1.Pharmacological modulation of mitochondrial function as novel strategies for treating intestinal inflammatory diseases and colorectal cancer.
Boya WANG ; Xinrui GUO ; Lanhui QIN ; Liheng HE ; Jingnan LI ; Xudong JIN ; Dapeng CHEN ; Guangbo GE
Journal of Pharmaceutical Analysis 2025;15(4):101074-101074
Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal disease, and has become a major global health issue. Individuals with IBD face an elevated risk of developing colorectal cancer (CRC), and recent studies have indicated that mitochondrial dysfunction plays a pivotal role in the pathogenesis of both IBD and CRC. This review covers the pathogenesis of IBD and CRC, focusing on mitochondrial dysfunction, and explores pharmacological targets and strategies for addressing both conditions by modulating mitochondrial function. Additionally, recent advancements in the pharmacological modulation of mitochondrial dysfunction for treating IBD and CRC, encompassing mitochondrial damage, release of mitochondrial DNA (mtDNA), and impairment of mitophagy, are thoroughly summarized. The review also provides a systematic overview of natural compounds (such as flavonoids, alkaloids, and diterpenoids), Chinese medicines, and intestinal microbiota, which can alleviate IBD and attenuate the progression of CRC by modulating mitochondrial function. In the future, it will be imperative to develop more practical methodologies for real-time monitoring and accurate detection of mitochondrial function, which will greatly aid scientists in identifying more effective agents for treating IBD and CRC through modulation of mitochondrial function.
2.Prevalence and clinical relevance of carbapenem-resistant bacteria in untreated hospital wastewater
Feinan QIAN ; Yaxuan ZHAI ; Jiayao LIN ; Liang WANG ; Zhichen ZHU ; Yicheng WEN ; Jingnan LYU ; Hong DU
Chinese Journal of Preventive Medicine 2024;58(4):532-538
To analyze the prevalence, genomic characteristics and clinical relevance of carbapenem-resistant bacteria in untreated hospital wastewater, and to provide a reference basis for in-hospital assessment of public health situation and prevention of cross-infection. In March 2023, untreated wastewater in the wastewater treatment station of the Second Affiliated Hospital of Soochow University and wastewater in the U-shaped wastewater pipes of the hand-washing sinks in 26 wards were collected, centrifuged and diluted, and the drug-resistant bacteria were isolated by using LB solid plates containing meropenem (2 μg/ml) for species identification, drug sensitivity analysis, carbapenenase gene PCR detection and whole genome sequencing. The genome sequence was identified for drug resistance genes. Retrospective research was used, combining multilocus sequence typing (MLST) and single nucleotide polymorphism (SNP) analysis, to compare their homology with clinical isolates of the same quarter. The results showed that 56 carbapenem-resistant gram-negative bacteria were isolated from hospital wastewater, originating from 13 genera, of which 17 were isolated from the total hospital wastewater, with Aeromonas spp. as the most dominant genus (35.3%, 6/17), and 39 were isolated from the wastewater of 17 wards, with Pseudomonas spp. as the most dominant genus (30.8%, 12/39). All common wastewater isolates from our hospital were multidrug-resistant bacteria, with up to 100% resistant to some second-and third-generation cephalosporins. A total of 8 carbapenemase genes originated from wastewater isolates, including blaKPC, blaNDM, blaIMP, blaVIM, blaIND, blaOXA-58-like, blaOXA-48-like, and blaOXA-427-like. 39 wastewater isolates carried the carbapenemase genes, and the total wastewater of the hospital carried the highest isolation rate of blaKPC-2 bacteria (35.3%, 6/17) and the highest isolation rate of blaIMP-8 bacteria (31.8%, 7/22) were found in the wastewater from 26 wards. 14 wastewater isolates were found to carry both carbapenemase genes, with a total of 6 combinations. A new blaIMP-101 isoform was also identified for the first time. 4 wastewater isolates and 11 clinical isolates were screened for inclusion in the SNP analysis, in which only 15 SNPs differed between the two strains of ST11 Klebsiella pneumoniae of clinical and wastewater origin, which was highly homologous. In conclusion, the presence of multiple multi-drug resistant conditionally pathogenic bacteria in untreated hospital wastewater has the potential risk of spreading drug-resistant genes in the environment. The highly homologous Klebsiella pneumoniae isolated from hospital wastewater and clinics indicates the close association between hospital wastewater and clinical infections. Hospitals need to strengthen the monitoring of drug-resistant bacteria and drug-resistant genes in the wastewater environment, to prevent the widespread dissemination of drug-resistant bacteria and drug-resistant genes in hospital wastewater and to prevent nosocomial infections caused by drug-resistant bacteria in wastewater.
