1.Experimental study of biomimetic nanoparticle probe containing hematoporphyrin monomethyl ether and its imaging and sonodynamic therapy for breast cancer
Xiaohong LIN ; Pan LI ; Qianru LI ; Ju HUANG ; Qinqin JIANG ; Li WAN ; Rui TANG ; Tao HE
Chinese Journal of Ultrasonography 2021;30(2):173-179
Objective:To develop a biomimetic nanoparticle probe of hematoporphyrin monomethyl ether (HMME) coated with breast cancer cell membrane, to observe its ability to target homologous breast cancer cells in vitro, and to investigate its effect of enhanced photoacoustic imaging and sonodynamic therapy (SDT) for breast cancer in vitro.Methods:The cell membrane of breast cancer 4T1 was extracted by chemical cleavage and repeated freezing and thawing. Then the HMME-coated polylactic acid-glycolic acid copolymer biomimetic nanoparticle was prepared by double emulsification and extrusion. The basic characteristics of nanoparticles were detected. The target ability of nanoparticles to homologous breast cancer cells and the enhancement of photoacoustic imaging were observed in vitro. Singlet oxygen sensor green (SOSG) was used to verify the reactive oxygen species (ROS) production of nanoparticles, and its SDT effect on breast cancer cells was evaluated by CCK8 cytotoxicity assay.Results:The size of the prepared CHP-NPs was uniform, the morphology was spherical "core-shell structure" , the particle size was (275.23±8.25)nm, and the surface potential was (-18.43±0.45)mV. It was observed that CHP-NPs could target homologous 4T1 cells under laser confocal microscopy. In vitro photoacoustic imaging experiments show that the photoacoustic signal of nanoparticles increases with the increase of its concentration. According to SOSG probe detection, CHP-NPs could produce ROS under ultrasonic irradiation.When CHP-NPs was incubated with 4T1 cells alone and no ultrasonic irradiation was used, the cell survival rate was not significantly affected. When the concentration was 0.6 mg/ml, the cell survival rate was still 95%. After ultrasonic irradiation, CCK8 experiment showed that the CHP-NPs had a significant SDT effect on breast cancer cells.Conclusions:The biomimetic nanomolecular probe of breast cancer cell membrane is successfully prepared. The probe has good ability to target homologous tumor, and can significantly enhance tumor photoacoustic imaging and SDT effect.
2.Association analysis of advanced glycation end-products in lens with diabetic retinopathy severity
Zhuoshi WANG ; Qianru ZHANG ; Pingli ZHU ; Liangbao AN ; Wei HE
Chinese Journal of Experimental Ophthalmology 2017;35(11):1030-1034
Background The deposition of advanced glycation end products (AGEs) in lens is the risk factor of diabetic complications.Researches revealed that AGEs has autofluorescence.Crystallin is a longevity protein.AGEs accumulation is probably associated with diabetic retinopathy (DR).Objective This study was to evaluate the association of AGEs autofluorescence intensity with diabetes and with DR.Methods A cross-sectional study was carried out under the approval of Ethic Committee of Shenyang He Eye Hospital and informed consent of each patient.One hundred eyes of 100 patients with age-related cataract aged 50-70 years were included in He Eye Hospital from September to December 2015.The patients were divided into non-diabetes group (40 patients) and diabetes group (60 patients),and then the patients in diabetes group were subdivided into non-DR (NDR) group,non-proliferating DR (NPDR) group and proliferating DR (PDR) group according to the DR grading criteria,20 patients for each.Glycosylated henoglobin A1c (HbA1c) and fasting plasma glucose (FPG) were detected for each subject,and the lens autofluorescence was assayed with lens fluorescence biomicroscope (Clearpath DS120).The association of lens autofluorescence intensity with serum HbA1c level or DR severity was analyzed.Results The age and diabetes course were matched among the non-diabetes group,NDR group,NPDR group and PDR group (F=2.587,2.899,both at P>0.05),and the FBS and HbA1c level were evidently higher in the NDR group,NPDR group and PDR group than those in the non-diabetes group (all at P<0.01).The autofluorescence intensity of lens was (0.159±0.032),(0.256±0.024),(0.319 ±0.013) and (0.394±0.035) cd in the non-diabetes group,NDR group,NPDR group and PDR group,respectively,showing a significant difference among the groups (F =90.265,P =0.000).The autofluorescence intensity of lens in the NDR group,NPDR group and PDR group was significantly increased in comparison with the non-diabetes group and the autofluorescence intensity of lens was gradually increased with the severity of DR (all at P<0.01).A positive linear correlation was found between autofluorescence intensity of lens and serum HbA1 c level in diabetes patients (r =0.654,P < 0.05).Conclusions The autofluorescence intensity of AGEs in lens appears to be associated with the severity of DR and HbA1 c.The autofluorescence intensity of AGEs in the lens of diabetes patient is probably one of the evaluation indexes of early stage of DR.
