Objective: To investigate the natural regression and related factors of high-grade squamous intraepithelial lesion (HSIL) in the cervix of childbearing age women, and to evaluate the applicability of conservative management for future fertility needs. Methods: This study included 275 patients of reproductive age with fertility needs, who were diagnosed as HSIL by biopsy from April 30, 2015 to April 30, 2022, including 229 cases (83.3%) cervical intraepithelial neoplasia (CIN) Ⅱ and 46 cases (16.7%) CIN Ⅱ-Ⅲ. They were followed-up without immediate surgery in the First Affiliated Hospital of Nanjing Medical University. The median follow-up time was 12 months (range: 3-66 months). The regression, persistence and progression of lesions in patients with HSIL were analyzed during the follow-up period, the influencing factors related to regression and the time of regression were analyzed. Results: (1) Of the 275 HSIL patients, 213 cases (77.5%, 213/275) experienced regression of the lesion during the follow-up period. In 229 CIN Ⅱ patients, 180 cases (78.6%) regressed, 21 cases (9.2%) persisted, and 28 cases (12.2%) progressed. In 46 CIN Ⅱ-Ⅲ patients, 33 cases (71.7%) regressed, 12 cases (26.1%) persisted, and 1 case (2.2%) progressed to invasive squamous cell carcinoma stage Ⅰ a1. There was no significant difference in the regression rate between the two groups (χ²=1.03, P=0.309). (2) The average age at diagnosis, age <25 years old at diagnosis were independent influencing factor of HSIL regression in univariate analysis (all P<0.05). There was no significant difference between HSIL regression and pathological grading, the severity of screening results, human papillomavirus (HPV) genotype, colposcopy image characteristics, number of biopsies during follow-up and pregnancy experience (all P>0.05). (3) The median regression times for patients aged ≥25 years and <25 years at diagnosis were 15 and 12 months, respectively. Kaplan-Meier analysis showed that age ≥25 years at diagnosis significantly increased the median regression time compared to <25 years (χ²=6.02, P=0.014). Conclusions: For HSIL patients of childbearing age, conservative management without immediate surgical intervention is preferred if CINⅡ is fully evaluated through colposcopy examination. Age ≥25 years at diagnosis is a risk factor affecting the prognosis of HSIL patients.
Pregnancy ; Humans ; Female ; Adult ; Cervix Uteri/pathology* ; Uterine Cervical Neoplasms/pathology* ; Uterine Cervical Dysplasia/pathology* ; Biopsy ; Colposcopy/methods* ; Squamous Intraepithelial Lesions/pathology* ; Carcinoma in Situ/pathology* ; Papillomaviridae/genetics* ; Papillomavirus Infections/diagnosis* ; Squamous Intraepithelial Lesions of the Cervix/pathology*

Objective To investigate the effect of phenformin combined with hexokinase inhibitor 2-deoxyglucose (2-DG) on the treatment of triple-negative breast cancer cell lines 4T1 and MDA-MB-231. Methods Following treatment with phenformin, 2-DG or phenformin combined with 2-DG on 4T1 and MDA-MB-231 cells for 48 h, the cell proliferation in each group was detected by SRB and the apoptosis of cells was detected by flow cytometry. The concentration of glucose and lactic acid in cell culture supernatant was detected by ELISA. The activity of mitochondrial respiratory chain complex Ⅰ was detected by FlexStation3 and the mitochondrial oxygen consumption (OCR) was assayed with the Seahorse X Fe Analyzer. Results The hexokinase expression (4.6±0.17,3.73±0.21), glucose consumption (356±31，397±42) μg/10⁵ cells , Lactic acid concentration (5.59±0.52, 7.83±0.78) μmol/L in the supernatant of 4T1 and MDA-MB-231 cells in Phenformin group were higher than that in control group ( 1±0.15，1±0.12 ) , ( 289±25，301±32) μg/10⁵cells , ( 2.37±0.18，4.01±0.45) μmol/L (P < 0.01). Even if the dose was reduced by 90%, the cell viability of phenformin combined with 2-DG group (64.63±2.28, 51.97±2.29) % was still higher than that of phenformin group (86.70±1.83, 85.53±1.46) % (P<0.001). The combination of the two drugs significantly promoted the apoptosis of 4T1 and MDA-MB-231. In addition, compared with the phenformin group (5.59±0.52, 7.83±0.78) μmol/L, the phenformin combined with 2-DG group (3.46±0.37, 5.18±0.62) μmol/L cell lactic acid production also greatly reduced (P<0.01). Compared with the phenformin or 2-DG single-drug group, the phenformin combined with 2-DG group can significantly inhibit the growth rate of tumors in tumor-bearing mice (P<0.01). The median survival time of tumor-bearing mice in the phenformin combined with 2-DG group was 72.5 d, which was higher than that in the phenformin group 57 d and 2-DG group 55.5 d (P<0.01). Conclusion Hexokinase inhibitor 2-DG significantly enhances the therapeutic effects of phenformin on triple-negative breast cancer cells.

