1.Near-infrared targeted probe designed for intraoperative imaging of prostatic neurovascular bundles.
Zhan Yi ZHANG ; Fan ZHANG ; Ye YAN ; Cai Guang CAO ; Chang Jian LI ; Shao Hui DENG ; Yue Hao SUN ; Tian Liang HUANG ; Yun He GUAN ; Nan LI ; Min LU ; Zhen Hua HU ; Shu Dong ZHANG
Journal of Peking University(Health Sciences) 2023;55(5):843-850
OBJECTIVE:
To investigate the imaging effect of a near-infrared fluorescent targeted probe ICG-NP41 on the neurovascular bundles (NVB) around the prostate in rats.
METHODS:
A near-infrared fluorescent targeted probe ICG-NP41 was synthesized. An animal model for NVB imaging was established using Sprague-Dawley rats (250-400 g). Experiments were conducted using a custom-built near-infrared windowⅡ(NIR-Ⅱ) small animal in vivo imaging system, and images collected were processed using ImageJ and Origin. The fluorescence signal data were statistically analyzed using GraphPad Prism. The signal-to-background ratio (SBR) for NVB was quantitatively calculated to explore the effective dosage and imaging time points. Finally, paraffin pathology sections and HE staining were performed on the imaging structures.
RESULTS:
Except for rats in the control group (n=2), right-sided NVB of the rats injected with ICG-NP41 (n=2 per group) were all observed in NIR-Ⅱ fluorescence mode 2 h and 4 h after administration. At 2 h and 4 h, average SBR of cavernous nerve in 2 mg/kg group in fluorescence mode was 1.651±0.142 and 1.619±0.110, respectively, both higher than that in white light mode (1.111±0.036), with no significant difference (P>0.05); average SBR of 4 mg/kg group in fluorescence mode were 1.168±0.066 and 1.219±0.118, respectively, both higher than that in white light mode (1.081±0.040), with no significant difference (P>0.05). At 2 h and 4 h, the average SBR of 2 mg/kg and 4 mg/kg groups in fluorescence mode were higher than that of the control group (SBR=1), the average SBR of the 2 mg/kg group was higher than that of the 4 mg/kg group, and all the above with no significant difference (P>0.05). The average diameter of the nerve measured by full width at half maxima method was about (178±15) μm. HE staining of paraffin sections showed the right major pelvic ganglion.
CONCLUSION
The near-infrared fluorescent targeted probe ICG-NP41 can be used for real-time imaging of the NVB around the prostate in rats, providing a potential feasible solution for localizing NVB in real time during nerve-sparing radical prostatectomy.
Male
;
Rats
;
Animals
;
Prostate/diagnostic imaging*
;
Paraffin
;
Indocyanine Green
;
Rats, Sprague-Dawley
;
Fluorescent Dyes
2.Costunolide covalently targets NACHT domain of NLRP3 to inhibit inflammasome activation and alleviate NLRP3-driven inflammatory diseases.
Haowen XU ; Jiahao CHEN ; Pan CHEN ; Weifeng LI ; Jingjing SHAO ; Shanshan HONG ; Yi WANG ; Lingfeng CHEN ; Wu LUO ; Guang LIANG
Acta Pharmaceutica Sinica B 2023;13(2):678-693
The NLRP3 inflammasome's core and most specific protein, NLRP3, has a variety of functions in inflammation-driven diseases. Costunolide (COS) is the major active ingredient of the traditional Chinese medicinal herb Saussurea lappa and has anti-inflammatory activity, but the principal mechanism and molecular target of COS remain unclear. Here, we show that COS covalently binds to cysteine 598 in NACHT domain of NLRP3, altering the ATPase activity and assembly of NLRP3 inflammasome. We declare COS's great anti-inflammasome efficacy in macrophages and disease models of gouty arthritis and ulcerative colitis via inhibiting NLRP3 inflammasome activation. We also reveal that the α-methylene-γ-butyrolactone motif in sesquiterpene lactone is the certain active group in inhibiting NLRP3 activation. Taken together, NLRP3 is identified as a direct target of COS for its anti-inflammasome activity. COS, especially the α-methylene-γ-butyrolactone motif in COS structure, might be used to design and produce novel NLRP3 inhibitors as a lead compound.
3.Genetic Subtypes and Pretreatment Drug Resistance in the Newly Reported Human Immunodeficiency Virus-Infected Men Aged≥50 Years Old in Guangxi.