3.Survey of hepatitis B virus infection for liver cancer screening in China: A population-based, cross-sectional study
Yongjie XU ; Changfa XIA ; He LI ; Maomao CAO ; Fan YANG ; Qianru LI ; Mengdi CAO ; Wanqing CHEN
Chinese Medical Journal 2024;137(12):1414-1420
Background::Hepatitis B virus (HBV) infection is the primary cause of hepatocellular carcinoma (HCC) in China. The target population for HCC screening comprises individuals who test positive for hepatitis B surface antigen (HBsAg). However, current data on the prevalence of HBV infection among individuals who are eligible for HCC screening in China are lacking. We aimed to assess the seroepidemiology of HBV infection among Chinese individuals eligible for HCC screening to provide the latest evidence for appropriate HCC screening strategies in China.Methods::Questionnaires including information of sex, age, ethnicity, marital status, educational level, source of drinking water, as well as smoking and alcohol consumption history and serum samples were collected from females aged 45–64 years and males aged 35–64 years in 21 counties from 4 provinces in eastern and central China between 2015 and 2023. Enzyme-linked immunosorbent assay methods were used to detect the serum HBV marker HBsAg.Results::A total of 603,082 individuals were enrolled, and serum samples were collected for analysis from January 1, 2015 to December 31, 2023. The prevalence of HBsAg positive in the study population was 5.23% (31,528/603,082). The prevalence of HBsAg positive was greater in males than in females (5.60% [17,660/315,183] vs 4.82% [13,868/287,899], χ 2 = 187.52, P <0.0001). The elderly participants exhibited a greater prevalence of HBV infection than younger participants (χ 2 = 41.73, P <0.0001). Birth cohort analysis revealed an overall downward trend in HBV prevalence for both males and females. Individuals born in more recent cohorts exhibited a lower prevalence of HBV infection as compared to those born earlier. Conclusions::The current prevalence of HBV infection remains above 5% in populations eligible for HCC screening in China.