3.Epidemioloical characteristics and economic burden analysis of palmoplantar pustulosis in urban areas of China
Qian ZHANG ; Jingnan FENG ; Jinzhu GUO ; Lin ZHUO ; Lu XU ; Lili LIU ; Pei GAO ; Shengfeng WANG ; Siyan ZHAN ; Wenhui WANG
Chinese Journal of Preventive Medicine 2024;58(5):642-648
Objective:To analyze the epidemiological characteristics and economic burden of palmoplantar pustulosis (PPP) in China.Methods:A population-based retrospective study was conducted using the data from China′s Urban Basic Medical Insurance data from January 1, 2012, to December 31, 2016. International Classification of Diseases code and diagnoses in Chinese for PPP were used to identify cases and estimate the prevalence, incidence, and cost. Subgroup analyses were performed according to age and sex, and sensitivity analyses were conducted to evaluate the robustness of the results. Age-adjusted prevalence rates were calculated based on the 2010 national census data.Results:The crude prevalence and incidence rate of PPP in 2016 were 2.730/100 000 (95% CI: 2.218/100 000-3.242/100 000) and 1.556/100 000 (95% CI: 1.154/100 000-1.958/100 000), and the prevalence rate of females (2.910/100 000) was higher than that of males (2.490/100 000, χ2=97.48, P=0.001). The incidence rate of females (1.745/100 000) was also higher than that of males (1.418/100 000, χ2=85.02, P=0.001). The age peak of incidence and prevalence of patients with PPP was in the 30-39-year age group and a small peak existed in the 0-3-year age group among people under 20 years old. From 2012 to 2016, the average number of visits was (2.44±0.04) per patient, and the total per-capita cost per year was (982.40±39.19) yuan. Conclusion:In 2016, the prevalence and incidence rate of PPP in China were higher in females than in males, and the highest age peak was in the 30-39-year age group.
4.Personalized treatment of well-differentiated gastric neuroendocrine tumors based on clinicopathological classification and grading: A multicenter retrospective study
Ju HUANG ; Huimin LIU ; Dekun YANG ; Tianming XU ; Jing WANG ; Jingnan LI
Chinese Medical Journal 2024;137(6):720-728
Background::The incidence of well-differentiated gastric neuroendocrine tumors (G-NET) is increasing annually, and while they have a good prognosis and low mortality rate, their high recurrence rate makes treatment options controversial. This study aims to determine the relationship between individualized treatment plans and the recurrence of G-NET.Methods::We performed a multicenter, retrospective study of 94 patients with highly differentiated G-NET and treated at Peking Union Medical College Hospital, Yantai Yuhuangding Hospital, and Beijing Zhong-Neng-Jian Hospital from November 2015 to September 2023. Risk factors for recurrence of G-NETs were investigated using chi-squared test and multifactorial logistic regression analysis.Results::After a median follow-up of 49 months, the overall recurrence rate among the 94 G-NET patients was 14% (13/94). The recurrence rates of endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), somatostatin analog (SSA) therapy, and surgery were 43% (6/14), 10% (5/49), 5% (1/22), and 11% (1/9), respectively. Post-treatment recurrence rates were significantly different ( P = 0.014) among four treatments (EMR, ESD, SSA, and surgery), and further subgroup comparisons revealed lower recurrence rates in the ESD and SSA groups than in the EMR group. From the second month onward, SSA therapy considerably reduced the gastrin levels from 1081.0 (571.5, 2472.8) pg/mL to 461.5 (255.3, 795.0) pg/mL ( Z = -3.521, P <0.001). Both chi-squared test and multifactorial logistic regression analysis suggested that among the clinicopathological parameters studied, only the pre-treatment gastrin level ( P = 0.018 and 0.005) and the type of treatment ( P = 0.014 and 0.017) were significantly associated with G-NET recurrence. Conclusions::Individualized treatment strategies may reduce the risk of relapse after G-NET treatment. Long-term SSA therapy may be a secure and efficacious treatment option for type 1 G-NET with more than six lesions, and it substantially decreases the incidence of post-treatment recurrence.