Ning-Ye FANG ; Wen-Cui WEI ; Jian-Jun LI ; Ping CEN ; Xian-Xiang FENG ; Dong YANG ; Kai-Ling TANG ; Shu-Jia LIANG ; Yu-Lan SHAO ; Hua-Xiang LU ; He JIANG ; Qin MENG ; Shuai-Feng LIU ; Qiu-Ying ZHU ; Huan-Huan CHEN ; Guang-Hua LAN ; Shi-Xiong YANG ; Li-Fang ZHOU ; Jing-Lin MO ; Xian-Min GE
Acta Academiae Medicinae Sinicae 2023;45(3):399-404
Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ2=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male
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Humans
;
Middle Aged
;
Reverse Transcriptase Inhibitors/therapeutic use*
;
HIV Infections/drug therapy*
;
Drug Resistance, Viral/genetics*
;
China/epidemiology*
;
Mutation
;
HIV-1/genetics*
;
Protease Inhibitors/therapeutic use*
;
Genotype
4.Predictive values of serum 8-hydroxydeoxyguanosine on disease progression and prognosis of patients with sepsis.
Xiao Rong CHEN ; Dan Wei JIANG ; Ya Hui TANG ; Chang XU ; Shao Ce ZHI ; Guang Liang HONG ; Zhong Qiu LU ; Guang Ju ZHAO
Chinese Journal of Burns 2022;38(3):207-214
Objective: To investigate the values of serum 8-hydroxydeoxyguanosine (8-OHdG) in predicting disease progression and prognosis of patients with sepsis. Methods: The prospective observational research methods were used. A total of 124 patients with sepsis who met the inclusion criteria were admitted to the Department of Emergency of the First Affiliated Hospital of Wenzhou Medical University from April 2015 to July 2016, including 79 males and 45 females, aged (62±15) years. The sepsis-related organ failure assessment (SOFA) scores of all patients on admission and on the second day of admission and their difference (ΔSOFA) were calculated. The patients were divided into non-progression group with ΔSOFA score <2 (n=101) and progression group with ΔSOFA score ≥2 (n=23), and according to the survival during hospitalization, the patients were divided into survival group (n=85) and death group (n=39). Data of patients between non-progression group and progression group, survival group and death group were compared, including the gender, age, days in emergency intensive care unit (ICU), smoking, hypertension, diabetes mellitus, serum white blood cell count, serum C-reactive protein, and serum procalcitonin on admission, and serum 8-OHdG within 24 h of admission. The multivariate logistic regression analysis was used to screen the independent risk factors of disease progression and death during hospitalization in 124 patients with sepsis, the receiver's operating characteristic (ROC) curves were drawn according to the independent risk factors, and the area under the curve (AUC), the best threshold, and the sensitivity and specificity under the best threshold were calculated. The patients were divided into high 8-OHdG group (n=35) and low 8-OHdG group (n=89) according to the best threshold in ROC curve of death during hospitalization. The data including the gender, age, SOFA score on admission, SOFA score on the second day of admission, and ΔSOFA score of patients in the two groups were compared. The survival rates of patients within 90 d of admission in the two groups were compared by the Kaplan-Meier method. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, chi-square test, and Log-rank test. Results: The gender, age, days in emergency ICU, smoking, complicated with hypertension, complicated with diabetes mellitus, serum white blood cell count, serum C-reactive protein, and serum procalcitonin on admission of patients in non-progression group and progression group were similar (P>0.05). The serum 8-OHdG within 24 h of admission of patients in progression group was significantly higher than that in non-progression group (Z=-2.31, P<0.05). Multivariate logistic regression analysis showed that the serum 8-OHdG within 24 h of admission was the independent risk factor for disease progression of 124 patients with sepsis (odds ratio=1.06, with 95% confidence interval of 1.01-1.11, P<0.05). The AUC under the ROC curve of serum 8-OHdG within 24 h of admission to predict disease progression of 124 patients with sepsis was 0.65 (with 95% confidence interval of 0.52-0.79, P<0.05), the optimal threshold was 32.88 ng/mL, and the sensitivity and specificity under the optimal threshold was 52.2% and 79.2%, respectively. The gender, age, days in emergency ICU, smoking, complicated with hypertension, complicated with diabetes mellitus, and serum white blood cell count, serum C-reactive protein, and serum procalcitonin on admission of patients in survival group and death group were similar (P>0.05). The serum 8-OHdG within 24 h of admission of patients in death group was significantly higher than that in survival group (Z=-2.37, P<0.05). Multivariate logistic regression analysis showed that the serum 8-OHdG within 24 h of admission was the independent risk factor for death of 124 patients with sepsis (odd ratio=1.04, with 95% confidence interval of 1.00-1.09, P<0.05). The AUC under the ROC curve of serum 8-OHdG within 24 h of admission to predict death of patients during hospitalization was 0.63 (with 95% confidence interval of 0.52-0.75, P<0.05), the optimal threshold was 32.43 ng/mL, the sensitivity and specificity under the optimal threshold was 51.3% and 84.7%, respectively. The gender and age of patients in high 8-OHdG group and low 8-OHdG group were similar (P>0.05). The SOFA score on admission, SOFA score on the second day of admission, and ΔSOFA score of patients in high 8-OHdG group were significantly higher than those in low 8-OHdG group (with Z values of -2.49, -3.01, and -2.64, respectively, P<0.05 or P<0.01). The survival rate within 90 d of admission of patients in low 8-OHdG group was significantly higher than that in high 8-OHdG group (χ2=14.57, P<0.01). Conclusions: Serum 8-OHdG level is an independent risk factor for disease progression and death in sepsis patients with limited ability for predicting disease progression and prognosis of sepsis of patients. The patients with higher serum 8-OHdG level have higher death risk within 90 d of admission.
