Unveiling the Complex World of Extracellular Vesicles: Novel Characterization Techniques and Manufacturing Considerations / 전남의대학술지

Extracellular vesicles (EVs) function as potent mediators of intercellular communication for many in vivo processes, contributing to both health and disease related conditions. Given their biological origins and diverse functionality from correspondingly unique “cargo” compositions, both endogenous and modified EVs are garnering attention as promising therapeutic modalities and vehicles for targeted therapeutic delivery applications. Their diversity in composition, however, has revealed a significant need for more comprehensive analytical-based characterization methods, and manufacturing processes that are consistent and scalable. In this review, we explore the dynamic landscape of EV research and development efforts, ranging from novel isolation approaches, to their analytical assessment through novel characterization techniques, and to their production by industrial-scale manufacturing process considerations. Expanding the horizon of these topics to EVs for in-human applications, we underscore the need for stringent development and adherence to Good Manufacturing Practice (GMP) guidelines. Wherein, the intricate interplay of raw materials, production in bioreactors, and isolation practices, along with analytical assessments compliant with the Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines, in conjunction with reference standard materials, collectively pave the way for standardized and consistent GMP production processes.

Characteristics of HIV-infected persons without long term disease progress and related factors in Guangxi Zhuang Autonomous Region / 中华流行病学杂志

Objective: To understand the characteristics of HIV infected persons without long term disease progress [also known as long term non-progressors (LTNPs)], and related factors in Guangxi Zhuang Autonomous Region (Guangxi). Methods: Data of persons living with HIV and receiving no antiretroviral therapy in Guangxi by the end of 2016 were collected from the national HIV/AIDS comprehensive control and prevention information system of China. Results: By the end of 2016, there were 313 LTNPs in Guangxi, accounting for 2.3% of those being reported for more than 10 years, 5.4% of those being reported for more than 10 years and surviving, and 26.6% of those being reported for more than 10 years, surviving and receiving no antiretroviral therapy. Among the LTNPs, 87.2%(273) were men, 94.9% (297) were aged ≤ 40 years, 32.3% (101) were farmers, 55.6% (174) were single, divorced or widowed, 69.3% (217) were of Han ethnic group, 68.1% (213) were injecting drug users, and 52.1% (163) were from custody facilities. Multiple logistic regression analysis indicated that factors associated with delayed disease progression included age ≤40 years (compared with age >40 years, aOR=1.55, 95%CI: 1.31-3.12) and injection drug use (compared with sexual transmission, aOR=1.23, 95%CI: 1.10-1.74). Conclusions: A number of LTNPs existed in HIV-infected individuals in Guangxi. Further research are needed to identify the related factors, and it is necessary to conduct large sample size studies on host immunology, genetics and the virology of HIV to explore the related mechanism.

Effect of comprehensive intervention on hypertension control program in workplaces in China / 中华流行病学杂志

Objective: To evaluate the effect of comprehensive intervention program on hypertension control in workplaces in China. Methods: The study design was a non-randomized controlled trial. First, 20 sub-centers were selected across China, then hypertension patients in 2-4 workplaces were selected as the intervention group, and hypertension patients in 1 comparable workplace selected, as the control group in each sub-center. The comprehensive intervention strategy which integrating workplace primary prevention of cardiovascular diseases and standardized management of hypertension was adopted in the intervention group for at least 2 years. Patients in the control group continued their usual health care, and only baseline data and 2-year data was collected. Analyses were conducted for hypertension patients in 30 stated-owned enterprises (SOEs), including 20 for the intervention group and 10 for the control group. The primary outcome was the control rate ofhypertension while the intervention effect (IE) was estimated by using the formula: differential value of intervention group[rate (mean)]-differential value of control group[rate (mean)]. Results: Overall, 2 622 patients completed the 2-year follow-up, of which 2 055 were in the intervention group and 567 in the control group, respectively. After 2 years of intervention, the IE on the level of SBP and DBP for intervention group and control group were-7.5 and-3.9 mmHg, respectively (P<0.05). BMI decreased by 0.4 kg/m(2), with the regular exercise rate as 36.4% and alcohol consumption rate decreased by 14.0%, respectively (P<0.05). The smoking rate decreased by 6.1% (P>0.05). The overall hypertension control rate was 25.0%, and further subgroup analysis showed that our intervention program was particularly effective for those with high education level (27.6%), white-collar employees (41.9%), and those from SOEs whose affiliated hospital had been separated away (41.9%). Conclusion: The comprehensive intervention program could greatly improve the hypertension control in the workplaces in China.

