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Shidong Tan,1 Guangyao Zang,1 Ying Wang,1 Zhen Sun,1 Yalan Li,1 Cheng Lu,2 Zhongqun Wang1 1Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of China; 2General Office, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of ChinaCorrespondence: Cheng LuGeneral Office, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, 212001, People’s Republic of China, +86 511 88986902Email jdfylz@sina.comZhongqun WangDepartment of Cardiology, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, 212001, People’s Republic of ChinaTel +86 511 85030586Email wangtsmc@126.comAbstract: Angiogenesis, as a process occurring under the regulation of a variety of factors, is one of the important ways of vascular development. It coexists in a variety of pathological and physiological processes. Now a large number of studies have proved that tumor growth, metastasis, and various vascular complications of diabetes are closely related to angiogenesis, and an increasing number of studies have shown that there are many common factors between the two. But angiogenesis is the opposite of the two: it is enhanced in tumors and suppressed in diabetes. Therefore, this review discusses the causes of the phenomenon from the expression of various factors affecting angiogenesis in these two diseases and their effects on angiogenesis in the relevant microenvironment, as well as the application status of these factors or cells as therapeutic targets in the treatment of these two diseases.Keywords: diabetes mellitus, tumor, angiogenesis, differences, tumor microenvironment, hypoxia

Yuanjun Cheng, 1 Yongbing Chen, 2 Guohui Zang, 1 Bin Chen, 1 Jie Yao, 1 Wenguang Zhang, 1 Haibing Wang, 1 Liu Yu, 1 Pinghai He, 1 Youming Zhang, 1 Hanqing Wu 1 1Department of Cardiothoracic Surgery, People’s Hospital of Chizhou, Chizhou, People’s Republic of China; 2Department of Thoracic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of ChinaCorrespondence: Yuanjun Cheng3 Baiya Road, Guichi District, Chizhou 247000, Anhui Province, People’s Republic of ChinaEmail cyjlfqr1985@163.com Background: The most common cancer among humans is lung cancer. Non-small cell lung cancer (NSCLC) comprises the majority of these cases. In the development and progression of cancers across the spectrum, tumor abnormal protein (TAP) plays crucial roles. Additionally, in the advancement of the bladder and colorectal cancers, the involvement of glycoproteins like TAP is present. However, it is worth noting that current literature has yet to clarify the clinical significance of the TAP in NSCLC.Methods: In the present study, to evaluate the relative level of TAP, we utilized a TAP detection agent in 154 cases of NSCLC and normal patients who underwent surgical resection anytime from March 2013 to January 2019 at the People’s Hospital of Chizhou.Results: Our results demonstrated that in NSCLC patients, the expression level of TAP was significantly higher than in normal patients. Moreover, after surgery, TAP expression was significantly downregulated in NSCLC patients. TAP expression is associated with an array of factors, which include the patient’s sex, history of smoking use, tumor size, pTNM, distant cancer, metastasis of lymph nodes, invasive and aggressive indicator pleural invasion, and differentiation degree of NSCLC. Additionally, TAP has no association with the patient’s age, history of drinking, location of the tumor, hypertension, and diabetes. In NSCLC patients, a poor overall survival rate within 5 years is significantly correlated with the increased TAP expression. For NSCLC patients, an independent prognostic factor is the TAP, which is confirmed using the multivariate survival analysis.Conclusion: In the malignant progression of NSCLC, our results demonstrate how the promoting role of the upregulated TAP expression takes place. Hence, a therapeutic aim for NSCLC and a potential biomarker for NSCLC progress is a TAP.Keywords: tumor abnormal protein, TAP, lung, cancer, prognosis, predictive