5.Prevalence and clinical relevance of carbapenem-resistant bacteria in untreated hospital wastewater
Feinan QIAN ; Yaxuan ZHAI ; Jiayao LIN ; Liang WANG ; Zhichen ZHU ; Yicheng WEN ; Jingnan LYU ; Hong DU
Chinese Journal of Preventive Medicine 2024;58(4):532-538
To analyze the prevalence, genomic characteristics and clinical relevance of carbapenem-resistant bacteria in untreated hospital wastewater, and to provide a reference basis for in-hospital assessment of public health situation and prevention of cross-infection. In March 2023, untreated wastewater in the wastewater treatment station of the Second Affiliated Hospital of Soochow University and wastewater in the U-shaped wastewater pipes of the hand-washing sinks in 26 wards were collected, centrifuged and diluted, and the drug-resistant bacteria were isolated by using LB solid plates containing meropenem (2 μg/ml) for species identification, drug sensitivity analysis, carbapenenase gene PCR detection and whole genome sequencing. The genome sequence was identified for drug resistance genes. Retrospective research was used, combining multilocus sequence typing (MLST) and single nucleotide polymorphism (SNP) analysis, to compare their homology with clinical isolates of the same quarter. The results showed that 56 carbapenem-resistant gram-negative bacteria were isolated from hospital wastewater, originating from 13 genera, of which 17 were isolated from the total hospital wastewater, with Aeromonas spp. as the most dominant genus (35.3%, 6/17), and 39 were isolated from the wastewater of 17 wards, with Pseudomonas spp. as the most dominant genus (30.8%, 12/39). All common wastewater isolates from our hospital were multidrug-resistant bacteria, with up to 100% resistant to some second-and third-generation cephalosporins. A total of 8 carbapenemase genes originated from wastewater isolates, including blaKPC, blaNDM, blaIMP, blaVIM, blaIND, blaOXA-58-like, blaOXA-48-like, and blaOXA-427-like. 39 wastewater isolates carried the carbapenemase genes, and the total wastewater of the hospital carried the highest isolation rate of blaKPC-2 bacteria (35.3%, 6/17) and the highest isolation rate of blaIMP-8 bacteria (31.8%, 7/22) were found in the wastewater from 26 wards. 14 wastewater isolates were found to carry both carbapenemase genes, with a total of 6 combinations. A new blaIMP-101 isoform was also identified for the first time. 4 wastewater isolates and 11 clinical isolates were screened for inclusion in the SNP analysis, in which only 15 SNPs differed between the two strains of ST11 Klebsiella pneumoniae of clinical and wastewater origin, which was highly homologous. In conclusion, the presence of multiple multi-drug resistant conditionally pathogenic bacteria in untreated hospital wastewater has the potential risk of spreading drug-resistant genes in the environment. The highly homologous Klebsiella pneumoniae isolated from hospital wastewater and clinics indicates the close association between hospital wastewater and clinical infections. Hospitals need to strengthen the monitoring of drug-resistant bacteria and drug-resistant genes in the wastewater environment, to prevent the widespread dissemination of drug-resistant bacteria and drug-resistant genes in hospital wastewater and to prevent nosocomial infections caused by drug-resistant bacteria in wastewater.
6.Epidemioloical characteristics and economic burden analysis of palmoplantar pustulosis in urban areas of China
Qian ZHANG ; Jingnan FENG ; Jinzhu GUO ; Lin ZHUO ; Lu XU ; Lili LIU ; Pei GAO ; Shengfeng WANG ; Siyan ZHAN ; Wenhui WANG
Chinese Journal of Preventive Medicine 2024;58(5):642-648
Objective:To analyze the epidemiological characteristics and economic burden of palmoplantar pustulosis (PPP) in China.Methods:A population-based retrospective study was conducted using the data from China′s Urban Basic Medical Insurance data from January 1, 2012, to December 31, 2016. International Classification of Diseases code and diagnoses in Chinese for PPP were used to identify cases and estimate the prevalence, incidence, and cost. Subgroup analyses were performed according to age and sex, and sensitivity analyses were conducted to evaluate the robustness of the results. Age-adjusted prevalence rates were calculated based on the 2010 national census data.Results:The crude prevalence and incidence rate of PPP in 2016 were 2.730/100 000 (95% CI: 2.218/100 000-3.242/100 000) and 1.556/100 000 (95% CI: 1.154/100 000-1.958/100 000), and the prevalence rate of females (2.910/100 000) was higher than that of males (2.490/100 000, χ2=97.48, P=0.001). The incidence rate of females (1.745/100 000) was also higher than that of males (1.418/100 000, χ2=85.02, P=0.001). The age peak of incidence and prevalence of patients with PPP was in the 30-39-year age group and a small peak existed in the 0-3-year age group among people under 20 years old. From 2012 to 2016, the average number of visits was (2.44±0.04) per patient, and the total per-capita cost per year was (982.40±39.19) yuan. Conclusion:In 2016, the prevalence and incidence rate of PPP in China were higher in females than in males, and the highest age peak was in the 30-39-year age group.
