Preparation and preliminary evaluation of SARS-CoV-2 DNA vaccine based on PLGA nanoparticles / 药学学报

We constructed and optimized the plasmid DNA (pDNA) Opt-S encoding the gene of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, using poly (lactic-co-glycolic acid) copolymer (PLGA) as a delivery carrier for pDNA. PLGA-pDNA NPs were loaded by nanoprecipitation and its properties in vitro were preliminary evaluated. The results showed that the prepared PLGA-pDNA NPs were regular morphology, clear edges, with an average particle size of (184.2 ± 2.4) nm, polydisperse index (PDI) of 0.093 ± 0.013, zeta potential of (-68.10 ± 0.36) mV, and encapsulation rate of (98.92 ± 0.22)%. The PLGA-pDNA NPs were stable at -20 ℃ for 7 months and could protect pDNA against nuclease degradation. And they also exhibited sustained release of pDNA in vitro. The PLGA-pDNA NPs have low cytotoxicity and high safety. In addition, in vitro transfection experiments showed that the SARS-CoV-2 S gene could enter cells and be expressed. These results indicate that PLGA-pDNA NPs non-viral gene vector have simple preparation process and good performance, which are expected to provide a new idea for the research and development of SARS-CoV-2 vaccine.

Influencing factors of corneal epithelial punctate staining in patients wearing orthokeratology / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the influencing factors of punctate staining of corneal epithelium in patients wearing orthokeratology.METHOD: Data of 280 cases wearing orthokeratology were collected, including 185 cases in the group without corneal staining and 95 cases in the group with corneal staining. All patients were examined for general distant vision, intraocular pressure, slit lamp, fundus examination after mydriasis, comprehensive optometry, corneal topography, corneal thickness, corneal endothelium, axial length, Schirmer Ⅰtest(SⅠt)before wearing lenses, meibomian gland loss score before wearing lenses, eccentric distance, interleukin-2(IL-2)in tear, tumor necrosis factor-α(TNF-α)content analysis and so on. The influencing factors of corneal epithelium punctate staining were analyzed by univariate and multivariate Logistic regression.RESULTS: There were significant differences in preoperative diopter, preoperative meibomian gland deletion score, IL-2, TNF-α and lens sediment between the two groups(all P<0.05). Logistic regression analysis showed that diopter before wearing lenses was a protective factor for corneal epithelium punctate staining. Before wearing lenses, the loss of meibomian gland score, IL-2, TNF-α and lens deposits were the risk factors of corneal epithelium punctate staining. In the detection of corneal epithelium punctate staining, the comprehensive advantage of lens deposits was obvious, the specificity of lens deposits was higher, and the sensitivity of IL-2 was the highest. CONCLUSIONS: Before wearing lenses, diopter is the protective factor of corneal epithelium punctate staining, and the loss of meibomian gland score, IL-2, TNF-α and lens deposits are the risk factors of corneal epithelium punctate staining.

Research advances of adipose stem cell matrix gel in promoting wound healing / 中华烧伤杂志

In recent years, with the problem of aging population in China being prominant, the number of patients with chronic wounds such as diabetic foot, pressure ulcer, and vascular ulcer is increasing. Those diseases seriously affect the life quality of patients and increase the economy and care burden of the patients' family, which have been one of the most urgent clinical problems. Many researches have confirmed that adipose stem cells can effectively promote wound healing, while exogenous protease is needed, and there are ethical and many other problems, which limit the clinical application of adipose stem cells. Adipose stem cell matrix gel is a gel-like mixture of biologically active extracellular matrix and stromal vascular fragment obtained from adipose tissue by the principle of fluid whirlpool and flocculation precipitation. It contains rich adipose stem cells, hematopoietic stem cells, endothelial progenitor cells, and macrophages, etc. The preparation method of adipose stem cell matrix gel is simple and the preparation time is short, which is convenient for clinical application. Many studies at home and abroad showed that adipose stem cell matrix gel can effectively promote wound healing by regulating inflammatory reaction, promoting microvascular reconstruction and collagen synthesis. Therefore, this paper summarized the preparation of adipose stem cell matrix gel, the mechanism and problems of the matrix gel in promoting wound repair, in order to provide new methods and ideas for the treatment of chronic refractory wounds in clinic.