8-Hydroxy-2'-Deoxyguanosine
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Aged
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Disease Progression
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Female
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Humans
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Male
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Middle Aged
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Prognosis
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ROC Curve
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Retrospective Studies
;
Sepsis
6.Research Progress in Clinical Electrophysiological Assessment of Patients with Sepsis-Associated Encephalopathy.
Meng-Lu ZHOU ; Guang-Yong JIN ; Shao-Song XI ; Jia-Yi CHEN ; Dong-Cheng LIANG
Acta Academiae Medicinae Sinicae 2022;44(5):876-884
Sepsis-associated encephalopathy(SAE) caused by infections outside the central nervous system always presents extensive brain damage.It is common in clinical practice and associated with a poor prognosis.There are problems in the assessing and diagnosing of SAE.Many factors,such as sedation and mechanical ventilation,make it difficult to assess SAE,while electrophysiological examination may play a role in the assessment.We reviewed the studies of electrophysiological techniques such as electroencephalography and somatosensory evoked potentials for monitoring SAE,hoping to provide certain evidence for the clinical evaluation and diagnosis of SAE.
Humans
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Sepsis-Associated Encephalopathy/complications*
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Sepsis/diagnosis*
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Electroencephalography
7.Association between age at arrival, duration of migration, and overweight/obesity in Chinese rural-to-urban migrants: the Yi migrant study
Ye WANG ; Li PAN ; Shao-Ping WAN ; Fang YANG ; Hui-Jing HE ; Zheng LI ; Jia ZHANG ; Zheng-Ping YONG ; Guang-Liang SHAN
Chinese Medical Journal 2021;134(1):60-67
Background::Urbanization in China is rapidly proceeding, but rural-to-urban migration and its association with overweight and obesity is not well studied. This study aimed to explore the age at arrival, duration of migration, and the corresponding association with overweight/obesity in Yi migrants in China.Methods::A cross-sectional study was conducted in rural and urban areas in 2015 in Sichuan province, China. Demographic characteristics, lifestyle factors, and anthropometry were collected. General linear regression models were used to assess the effect of duration of migration (1-10, 11-20, 21-30, and >30 years) on body mass index (BMI). Multi-variable logistic regression was used to examine the association between duration of migration and overweight/obesity (BMI ≥ 25 kg/m 2). Results::A total of 3056 Yi people (1894 Yi farmers and 1162 Yi migrants) aged 20 to 80 years were enrolled. After adjusting for age, sex, and other potential confounders, Yi migrants had 1.71 kg/m 2 (95% confidence interval [CI]: 1.36-2.06) higher BMI and a 2.13-fold (95% CI: 1.71-2.65) higher risk of overweight/obesity than Yi farmers. In Yi migrants, stratified by age at arrival, no significant association between duration of migration and overweight/obesity was observed in those who were 0 to 20 years old at arrival. In comparison, in migrants >20 years old at arrival, compared with the reference group (1-10 years), long-term migration (>30 years) was found to be associated with overweight/obesity after adjustment (odds ratio: 1.85, 95% CI: 1.04-3.29). Conclusions::Yi migrants were observed to have greater risk of overweight/obesity than Yi farmers. In Yi migrants, the risk of overweight/obesity increased according to the duration of migration, especially in those who were older upon their arrival.
8.Prevalence of Hyperuricemia and Associated Factors in the Yi Farmers and Migrants of Southwestern China: A Cross-sectional Study.