4.Role of group 3 innate lymphoid cells in skin wound healing and underlying mechanisms
Wei ZHANG ; Xingyu MU ; Qianru HANG ; Yijie HUANG ; Tengjiao XU ; Xiaojie HE ; Yan DING
Chinese Journal of Dermatology 2024;57(6):516-523
Objective:To investigate the role of group 3 innate lymphoid cells (ILC3) in skin wound healing, and to explore the underlying mechanisms.Methods:Twenty-four 5-week-old male C57BL/6 mice were randomly and equally allocated into 3 groups: the skin wound + ILC3 inhibitor group (referred to as ILC3 inhibitor group), the skin wound group, and the control group, with 8 mice in each group. Four days before the establishment of the wound model, mice in the ILC3 inhibitor group were intraperitoneally injected with 1 μg of ILC3 inhibitor every 2 days for a total of 2 doses, mice in the skin wound group were injected with an equal volume of physiological saline solution, and mice in the control group were fed normally. To establish a mouse skin wound model, a full-thickness circular incision with a diameter of 0.6 cm was made around the midpoint of the dorsal midline using a biopsy punch after the intraperitoneal injection of anesthetics, which was histologically confirmed to be a full-thickness injury. The size of the wounds was observed and recorded, photographs of the wounds were taken on days 0, 1, 3, 5, 7, and 9 after wounding, and corresponding wound healing rates were calculated. On day 9 after wounding, tissue samples were collected from the wound edges, and subjected to flow cytometry analysis to quantify ILC3 infiltrating around the skin wound, and hematoxylin and eosin (HE) staining was performed to assess the healing status of the skin wounds. Real-time quantitative polymerase chain reaction (qRT-PCR) was conducted to determine the mRNA expression of vitamin D receptor (VDR), Notch1, tumor necrosis factor-alpha (TNF-α), interleukin (IL) -17A, IL-17F, and IL-22 in the wound-edge tissues, and Western blot analysis to determine their protein expression. Statistical analysis was carried out by using one-way analysis of variance and t test. Results:On day 9 after wounding, the skin wound group showed an increased number of ILC3 in the wound-edge tissues (5.31% ± 1.47% vs. 3.10% ± 0.54%, P < 0.01), increased mRNA and protein expression of TNF-α, IL-22, IL-17A, and IL-17F (all P < 0.05), but decreased mRNA and protein expression of VDR (both P < 0.05) compared with the control group; the protein expression of Notch1 was significantly higher in the skin wound group than in the control group ( P < 0.05), but there was no significant difference in its mRNA expression between the two groups ( P > 0.05). On days 1, 3 and 5, the wound healing rates were significantly higher in the ILC3 inhibitor group (45.17% ± 9.90%, 61.58% ± 11.61%, 75.61% ± 9.12%, respectively) than in the skin wound group (25.87% ± 10.96%, 47.78% ± 13.81%, 64.55% ± 10.29%, respectively, all P < 0.05). On day 9, the ILC3 inhibitor group showed a decreased number of ILC3 around the wound (2.69% ± 0.95%, P < 0.01), decreased mRNA and protein expression of TNF-α, IL-22, IL-17A, and IL-17F in the wound-edge tissues (all P < 0.05), but increased mRNA and protein expression of Notch1 and VDR in the wound-edge tissues (all P < 0.05) compared with the skin wound group. On day 9 after wounding, histopathological examination with HE staining revealed continuous and intact epithelial structure, as well as dense and neatly arranged collagen fibers in the ILC3 inhibitor group, and the structures of hair follicles, blood vessels, and sebaceous glands were similar to those in the control group. Conclusions:Skin ILC3 infiltrated local wounds and were involved in the skin wound healing process through inflammatory factors such as TNF-α, IL-17A, IL-17F, and IL-22. Downregulating the number of ILC3 may promote skin wound healing by activating VDR and Notch1, as well as inhibiting the TNF-α signaling pathway and the expression of downstream inflammatory factors.