Research progress of exosomes based targeted delivery of antitumor drugs / 药学学报

Exosomes are one of the most important ways of cell-to-cell communication in living lives. They are involved in major physiological and pathological processes, including drug resistance, infection propagation, cancer development and cardiovascular diseases. The biological functions of exosomes made it possess characteristics of low immunogenicity, high delivery efficiency, ability to cross multiple biological barriers and targeting capacity, which also encourage people to try to use it as a drug carrier to overcome the disadvantages of poor stability, low solubility, low bioavailability and high toxicity of some drugs. In this paper, the latest progress of exosomes in the delivery of antitumor drugs, including small chemotherapeutic drugs, biological macromolecules and nucleic acid drugs, is reviewed. In addition, the isolation, drug loading, and modification method and the application prospect of exosomes are also discussed.

Mechanism of intestinal flora in process of knee osteoarthritis in mice alleviated by Jiawei Duhuo Jisheng Mixture / 中国药理学通报

Aim To investigate the potential mechanism of Jiawei Duhuo Jisheng Mixture regulating intestinal flora in the treatment of knee osteoarthritis(KOA)by 16S rRNA sequencing.Methods Eight-week-old male C57 mice were randomly divided into three groups:sham group,DMM group,and model+Jiawei Duhuo Jisheng Mixture group(Mixture group),6 mice per group.KOA model was induced by destabilization of medial meniscus surgery.16.25 mL·kg-1 dose mixture was given daily to the mixture group,and normal saline was given to the sham and DMM group.After eight weeks,the knee joints and colons of mice were collected,and the knee joints were prepared into paraffin sections,and the cartilage changes were observed with Safranin O-Fast Green and immunohistochemistry staining.16S rRNA sequencing of intestinal contents was performed to observe the changes of intestinal flora.Results Compared with model group,Jiawei Duhuo Jisheng Mixture could significantly reduce cartilage wear and OARSI score(P=0.033 5,P=0.029 5).16S rRNA sequencing showed that Jiawei Duhuo Jisheng Mixtrue could change the intestinal flora richness of KOA model mice,and improve the Alpha diversity(Chao1,Simpson)and Beta diversity(PCoA,NMDS).LefSe analysis showed that there were species with significant difference in abundance among the three groups(P=0.001),mainly including Lactobacillus,Firmicutes,Proteobacteria and other species.MetaCyc analysis indicated that Jiawei Duhuo Jisheng Mixture had effects on various metabolic pathways such as fatty acid,sugar and amino acid of intestinal flora(P<0.05).Conclusions Jiawei Duhuo Jisheng Mixtrue can effectively protect the articular cartilage and delay the progression of KOA.The mechanism may be through regulating the intestinal flora structure,protecting the intestinal barrier and reducing the inflammatory response.

Main Chemical Constituents and Modern Pharmacological Action of Schisandrae Chinensis Fructus： A Review / 中国实验方剂学杂志

Schisandrae Chinensis Fructus （SCF）， a commonly used clinical Chinese medicine， is rich in chemical components， including lignans， volatile oils， polysaccharides， organic acids， terpenoids， and flavonoids. It has a high medicinal value， which is manifested in the treatment of palpitation， insomnia， spontaneous perspiration， internal heat， consumptive thirst， fluid injury， chronic cough， asthma， frequent urination， enuresis， nocturnal emission， chronic diarrhea， etc. Modern pharmacological studies have found that SCF has sedative， hypnotic， brain invigorating， analgesic， anticonvulsant， and antidepressant effects in the central nervous system. In the digestive system， it can regulate gastrointestinal motility and protect the liver. In the immune system， it is effective in resisting tumors and human immunodeficiency virus （HIV）， and also potent in protecting the cardiovascular system， lung and kidney， reducing blood sugar， promoting reproduction， inhibiting bacteria， resisting hyperprolactinemia and osteoporosis， and protecting against embryo damage and retina injury. This study reviewed the available research on clinical pharmacological effects of SCF in recent years and provided ideas for further research on SCF and theoretical basis for its rational development and utilization， which was of great guiding significance in clinical disease treatment.

