Small interfering RNA (siRNA) has a promising future in the treatment of ocular diseases due to its high efficiency, specificity, and low toxicity in inhibiting the expression of target genes and proteins. However, due to the unique anatomical structure of the eye and various barriers, delivering nucleic acids to the retina remains a significant challenge. In this study, we rationally design PACD, an A-B-C type non-viral vector copolymer composed of a hydrophilic PEG block (A), a siRNA binding block (B) and a pH-responsive block (C). PACDs can self-assemble into nanosized polymeric micelles that compact siRNAs into polyplexes through simple mixing. By evaluating its pH-responsive activity, gene silencing efficiency in retinal cells, intraocular distribution, and anti-angiogenesis therapy in a mouse model of hypoxia-induced angiogenesis, we demonstrate the efficiency and safety of PACD in delivering siRNA in the retina. We are surprised to discover that, the PACD/siRNA polyplexes exhibit remarkable intracellular endosomal escape efficiency, excellent gene silencing, and inhibit retinal angiogenesis. Our study provides design guidance for developing efficient nonviral ocular nucleic acid delivery systems.

OBJE CTIVE To establish the finger prints for Yinhuang solution for inhalation and determine the contents of neochlorogenic acid ，chlorogenic acid and cryptochlorogenic acid simultaneously. METHODS Using baicalin as reference ，the fingerprints of Yinhuang solution for inhalation were established by high performance liquid chromatography （HPLC）. Relative correction factors of neochlorogenic acid and cryptochlorogenic acid were calculated by slope correction method ，using chlorogenic acid as reference ；the contents of them were calculated according to relative correction factor. The results of quantitative analysis of multi-components by single marker （QAMS）were compared with those of external standard method （ESM）. RESULTS There were 18 common peaks in the fingerprints of 10 batches of Yinhuang solution for inhalation ，and their similarities with reference fingerprint were higher than 0.90. A total of 7 common peaks were identified as baicalin ，neochlorogenic acid ，chlorogenic acid ， cryptochlorogenic acid ，isochlorogenic acid B ，3，5-di-O-caffeoylquinic acid and 4，5-di-O-caffeoylquinic acid. The linear range of neochlorogenic acid ，chlorogenic acid and cryptochlorogenic acid were 0.025 0-1.247 4 μg（r＝0.999 7），0.039 3-1.178 7 μg（r＝ 0.999 9），0.031 6-1.184 1 μg（r＝0.999 9），respectively. RSDs of precision ，reproducibility and stability tests （48 h）were all lower than 1.0％. The average recoveries were 93.92％（RSD＝1.32％ ，n＝6），94.46％（RSD＝1.45％，n＝6），93.93％（RSD＝ 1.57％，n＝6）. Relative correction factors of neochlorogenic acid and cryptochlorogenic acid were 1.068 and 1.233. The contents of neochlorogenic acid and cryptochlorogenic acid determined by QAMS method were 0.301 8-0.386 3 and 0.262 5-0.362 5 mg/mL， respectively. The contents of neochlorogenic acid ，chlorogenic acid and cryptochlorogenic acid by ESM were 0.302 6-0.387 2， 0.231 0- 0.334 0，0.261 6-0.361 3 mg/mL，respectively. The deviations of the content determination results of the two methods（except for chlorogenic acid ）were both not higher than 0.20％. CONCLUSIONS Established HPLC fingerprints are stable and feasible. Established QAMS method is accurate and rapid. HPLC fingerprint combined with QAMS can be used for the quality control for Yinhuang solution for inhalation ．

Objective: To investigate the role and mechanisms of empagliflozin(EMPA) on myocardial ischemia/reperfusion(MI/R) injury. Methods : Forty male SD rats were randomly divided into Control group, MI/R group,2. 5 μmol/L EMPA combined with MI/R group(EMPA + MI/R) as well as EMPA and 10 μmol/L SIRT1 inhibitor EX527 combined with MI/R group(EMPA + EX527 + MI/R). Cardiac function, myocardial fiber morphology and infarct size were detected. The content of malonaldehyde(MDA), the activities of superoxide dismutase(SOD)and succinodehydrogenase(SDH) in myocardium were determined by ELISA. The protein expressions of Cytochrome c, Cleaved caspase-3, SOD2, gp91phoxand SIRT1 were observed by Western blot. The ROS level was detected by DHE staining. Results: Compared with Control group, MI/R group manifested the decreased cardiac function and myocardial fiber rupture. Myocardial infarction area, the expressions of Cytochrome c, Cleaved caspase-3 and gp91phox, as well as the MDA content and ROS level increased, while decreased the activities of SOD and SDH, and the expressions of SOD2 and SIRT1. Compared with MI/R group, EMPA + MI/R group improved cardiac function and inhibited myocardial fiber rupture, myocardial infarction area, the expressions of Cytochrome c and Cleaved caspase-3. The expression of gp91phox, the MDA content and ROS level were also downregulated,while the activities of SOD and SDH and the expressions of SOD2 and SIRT1 were upregulated. However, the protective effects of EMPA on MI/R heart were blocked by EX527. Conclusion EMPA alleviates MI/R injury by inhibiting mitochondrial oxidative stress and apoptosisviaactivating SIRT1.