5.Analysis of the change trend of etiological burden of disease of liver cancer in the Chinese population from 1990 to 2019
Shaoli ZHANG ; Maomao CAO ; Fan YANG ; He LI ; Xinxin YAN ; Siyi HE ; Qianru LI ; Yi TENG ; Changfa XIA ; Wanqing CHEN
Chinese Journal of Digestive Surgery 2023;22(1):122-130
Objective:To investigate the change trend of etiological burden of disease of liver cancer in the Chinese population from 1990 to 2019.Methods:The descriptive epidemiologic method was conducted. Based on the Global Burden of Disease data from the Institute for Health Metrics and Evaluation at the University of Washington, the data related to liver cancer burden caused by hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, alcohol, nonalcoholic steatohepatitis (NASH) and other factors, including number of new cases, the crude incidence rate, age-specific incidence rate, number of deaths, crude mortality rate and age-specific mortality rate, in the Chinese population from 1990 to 2019 were collected. The age-standardized rate was calculated based on the world standardized population structure in 2019 from the Global Burden of Disease data. Observation indicators: (1) the incidence of liver cancer caused by different etiologies in the Chinese population from 1990 to 2019; (2) the mortality of liver cancer caused by different etiologies in the Chinese population from 1990 to 2019; (3) the change trend of age-specific incidence rate of liver cancer caused by different etiologies in the Chinese population from 1990 to 2019; (4) the age-specific mortality rate of liver cancer caused by different etiologies in the Chinese population from 1990 to 2019. Count data were expressed as absolute numbers, percentages and ratio. Based on the junction point regression model, the Joinpoint software (V.4.9.1.0) was used to calculate the annual percentage change, average annual percentage change (AAPC) and 95% confidence intervals ( CI) of age-specific incidence rate and age-specific mortality rate of liver cancer caused by different etiologies. Results:(1) The incidence of liver cancer caused by different etiologies in the Chinese population from 1990 to 2019. From 1990 to 2019, the number of new cases of liver cancer in Chinese population decreased from 236 825 to 210 462, and the crude incidence rate decreased from 20.01/100,000 to 14.80/100,000. The new cases of liver cancer caused by HBV infection, HCV infection and other factors showed a downward trend, and the absolute change rates were ?14.76%, ?3.98% and ?26.67%, respectively. The new cases of liver cancer caused by alcohol and NASH showed a increase trend, and the absolute change rates were 9.31% and 13.91%, respectively. (2) The mortality of liver cancer caused by different etiologies in the Chinese population from 1990 to 2019. From 1990 to 2019, the number of deaths of liver cancer in Chinese population decreased from 232 449 to 187 700, and the crude mortality rate decreased from 19.64/100,000 to 13.20/100,000. The number of deaths of liver cancer caused by HBV infection, HCV infection and other factors showed a down-ward trend, and the absolute change rates were ?23.34%, ?10.99% and ?33.75%, respectively. The number of deaths of liver cancer caused by alcohol showed a slow downward trend, and the absolute change rate was ?0.51%. The number of deaths of liver cancer caused by NASH showed a increase trend, and the absolute change rate was 6.03%. (3) The change trend of age-specific incidence rate of liver cancer caused by different etiologies in the Chinese population from 1990 to 2019. From 1990 to 2019, the AAPC of age-specific incidence rate of liver cancer caused by HBV infection, HCV infection, alcohol, NASH and other factors was ?3.61%(95% CI as ?4.10% to ?3.11%), ?3.57%(95% CI as ?3.99% to ?3.14%), ?2.79%(95% CI as ?3.24% to ?2.33%), ?2.65%(95% CI as ?3.09% to ?2.21%) and ?3.62%(95% CI as ?4.05% to ?3.19%), respectively. (4) The age-specific mortality rate of liver cancer caused by different etiologies in the Chinese population from 1990 to 2019. From 1990 to 2019, the AAPC of age-specific mortality rate of liver cancer caused by HBV infection, HCV infection, alcohol, NASH and other factors was ?3.92%(95% CI as ?4.42% to ?3.41%), ?3.90%(95% CI as ?4.45% to ?3.35%), ?3.15%(95% CI as ?3.71% to ?2.58%), ?2.86%(95% CI as ?3.34% to ?2.38%) and ?4.09%(95% CI as ?4.64% to ?3.55%), respectively. Conclusions:From 1990 to 2019, the liver cancer burden of the Chinese population shows an overall downward trend, in which the liver cancer burden caused by HBV and HCV infection decreases the most, but HBV and HCV infection is still the main reason for the heavy burden of liver cancer. The age-specific incidence rate and age-specific mortality rate of liver cancer caused by alcohol and NASH show a downward trend, but the number of new cases of liver cancer caused by alcohol and NASH shows significant growth. The liver cancer burden caused by other factors shows a downward trend.