Tingting Li, Mengjiao Lv, Xiaohua Chen, Yongsheng Yu, Guoqing Zang, Zhenghao TangDepartment of Infectious Disease, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, People’s Republic of ChinaPurpose: Plumbagin is thought to be a bioactive phytochemical drug and exerts an antitumor effect on various cancers. However, few studies focus on the antitumor activity of plumbagin on liver cancer. This study first investigated the antitumor activity of plumbagin on liver cancer and further investigated the molecular mechanism of its antitumor activity against hepatocellular carcinoma, both in vitro and in vivo.Methods: The antiproliferative activity of plumbagin was evaluated through CCK-8, EdU, and colony forming test. The cell cycle and apoptosis were then analyzed by flow cytometer. Western blot was used to detect the expression of apoptosis related protein, SIVA, and mTOR pathway. RNA-seq was performed to determine the gene expression profiles and overexpressed or knocked down SIVA to validate its role in plumbagin’s antitumor activity. Regarding animal experiment, a xenograft model in BALB/c nude mice was built using LM3-Luci cells. Then bioluminescence imaging and further immunohistochemistry were performed to study the antitumor activity and the expression of SIVA and mTOR in the plumbagin-treated group.Results: Plumbagin can inhibit proliferation and induce apoptosis of liver cancer cells in vitro. Further experiment demonstrated that plumbagin could inhibit the expression of SIVA and subsequently downregulate the mTOR signaling pathway, and upregulating the expression of SIVA will alleviate the antitumor activity of plumbagin on liver cancer, which confirmed the important role of the SIVA/mTOR signaling pathway in the antitumor activity of plumbagin. In vivo bioluminescence imaging showed a decreased signal in the plumbagin-treated group, and further immunohistochemistry demonstrated that plumbagin could inhibit the SIVA/mTOR signaling pathway in tumor tissues.Conclusion: Our promising results showed that plumbagin could inhibit proliferation and induce apoptosis of hepatic cancer through inhibiting the SIVA/mTOR signaling pathway for the first time, which indicated that plumbagin might be a good candidate against liver cancer.Keywords: hepatocellular carcinoma, plumbagin, antitumor, apoptosis, SIVA, mTOR

Yongxue Zhao, Long Wang, Mina Yan, Yanling Ma, Guangxi Zang, Zhennan She, Yihui DengCollege of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, People’s Republic of ChinaAbstract: Surface modification of nanocarriers with amphiphilic polymer polyethylene glycol (PEG), known as PEGylation, is regarded as a major breakthrough in the application of nanocarriers. However, PEGylated nanocarriers (including liposomes and polymeric nanoparticles) induce what is referred to as the “accelerated blood clearance (ABC) phenomenon” upon repeated injection and consequently they lose their sustained circulation characteristics. Despite this, the present authors are not aware of any reports of accelerated clearance due to repeated injection for PEGylated solid lipid nanoparticles (SLNs), another promising nanocarrier. This study investigated the pharmacokinetics of PEGylated SLNs upon repeated administration in mice; moreover, the impact of circulation time on the induction of the ABC phenomenon was studied in beagles for the first time. The ABC index, selected as the ratio of the area under the concentration-time curve from time 0 to the last measured concentration of a second injection to that of the first injection, was used to evaluate the extent of this phenomenon. Results showed that the PEGylated SLNs exhibited accelerated clearance from systemic circulation upon repeated injection, both in mice and in beagles, and the ratio for the different time intervals, which showed that the ABC index exhibited significant difference within 30 minutes following the second injection, was good enough to evaluate the magnitude of ABC. This ABC index indicated that the 10 mol% PEG SLNs with a suitable prolonged circulation time induced the most marked ABC phenomenon in this research. This study demonstrated that, like PEGylated nanocarriers such as liposomes and polymeric nanoparticles, PEGylated SLNs induced the ABC phenomenon upon repeated injection – the beagle was a valuable experimental animal for this research. Furthermore, the authors considered that a relatively extended circulation time of the initial dose may be the underlying major factor determining the induction of the ABC phenomenon.Keywords: SLNs, polyethylene glycol, ABC phenomenon, circulation time

BackgroundHepatitis C virus (HCV) testing and counselling have the potential to impact individual behaviour and transmission dynamics at the population level. Evidence of the impact of an HCV-positive status notification on injection risk reduction is limited. The objective of our study was to (1) assess drug and alcohol use and injection risk behaviours following notification; (2) to compare behaviour change in people who inject drugs (PWID) who received a positive test result and those who remained negative; and (3) to assess the effect of age on risk behaviour.MethodsData from the International Collaboration of Incident HIV and HCV Infection in Injecting Cohorts (InC3 Study) were analysed. Participants who were initially HCV seronegative were followed prospectively with periodic HCV blood testing and post-test disclosure and interview-administered questionnaires assessing drug use and injection behaviours. Multivariable generalised estimating equations were used to assess behavioural changes over time.ResultsNotification of an HCV-positive test was independently associated with a small increase in alcohol use relative to notification of a negative test. No significant differences in postnotification injection drug use, receptive sharing of ancillary injecting equipment and syringe borrowing postnotification were observed between diagnosis groups. Younger PWID receiving a positive HCV test notification demonstrated a significant increase in subsequent alcohol use compared with younger HCV negative.ConclusionsThe proportion of PWID reporting alcohol use increased among those receiving an HCV-positive notification, increased the frequency of alcohol use postnotification, while no reduction in injection drug use behaviours was observed between notification groups. These findings underscore the need to develop novel communication strategies during post-test notification to improve their impact on subsequent alcohol use and risk behaviours.