Association between macroscopic-factors and identified HIV/AIDS cases among injecting drug users: an analysis using geographically weighted regression model / 生物医学与环境科学（英文）

Drug use (DU), particularly injecting drug use (IDU) has been the main route of transmission and spread of Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) among injecting drug users (IDUs). Previous studies have proven that needles or cottons sharing during drug injection were major risk factors for HIV/AIDS transmission at the personal level. Being a social behavioral issue, HIV/AIDS related risk factors should be far beyond the personal level. Therefore, studies on HIV/AIDS related risk factors should focus not only on the individual factors, but also on the association between HIV/AIDS cases and macroscopic-factors, such as economic status, transportation, health care services, etc. The impact of the macroscopic-factors on HIV/AIDS status might be either positive or negative, which are potentially reflected in promoting, delaying or detecting HIV/AIDS epidemics.

Effect of artificial colloids on blood coagulation during shock stage of severe burn injury / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>There are controversies about the use of artificial colloids. This research was aimed to determine the effect of various artificial colloids on blood coagulation in the shock stage of severe burn injury.</p><p><b>METHODS</b>Totally, 18 female Ba-Ma mini-pigs were subjected to a 40% total body surface third-degree flame burn under anesthesia. Resuscitation therapy was applied 2 hours after the injury, using the burn shock fluid resuscitation formula commonly accepted in the surgical treatment of burns. The Ba-Ma mini-pigs were randomly assigned to three groups (six pigs in each group): succinylated gelatin group (the artificial colloid used was succinylated gelatin Injection), hydroxyethyl starch group (the artificial colloid used was hydroxyethyl starch (130/0.4)), and allogeneic plasma group (the colloid used was allogeneic plasma). Blood samples were collected from the animals prior to the burn injury and again at intervals of 4, 8, 24 and 48 hours post-injury. The platelet count (PLT), prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), and fibrinogen (Fib) were measured, followed by a statistical analysis of all results.</p><p><b>RESULTS</b>The PLT of succinylated gelatin group and hydroxyethyl starch group at intervals of 24 and 48 hours were (124.3 ± 52.7), (78.8 ± 16.4) × 10(9)/L and (159.0 ± 62.8), (87.3 ± 32.0)× 10(9)/L respectively. But in the allogeneic plasma group at intervals of 8, 24, and 48 hours were (234.3 ± 52.6), (136.0 ± 47.4), (75.8 ± 31.0) × 10(9)/L. The decrease were all statistically significant (P < 0.05, P < 0.01) when compared to pre-burn ((383.3 ± 77.9), (382.7 ± 65.7), (381.0 ± 49.4)× 10(9)/L). The PLT among the three groups, at all the time points, had no statistical difference (P > 0.05). Compared to pre-burn ((10.8 ± 0.9), (11.4 ± 0.8), (10.6 ± 0.7) seconds), the PT of succinylated gelatin group and hydroxyethyl starch group at 24 hours were (14.5 ± 1.5) and (16.2 ± 1.3) seconds, whereas in the allogeneic plasma group at 8 and 24 hours the PT were (13.0 ± 0.9) and (14.5 ± 1.5) seconds, i.e., an increase in the statistical significance (P > 0.01). Statistical significance was observed at 8 and 48 hours between the succinylated gelatin group and hydroxyethyl starch group, and at 48 hours between the hydroxyethyl starch and allogeneic plasma group (P < 0.05). The INR at 24 hours were (1.26 ± 0.13) in the succinylated gelatin group, (1.40 ± 0.11) in the hydroxyethyl starch group, and (1.13 ± 0.07) and (1.26 ± 0.13) at 8 and 24 hours in the allogeneic plasma group. When compared with pre-burn ((0.94 ± 0.08), (0.99 ± 0.07), and (0.92 ± 0.06) seconds), the other groups have increased significantly (P > 0.01). The comparison at 8 and 48 hours between the succinylated gelatin group and the hydroxyethyl starch group, at 48 hours between hydroxyethyl starch group and allogeneic plasma group showed statistical difference (P < 0.01). The APTT of succinylated gelatin group and hydroxyethyl starch group at 24 hours were (13.1 ± 1.1) and (14.6 ± 2.9) seconds. The APTT of the allogeneic plasma group at 4, 8 and 24 hours were (10.9 ± 1.4), (11.8 ± 1.1), and (13.7 ± 1.5) seconds. Compared to pre-burn ((11.5 ± 4.2), (11.2 ± 3.3), (10.1 ± 1.4) seconds), they were statistically significant (P < 0.05). There was no statistical difference in the APTT between the three groups, at all the time points. The Fib of the succinylated gelatin group at 24 and 48 hours were (4.3 ± 0.3) and (4.7 ± 0.2) g/L, (4.1 ± 0.3), and (5.0 ± 0.1) g/L in allogeneic plasma group, and at 8, 24, and 48 hours the Fib for the hydroxyethyl starch group was (2.9 ± 0.4), (4.0 ± 0.5), and (4.6 ± 0.6) g/L. Compared to pre-burn ((2.4 ± 0.2), (2.5 ± 0.3), (2.6 ± 0.5) g/L), they were all statistically significant (P < 0.01). There was no statistical difference in APTT between the three groups, at all time points.</p><p><b>CONCLUSION</b>The changes of the indices in blood coagulation during the shock phase of a severe burn injury correlate with the stress response to the burn, rather than to the application of HES (130/0.4) and succinylated gelatin.</p>