Objective:To observe and compare the therapeutic effects of glucosamine sulfate (GS) and diacerein (DCN) on adult Kashin-Beck disease (KBD).Methods:A clinical randomized controlled trial was conducted in the historical severe KBD areas Fanrong Township, Fulu Town, Long'anqiao Town, Lianghe Town, Shaowen Township of Heilongjiang Province, and 240 patients were selected according to the criteria of "Diagnosis of Kashin-Beck Disease" (WS/T 207-2010), then divided into GS and DCN groups (gender, age, and KBD condition balanced) via the random number table method, with 120 patients in each group. Followed up once a month to investigate the patient's medication and clinical symptoms, and distributed drugs for the next stage. Fasting blood samples and urine samples were collected before, during, and at the end of treatment (0, 90, and 180 days). Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum interleukin (IL)-1β level and urine pyridinol (PYD) level. Visual analog scale (VAS) scores, evaluation of affected joints, self-evaluated efficacy, and evaluation of adverse reactions were carried out through questionnaires. Joint dysfunction scores and medications efficacy determination were performed according to the "Judgment of Kaschin-Beck Disease Treatment Effect" (WS/T 79-2011).Results:Expression of cytokines related to cartilage metabolism: after 180 days of treatment, serum IL-1β levels, urine PYD levels in GS group and urine PYD levels in DCN group were lower than those in the same group at 0 day of treatment ( Z = - 2.332, - 5.420, - 5.204, P < 0.05). VAS scores: after 90 days of treatment, the pain, stiffness scores of patients in GS group and the pain, stiffness, and function scores in DCN group were lower than those in the same group at 0 day of treatment ( Z = - 2.612, - 2.359, - 3.637, - 2.881, - 2.238, P < 0.05); after 180 days of treatment, the pain, stiffness and function scores of patients in GS and DCN groups were significantly lower than those of the same group at 0 day of treatment ( Z = - 6.738, - 9.530, - 7.781, - 5.428, - 3.761, - 3.587, P < 0.01). Evaluation of affected joints: after 90 and 180 days of treatment, except for pain of weather changes in DCN group, the scores of symptomatic joints in the two groups were lower than those at 0 day of treatment ( P < 0.05). Efficacy self-evaluation: after 180 days of treatment, the self-evaluated efficacy ratio of DCN group was higher than that of GS group and the same group after 90 days of treatment (χ 2 = 4.165, 4.022, P < 0.05). Evaluation of adverse reactions: after 90 and 180 days of treatment, the main adverse reactions of patients in GS and DCN groups were gastrointestinal symptoms. Joint dysfunction scores: after 90 days of treatment, the sum of the effective rate and the markedly effective rate of GS group was higher than that of DCN group (χ 2 = 4.993 , P < 0.05); while after the 180 days of treatment, there was no significant difference between the two groups (χ 2 = 0.417 , P > 0.05). Conclusions:Both GS and DCN have a certain therapeutic effect on adult KBD and can improve clinical symptoms. The GS takes effect quickly, and long-term use can protect cartilage from inflammatory factors to a certain extent.

Objective:To investigate the clinical characteristics and therapeutic methods of coronary artery aneurysm (CAA).Methods:The clinical data and coronary angiography of 32 patients confirmed by coronary angiography as coronary aneurysm in Shenzhen Hospital of Southern Medical University and Shenzhen People′s Hospital were collected. They were followed up, and the different therapeutic methods were analyzed.Results:Thirty-two cases (1.8%) of coronary artery aneurysms were found in 1 778 patients undergoing coronary angiography. The main sites of coronary ectasia were right coronary artery, anterior descending branch and circumflex branch, and the left main branch was rare. Among the patients with coronary artery aneurysms, there were 25 patients with coronary artery stenosis. All the 32 patients were given anticoagulant, antiplatelet, improvement of coronary spasm and statin therapy, among whom 2 patients were treated with stent implantation and 6 patients were treated with coronary artery bypass graft (CABG) and ligation of coronary aneurysm. During the follow-up (average 15 months) of 1 patient, acute myocardial infarction reoccurred, and coronary angiography indicated that the stenosed coronary segments after artery ectasia was occluded because of thromboembolism. In the remaining patients, there were no major cardiovascular events such as angina pectoris, acute myocardial infarction and sudden cardiac death.Conclusions:Coronary artery aneurysm is not a rare heart disease. Coronary thromboembolism, thrombosis and vasospasm are the main causes of angina pectoris and myocardial infarction. Anticoagulant, antiplatelet, antispasmodic drugs and suitable coronary artery bypass can significantly improve the clinical prognosis of patients with coronary artery aneurysm.