OBJECTIVE: A retrospective study was conducted to investigate the efficacy of azelastine nasal spray combined with mussel mucin in the treatment of allergic rhinitis (AR) and the effects of CCL26 and CC chemokine receptor-3 (CCR3). PATIENTS AND METHODS: A total of 80 patients with AR admitted to our hospital from March 2020 to March 2022 were included as the research objects. All subjects were divided into two groups according to the different therapeutic strategies by reviewing the patient's treatment. The control group (n = 40) was given azelastine nasal spray, while the study group (n = 40) was treated with a combination of mussel mucin and azelastine nasal spray. The clinical efficacy, clinical symptoms, and sleep quality improvement of the two groups were calculated and compared retrospectively. The serological indexes were compared, and the incidence of adverse reactions between the two groups was calculated retrospectively based on the patient's medical records. RESULTS: In the study and control groups, the effective rate was 95.00% and 72.50%. After treatment, the symptom scores of nasal congestions, nasal itching, sneezing, and runny nose and the total score of Pittsburgh sleep quality index (PSQI) in the study group were remarkably less. After treatment, the serum levels of sVCAM-1, interleukin-4 (IL-4), and immunoglobulin E (IgE) were decreased, and the levels of IL-12 were upregulated. Following treatment, Minimum nasal cross-section (NMCA) and total nasal resistance (TNR) at 75Pa in the study group were reduced more noticeably (p < 0.05). After treatment, the expression levels of CCL26 and CCR3 in peripheral blood were significantly decreased. In the control and study groups, the incidence of adverse reactions was 7.50% and 10.00%. CONCLUSIONS: Azelastine nasal spray combined with mussel mucin is effective in the treatment of allergic rhinitis, which can effectively improve patients' clinical symptoms, alleviate nasal ventilation disorders, reduce inflammatory reactions, and improve sleep quality. This strategy of combined treatment is safe and, therefore, worth advocating. [ABSTRACT FROM AUTHOR]

Background: Adipose‐derived stem cells have been considered as a promising therapy for erectile dysfunction. However, the therapeutic efficacy of adipose‐derived stem cell‐based therapy requires improvement. Objective: To determine whether the inhibition of phosphodiesterase type 5 in adipose‐derived stem cells would improve stem cell therapy for rats with diabetes‐induced erectile dysfunction. Materials and Methods: A phosphodiesterase type 5 siRNA was incorporated into lentiviral vectors and transduced into adipose‐derived stem cells. The mRNA and protein levels of phosphodiesterase type 5 were evaluated. Three days after transduction, the adipose‐derived stem cell supernatant was collected to determinate the levels of insulin‐like growth factor 1 and vascular endothelial growth factor. Streptozotocin‐induced diabetic rat models were established and used for comparative analysis of 1‐ and 2‐week treatment regimens with intracavernosal injection of adipose‐derived stem cells or Lv‐siPDE5‐modified adipose‐derived stem cells. Results: Lv‐siPDE5‐ADSCs secreted more insulin‐like growth factor 1 and vascular endothelial growth factor in supernatants than unmodified adipose‐derived stem cells. Preconditioned Adipose‐derived stem cells‐treated diabetic rats showed consistently superior erectile function when compared with non‐preconditioned adipose‐derived stem cells after 2 weeks of treatment. Lv‐siPDE5‐ADSCs provided additional benefits in recovery of cavernous structures with rapid effects (1 week) when compared to plain adipose‐derived stem cells. These features were associated with the significantly increased levels of insulin‐like growth factor 1 and vascular endothelial growth factor in Lv‐siPDE5‐ADSC‐treated diabetic rats. Conclusions: Adipose‐derived stem cell therapy could serve as an alternate approach for diabetes‐induced erectile dysfunction, albeit with a long onset period. In vitro preconditioning of adipose‐derived stem cells could accelerate the functional and structural recovery in vivo, indicating that preconditioning by inhibition of phosphodiesterase type 5 may improve adipose‐derived stem cells therapy following diabetes‐induced erectile dysfunction. [ABSTRACT FROM AUTHOR]