Effects of resuscitation with different kinds of colloids on pulmonary edema in swine in shock stage of severe burn injury / 中华烧伤杂志

<p><b>OBJECTIVE</b>To observe and compare the effects of natural colloid and artificial colloid on pulmonary edema of swine during shock stage of severe burn injury.</p><p><b>METHODS</b>Twelve Guangxi Bama miniature swine were inflicted with 40% TBSA full-thickness burn on the back, and then they were divided into natural colloid group (N) and artificial colloid group (A) according to the random number table, with six swine in each group. At post injury hour (PIH) 2, fluid resuscitation was begun. The main part of electrolyte was lactic acid Ringer's solution. The colloids included swine plasma and hydroxyethyl starch 130/0.4. Before injury and at every hour within PIH 48, heart rate, blood pressure, urine volume, central venous pressure (CVP), and pulmonary arterial wedge pressure (PAWP) were recorded. The mean heart rate, blood pressure, urine volume per hour per kg of body weight, CVP, PAWP, resuscitation liquid volume, and the ratio of fluid intake to output during the first and second PIH 24 were calculated. At PIH 48, lung tissue was harvested for histopathological observation and calculation of lung water ratio. Data were processed with one-way analysis of variance, analysis of variance of repeated measurement, LSD test and independent sample t test.</p><p><b>RESULTS</b>(1) There were no statistically significant differences between two groups in heart rate, blood pressure, and urine volume before injury and during the first and second PIH 24 (P values all above 0.05); during the first PIH 24, the CVP and PAWP of group A were significantly higher than those of group N (P values all below 0.05). Compared with those before injury, the heart rate, CVP and PAWP of two groups during the first and second PIH 24 were significantly higher (P < 0.05 or P < 0.01); the urine volume of group N was decreased during the first PIH 24 (P < 0.05), while there was no significant change in group A (P > 0.05); the urine volumes of two groups during the second PIH 24 were increased, while no statistically significant differences were observed (P values all above 0.05). There were no statistically significant differences in blood pressure of two groups between the first, second PIH 24 and before injury (P values all above 0.05). (2) There were no statistically significant differences in the resuscitation liquid volume and fluid intake to output ratio between two groups during the first and second PIH 24 (P values all above 0.05). (3) The alveolar septum was found widened in varying degrees, and there were edema fluid accumulating and inflammatory cell infiltrating within the pulmonary interstitial of lung tissue sections in both two groups. (4) The lung water ratio of group N [(71 ± 10)%] was not statistically significant different from that of group A [(79 ± 4)%, t = -1.753, P > 0.05].</p><p><b>CONCLUSIONS</b>The natural colloid or artificial colloid (hydroxyethyl starch 130/0.4) applied during shock stage had similar effects on pulmonary edema in swine with severe burn.</p>

Comparison among several foam dressings in the properties of water-absorption, water-locking and air permeability / 中华烧伤杂志