Objective:To investigate the degree of limb dysfunction in adult patients with Kashin-Beck disease (KBD), and the correlation between clinical grade of KBD and physical disability classification.Methods:Based on the monitoring data, using typical survey methods, 10 natural villages were selected as survey sites in the historical critical area of KBD in Heilongjiang Province in 2015. Patients over 40 years old with KBD were investigated by questionnaire, joint range of motion(ROM) examination, and X-ray film were performed. The degree of physical disability of the surveyed patients was evaluated according to the national standard of "Classification and Grading of Disability of the Disabled" (GB/T 26341-2010). The correlation between clinical classification of KBD and limb disability classification was analyzed.Results:A total of 137 adult patients with KBD were investigated, the age was (57.4 ± 9.9) years old. Among them, 84 were males and 53 were females; 95 were grade Ⅰ, 30 were grade Ⅱ and 12 were grade Ⅲ. The most common joint pain of upper limb was interphalangeal joint(126 cases, 126/137), followed by elbow joint (116 cases, 116/137); the lower limbs were mainly ankle joint (118 cases, 118/137) and knee joint (107 cases, 107/137). There were significant differences of detection rates in elbow, knee, ankle, hip and wrist joints dysfunction among different age groups ( P < 0.05). The detection rate increased with age. There was no correlation between the clinical grade of KBD and the classification of physical disability ( rs = - 0.142, P > 0.05). KBD patients accounted for the highest proportion of tertiary disability (60 cases, 60/137). The physical disability of male patients was more serious than that of female patients (χ 2 = 22.610, P < 0.01). Conclusions:In adults with KBD, interphalangeal joint pain is the most common in the upper limbs, and the ankle and knee joints are the most common in the lower limbs. There is no correlation between clinical grade of KBD and the level of physical disability. The degree of physical disability in male patients is higher than that in female patients.

Objective To study the trends of lung cancer mortality among adult residents in Macheng City, Hubei Province from 1984 to 2018． Methods Mortality data was extracted from Macheng City disease surveillance points (DSPs) system and China Demographic Yearbook. The age-period-cohort (APC) model and Intrinsic Estimator algorithm were used to estimate the age effect, period effect and cohort effect of lung cancer mortality. Results The age effect coefficient of lung cancer mortality increased with age from 20 to 74 years old. The mortality risk of the 70-74 group was 42.62 times that of the 20-24 group. The period effect coefficient of lung cancer mortality also continued to rise with time. The cohort effect coefficient was parabolic, and residents born in 1939-1943 had the highest coefficient (1.298 4). Conclusion The risk of lung cancer death of adult residents in Macheng City significantly increased with the year and the rapid development of socio-economics.

To analyze the difficulty, distinction and result of the first national public health practice skills competition among college students, it showed the general situation of this competition, and discussed the present situation, problems and countermeasures of skills training for students majoring in preventive medicine. Based on such competition, educators can promote teaching reform and post competency training.

Purpose: RIOK1 has been proved to play an important role in cancer cell proliferation and migration in various types of cancers—such as colorectal and gastric cancers. However, the expression of RIOK1 in breast cancer (BC) and the relationship between RIOK1 expression and the development of BC are not well characterized. In this study, we assessed the expression of RIOK1 in BC and evaluated the mechanisms underlying its biological function in this disease context. Materials and Methods: We used immunohistochemistry, western blot and quantitative real-time polymerase chain reaction to evaluate the expression of RIOK1 in BC patients. Then, knockdown or overexpression of RIOK1 were used to evaluate the effect on BC cells in vitro and in vivo. Finally, we predicted miR-204-5p could be a potential regulator of RIOK1. Results: We found that the expression levels of RIOK1 were significantly higher in hormone receptor (HR)–negative BC patients and was associated with tumor grades (p=0.010) and p53 expression (p=0.008) and survival duration (p=0.011). Kaplan-Meier analysis suggested a tendency for the poor prognosis. In vitro, knockdown of RIOK1 could inhibit proliferation, invasion, and induced apoptosis in HR-negative BC cells and inhibited tumorigenesis in vivo, while overexpression of RIOK1 promoted HR-positive tumor progression. MiR-204-5p could regulate RIOK1 expression and be involved in BC progression. Conclusion These findings indicate that RIOK1 expression could be a biomarker of HR-negative BC, and it may serve as an effective prognostic indicator and promote BC progression.

In order to enhance the level of public health practical skills among undergraduates majoring in preventive medicine and improve the professional skills of disease prevention and control staff in case of public health emergencies,Nanjing Medical University School of Public Health performed an individual protection training for senior undergraduates majoring in preventive medicine in 2017.After related experience was summarized and students' feedback was collected,comprehensive training of public health practical skills was pedormed for senior undergraduates majoring in preventive medicine in 2018,with the inclusion of virtual experiments for public health.The results showed that the students were interested in practical skill training,mastered the contents of the training,and took pride in their major.This training has an excellent teaching effect and can enhance the ability to deal with public health emergencies among students majoring preventive medicine.