Dynamic variations of BMI and influencing factors among HIV/AIDS patients receiving highly active antiretroviral therapy in Liuzhou, Guangxi Zhuang Autonomous Region, 2013-2014 / 中华流行病学杂志

Objective: To understand the dynamic variation of BMI and influencing factors among HIV/AIDS patients receiving highly active anti-retroviral therapy (HAART) in Liuzhou, Guangxi Zhuang Autonomous Region (Guangxi). Methods: HIV/AIDS patients receiving HAART for the first time since 1 January 2013 were selected. Data on BMI was analyzed among patients receiving HAART at baseline,6 months and 12 months after treatment. By using the general linear model repeated measures of analysis of variance, BMI dynamic variations and influencing factors were described and analyzed. Results: The average BMI of 2 871 patients at baseline, 6th months and 12th months appeared as (20.65±3.32), (20.87±3.22) and (21.18±3.20), respectively, with differences all statistically significant (F=18.86, P<0.001). BMI were increasing over time with treatments (F=37.25, P<0.001). Main influencing factors were noticed as: age, sex, marital status, baseline data of CD(4)(+)T cells and the WHO classification on clinical stages. Conclusions: Higher proportion of BMI malnutrition counts was seen among patients before receiving HAART in Liuzhou. BMI of the patients that were on HAART seemed being influenced by many factors. It is necessary to select appropriate treatment protocols on different patients so as to improve the nutritional status of the patients.

Relationship between daily exposure to bisphenol A and male sexual function-a study from the reproductive center / 中华流行病学杂志

Objective: To explore the relationship between male sexual function and daily exposure to bisphenol A (BPA) at a reproductive center in Taiyuan. Methods: Male patients who were seeking treatment of infertility due to problems caused by either of the spouse were selected from the Shanxi reproductive center between September 2014 and April 2015. Information on general characteristics, sexual function and fasting venous blood samples were collected. Total scores of sexual function were evaluated by Delphi expert scoring method. Levels of serum BPA were measured by high-performance liquid chromatography. Data was analyzed by Spearman rank correlation, rank sum test, multivariate logistic regression analysis and χ(2) trend test. Relationship between BPA and sexual function was presented as OR and corresponding 95%CI. Results: Among the 353 participants, 45.0% was defined as sexual dysfunction with low sexual desire (47.3%) as the major reason. BPA was detected in all the 353 patients, with a range of concentration as 0.38-21.93 ng/ml and an average as 5.79 ng/ml. Results from the Spearman rank correlation analysis revealed significant negative correlations between serum BPA and sexual function, sexual desire, erectile ability and ejaculation intensity, while serum BPA was positively correlated with premature ejaculation. According to the four percentile of BPA concentration (ng/ml), the subjects were divided into four groups. Compared with the low concentration group (0.38-3.79 ng/ml), the risk of sexual dysfunction significantly increased in the groups with higher BPA levels. Particularly, in the highest BPA group (8.68-21.93 ng/ml), more obvious effects were seen on sexual dysfunction (OR=1.55, 95%CI:1.00-3.23), reduced sexual desire (OR=4.75, 95%CI: 2.44-9.22), reduced erection ability (OR=2.40, 95%CI: 1.18-4.88), reduced ejaculation intensity (OR=2.53, 95%CI: 1.25-5.16) and premature ejaculation (OR=1.95, 95%CI: 1.02-3.72). Conclusion: Low sexual desire appeared as the main type of male sexual dysfunction, the exposure to higher levels of BPA in daily life might lead to male sexual dysfunction.