<p><b>OBJECTIVE</b>To compare the properties of water-absorption, water-locking, and air permeability among several foam dressings, and to provide references for clinician in choosing dressings for different types of wounds.</p><p><b>METHODS</b>The comparison was made among Allevyn foam dressing, Mepilex foam dressing, and Biatain foam dressing that were commonly used in clinic. NaCl and CaCl2·H2O respectively in the weight of 8.3 g and 0.367 g were diluted with distilled water to the volume of 1 L to simulate wound exudation. The simulated wound exudation was used to test the water-absorbing rate of dressings at post immersion hour (PIH) 24, water-absorbing speed of dressings at post immersion minute (PIM) 1, 5, 10, and 20, the diffusion diameter of exudation dripped on the surface of dressings for 5 min to reflect the water-locking capacity of dressings, and the water evaporation capacity of exudation after being sealed up by dressings for 24 h to reflect the air permeability of dressings. Five samples of each dressing were used for each index. Data were processed with one-way analysis of variance and analysis of variance of repeated measurement, and LSD method was applied in paired comparison.</p><p><b>RESULTS</b>(1) The water-absorbing rate at PIH 24 of Allevyn foam dressing, Mepilex foam dressing, and Biatain foam dressing were respectively (646 ± 18)%, (616 ± 19)%, and (499 ± 11)% (F = 423.854, P < 0.01). The differences between each two dressings in water-absorbing rate were statistically significant (with P values all below 0.01). (2) The water-absorbing speed of Allevyn foam dressing at PIM 1, 5, 10, and 20 were (35.20 ± 2.31), (12.48 ± 0.37), (6.63 ± 0.23), and (3.39 ± 0.08) g×s(-1)×m(-2), which were obviously lower than those of Mepilex foam dressing [(119.68 ± 2.59), (24.39 ± 0.62), (12.33 ± 0.29), and (6.18 ± 0.13) g×s(-1)×m(-2)] and Biatain foam dressing [(121.09 ± 3.41), (24.73 ± 0.52), (12.37 ± 0.25), (6.18 ± 0.13) g×s(-1)×m(-2)], with P values all below 0.01. The water-absorbing speed of each dressing showed the trend of declination among three dressings with prolongation of time. The differences between two adjacent time points within each dressing in water-absorbing speed were statistically significant (with P values below 0.01). (3) Diffusion diameters of exudation dripped on the surface of Allevyn foam dressing, Mepilex foam dressing, and Biatain foam dressing were respectively (5.66 ± 0.15), (4.84 ± 0.15), (3.94 ± 0.21) cm (F = 124.742, P < 0.01). The differences between each two of the three dressings in diffusion diameter were statistically significant (with P values all below 0.01). (4) The water evaporation capacity of exudation after being sealed up by each dressing for 24 h decreased in succession for Allevyn foam dressing, Mepilex foam dressing, and Biatain foam dressing, which were respectively (31.2 ± 3.1), (29.7 ± 8.7), (5.6 ± 2.8) g×h(-1)×m(-2) (F = 24.324, P < 0.01). The water evaporation capacity of exudation sealed with Biatain foam dressing was significantly lower than that of exudation sealed with Allevyn foam dressing and Mepilex foam dressing (with P values below 0.01).</p><p><b>CONCLUSIONS</b>Among the three kinds of foam dressings, Allevyn performs best in water-absorbing rate, water-locking capacity, and air permeability, while Mepilex and Biatain perform best in water-absorbing speed. For selecting foam dressing in clinic, the properties of foam dressings and wound characteristics should be considered at the same time.</p>

Study on application of rep-PCR fingerprint in rapid identification of beer-spoilager / 生物工程学报

The application potential of rep-PCR in typing beer-spoilage isolates was studied. The effects of different factors, including DNA templates and primers, on the quality and reproducibility of fingerprints were investigated. The CTAB protocol was shown to be the feasible method for DNA extraction. Primers BOXA1R and (GTG)5 were used in rep-PCR, and the PCR products were sequenced to identify strains isolated from two breweries. Rep-PCR fingerprint profiles were obtained by using GelCompar II software. Cluster analysis showed that the isolates belonging to Lactobacillus brevis, L. buchneri, L. casei/paracasei, L. plantarum are divided into 2 or 3 subgroups. In addition, the two rep-PCR fingerprint profiles complemented with each other in typing these isolates. Combining the similarity coefficient cut-off (SCC) of species, 9 unknown isolates were identified rapidly by using both fingerprint databases. The results indicate that rep-PCR is a simple, reliable and promising method for rapid identification of beer-spoilager.