6.Analysis on characteristics of untreated 16-25 years old people living with HIV-1 at the China-Myanmar border from 2009 to 2017 based on molecular network method
Yibo DING ; Min CHEN ; Jibao WANG ; Yi FENG ; Mengze GAN ; Lijie WANG ; Qianru LIN ; Lin HE ; Yanling MA ; Mengjie HAN ; Liying MA
Chinese Journal of Experimental and Clinical Virology 2021;35(2):124-129
Objective:To analyze the epidemiological characteristics of untreated 16-25 years old people living with HIV-1 (PLWH) in Dehong on the China-Myanmar border during 2009 to 2017, by using molecular network method and to provide references for precise prevention and reduction of the spread of HIV-1 in Dehong.Methods:Screening people living with HIV-1, collecting blood sample and separating plasma, extracting RNA were performed to amplify HIV-1 pol sequence, construct molecular network by HIV-TRACE program and conduct statistical analysis. Results:Among the 573 infected persons in the group, 319 were Chinese (55.67%), 254 were Burmese (44.33%); 351 were males (61%), and 222 were females (39%); 404 had heterosexual transmission (HET, 70.51%), 110 people injected drugs (PWID, 19.20%), 51 men had sex with men (MSM, 8.9%); genotypes included 252 unique recombinant forms (43.98%), and 222 had circular recombinant forms (39.02%), 76 had HIV-1 C (13.26%) and 23 HIV-1 B (4.01%) infection. The 83 molecular networks constructed through HIV-TRACE involved 250 PLWH, 49% were the China-Myanmar mixed network (41/83). Myanmar citizens were at high risk of accessing the China-Myanmar mixed network ( AOR=2.676, p=0.002). Chinese male PWID network assortativity is 0.34, Myanmar male PWID was 0.14, MSM was 0.12. Conclusions:There is a continuous risk of cross-border transmission of HIV-1 in Dehong on the China-Myanmar border; attention should be paid to the mixed transmission of MSM and Myanmar male PWID populations with other transmission routes.
7.Establishment of an in vitro growth competition assay for HIV-1 CRF07_BC viral fitness
Lin HE ; Yang JIAO ; Yibo DING ; Yuanyuan ZHANG ; Qianru LIN ; Lijie WANG ; Dan LI ; Kunxue HONG ; Liying MA
Chinese Journal of Experimental and Clinical Virology 2021;35(4):457-462
Objective:To establish an in vitro growth competition assay using HIV-1 CRF07_BC infectious clone containing the mouse Thy1.1 gene or Thy1.2 gene. Methods:The mouse Thy1.1 gene and Thy1.2 gene were used to replace the 218 bases of Nef region of the CRF07_BC infectious clone (pXJDC6291-13) and construct the CRF07_BC infectious clones BCEA1 and BCEA2 plasmid. BCEA1 and BCEA2 plasmids were transfected into 293T to obtain the virus and the viral titration was measured. PM1 cells were co-infected with an equal virus. On the 3 rd to 6 th day of infection the cells were collected and labeled with specific antibodies Thy1.1 and Thy1.2. The viral fitness was detected by flow cytometry. Through "TFitness" (http: //bis.urmc.rochester.edu/vFitness) the relative viral fitness was calculated. The influence K103 N and K166R on the relative fitness of HIV-1 CRF07_BC were observed. Results:The relative fitness (1+ s) of CRF07_BC subtypes BCEA1 and BCEA2 viruses were 1.06±0.23693, which was not statistically significant. An in vitro growth competition assay for CRF07_BC was established. The in vitro growth competition assay was used to verify the relative fitness of the K103 N and K166R mutant strains to the wild strain. The relative fitness of BCEA2-K103 N/BCEA1 was 0.728282±0.16608, BCEA2-K166R/BCEA1 was 0.883385±0.19023, BCEA2-K103 N+ K166R/BCEA1 was 0.804604±0.06164. The relative fitness of K103 N resistant mutant strain and the wild strain was significantly different.Conclusions:An in vitro growth competition assay for the fitness of HIV-1 CRF07_BC virus was established. Based on the in vitro growth competition assay, the HIV-1 K103 N resistant mutant strain has reduced viral fitness.