7.Application value of liver/spleen CT value, controlled attenuation parameter, and magnetic resonance imaging-proton density fat fraction in chronic hepatitis B patients with hepatic steatosis
Jingnan LU ; Yansong LI ; Ya WEN ; Xionghui WANG ; Zhaoyu QU ; Jianlong LI ; Wei ZHANG
Journal of Clinical Hepatology 2024;40(1):46-51
ObjectiveTo investigate the application value of liver/spleen CT value (CTL/S), controlled attenuation parameter (CAP), and magnetic resonance imaging-proton density fat fraction (MRI-PDFF) in chronic hepatitis B (CHB) patients with hepatic steatosis. MethodsA retrospective analysis was performed for the clinical data of 213 CHB patients who underwent liver CT, CAP, and MRI-PDFF examinations in Affiliated Hospital of Yan’an University from October 2018 to December 2022. According to MRI-PDFF, the 213 patients were divided into CHB group with 111 patients (MRI-PDFF<5%) and CHB+hepatic steatosis group with 102 patients (MRI-PDFF≥5%), among whom there were 69 patients with mild hepatic steatosis and 33 patients with moderate to severe hepatic steatosis. The independent-samples t test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The Bland-Altman plot was used to evaluate the consistency in MRI-PDFF measurement between two physicians. The Spearman’s correlation coefficient was used to analyze the correlation between CTL/S and MRI-PDFF and between CAP and MRI-PDFF. The receiver operating characteristic (ROC) curve was plotted and the area under the ROC curve (AUC) was calculated to investigate the value of CTL/S and CAP in the diagnosis of different degrees of hepatic steatosis, and the DeLong test was used to compare the AUCs of the two radiological examinations. ResultsMRI-PDFF had relatively high repeatability and stability in CHB patients. There is a significant negative correlation between CTL/S and MRI-PDFF (r=-0.800, P<0.001) and a significant positive correlation between CAP and MRI-PDFF (r=0.692, P<0.001). Both CTL/S and CAP had a relatively high accuracy in the diagnosis of hepatic steatosis in CHB patients, with an AUC of 0.951 and 0.902, respectively, and CTL/S had a better accuracy than CAP (P<0.05). In the diagnosis of mild and moderate-to-severe hepatic steatosis, CTL/S had an AUC of 0.921 and 0.895, respectively, and CAP had an AUC of 0.859 and 0.825, respectively, suggesting that CTL/S had a slightly higher diagnostic efficiency than CAP. ConclusionMRI-PDFF has high repeatability and stability in CHB patients, and CTL/S and CAP have a high diagnostic value for different degrees of hepatic steatosis in CHB patients.
8.Effects of light regulation on the synthesis of secondary metabolites in medicinal plants
Wei ZHANG ; Xiangqing MENG ; Xiaohui SU ; Jinyi WANG ; Lihua LI ; Min JIA
Journal of Pharmaceutical Practice and Service 2024;42(2):50-59
Secondary metabolites of medicinal plants are extremely important to human health because of their special pharmacological activities or efficacy. They are the main source of drugs, health care products, and cosmetics. As human beings continue to pursue health and longevity, the demand in the pharmaceutical market continues to grow. It becomes especially important to improve the production and quality of secondary metabolites of medicinal plants. Plant secondary metabolites are a kind of adaptation of plants to their environment and are the result of the interaction between plants and biotic and abiotic factors during the long-term evolution process. The production and accumulation of secondary metabolites in medicinal plants are mainly affected by plant genetic factors and environmental factors. Among them, light environment is extremely important for their synthesis. Therefore, light regulation has long been a research focus for many scholars in China and abroad. In this article, we the recent research progress on the effects of light regulation on the secondary metabolites of medicinal plants were reviewed, mainly focusing on the effects of light quality, light intensity and photoperiod, in order to provide theoretical basis and practical guidance for the efficient production of secondary metabolites with important pharmacological activities.