To develop a magnetic nanoparticle chemiluminescence immunoassay (CLIA) for the determination of type Ⅰ procollagen N-terminal peptide (PINP) in human serum, we expressed a recombinant PINP-α1 protein in Corynebacterium glutamicum and used it as an immunogen to immunize BALB/c mice. We obtained three hybridoma cell lines that stably secret antibody against PINP-α1 protein. After further pairing and screening, we chose a monoclonal antibody 8C12 coupled with biotin as the capture antibody, and a monoclonal antibody 1F11 labeled horseradish peroxidase as the detection antibody. The antibodies combined with the serum samples, forming a sandwich complex which was used to detect the concentration of PINP in serum. After optimizing the conditions, we determined that the best working concentration of the capture antibody and the detection antibody were 3 μg/mL, and the incubation time was 30 minutes. The quantitative assay had a detection range of 5-1 100 ng/mL, with recovery rates between 93%-107% and the minimum detection limit of 1.22 ng/mL achieved. The intra-and inter-assay precisions were lower than 10%. The correlation coefficient of PINP results between this CLIA method and the Roche electrochemiluminescence immunoassay system was 0.906 2. Therefore, this CLIA method is specific and can be used to quantitatively detect the content of PINP in serum, which has the potential to become an auxiliary approach for bone disease examination.
Animals ; Humans ; Immunoassay ; Luminescence ; Mice ; Mice, Inbred BALB C ; Peptide Fragments/isolation & purification* ; Procollagen/isolation & purification*

Objective To explore the spatio-temporal characteristics of Oncomelania hupensis snails along the Danyang section of the Beijing-Hangzhou Grand Canal and the Danyang-Jintan-Liyang Canal, so as to provide scientific evidence for the dynamic assessment of the risk of snail spread in this region. Methods O. hupensis snail status was collected in the plain regions with waterway networks in the study area from 2012 to 2017. The spatio-temporal variations of snail distribution were investigated along the Danyang section of the Beijing-Hangzhou Grand Canal and the Danyang-Jintan-Liyang Canal using buffer zone analysis, spatial autocorrelation, hotspot analysis and standard deviational ellipse with the geographical information system (GIS) tools. Results The number of snail habitats showed a tendency towards a rise in the study area from 2012 to 2017, and snail habitats were predominantly distributed in the 1 000 m long buffer zone of the Danyang-Jintan-Liyang Canal, notably along the Jiuqu River at the junction between the Beijing-Hangzhou Grand Canal and the Danyang-Jintan-Liyang Canal. The distribution of snail habitats appeared spatial autocorrelations in 2014, 2016 and 2017, and the hotspot areas were mainly identified at the junction between the Danyang-Jintan-Liyang Canal and the Beijing-Hangzhou Grand Canal. In addition, the overall distribution of snail habitats was located in the northeastern-southwestern part of the study aera, and gradually shifted to the southern and northern parts with the time. Conclusions The spatial distribution of O. hupensis snails is complex along the Danyang section of the Beijing-Hangzhou Grand Canal and the Danyang-Jintan-Liyang Canal, and there is a risk of snail spread from the upper reaches to the lower reaches, where snail control needs to be intensified.