8.Global epidemiology of liver cancer 2022: An emphasis on geographic disparities
Qianru LI ; Chao DING ; Maomao CAO ; Fan YANG ; Xinxin YAN ; Siyi HE ; Mengdi CAO ; Shaoli ZHANG ; Yi TENG ; Nuopei TAN ; Jiachen WANG ; Changfa XIA ; Wanqing CHEN
Chinese Medical Journal 2024;137(19):2334-2342
Background::Liver cancer remains the sixth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide, causing a heavy burden globally. An updated assessment of the global epidemiology of the liver cancer burden that addresses geographical disparities is necessary to better understand and promote healthcare delivery.Methods::Data were extracted from the GLOBOCAN 2022 database, including the number, crude, and age-standardized rates of incidence and mortality at the global, country, continent, and human development index (HDI) regional levels. Age-standardized rates (incidence and mortality) per 100,000 person-years were adjusted based on the Segi-Doll World standard population. The mortality-to-incidence ratios (MIR) for each region and country were calculated. The HDI and gross national income (GNI) for 2022 were obtained, and a Pearson correlation analysis was conducted with the incidence, mortality, and MIR.Results::In 2022, approximately 866,136 new liver cancer cases and 758,725 related deaths were recorded worldwide, with a global MIR of 0.86. Males had a disproportionately higher burden than females across all levels, and the highest burden was observed in the elderly population. Geographically, the regions with the highest incidence rates included Micronesia, Eastern Asia, and Northern Africa, and the regions with the highest mortality rates included Northern Africa, Southeastern Asia, Eastern Asia, and Micronesia. Notably, Mongolia had a strikingly high burden compared to other countries. The highest MIR was observed in North America and the lowest in Africa. Negative associations of HDI and GNI with liver cancer mortality and MIR were identified, irrespective of sex.Conclusions::The current liver cancer burden underscores the presence of remarkable geographic heterogeneity, which is particularly evident across countries with varying HDI levels, highlighting the urgent need to prioritize health accessibility and availability to achieve health inequities.
10.Relationship between symmetry of lower limb function and gait symmetry in patients with incomplete spinal cord injury
Yiji WANG ; Hongjun ZHOU ; Zejia HE ; Genlin LIU ; Ying ZHENG ; Chunxia HAO ; Bo WEI ; Haiqiong KANG ; Ying ZHANG ; Xiaolei LU ; Yuan YUAN ; Qianru MENG
Chinese Journal of Rehabilitation Theory and Practice 2023;29(6):639-645
ObjectiveTo observe the characteristics of gait symmetry and its influencing factors in patients with incomplete spinal cord injury (ISCI). MethodsFrom May, 2018 to November, 2021, 34 patients with ISCI in Beijing Bo'ai Hospital were divided into symmetrical injury of lower limb (SI) group and asymmetrical injury of lower limb (ASI) group according to the lower extremities motor score (LEMS). Three dimensional motion acquisition system and plantar pressure acquisition system were used for gait test. The symmetry indexes of step length, stance time and swing time were caculated. ResultsThe symmetry indexes of step length, stance time and swing time were significant lower in SI group than in ASI group (|t| > 2.619, P < 0.01). Stance time and swing time significantly correlated to the difference of bilateral LEMS in ASI group (r > 0.468, P < 0.01). Discriminant analysis showed that gait parameter equations were different for patients with different symmetry of lower limb injuries. ConclusionThe symmetry of lower limb motor function impacts gait symmetry for patients with ISCI, especially the difference value of bilateral total LEMS. Gait parameters can be used to determine the symmetry of lower limb injury in patients with ISCI.