The exploration and pilot studies of applying blockchain to drug supply chain show great potential in promoting information sharing, collaboration competence among the actors, regulatory efficiency, and etc. In the future, with the help of blockchain, the optimization of the entire supply chain for orphan drugs is expected to be realized. However, there is no such exploration in China at present. This paper systematically sorts out the whole process of supply chain for orphan drugs and the existing problems of the chain. The article concludes that at present, blockchain is mainly used in the " circulation" and " use" of the drug supply chain. It helps to improve the traceability of drugs, to cope with the problem of counterfeit drugs, to enable actors of the drug supply chain to form a collaborative network in optimizing resource allocation, and to improve the operation and supervision efficiency of the supply chain. In the future, the application faces challenges such as high costs in system conversion, lack of personnel awareness, and incomplete supporting systems. Based on the three dimensions of technology, practice, and research, this paper also looks into the future and suggests for the future use of blockchain in the supply chain of orphan drugs by constructing a practice model, the so called DI-GIVE (Digital, Intelligence, Government′s supervision, Innovation, Views of variety, Evaluation-based) hoping to innovate the supply chain of orphan drugs and to ensure the drug use for the patients with rare diseases in China.

OBJECTIVES: Cervical squamous cell carcinoma is the most common cancer in female reproductive system. This study aims to explore the effect of microRNA-9-5p (miR-9-5p) on the migration, invasion, and epithelial-mesenchymal transition (EMT) process of cervical squamous cells. METHODS: Bioinformatics were used to predict the miRNAs that could bind to E-cadherin (E-cad). The Cancer Genome Atlas (TCGA) database was used to analyze and extract significantly differentially expressed miRNAs from part of cervical squamous cell carcinoma tissues and normal cervical tissues, and miR-9-5p was selected as the main research target. The translated regions (UTR) of wild-type E-cad (E-cad-WT 3'-UTR) or the 3'-UTR of mutant E-cad (E-Cad-MUT 3'-UTR) was transfected with miR-9-5p mimic normal control (NC), and miR-9-5p mimic was co-transfected human embryonic kidney cells (293T). The relationship between miR-9-5p and E-cad was detected by double luciferase assay. The expression of miR-9-5p in normal cervical epithelial cell lines (H8) and cervical squamous cell lines (C33A, siha, caski and Me180) were detected by quantitative real-time PCR. Then, the experiments were divided into groups as follows: a block control group, an overexpression control group (mimic-NC group), a miR-95p overexpression group (mimic group), an inhibitory expression control group (inhibitor-NC group), and a miR-9-5p inhibitory expression group (inhibitor group). The changes of migration ability were detected by scratch assay. Transwell invasion assay was used to analyze the changes of invasion ability, and the mRNA and protein changes of E-cad and vimentin were detected by quantitative real-time PCR and Western blotting. RESULTS: MiR-9-5p had a targeting binding relationship with E-cad. Compared with the normal cervical tissue H8 cell line, the miR-9-5p was highly expressed in cervical cancer cell lines (C33A, siha, caski and Me180) (all P<0.05). The luciferase activity of E-cad-MUT was increased compared with that of E-cad-WT in miR-9-5p mimic cells (P<0.05). Compared with the blank control group, the protein and mRNA expressions of E-cad were decreased in the miR-9-5p mimic group (both P<0.05), which were increased in the miR-9-5p inhibitor group (both P<0.05). Compared with H8 cell line, the miR-9-5p was highly expressed in the cervical squamous cell lines (all P<0.05). Compared with the mimic-NC group, the distance of wound healing, the number of caski and Me180 cells invaded below the membrane, and the mRNA and protein expressions of vimentin were all increased in the miR-9-5p mimic group (all P<0.05), while the mRNA and protein of E-cad were decreased (both P<0.05). Compared with the inhibitor-NC group, the distance of wound healing, the number of caski and Me180 cells invading the membrane, and the mRNA and protein expressions of vimentin were decreased in the miR-9-5p inhibitor group (all P<0.05), but the mRNA and protein expressions of E-cad were increased (both P<0.05). CONCLUSIONS The miR-9-5p is highly expressed in cervical squamous cell carcinoma, which can increase the migration and invasion ability, and promote the EMT process of cancer cells.
Humans ; Female ; Cell Line, Tumor ; Vimentin/metabolism* ; Uterine Cervical Neoplasms/genetics* ; Epithelial-Mesenchymal Transition/genetics* ; MicroRNAs/metabolism* ; Carcinoma, Squamous Cell/genetics* ; Cell Movement/genetics* ; RNA, Messenger ; Cell Proliferation/genetics* ; Gene Expression Regulation, Neoplastic