Objective To investigate the protective effect of excretory-secretory protein (AES) from adult Trichinella spiralis on ovalbumin (OVA)-induced allergic rhinitis in mice. Methods Eighteen female BALB/c mice were randomly divided into three groups, including the blank control group (Group A), OVA-induced rhinitis group (Group B) and AES treatment group (Group C). Mice in Group A were given PBS. Mice in Group B were intraperitoneally injected with antigen adjuvant suspension for systemic sensitization, once every other day for seven times; then, local excitation was intranasally induced with 5% OVA solution once a day for seven times to establish a mouse model of allergic rhinitis. In addition to induction of allergic rhinitis, mice in Group C were given 25 μg AES at baseline sensitization and local excitation. Following the final challenge, mice were observed for 30 min in each group, and the behavioral score was evaluated. The serum levels of IFN-γ, IL-4, IL-5, IL-10 and TGF-β were determined using an enzyme-linked immunosorbent assay in mice, and the pathological changes of mouse nasal mucosa were observed under a microscope. Results There was a significant difference in the mouse behavioral scores among the three groups (F = 110.12, P < 0.01). The mouse behavioral score was significantly higher in Group B than in Group A (7.17 ± 0.75 vs. 1.33 ± 0.52, P < 0.01), and more remarkable pathological damages of mouse nasal mucosa were seen in Group B than in Group A, while the mouse behavioral score was significantly decreased in Group C than in Group B (P < 0.01), and the pathological damages of mouse nasal mucosa remarkably alleviated in Group C relative to Group B. There was a significant difference in serum IFN-γ level among the three groups (F = 7.50, P < 0.01) and the serum IFN-γ level in Group B was significantly lower than in group A and C (both P < 0.05). There were significant differences in serum IL-4 (F = 470.81, P < 0.01) and IL-5 levels (F =68.20, P < 0.01) among the three groups, and significantly greater serum IL-4 and IL-5 levels were detected in Group B than in Group A (P < 0.01), while significantly lower serum IL-4 and IL-5 levels were detected in Group C than in Group B (P < 0.01). There were significant differences in serum IL-10 (F = 174.91, P < 0.01) and TGF-β levels (F = 9.39, P < 0.01) among the three groups, and significantly greater serum IL-10 and TGF-β levels were seen in Group C than in Group B (both P < 0.05). Conclusion T. spiralis AES has a remarkable protective activity against OVA-induced allergic rhinitis in mice.

Objective To investigate the spatio-temporal characteristics of Oncomelania hupensis snails along the Jiangsu section of the Yangtze River, so as to provide evidence for eliminating schistosomiasis and formulating precision control measures in Jiangsu Province. Methods A total of 75 marshlands were randomly sampled from Nanjing, Zhenjiang and Yangzhou cities along the Jiangsu section of the Yangtze River basin, and the spatio-temporal distribution and changing patterns of O. hupensis snails were investigated using the spatial autocorrelation analysis, kernel density analysis and hotspot analysis during the period from 2015 through 2017. Results There was a spatial autocorrelation in the mean snail density along the Jiangsu section of the Yangtze River basin during the period from 2015 through 2017. The number of living snails and the density of living snails showed an overall decline in Yangzhou City; however, both showed a slight increase in 2016. Kernel density analysis and hotspot analysis showed that the hotspots of living snails were located in the regions neighboring the marshlands at the Yangzhou-Zhenjiang boundary areas along the Jiangsu section of the Yangtze River basin. Conclusion There is a spatial autocorrelation in the snail distribution with hotspots along the Jiangsu section of the Yangtze River basin, and the surveillance of snails should not be neglected in the marshlands in Jiangsu Province.