9.Pharmacokinetics of Esketamine hydrochloride nasal spray in rats and ciliary toxicity to maxillary mucosa of bullfrog
Jingyu ZHOU ; Haixia WU ; Jingnan QUAN ; Yanna YANG ; Shijie ZHONG ; Yi CHENG ; Meng LI ; Zengming WANG ; Nan LIU ; Aiping ZHENG ; Hui ZHANG
China Pharmacy 2024;35(10):1174-1178
OBJECTIVE To study the pharmacokinetics of Esketamine hydrochloride nasal spray in rats and ciliary toxicity to maxillary mucosa of bullfrog. METHODS The plasma concentration of esketamine hydrochloride in rats was determined by LC-MS/ MS after intravenous injection of esketamine hydrochloride solution and nasal administration of esketamine hydrochloride; the pharmacokinetic parameters were calculated by using Phoenix WinNonlin 8.1.0 software. Using the maxillary mucosa of isolated bullfrog as a model, the morphological changes of maxillary mucosa were investigated, and the duration and recovery of ciliary oscillation were recorded after nasal administration of esketamine hydrochloride. RESULTS The peak of blood concentration occurred 2 min after nasal administration of esketamine hydrochloride; cmax was (814.58±418.80) ng/mL, AUC0-∞ was (203.75± 92.76) ng·h/mL, and the absolute bioavailability was 60.68%. After nasal administration of esketamine hydrochloride, it was observed that the cilia of bullfrog were arranged neatly, the edges were clear, the cilia tissue structure was complete and the cilia moved actively. The cilia movement time was (178.17±13.30) min for the first time, and after the cilia moved again, the ciliary movement time measured again was (24.50±9.19)min with a relative movement percentage of 53.56%. CONCLUSIONS Esketamine hydrochloride nasal spray has a rapid onset of action, high bioavailability, and low ciliary toxicity.
10.Sanguisorbae Radix alleviates damage in ulcerative colitis model mice based on PPARG and SLC7A11/GPX4
Xiaoxi YIN ; Zixuan CHEN ; Yi YUAN ; Jingnan MA ; Jing WANG ; Tianyi LYU ; Miaomiao TONG ; Li LI
Chinese Journal of Comparative Medicine 2024;34(7):20-28
Objective To investigate the mechanism of Sanguisorbae Radix(SR)in the treatment of ulcerative colitis(UC).Methods Using the GSE92415 dataset from the Gene Expression Omnibus database,we analyzed differentially expressed genes and carried out weighted gene correlation network analysis and FerrDb analysis.Core genes were identified through protein-protein interaction(PPI)network and correlation analysis.UC mouse model induced by dextran sulfate sodium(DSS)was constructed and treated with SR via intragastric administration for 9 days.Disease activity index(DAI)and colon length were recorded.Pathological changes in colon tissue were observed using the HE staining.Levels of inflammatory cytokines such as tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were detected by enzyme linked immunosorbent assay(ELISA).Lipid peroxidantion factors such as malondialdehyde(MDA)and glutathione(GSH)were detected using biochemical test kits.Protein expression levels of zonula occludens protein-1(ZO-1)tight junction protein,peroxisome proliferator-activated receptor gamma(PPARG),solute carrier family 7 member 11(SCL7A11),and glutathione peroxidase 4(GPX4)were examined by Western blot or immunofluorescence labeling.Results Nine differentially expressed genes associated with ferroptosis were screened and PPARG was identified as a key gene.Correlation analysis showed a strong correlation between PPARG and ferroptosis.Subsequently,the potential mechanism of SR in improving UC in mice was discussed according to the bioinformatics screening results.The experimental results demonstrated that SR significantly reduced the DAI,prevented colon shortening and improved intestinal mucosal barrier function in the colon.SR decreased TNF-α and IL-6 levels,MDA content and GSH levels in colon tissues.SR also enhanced the expression of PPARG,SLC7A11 and GPX4,which reversed the effect of DSS in mice with colitis.Conclusions Ferroptosis is closely related to UC.SR can inhibit ferroptosis by regulating PPARG and SCL7A11/GPX4 expression,thereby improving colon epithelial injury and dysfunction in UC mice.This provides ideas and directions for UC treatment strategies.

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