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.
Female ; Humans ; Uterine Cervical Neoplasms/drug therapy* ; Prospective Studies ; Quality of Life ; Neoplasm Staging ; Chemoradiotherapy ; Chemotherapy, Adjuvant/adverse effects* ; Adjuvants, Immunologic ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Retrospective Studies

With the increased use of phosphodiesterase 5 inhibitors (PDE5Is) over the past years, several population based studies have suggested a potential association between PDE5Is and the risk for specific cancers. This paper systematically summarizes the current status of relatedstudies. Meta-analyses on current research indicated that the use of PDE5Is might be associated with the increased risk for melanoma ( RR=1.11, 95% CI: 1.02-1.22) and basal cell carcinoma ( RR=1.16, 95% CI: 1.13-1.20), but not for prostate cancer ( OR=0.71, 95% CI: 0.40-1.29), and might have chemoprophylaxis effect on colorectal cancer ( RR=0.85, 95% CI: 0.76-0.95). However, results of squamous cell carcinoma were still inconsistent. Further exploration based on the experience and limitations of current research is suggested.

Objective:To understand the research status of occupational health risk assessment in recent ten years.Methods:In April 2020, the literatures related to occupational health risk assessment published by CNKI and Web of Science core collection (WoSCC) databases from 2010 to 2019 were searched, and Excel 2016 software was used to organize the literature, CiteSpace 5.6.R2 software was used for visual analysis.Results:A total of 58 Chinese literatures and 407 English literatures were included. The authors of the high frequency posts were Zhang Meibian, and Alessandro Marinaccio, and the publishing institutions were mainly the National Institute for Occupational Health and Poison Control of Chinese Center for Disease Control and Prevention and Finnish Institute Occupational Health. The Chinese journal with the most articles was Chinese Journal of Industrial Hygiene and Occupational Diseases, and the English journal was Safety Science. Chinese high-frequency keywords mainly included risk assessment, occupational health, occupational exposure. English high-frequency keywords mainly included occupational health, risk, risk factor. The prominent words in Chinese literature were occupational health, coal dust, occupational hazards, occupational health and occupational disease hazards; Risk assessment, worker, exposure, heart disease, cardiovascular disease and so on were prominent words in English literature. Conclusion:The main research keywords in the field of occupational health risk assessment at home and abroad focus on occupational health and risk assessment, but the research direction and focus are slightly different.

Objective:To understand the research status of occupational health risk assessment in recent ten years.Methods:In April 2020, the literatures related to occupational health risk assessment published by CNKI and Web of Science core collection (WoSCC) databases from 2010 to 2019 were searched, and Excel 2016 software was used to organize the literature, CiteSpace 5.6.R2 software was used for visual analysis.Results:A total of 58 Chinese literatures and 407 English literatures were included. The authors of the high frequency posts were Zhang Meibian, and Alessandro Marinaccio, and the publishing institutions were mainly the National Institute for Occupational Health and Poison Control of Chinese Center for Disease Control and Prevention and Finnish Institute Occupational Health. The Chinese journal with the most articles was Chinese Journal of Industrial Hygiene and Occupational Diseases, and the English journal was Safety Science. Chinese high-frequency keywords mainly included risk assessment, occupational health, occupational exposure. English high-frequency keywords mainly included occupational health, risk, risk factor. The prominent words in Chinese literature were occupational health, coal dust, occupational hazards, occupational health and occupational disease hazards; Risk assessment, worker, exposure, heart disease, cardiovascular disease and so on were prominent words in English literature. Conclusion:The main research keywords in the field of occupational health risk assessment at home and abroad focus on occupational health and risk assessment, but the research direction and focus are slightly different.

Total hysterectomy is a treatment for cervical intraepithelial neoplasia Ⅲ (CINⅢ), and its recurrence rate is very small. In recent years, with the development of colposcopy and the increase of postoperative follow-up rate, the detection rate of vaginal intraepithelial neoplasia (VAIN) and vaginal cancer after CINⅢ hysterectomy has increased significantly. In recent years, a number of studies have found that persistent human papillomavirus (HPV) infection is the most important factor leading to the recurrence of vaginal stump after CINⅢ level hysterectomy, so eliminating HPV infection can improve the patient's performance. The prognosis of persistent HPV infection is affected by many factors. The author reviewed the factors related to the clearance of HPV after CINⅢ hysterectomy. The purpose of this study is to provide a theoretical basis for improving the prognosis of patients and delaying the recurrence time after CINⅢ hysterectomy.