Objective To understand the status of grass-roots schistosomiasis control professionals in Jiangsu Province, so as to provide scientific evidence for the rational resource allocation and the improvement of capability building. Methods A cross-sectional survey was conducted by telephone interview and e-mail among city- and county-level disease prevention and control institutions that undertook schistosomiasis control activities in Jiangsu Province, and the age, educational background, major, duration of working, professional title and professional capability were descriptively analyzed. Results There were totally 274 fulltime schistosomiasis control professionals working at grass-roots institutions in Jiangsu Province, with a mean age of (43.19 ± 9.47) years. The least professionals were below 30 years of age (12.77%, 35/274), and the most professionals were aged from 41 to 50 years (36.86%, 101/274). Among the 274 professionals, 43.07% (118/274) had duration of working of less than 10 years, 62.04% (170/274) had a bachelor degree, and 40.88% (112/274) had the medium-level professional title. Conclusions A schistosomiasis control team with a relatively high academic degree and professional title has been built at the grassroot level in Jiangsu Province. However, capability building remains to be improved through the participation of more young professionals and professional training with adaptation to local conditions.

The cornerstone of antimalarial treatment, artemisinin, has reduced malaria associated morbidity and mortality worldwide. However, Plasmodium falciparum parasites with reduced sensitivity to artemisinin have emerged, and this threatens malaria control and elimination efforts. In this minireview, we describe the initial development of artemisinin as an antimalarial drug, its use both historically and currently, and our current understanding of its mode of action and the mechanisms by which malaria parasites achieve resistance.

Background Researches showed that elevatory blood glucose level results in long-term damage of cells and tissue,or metabolic memory phenomenon,and manipulation of hyperglycemic memory is a good approach in the prevention of diabetic complications.However,its mechanism is not clear.It is speculated that the pathogenesis of diabetic retinopathy (DR) in diabetic patients may be associated to related mechanisms.Uncoupling proteins (UCPs) can decrease the production of reactive oxygen species (ROS),which may be related to DR.Objective This study was to explore the association between DR and the single nucleotide polymorphisms (SNPs) of UCP genes in Chinese Han population with type 2 diabetes.Methods A cross-sectional study was performed.This study was approved by Ethic Committee of Affiliated First Hospital of Shanghai Jiao Tong University and complied with Declaration of Helsinki,and written informed consent was obtained from each subject prior to any medical examination.One thousand eight hundreds and seventy-five patients with type 2 diabetes mellitus were enrolled in Xinjing district of Shanghai city by cluster sampling from November 2014 to January 2015.The demographic and medical baseline characteristics,ocular examination and laboratory tests were obtained and periphery blood of 2 ml was collected for extraction of DNA.Eight tag SNPs of UCP1,three tag SNPs of UCP2,and seven tag SNPs of UCP3 were selected as marker locus for the detection of genotype by Sequenom Mass ARRAY.Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry platform were used for genotyping.Hardy-Weinberg equilibrium (HWE) analysis,allele and genotype frequencies,haplotype analysis,and association tests for DR and SNPs were performed by SAS and SHEsis software.Results A total of 530 DR patients were checked out from 1 875 subjects with type 2 diabetes mellitus,with the detection rate of 28.27％.rs660339 locn of UCP2 gene and rs1626521,rs668514 locus of UCP3 gene appeared to have low detectable rates,and the secondary allele base frequency of rs632862 in UCP2 gene was ＜0.01 and rs15763 of UCP3 gene was unmatched with HWE,therefore,these locus analysis was not included.In 13 SNPs locus included in the analysis,only 2 SNPs of UCP1 gene were related to DR.Compared with the non-diabetic retinopathy (NDR) patients,the G allele frequency of rs10011540 was increased (P =0.03,OR =1.31,95 ％ confidence interval[CI] =1.03-1.67,and T allele frequency of rs3811787 was decreased (P=0.04,OR=0.86,95％ CI=0.75-0.99) in DR patients.Genotyping detection showed that the C/C and A/A frequencies of rs3811790 in UCP1 gene were significantly more and C/A frequency was less in DR patients than those in NDR patients (all at P＜0.01).The logistic regression analysis indicated an association of SNPs of rs10011540 and rs3811787 with DR independent from glucose and disease duration.Conclusions The SNPs of rs10011540 and rs3811787 locus in UCP1 gene are associated with DR in Chinese type 2 diabetes patients.

China ; Female ; Hepatitis A Vaccines ; administration & dosage ; Hepatitis B ; prevention & control ; Hepatitis B Vaccines ; administration & dosage ; Humans ; Male ; Vaccination ; methods ; Vaccines, Combined ; administration & dosage