Epidemiologic survey on the prevalence and distribution of infants' common gastrointestinal symptoms in 7 cities in China: a population-based study / 中华流行病学杂志

Objective: Regurgitation, infantile colic, and functional constipation are common gastrointestinal symptoms in childhood, the aim of this study was to explore the prevalence and distribution of these symptoms in China. Methods: A screening program in infants aged 0 to 3 years selected through stratified cluster random sampling was carried out in 7 cities in China. Questionnaires were filled, and then diagnosis were made according to Rome Ⅳ criteria. Areas, (urban-rural), age and gender distribution of prevalence of childhood common gastrointestinal symptoms were analyzed. Results: Totally, 20 932 effective questionnaires were returned. The total number of infants aged 0 to 1 years was 10 193. Regurgitation was diagnosed in 1 960 infants, with the prevalence of 19.2%, among infants aged 0 to 3 months that had highest prevalence (29.8%). The prevalence decreased with age, and differences among different age groups showed significant. For infantile colic, 4 470 infants aged 0 to 5 months were analyzed and the prevalence of infantile colic was 7.3%. The prevalence of infantile colic was the highest in infants aged 1 to 2 months (10.0%). Age specific difference was significant. Of all the infants, functional constipation was diagnosed in 1 755 infants with the prevalence of 8.4%, and the lowest prevalence was found in infants aged 0 to 3 months (6.2%), and the highest prevalence was in infants aged 30 to 36 months (10.0%). The differences in different age group were significant. Conclusion: Symptoms of regurgitation, infantile colic, and functional constipation are common in infants in China, with age specific difference in prevalence of the symptoms.

Effect of baseline CD(4)(+) T cell count on drop-out of antiretroviral therapy in HIV infected persons in Guangxi Zhuang Autonomous Region, 2008-2015 / 中华流行病学杂志

Objective: To investigate the effect of baseline CD(4)(+) T cell count (CD(4)) on drop-out of antiretroviral therapy (ART) in HIV infected persons. Methods: Retrospective cohort was conducted in this study. HIV infected persons aged≥18 years and receiving free ART for the first time in Guangxi Zhuang Autonomous Region (Guangxi) from 2008 to 2015 were selected from the antiretroviral treatment database of National Comprehensive HIV/AIDS Information System, with follow-up conducted till May 30, 2016. Cause-specific Cox proportional hazard models were used to evaluate effect of different CD(4) on the drop-out of ART in the HIV infected persons. Results: A total of 58 502 eligible study participants were included in this retrospective cohort study. The average drop-out ratio was 4.8/100 person-years. After controlling the following baseline covariates: age, sex, marital status, route of HIV infection, WHO clinical stage before ART, initial/current ART regiment, ART regiment adjustment, and year of initiating ART for potential confounding, the adjusted HR of drop-out for HIV infected persons with 200- cells/μl, 351-cells/μl and ≥500 cells/μl were 1.110 (95%CI: 1.053-1.171, P<0.001), 1.391 (95%CI: 1.278-1.514, P<0.001) and 1.695 (95%CI: 1.497-1.918, P<0.001), respectively, in risk for drop-out compared with those with baseline CD(4)<200 cells/μl. Among the HIV infected persons, 56.0% (1 601/2 861) of drug withdrawal was due to poor compliance with medication. Conclusions: With the increase of baseline CD(4) when initiating ART, the risk for the drop-out in HIV infected persons increased significantly. To further reduce the drop-out of ART, it is important to take CD(4) into account in initiating ART and to strengthen the health education on treatment compliancy and training for healthcare providers.

Fewer beams and segments result in a shorter delivery time and a better quality intensity-modulated radiotherapy plan in gastric cancer

Background: This study evaluated whether IMRT using fewer beams and segments could reduce delivery time without compromising plan quality in gastric cancer adjuvant radiotherapy

Materials and Methods: Fifteen patients with advanced gastric cancer who underwent D2, R0 surgery were included in this study. IMRT plans for each patient were designed as 7 equal beams with 40 segments, 5 beams with 25 segments and 4 beams with 20 segments. The dosimetric parameters were compared for the planned target volume [PTV]. The dose of normal organs at risk [OARs] was also assessed. The monitor units and treatment times of the different IMRT plans were calculated

Results: The 20-segment IMRT plan significantly reduced the PTV maximum dose compared to the 40-segment IMRT plan. The 20-segment IMRT plan improved left kidney and liver dose sparing in V20 and V30 as well as the 40-segment IMRT plan did and provided be4er protection for the V20 [13.86+/-7.78] of the right kidney, the V30 [9.25+/-4.04] of the le kidney, the D mean [19.68+/-2.47] of liver and D max [38.79+/-3.57] of the spinal cord. Irradiation times in the 20-segment and 25-segment plans decreased by 2.5 and 1.9 min, respectively, compared to the 40-segment IMRT plan