Qing Qing WANG ; Shao Ping WAN ; Guang Liang SHAN ; Wen Bo WU ; Zheng Ping YONG ; Jiao PEI
Biomedical and Environmental Sciences 2020;33(6):448-453
Adult
;
Aged
;
Aged, 80 and over
;
China
;
epidemiology
;
Cross-Sectional Studies
;
Ethnic Groups
;
Farmers
;
statistics & numerical data
;
Female
;
Humans
;
Hyperuricemia
;
epidemiology
;
Male
;
Middle Aged
;
Prevalence
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Risk Factors
;
Transients and Migrants
;
statistics & numerical data
;
Young Adult
9.Serological Survey of Zika Virus in Humans and Animals in Dejiang Prefecture, Guizhou Province, China.
Fan LI ; Jing Zhu ZHOU ; Lei ZHOU ; Shi Hong FU ; Zhen Zao TIAN ; Qi WANG ; Nan SHAO ; Dan LI ; Ying HE ; Wen Wen LEI ; Guang Peng TANG ; Guo Dong LIANG ; Ding Ming WANG ; Yan Ping ZHANG ; Huan Yu WANG
Biomedical and Environmental Sciences 2019;32(12):875-880
OBJECTIVE:
The current outbreak of Zika virus (ZIKV) poses a severe threat to human health. Two ZIKV strains were isolated from mosquitoes collected from the Dejiang prefecture in China in 2016, which was the first isolation of ZIKV in nature in China.
METHODS:
In this study, serum samples were collected from 366 healthy individuals and 104 animals from Dejiang prefecture in 2017, and the plaque reduction neutralization test (PRNT) was used to evaluate the seroprevalence of ZIKV.
RESULTS:
None of the 366 residents from whom the samples were collected were seropositive for ZIKV. None of the 11 pigs from whom the samples were collected were seropositive for ZIKV, while 1 of 63 (1.59%) chickens and 2 of 30 (6.67%) sheep were seropositive for ZIKV.
CONCLUSION
The extremely low seropositivity rate of ZIKV antibodies in animals in the Dejiang prefecture, Guizhou province in this study indicates that ZIKV can infect animals; however, there is a low risk of ZIKV circulating in the local population.
10.Anti-cyclic citrullinated peptide antibody predicts the development of rheumatoid arthritis in patients with undifferentiated arthritis
Li CHUN ; Zhang YAN ; Song HUI ; Gao JIE ; Zhao DONG-BAO ; Zhu QI ; He DONG-YI ; Wang LI ; Li XIANG-PEI ; Liu XU-DONG ; Xiao WEI-GUO ; Wu XIN-YU ; Wu HUA-XIANG ; Tu WEI ; Hu SHAO-XIAN ; Wang XIN ; Li ZHI-JUN ; Lu ZHI-MIN ; Da ZHAN-YUN ; Liang BO ; Liu XIAO-MIN ; Zhao JIN-WEI ; Li LING ; Han FENG ; Qi WU-FANG ; Wei WEI ; Ma XU ; Li ZHEN-BIN ; Zheng GUI-MIN ; Zhang FENG-XIAO ; Li YI ; Wang YOU-LIAN ; Ling GUANG-HUI ; Chen JIN-WEI ; Hou XIAO-QIANG ; Zhang JING ; Chen QING-PING ; Liu CHANG-LIAN ; Zhang YAN ; Zeng JIA-SHUN ; Zou QING-HUA ; Fang YONG-FEI ; Su YIN ; Li ZHAN-GUO
Chinese Medical Journal 2019;132(24):2899-2904
Background:Clinical outcomes of undifferentiated arthritis (UA) are diverse,and only 40 % of patients with UA develop rheumatoid arthritis (RA) after 3 years.Discovering predictive markers at disease onset for further intervention is critical.Therefore,our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.Methods:We performed a prospective,multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals.Clinical and serological parameters were obtained at recruitment.Follow-up was undertaken in all patients every 12 weeks for 2 years.Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.Results:A total of 234 patients were recruited in this study,and 17 (7.3%) patients failed to follow up during the study.Among the 217 patients who completed the study,83 (38.2%) patients went into remission.UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9% vs.16.8%,x2=8.228,P=0.008),anti-cyclic citrullinated peptide (CCP) antibodypositivity (66.7% vs.10.7%,x2 =43.897,P < 0.001),and double-positivity rate of RF and anti-CCP antibody (38.1% vs.4.1%,x2 =32.131,P < 0.001) than those who did not.Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017,95% confidence interval:5.803-55.938;P < 0.001).Conclusion:As an independent predictor of RA,anti-CCP antibody should be tested at disease onset in all patients with UA.

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