therapies
Tiantian YANG ; Lu HUANG ; Xiao ZHANG ; Yali REN ; Weitian XU ; Song ZHANG
Journal of Clinical Hepatology 2025;41(9):1956-1960
Hepatic ischemia-reperfusion injury (HIRI) is an inevitable major complication during surgical procedures such as liver transplantation and partial hepatectomy, and its prevention and treatment are hotspots and difficulties in clinical practice. This article reviews the mechanism of injury caused by energy metabolism disorders during liver ischemia-reperfusion and related treatment strategies and summarizes the current advances in metabolism-related therapies, in order to provide new ideas for further clarifying the onset mechanism of HIRI and exploring effective clinical prevention and treatment strategies for HIRI.
8.Trends and factors associated with overweight and obesity among primary and secondary school students in Tianjin from 2019 to 2023
Chinese Journal of School Health 2024;45(8):1176-1180
Objective:
To understand trends and related factors influencing overweight and obesity among primary and secondary school students in Tianjin, so as to provide a basis for formulating overweight and obesity prevention and control strategies.
Methods:
In September of each year from 2019 to 2023, a survey was conducted among 197 707 primary and secondary school students in 16 districts of Tianjin through a stratified random cluster sampling method. Physical examination was carried out in accordance with the Technical Standard for Physical examination for Student, and overweight and obesity survey was carried out. Basic information, smoking, drinking, diet, physical exercise, and sleep status were collected through questionnaire surveys.
Results:
The detection rates of overweight and obesity among primary and secondary school students in Tianjin from 2019 to 2023 were 39.07%, 43.33%, 41.54%, 43.92%, and 40.24%, respectively,showing an increasing trend(χ2trend=7.96,P<0.01). The detection rates of overweight increased in both vocational high schools and suburban counties (χ2trends=9.08, 47.18, P<0.01). The detection rates of obesity increased among both male and female students, in primary and vocational high schools and suburban counties (χ2trends=108.34, 15.99, 7.32, 10.95, 14.75, P<0.01). Multivariate Logistic regression analysis showed that smoking, drinking, unhealthful diet, and lack of proper physical exercise had a higher risk of obesity among primary and secondary school students (OR=1.26, 1.13, 1.08, 1.21, P<0.05). Stratified analysis showed that the risk of obesity was higher among boys with unhealthful and moderate lifestyle habits, as well as primary school students with unhealthful lifestyle habits (OR=1.15, 1.11, 1.27, P<0.05). Boys, girls and primary school students with unhealthful lifestyle habits, girls and ordinary high school students with moderate lifestyle habits had higher risk of being overweight (OR=1.14, 1.32, 1.21, 1.18, 1.40, P<0.05).
Conclusions
The detection rates of overweight and obesity among primary and secondary school students in Tianjin shows an increasing trend. Comprehensive lifestyle should be implemented to better prevent and control the risk of overweight and obesity.
9.Sappanone A attenuates renal ischemia-reperfusion injury in rats by regulating JNK signal pathway
Tai-wei JIN ; Xiao-ning GAO ; Wen-lin SONG ; Yan-yan WANG ; Lin SUN ; Ling-hong LU
Acta Pharmaceutica Sinica 2024;59(6):1639-1646
This study aimed to investigate the role and mechanism of sappanone A (SA) in regulating renal ischemia-reperfusion injury (IRI) in rats. The animal experiment has been approved by the Ethics Committee of Suzhou Wujiang District Children's Hospital (approval number: 2022010). First, hematoxylin-eosin (H&E) staining was used to evaluate the effects of SA on IRI, and renal damage was scored. Serum creatinine (SCr), blood urea nitrogen (BUN) and cystatin C (Cystatin C) were analyzed. The effect of sappanone A on the apoptosis of renal tubular epithelial cells induced by IRI was analyzed by TUNEL staining. Protein expression levels of p-JNK/JNK, p-ERK/ERK, Bcl2, Bax and cleaved-caspase 3 in renal tissues were detected by Western blot. Finally, H&E staining, serological analysis, TUNEL staining and Western blot were used to determine whether JNK activator anisomycin could reverse the effect of SA on IRI in rats. The results showed SA significantly reduced the renal tubule injury caused by ischemia-reperfusion, and decreased the level of SCr, BUN and Cys C in serum. TUNEL staining showed that SA significantly reduced the apoptosis of renal tubular epithelial cells induced by IRI. Western blot analysis of kidney tissue showed that SA significantly promoted the expression of apoptosis inhibiting protein Bcl2 and inhibited the expression of apoptosis-promoting proteins Bax and cleaved-caspase 3. Further analysis elucidated that SA did not affect the phosphorylation of ERK but decreased the phosphorylation of JNK. Finally, H&E staining, serological analysis, TUNEL staining and Western blot confirmed that JNK activator anisomycin could reverse the alleviating effect of SA on IRI in rats. The above findings suggest that SA could alleviate IRI in rats by inhibiting JNK phosphorylation.
10.Influence of Modified Shashen Maidong Decoction Combined with Camrelizumab Immunotherapy Plus Chemotherapy on the Efficacy,Survival Status,and Serum CYFRA21-1 and NSE Levels in Patients with Advanced Non-Small Cell Lung Cancer
Hai-Feng WANG ; Yi-Qun ZHAO ; Xiao-Li DU ; Lu LIU ; Bao-Song HOU ; Wen-Yan ZHAN
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(3):606-611
Objective To investigate the influence of modified Shashen Maidong Decoction combined with Camrelizumab immunotherapy plus chemotherapy on the efficacy,survival status and serum cytokeratin 19 fragment(CYFRA21-1)and neuron-specific enolase(NSE)levels in patients with advanced non-small cell lung cancer(NSCLC).Methods Forty patients with advanced NSCLC of lung-stomach yin deficiency with intense heat-toxin type were randomly divided into a control group and a study group,with 20 patients in each group.The patients in the control group were given Camrelizumab immunotherapy plus chemotherapy,and the patients in the study group were given modified Shashen Maidong Decoction combined with Camrelizumab immunotherapy plus chemotherapy,with 21 days as a course of treatment and for a total of 4 courses of treatment.The changes of serum NSE and CYFRA21-1 levels in the two groups before and after treatment were observed,and the clinical efficacy,survival status and the incidence of toxic and side effects were compared between the two groups.Results(1)After 4 courses of treatment,the total effective rate of the study group was 70.00%(14/20),which was significantly higher than that of the control group(9/20,45.00%),but the intergroup comparison(tested by chi-square test)showed that the difference was not statistically significant(P>0.05).(2)After 2 years of follow-up,the overall survival(OS),time to progression(TTP),and progression-free survival(PFS)of the patients in the study group were significantly prolonged compared with those in the control group(P<0.01).(3)After treatment,the serum NSE and CYFRA21-1 levels of the patients in the two groups were decreased compared with those before treatment(P<0.05),and the decrease of serum NSE and CYFRA21-1 levels in the study group was significantly superior to that in the control group(P<0.01).(4)The incidence of toxic and side effects in the study group was 25.00%(5/20),which was significantly lower than that of 65.00%(13/20)in the control group,and the intergroup comparison showed that the difference was statistically significant(P<0.05).Conclusion Modified Shashen Maidong Decoction combined with Camrelizumab immunotherapy plus chemotherapy has satisfactory therapeutic effect on patients with advanced NSCLC,which can reduce the toxic and side effects of chemotherapy,lower the level of serum tumor markers,and prolong the survival period and time to progression(TTP)of the patients.


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