Conclusion: IMRT using fewer beams and segments reduced delivery time without compromising plan quality in gastric cancer adjuvant radiotherapy. Fewer segments IMRT plans lowered the monitor units and the treatment time

Ultrasonography of immature teratomas: 11 case reports

Ovarian immature teratoma is a very rare type of tumor associated with a high relapse rate and mortality. Correspondingly, early diagnosis is important for effective treatment. The goal of this study was to retrospectively analyze the ultrasound characteristics of 11 cases of immature teratomas. Between January 2002 and December 2010, 11 patients were diagnosed with pathologically confirmed immature teratomas. Patients enrolled in this study underwent a transabdominal ultrasound examination prior to surgery. Tumor size, shape, internal echo, calcification, cystic degeneration, and blood flow for each immature teratoma were analyzed. Levels of alpha fetal protein [alphaFP] were also evaluated. The average tumor size was 8 cm [range, 4-13]. Echo patterns obtained included mixed echo [n = 7], solid echo [n = 2], and cystic echo [n = 2]. Coarse calcifications were detected in five cases, while blood flow signal was detected in one case, and ascites were detected in three cases. Only one case had elevated levels of alphaFP. Ultrasound imaging of immature teratomas detected large tumors that were predominantly involved mixed-echo masses, cystic degeneration, and coarse calcification on the cavity wall. In some cases, blood flow signal was detected in the mass and ascites were present in the abdominal cavity

Lack of efficacy of a herbal preparation (RCM-102) for seasonal allergic rhinitis: a double blind, randomised, placebo-controlled trial

BACKGROUND: A herbal preparation, known as RMIT Chinese Medicine 102 (RCM-102) consisting of eight herbs which demonstrates inhibition of the release of key inflammatory mediators associated with seasonal allergic rhinitis (SAR) was used. This study evaluated the efficacy and safety of RCM-102 for SAR. OBJECTIVE: This study evaluated the efficacy and safety of RCM-102 for SAR. METHODS: This randomised placebo-controlled trial involved subjects aged between 18 and 65 who were randomly assigned to either RCM-102 or a placebo group. After a two-week baseline period, all subjects took either RCM-102 or placebo capsules (two capsules each time, three times daily with a four hour interval) for a period of eight weeks. The primary end-points were the Five-Point Scale symptom scores. Rhinoconjunctivitis Quality of Life Questionnaire, relief medication usage, adverse events, kidney and liver function tests and full blood examination were secondary end-points. Intention-to-treat analysis was applied. RESULTS: One hundred and four subjects were randomised with 52 in each group. Ninety-five subjects (47 and 48 subjects in RCM-102 and placebo groups) completed the trial. Nine subjects withdrew from the study prior to the end of the second treatment week. At the end of the trial, there were no significant differences between the two groups with respect to all outcome measures. There were no liver or kidney function abnormalities reported. CONCLUSION: This mechanism-based RCM-102 was safe but not more beneficial than placebo for patients with SAR.

Key uncertainty sources analysis of water quality model using the first order error method

In this study, key uncertainty sources analysis was undertaken for a dynamic water model using a First order error analysis method. First, a dynamic water quality model for the Three Gorges Reservoir Regions was established using data after impoundment by the environmental fluid dynamics code model package. Model calibration and verification were then conducted using measured data collected during 2004 and 2006. Four statistical indices were employed to assess the modeling efficiency. The results indicated that the model simulated the variables well, with most relative error being less than 25%. Next, input and parameter uncertainty analysis were conducted for ammonia nitrogen, nitrate nitrogen, total nitrogen, and dissolved oxygen at 3 grid cells located in the upper, middle and downstream portions of the research area. For the nitrogen related variables, input from Zhutuo Station, the Jialingjiang River, and the Wujiang River were the main sources of uncertainty. Point and nonpoint sources also accounted for a large ratio of uncertainty. Moreover, nitrification contributed some uncertainty to the estimated ammonia nitrogen and nitrate nitrogen. However, reaeration was found to be a key source of uncertainty for dissolved oxygen, especially at the middle and downstream reaches. The analysis conducted in this study gives a quantitative assessment for uncertainty sources of each variable, and provides guidance for further pollutant loading reduction in the Three Gorge Reservoir Region