This study aimed to investigate the prevalence, clinical characteristics, and prognostic impact of 1p32.3 deletion in patients with newly diagnosed multiple myeloma (MM). A retrospective analysis was conducted on 411 patients with newly diagnosed MM; among which, 270 received bortezomib-based therapies, and 141 received thalidomide-based therapies. Fluorescence in situ hybridization (FISH) was performed to detect six cytogenetic abnormalities, namely, del(1p32.3), gain(1q21), del(17p13), del(13q14), t(4;14), and t(11;14). Results showed that 8.3% of patients with MM were detected with del(1p32.3) and had significantly more bone marrow plasma cells (P = 0.025), higher β2-microglobulin levels (P = 0.036), and higher lactate dehydrogenase levels (P = 0.042) than those without del(1p32.3). Univariate analysis showed that patients with del(1p32.3) under thalidomide-based therapies (median PFS 11.6 vs. 31.2 months, P = 0.002; median OS 16.8 vs. 45.9 months, P < 0.001) were strongly associated with short progression-free survival (PFS) (P = 0.002) and overall survival (OS) (P < 0.001). Multivariate analysis revealed that del(1p32.3) remained a powerful independent factor with worse PFS (P = 0.006) and OS (P = 0.016) for patients under thalidomide-based treatments. Patients with del(1p32.3) under bortezomib-based treatments tended to have short PFS and OS. In conclusion, del(1p32.3) is associated with short PFS and OS in patients with MM who received thalidomide- or bortezomib-based treatments.

Objective To measure the levels of cross-reactive neutralizing antibodies responding to various subtypes of HIV-1 strains in people with HIV-1 infection in Chongqing and to analyze their character-istics.Methods Two hundred and thirty-six plasma samples were collected from patients with chronic HIV-1 infection in Chongqing city.The single-round-infection assay in TZM-bl cells were performed to screen the plasma samples with cross-reactive neutralizing antibodies against various subtypes of HIV-1 strains by using HIV-1 pseudovirus strains and to measure the 50%inhibitory dose ( ID50 ) .Results Eight-een out of 236 (7.63%) plasma samples were able to neutralize various B subtypes and/or C subtypes of HIV-1 pseudovirus strains, among which 15 plasma samples showed the great ability to neutralize pseudovir-us strains of different subtypes.Conclusion The cross-reactive neutralizing antibodies against various sub-types of HIV-1 strains existed in plasma samples collected from people with chronic HIV-1 infection in Chongqing city.

AIM: To investigate whether Programmed death-1 (PD-1) expression on peripheral CD4~+CD25~(nt/hi)CD127~(lo) regulatory T cells (Treg) was associated with disease progression in HIV-1-infected patients. METHODS: Peripheral blood from 108 HIV-1-infected patients in distinct disease progression statuses and 27 healthy individuals were collected in the present investigation. PBMCs were isolated by centrifugation on Ficoll-Hypaque, followed by staining with anti-CD4-PerCP, anti-CD25-FITC, anti-CD127-PE and anti-PD-1-APC. PD-1 expression on Treg was analyzed by four-color staining flow cytometry. CD4~+T cell absolute counts were determined using Multitest CD3/CD4/CD8/CD45 kit and plasma viral loads were detected on NucliSens EasyQ. All data were analyzed using SPSS14.0 software. RESULTS: In peripheral blood of healthy individuals, Treg expressed PD-1 at very low levels (1.72%±0.65%). In contrast, Treg from HIV-1-infected patients showed a significantly increased PD-1 expression (5.33%±2.24%, P<0.01). Moreover, AIDS patients exhibited statistically higher PD-1 expression on Treg (7.87%±2.23%) than newly HIV-1 infected patients (3.22%±1.01%, P<0.05) and patients in progression to AIDS(5.21%±1.72%, P<0.05). PD-1 up-regulation on Treg was closely correlated with reduced CD4~+T cell absolute counts but elevated plasma viral load. CONCLUSION: Overall, we found that PD-1 expression on peripheral Treg was up-regulated and correlated with disease progression in HIV-1-infected patients for the first time. These findings not only extend our understanding of how Treg functions in HIV-1-infected patients but also support the notion that blocking PD-1/PD-L1 interactions may represent a potential therapeutic strategy for HIV-1-infected patients.